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2017
Product Name Manufacturer Contents
2-4 Zalf Nufarindo Salicylic acid 2%, sulfur precipitated 4%
Acendril Captopril
Acenor-M Fosinopril Na
Acepress Captopril
Aciblock Ranitidine
Aclonac Diclofenac K
Acrios Acarbose
Actal/Actal Plus Per Actal tab Creamaline spray dried powd 360
mg [equiv to Al(OH)3 216 mg]. Per Actal Plus tab
Creamaline spray dried powder 360 mg [equiv to
Al(OH)3 216 mg], Mg(OH)2 monohydrate [equiv
to Mg(OH)2 150 mg], simethicone 25 mg
Acticoat Nanocrystalline Ag
A-D Plex Per 0.3 mL Vit A 1,500 iu, vit B1 0.6 mg, vit B2 0.5
mg, vit B3 5 mg, vit B5 2.5 mg, vit B6 0.5 mg, vit
B12 1.5 mcg, vit D 400 iu
Adalat Nifedipine
Adebion Per mL Vit A 5,000 iu, vit D 500 iu, vit B1 2 mg, vit
B2 3 mg, vit B6 2 mg, vit B12 2 mcg, nicotinamide
20 mg, D-panthenol 5 mg, L-lysine HCl 25 mg
Adelysin Per mL Vit A 5,000 iu, vit B1 2 mg, vit B2 3 mg, vit
B6 2 mg, vit B12 2 mcg, vit D 500 iu,
nicotinamide 20 mg, panthenol 5 mg, lysine HCl
25 mg
Adfer Fahrenheit Fe gluconate 250 mg, manganese sulfate 200
mcg, copper sulfate 200 mcg, vit C 50 mg, folic
acid 1,000 mcg, vit B12 7.5 mcg, sorbitol 25 mg
Aerius D-12 Merck Sharp & Dohme Desloratadine 2.5 mg, pseudoephedrine sulphate
120 mg
Aeroson Dimethicone
Aerrane Isoflurane
Afinitor Everolimus
Afomix Folic acid 1,000 mcg, vit B1 100 mg, vit B6 100
mg, vit B12 100 mcg, DHA powd 60 mg, amino
acid 5 mg, ginger extr 50 mg
Afrin Bayer Indonesia Oxymetazoline HCl
Aggravan Cilostazol
Agrezol Cilostazol
Akrofen Phenylbutazone
Akta Vol Per 5 mL Vit A 4,000 IU, vit B1 2.5 mg, vit B2 2.5
mg, vit B6 0.75 mg, nicotinamide 15 mg,
panthenol 5 mg, vit C 60 mg, vit D 200 IU, Fe 3.6
mg. Per mL Vit A 3,600 IU, vit B1 1.2 mg, vit B2
1.8 mg, vit B6 0.3 mg, nicotinamide 15.8 mg,
panthenol 1 mg, vit C 60 mg, vit D 666 IU
Alabetic Futamed a-lipoic acid (ALA) 300 mg, folic acid 400 mcg,
cyanocobalamin (vit B12) 100 mcg
Albucid Sulfacetamide Na
Alco/Alco Plus/Alco Plus DMP Interbat Per 0.8 mL Alco drops Pseudoephedrine HCl 7.5
mg. Per 5 mL Alco Plus syr Pseudoephedrine HCl
30 mg, brompheniramine maleate 2 mg. Per 5
mL Alco Plus DMP syr Pseudoephedrine HCl 30
mg, brompheniramine maleate 2 mg,
dextromethorphan HBr 10 mg
Aldactone Spironolactone
Aldiab Glipizide
Alegysal Pemirolast K
Alernitis Loratadine
Aleros Actavis Desloratadine
Alexan Cytarabine
Alflam Diclofenac K
Alganax Alprazolam
Algisite M Ca alginate
Algut Allopurinol
Alista Cilostazol
Alkeran Melphalan
Allohex Loratadine
Alluric Allopurinol
Alodan Allopurinol
Alofar Allopurinol
Alomide Lodoxamide
Alopros Finasteride
Alora Vit A 5,000 IU, vit C 100 mg, vit D 100 IU, vit E 10
IU, vit K 85 mcg, thiamine 1.2 mg, riboflavin 1.2
mg, vit B6 2 mg, folic acid 800 mcg, vit B12 1.3
mcg, Ca 128 mcg, Fe 20 mg, phosphorus 100 mg,
iodine 150 mcg, Mg 200 mg, Zn 20 mg, copper
1.5 mg, DHA 50 mg
Aloxid Minoxidil
Alpenaso Terfenadine
Alphadine Povidone-iodine
Alphadine Gargle Povidone-iodine
Alphagesic Paracetamol
Alphamol Paracetamol
Alsine Per 5 mL Vit A 4,000 iu, vit D 300 iu, vit B1 3 mg,
vit B2 2 mg, vit B6 1 mg, vit B12 5 mcg, vit C 50
mg, niacinamide 20 mg, Ca pantothenate 5 mg,
L-lysine HCl 200 mg
Aludonna D Armoxindo Farma Per chewable tab/5 mL susp Al(OH)3 dried gel
200 mg, Mg(OH)2 200 mg, simethicone 20 mg
Amaropo Plus Phapros ß-carotene 6 mg, vit C 100 mg, vit E 25 mg,
lycopene 6 mg
Amaryl M Sanofi Group Indonesia Per 1/250 mg Glimepiride 1 mg, metformin HCl
250 mg. Per 2/500 mg Glimepiride 2 mg,
metformin HCl 500 mg
Ambiopi Mersifarma TM Ampicillin trihydrate
Aminoleban Infusion Otsuka High conc of branched chain amino acid & low
conc of aromatic amino acid (no tyrosine), Na, Cl,
other important amino acids
Aminoleban Oral Per sachet Protein 13.5 g, fat (rice oil) 3.5 g,
carbohydrate 32.35 g, L-isoleucine 1.92 g, L-
leucine 2.04 g, L-valine 1.6 g, other important
amino acids, vits & minerals. Energy: 210 kCal.
Amiparen Otsuka Per L Total free amino acids 100 g, nitrogen 15.7
g, Na 2 meq, acetate 120 meq
Amnorel 600 Sanbe Per 1,000 mL Amino acid 5% (BCAA 16.4%) (L-
isoleucine 3.2 g, L-leucine 2.4 g, L-lysine, L-
malate 3.83 g, L-methionine 3 g, L-phenylalanine
4 g, L-threonine 2 g, L-tryptophan 1 g, L-valine
3.2 g, L-arginine HCl 7.5 g, L-histidine 1 g, L-
alanine 6 g, glycine 14 g, L-proline 2 g, L-malic
acid 0.56 g, d-sorbitol 50 g), sorbitol 5%, vit B2,
vit B3, vit B6, vit C, Na 35 meq, K 25 meq, Mg 10
meq, acetate 35 meq, malate 22 meq, Cl 38 meq.
Osmolarity: 1,286 mOsm/L. Energy: 600 kCal
Amoxillin Amoxicillin
Amoxsan/Amoxsan Forte ManufacturerContentsIndications/ Amoxicillin (Oral: Trihydrate; Inj: Na)
UsesDosage/Directions for
UseAdministrationContraindicatio
nsSpecial PrecautionsAdverse
ReactionsInteractionsPreg Safety
(US)MIMS ClassATC
ClassificationRegulatory
ClassificationPresentation/Packing
Anabion Plus DHA DHA 10 mg, lysine HCl 200 mg, vit B1 5 mg, vit B2
2 mg, vit B6 25 mg, vit B12 3 mcg
Anafen Ibuprofen
Anavit Vit A 2,500 iu, vit B1 0.6 mg, vit B2 phosphate 0.5
mg, vit B6 0.5 mg, vit B12 1.5 mcg, vit D 500 iu,
niacinamide 5 mg, Ca pantothenate 2.5 mg
Andalan Pil KB/Andalan Fe Per Andalan PIL KB active tab Levonorgestrel 0.15
mg, ethinylestradiol 0.03 mg. Per Andalan Fe
active tab Levonorgestrel 0.15 mg,
ethinylestradiol 0.03 mg plus placebo tab
contains Fe fumarate 75 mg
Androlon Mesterolone
Anexate Flumazenil
Anfuhex Ketoconazole
Anhissen Loratadine
Anlos Loratadine
Anmerob Metronidazole
Anmum Infacare 1 Per 100 kCal Protein 2.6 g, whey protein 1.6 g,
alpha- lactalbumin (alpha-protein) 176.5 mg,
taurine 6.3 mg, nucleotides 4.9 mg, fat 5.5 g,
carbohydrate 11 g, lactose 10.5 g, water 0.5 g,
linoleic acid 588.2 mg, linolenic acid 58.8 mg,
DHA 7.8 mg, arachidonic acid 11.8 mg, lipid
complex 0.9 mg, vit A 92.2 mcg, ß-carotene 25.5
mcg, vit D 1.2 mcg, vit E 1 mg, vit K 7.6 mcg, vit
B1 98 mcg, vit B2 176.5 mcg, vit B3 1,058.8 mcg,
vit B5 647.1 mcg, vit B6 58.8 mcg, folic acid 11.6
mcg, vit B12 0.6 mcg, vit C 11.6 mg, biotin 2.2
mcg, choline 17.6 mg, Ca 96.1 mg, phosphorus
64.7 mg, Mg 12.4 mg, Fe 1.7 mg, manganese
15.3 mcg, copper 82.4 mcg, iodine 82.4 mcg, Na
36.5 mg, K 111.8 mg, Cl 96.1 mg. Energy: 100
kCal.
Anmum Infacare 2 Per 33 g Total fat 8 g, protein 5 g, carbohydrate
18 g, Na 75 mg, vit A 5 mcg, vit C 19 mg, vit D3 2
mcg/82 iu, vit E 2.2 mg/3.2 iu, vit K1 16 mcg, vit
B1 132 mcg, vit B2 296 mcg, vit B3 1,612 mcg, vit
B6 132 mcg, folic acid 18 mcg, vit B12 1 mcg, Ca
181 mg, Fe 2.4 mg, phosphorus 135 mg, Mg 21
mg, Zn 1.3 mg, iodine 32 mcg, manganese 25
mcg, linoleic acid 855 mg, linolenic acid 99 mg,
DHA 13 mg, arachidonic acid 13 mg, lipid
complex 1.9 mg, whey protein 2.7 g, a-
lactalbumin 329 mg, taurine 10.5 mg,
nucleotides 8.2 mg, ß-carotene 43 mcg, biotin
3.2 mcg, choline 30 mg, pantothenic acid 1,283
mcg, K 191 mg, Cl 161 mg, copper 135 mcg.
Energy: 160 kCal.
Anmum Lacta Chocolate Per 46 g Total fat 5 g, saturated fat 2.5 g, trans
fat, cholesterol 13 mg, linoleic acid (omega 6) 0.3
g, protein 13 g, total carbohydrate 23 g, fiber 3.4
g, sugar 10 g, Na 170 mg, K 550 mg, vit A 360
mcg, vit B3 8.5 mg, vit C 39 mg, vit D3 2.5 mcg,
vit B1 0.7 mg, vit B2 1.3 mg, vit B3 8.5 mg, vit B5
3.1 mg, vit B6 0.8 mg, vit B9 250 mcg, vit B12 1.4
mcg, Ca 500 mg, Fe 11 mg, Mg 51 mg,
phosphorus 396 mg, Zn 1.5 mg, iodine 56 mcg, a-
linolenic acid (omega 3) 0.08 g, DHA 25 mg, sialic
acid 94 mg, lactose 6.3 g, biotin 14 mcg, choline
359 mg, Cl 398 mg. Energy: 190 kCal.
Anmum Lacta Plain Per 37.5 g Total fat 4.5 g, saturated fat 2.5 g,
cholesterol 10 mg, linoleic acid (omega 6) 0.3 g,
protein 12 g, total carbohydrate 17 g, fiber 2.5 g,
Na 130 mg, K 520 mg, vit A 360 mcg, vit C 39 mg,
vit D3 2.5 mcg, vit B1 0.7 mg, vit B2 1.2 mg, vit
B3 8.5 mg, vit B5 2.6 mg, vit B6 0.8 mg, vit B9
250 mcg, vit B12 1.4 mcg, Ca 500 mg, Fe 7.4 mg,
Mg 40 mg, phosphorus 316 mg, Zn 1.4 mg,
iodine 56 mcg, a-linolenic acid (omega 3) 0.1 g,
DHA 25 mg, sialic acid 66 mg, lactose 4.8 g,
biotin 8.4 mcg, choline 322 mg, Cl 42 mg. Energy:
160 kCal.
Anmum Materna Chocolate Per 40 g Total fat 5 g, saturated fat 2.5 g, trans fat
6 g, cholesterol 13 mg, linoleic acid (omega 6) 0.3
g, protein 13 g, carbohydrate 24 g, sugar 10 g, Na
170 mg, K 550 mg, vit A 240 mcg, vit C 30 mg, vit
D3 2.5 mcg, vit B1 94 mcg, vit B2 0.7 mg, vit B5
0.7 mg, vit B6 1 mg, folic acid 340 mcg, vit B12 1
mcg, Ca 500 mg, Fe 7.5 mg, Mg 52 mg,
phosphorus 337 mg, Zn 1.6 mg, iodine 35 mcg,
linolenic acid 0.09 g, DHA 25 mg, gangliosides 4.2
mg, fiber 3 g, sialic acid 98 mg, lactose 9 g, biotin
13 mcg, choline 46 mg, Cl 403 mg. Energy: 190
kCal.
Anmum Materna Plain Per 37.5 g Total fat 4.5 g, saturated fat 2 g, trans
fat 4 g, cholesterol 10 mg, linoleic acid (omega 6)
0.3 g, protein 12 g, carbohydrate 18 g, sugar, Na
135 mg, K 530 mg, vit A 240 mcg, vit C 30 mg, vit
D3 2.5 mcg, vit B1 56 mcg, vit B2 0.9 mg, vit B5
1.1 mg, vit B6 1.1 mg, folic acid 340 mcg, vit B12
0.8 mcg, Ca 500 mg, Fe 75 mg, Mg 39 mg,
phosphorus 374 mg, Zn 1.6 mg, iodine 35 mcg,
linolenic acid 0.09 g, DHA 25 mg, gangliosides 3.4
mg, fiber 2.5 g, sialic acid 80 mg, lactose 7 g,
biotin 9 mcg, choline 41 mg, Cl 320 mg. Energy:
160 kCal.
Anmum/Anmum Chocolate Per 100 g Anmum powd Protein 32.8 g,
carbohydrate 45.1 g, lactose =22 g, fat 12.3 g,
linoleic acid 0.8 g, a-linolenic acid 0.2 g, food
fibre 6.4 g, vit A 640 mcg, vit D3 6.7 mcg, vit C 80
mg, vit B1 180 mcg, vit B2 1.7 mg, vit B6 230
mcg, pantothenic acid 3 mg, folic acid 900 mcg,
vit B12 3.2 mcg, biotin 32 mcg, choline 130 mg,
Ca 1,330 mg, phosphorus 860 mg, Fe 20 mg, Mg
110 mg, Zn 3.6 mg, iodine 94 mcg, Na 410 mg, K
1,350 mg, Cl 1,060 mg. Energy: 420 kCal. Per 100
g Anmum chocolate powd Protein 27.3 g,
carbohydrate 51.9 g, fat 10.3 g, linoleic acid 0.7 g,
a-linolenic acid 0.2 g, food fibre 7 g, vit A 530
mcg, vit D3 5.4 mcg, vit C 66 mg, vit B1 130 mcg,
vit B2 1.3 mg, vit B6 190 mcg, pantothenic acid 2
mg, folic acid 740 mcg, vit B12 2.9 mcg, biotin 28
mcg, choline 110 mg, Ca 1,090 mg, phosphorus
750 mg, Fe 17 mg, Mg 120 mg, Zn 3.4 mg, iodine
77 mcg, Na 340 mg, K 1,340 mg, Cl 900 mg.
Energy: 410 kCal.
Anore Norethisterone
Anthramed Dithranol
Antidine Famotidine
Antikun Piracetam
Antipres Sertraline
Antrain Metamizole Na
Anxibloc Clobazam
Anzatax Paclitaxel
Apazol Alprazolam
Aptivium Liver Support Silymarin 150 mg, turmeric 12.5 mg, a- lipoic acid
50 mg, pantothenic acid 5 mg, vit C 125 mg, vit E
50 iu, vit B1 0.75 mg, vit B2 0.85 mg, vit B6 1 mg,
vit B12 3 mcg, niacinamide 10 mg
Arava Leflunomide
Arbiten-I Irbesartan
Arclate Doxycycline
Ardivit-PL Vit A 0.8 mg, vit B1 1.5 mg, vit B2 1.6 mg, vit B6
2.2 mg, vit B12 2.5 mcg, vit C 100 mg, vit D 0.01
mg, vit E 10 mg, vit K 0.055 mg, folic acid 1 mg,
Fe fumarate 90 mg, nicotinamide 17 mg, Ca
lactate 250 mg, Zn 15 mg, iodine 0.15 mg, Mg 6
mg, biotin 0.03 mg, selenium 0.03 mg
Arnid Nimesulide
Artem Artemether
Artoflam Diacerein
Artricom Tenoxicam
Artrilox Meloxicam
Asepta Povidone-iodine
Askorbin Vit C
Asmacare Salbutamol
Ativan Lorazepam
Atmacid Per chewable tab Al(OH)3 300 mg, Mg(OH)2 300
mg, dimethicone 50 mg. Per 5 mL susp Al(OH)3
300 mg, Mg(OH)2 300 mg, dimethicone 50 mg
Atorsan Atorvastatin Ca
Atostin Atorvastatin Ca
Atranac Diclofenac Na
Augmentin/Augmentin Forte GlaxoSmithKline Pharmaceuticals Per 625 mg tab Amoxicillin 500 mg, clavulanate K
125 mg. Per 1 g tab Amoxicillin trihydrate 875
mg, clavulanate K 125 mg. Per 5 mL oral susp
Amoxicillin trihydrate 125 mg, clavulanate K
31.25 mg. Per 5 mL Forte oral susp Amoxicillin
trihydrate 250 mg, clavulanate K 62.5 mg
Aurorix Moclobemide
Azathioprine Azathioprine
Combiphar/Pharmachemie
Azopt Brinzolamide
Azvit ß-carotene 5,000 IU, vit C 500 mg, vit E 100 IU,
selenium 20 mcg, Zn 8 mg
bacbutINH/bacbutINH Forte Armoxindo Farma Per tab Ethambutol HCl 250 mg, INH 100 mg, vit
B6 5 mg. Per Forte tab Ethambutol HCl 500 mg,
INH 200 mg, vit B6 10 mg
Bartolium Flunarizine
Batrafen Ciclopiroxolamine
Baxima Cefotaxime Na
Bebelac Complete Fruit & Per serving (43 g) Total fat 7 g, saturated fat 3 g,
Veggie linoleic acid (omega 6) 133 mg, protein 7 g, total
carbohydrate 26 g, food fiber 1 g, total sugar 14
g, lactose 12 g, maltose 2 g, Na 95 mg, K 380 mg,
protein 36%, vit A 35%, vit D3 25%, vit E 30%, vit
K1 30%, vit C 35%, vit B1 25%, vit B2 85%, vit B3
20%, vit B5 50%, vit B6 30%, vit B9 45%, vit B12
120%, Ca 55%, phosphorus 65%, Mg 45%, Fe
30%, Zn 30%, iodine 35%, selenium 25%, fructo-
oligosaccharides 1 g, DHA 10 mg, a-linolenic acid
(omega 3) 46 mg, choline 25 mg, L-carnitine 3.4
mg, ß-carotene 32 mcg, biotin 6.5 mcg, inositol
20 mg, chloride 252 mg, copper 100 mcg,
manganese 23 mcg. Energy: 190 kCal
Bebelac EC Per 100 g Vegetable fat 25.5 g, linoleic acid 3.7 g,
a-linolenic acid 0.37 g, protein 11.2 g, casein 4.5
g, whey protein 6.7 g, carbohydrate 58.9 g,
lactose 33.7 g, dextrin (including glucose) 25.2 g,
moisture 2 g, vit, minerals, taurine, L-carnitine.
Energy: 510 kCal.
Bebelove 1 Nutricia Per 100 mL Protein 1.4 g, fat 3.4 g, linoleic acid
474 mg, a-linolenic acid 50 mg, DHA 6.7 mg, AA
6.7 mg, phospholipid 42 mg, carbohydrate 7.8 g,
lactose 7 g, fiber 0.55 g, fructo-oligosaccharides
0.04 g, galacto-oligosaccharides 0.36 g, L-
carnitine 1.7 mg, taurine 5.2 mg, vit A 63 mcg-RE,
ß-carotene 25 mcg, vit D3 0.84 mcg, vit E 1.3 mg
a-TE, vit K1 6.4 mcg, vit B1 63 mcg, vit B2 159
mcg, vit B3 0.53 mg, vit B5 0.46 mg, vit B6 53
mcg, vit B9 13 mcg, vit B12 0.38 mcg, vit C 14
mcg, biotin 3.3 mcg, choline 16 mg, inositol 6.5
mg, Ca 52 mg, P 29 mg, Mg 6.1 mg, Fe 1.1 mg, Zn
0.72 mg, manganese 9.5 mcg, copper 44 mcg,
selenium 1.6 mcg, iodine 13 mcg, Na 12 mg, K 82
mg, Cl 50 mg. Energy: 70 kCal
Bebelove 2 Nutricia Per 100 mL Total fat 6 g, linoleic acid 833 mg,
protein 5 g, carbohydrate 17 g, fiber 1 g, soluble
fiber 1 g, lactose 14 g, Na 60 mg, K 230 mg, vit A
45%, vit C 75%, vit D3 55%, vit E 50%, vit K 95%,
vit B1 30%, vit B2 80%, vit B3 25%, vit B5 50%, vit
B6 30%, vit B9 40%, vit B12 100%, Ca 40%, P
40%, Mg 30%, Fe 25%, iodine 30%, Zn 30%,
selenium 25%, fructo-oligosaccharides 0.08 g,
galacto-oligosaccharides 0.73 g, DHA 12 mg, AA
12 mg, phospholipid 81 mg, a-linolenic acid 87
mg, choline 34 mg, taurine 10 mg, L-carnitine 4.9
mg, biotin 5.9 mcg, inositol 14 mg, Cl 146 mg,
copper 96 mcg. Energy: 140 kCal
Bebemama Nutricia Per serving size (40 g) Total fat 3 g, saturated fat 1
g, linoleic acid (omega 6) 93 mg, protein 10 g,
total carbohydrate 25 g, food fiber 1 g, soluble
food fiber 1 g, FOS 1 g, total sugar 7 g, sucrose 4
g, fructose 3 g, Na 105 mg, K 450 mg, vit A 25%,
vit C 35%, vit D3 25%, vit E 35%, vit B1 20%, vit
B2 25%, vit B3 25%, vit B5 20%, vit B6 25%, vit B9
35%, vit B12 25%, Ca 30%, phosphorus 40%, Mg
10%, Fe 25%, iodine 30%, Zn 30%, selenium 20%,
a-linolenic acid (omega 3) 23 mg, DHA 41 mg,
biotin 6.2 mcg, choline 27 mg, chloride 277 mg.
Energy: 160 kCal
Becefort Phapros Per tab Vit B1 15 mg, vit B2 10 mg, vit B6 5 mg,
vit B12 100 mcg, vit C 500 mg, vit E 30 mg, Ca
pantothenate 20 mg, nicotinamide 50 mg. Per 5
mL syr Vit B1 10 mg, vit B2 6 mg, vit B6 10 mg, vit
B12 10 mcg, vit C 100 mg, nicotinamide 50 mg,
niacinamide 50 mg, d-pantothenol 10 mg
Becom-Zet Sanbe Vit E 30 IU, vit C 750 mg, vit B1 15 mg, vit B2 15
mg, vit B6 20 mg, vit B12 12 mcg, folic acid 400
mcg, pantothenic acid 20 mg, Zn 22.5 mg, niacin
100 mg
Benocetam Piracetam
Benocid Indomethacin
Benodin Povidone-iodine
Benofat Sucralfate
Benoson Betamethasone
Benoson G Betamethasone valerate 0.1%, gentamicin sulfate
0.1%
Benoxuric Allopurinol
Benzoquin Monobenzone
Berlison Phenylbutazone
Bernesten Clotrimazole
Berno Yeast Primary dried yeast 100 mg, vit B1 2 mg, vit B2 2
mg, vit B6 2 mg, vit B12 2 mcg, niacinamide 15
mg, Ca pantothenate 5 mg
Bernoflox Ciprofloxacin
Berocca Performance Bayer Indonesia Vit B1 15 mg, vit B2 15 mg, vit B3 50 mg, vit B5
23 mg, vit B6 10 mg, vit B12 10 mg, vit C 500 mg,
biotin 150 mcg, folic acid 400 mcg, Mg 100 mg,
Ca 100 mg, Zn 10 mg
Berry Vision Sanbe Vision Per tab Bilberry dry extr 80 mg, retinol 1,600 IU,
vit E 40 mg, ß-carotene 5 mg. Per Dispersible tab
Bilberry dry extr 40 mg, retinol 800 IU, vit E 20
mg, ß-carotene 2.5 mg
Berthyco Mecobalamin
Betablok Atenolol
Betaclav Per 250 mg Co-amoxiclav: Amoxicillin 250 mg, K
clavulanate 125 mg. Per 500 mg Co-amoxiclav:
Amoxicillin 500 mg, K clavulanate 125 mg
Betadine Povidone-iodine
Betaflox Ofloxacin
Betaslim Global Multi Pharmalab (GMP) Per FC caplet Chitosan 250 mg, Garcinia
cambogia extr 250 mg, L-carnitine 50 mg,
chromium picolinate 50 mcg, vit C 25 mg
Betason Betamethasone
Bexce/Bexce Plus Per Bexce caplet Vit B1 15 mg, vit B2 10 mg, vit
B6 5 mg, vit B12 10 mcg, vit C 500 mg, Ca
pantothenate 20 mg, nicotinamide 100 mg. Per 5
mL Bexce syr Vit B1 10 mg, vit B2 6 mg, vit B6 10
mg, vit B12 10 mcg, vit C 100 mg, panthenol 10
mg, nicotinamide 50 mg. Per mL Bexce Plus
drops Vit A 3,000 iu, vit B1 1 mg, vit B2 1.2 mg,
vit B6 0.8 mg, vit C 50 mg, nicotinamide 16 mg,
vit B12 3 mcg, panthenol 5 mg, vit D 400 iu, vit E
10 iu
Binozyt Azithromycin
Bintapen Ampicillin
Bioads (Anti Difteri Serum Biofarma Per mL Diphtheria antitoxin 20,000 IU, phenol 2.5
20,000 IU) mg
Bio-ATP Phapros ATP 20 mg, vit B1 100 mg, vit B6 200 mg, vit B12
200 mcg, vit E 30 mg
Biolectra Ikapharmindo Mg
Biolysin Per drag Vit A 2,000 IU, vit B1 3 mg, vit B2 1 mg,
vit B6 1 mg, vit B12 5 mcg, vit C 50 mg, vit D3
400 IU, D-panthenol 3 mg, L-lysine HCl 300 mg,
niacinamide 20 mg. Per 5 mL Vit A 2,000 IU, vit
B1 3 mg, vit B2 1 mg, vit B6 1 mg, vit B12 5 mcg,
vit C 50 mg, vit D3 400 IU, L-lysine HCl 300 mg,
niacinamide 20 mg, D-panthenol 3 mg
Biolysin Kids Per chewable tab Vit A 1,500 IU, vit B1 1.4 mg, vit
B2 1.6 mg, vit B6 1.6 mg, vit B12 3 mg, vit C 60
mg, vit D3 400 IU, vit E 5 mg, niacinamide 10 mg,
Ca pantothenate 3 mg, L-lysine HCl 100 mg
Biomex Vit B1 100 mg, vit B6 200 mg, vit B12 300 mcg
Bionemi Gracia Pharmindo Fe fumarate 360 mg, folic acid 1.5 mg, vit B12 15
mcg, vit C 75 mg, vit D3 400 IU, Ca carbonate 200
mg
Bioneuron Per drag Vit B1 disulfide 100 mg, vit B6 200 mg,
vit B12 200 mcg. Per 3 mL amp Vit B1 100 mg, vit
B6 100 mg, vit B12 1,000 mcg, lidocaine HCl 15
mg
Bioquinone Puspa Pharma Per softcap Co-enzyme Q10 100 mg, L-carnitine
500 mg, vit E 100 IU, soya bean oil 323.1 mg
Biosat 1.5 (Serum Anti Tetanus Biofarma Per mL Tetanus antitoxin 1,500 IU, phenol 2.5 mg
1,500 IU)
Biostatik Roxithromycin
Biostrum Lapi Colostrum bovine 300 mg, DHA 200 mg, cod liver
oil 10 mg, lysine HCl 200 mg, vit A 2,000 IU, vit D
200 IU, vit B1 0.6 mg, vit B2 0.15 mg, vit B6 0.6
mg, vit B12 1.5 mcg, nicotinamide 5 mg,
dexpanthenol 2.5 mg, Zn picolinate 5 mg
Biotamin Benfotiamine
Biothicol Sanbe Thiamphenicol
Biotopix Eye Bag & Dark Circle Meprofarm Niacinamide, tetrapeptide, oak extr
Biotopix Specific Lifting Cream Meprofarm Locust bean gum, 4 active peptides
Biotriax Ceftriaxone Na
Blecidex Ear Drops Sanbe Vision Per mL Framycetin sulfate 5 mg, gramicidin 0.05
mg, dexamethasone 0.5 mg
Blecidex Eye Drops Sanbe Vision Per mL Framycetin sulfate 5 mg, gramicidin 0.05
mg, dexamethasone 0.5 mg
Blenamax Bleomycin
Blue Cap Cream/Blue Cap Per Blue Cap cream Zn pyrithione 0.2%, moisture
Spray/Blue Cap Shampoo base 50 g. Per Blue Cap shampoo Zn pyrithione
1%, menthol 0.25%. Per Blue Cap spray Zn
pyrithione 0.2%, isopropyl myristate.
BMT Gold Kalbe Nutritionals Per 100 g Protein 11 g, fat 27 g, carbohydrate 57
g, linoleic acid 3 g, a-linolenic acid 0.4 g, DHA 50
mg, choline 80 mg, arachidonic acid (AA) 50 mg,
taurine 40 mg, phospholipids 230 mg, inositol 50
mg, L-carnitine 10 mg, lactoferrin 50 mg,
lactulose 300 mg, vit A 1,500 IU, vit C 80 mg, vit
D 350 IU, vit E 11 IU, vit K 30 mcg, vit B1 0.4 mg,
vit B2 0.7 mg, vit B3 4.2 mg, vit B5 5 mg, vit B6
0.3 mg, vit B9 100 mcg, vit B12 1.5 mcg, biotin 10
mcg, ß-carotene 45 mcg, Na 160 mg, K 540 mg,
Ca 380 mg, phosphorus 210 mg, Mg 45 mg, Fe 6
mg, manganese 50 mcg, selenium 7 mcg, Zn 3.3
mg, iodine 65 mcg, Cl 330 mg. Energy: 515 kCal
BMT P-HP Kalbe Nutritionals Per 100 g Protein 11.7 g, fat 27 g, carbohydrate
56 g, carnitine 10 mg, taurine 40 mg, cystein 200
mg, nucleotide 20 mg, arachidonic acid (AA) 100
mg, DHA 50 mg, a-linolenic acid 400 mg, linoleic
acid 3 g, phospholipids 600 mg, lactulose 300
mg, vit A 1,800 IU, vit D 350 IU, vit E 8.8 IU, vit K
25 mcg, vit B1 0.4 mg, vit B2 0.7 mg, vit B3 4.2
mg, vit B5 3 mg, vit B6 0.3 mg, vit B9 100 mcg, vit
B12 1.5 mcg, vit C 100 mg, biotin 10 mcg, choline
80 mg, inositol 50 mg, Ca 380 mg, phosphorus
210 mg, Mg 45 mg, Fe 6 mg, Zn 3.3 mg,
manganese 30 mcg, copper 320 mcg, iodine 65
mcg, Na 160 mg, K 540 mg, Cl 330 mg, selenium
7 mcg. Energy: 514 kCal
BMT Platinum Kalbe Nutritionals Per 100 g Protein 10.6 g, fat 27 g, carbohydrate
57.3 g, linoleic acid 3 g, a-linolenic acid 0.4 g,
DHA 50 mg, choline 80 mg, arachidonic acid (AA)
100 mg, taurine 40 mg, phospholipid 230 mg, a-
lactalbumin 1.8 g, inositol 50 mg, L-carnitine 10
mg, nucleotide 20 mg, lactoferrin 50 mg, cystein
0.2 g, lactulose 300 mg, vit A 1,500 IU, vit C 80
mg, vit D 350 IU, vit E 10 IU, vit K 30 mcg, vit B1
0.4 mg, vit B2 0.7 mg, vit B3 4.2 mg, vit B5 4 mg,
vit B6 0.3 mg, vit B9 100 mcg, vit B12 1.5 mcg,
biotin 10 mcg, ß-carotene 45 mcg, Na 160 mg, K
540 mg, Ca 380 mg, phosphorus 210 mg, Mg 45
mg, Fe 6 mg, manganese 50 mcg, selenium 7
mcg, Zn 3.3 mg, iodine 65 mcg, Cl 330 mg.
Energy: 515 kCal
bodrexin Flu & Batuk Paracetamol 100 mg, pseudoephedrine HCl 7.5
mg, glyceryl guaiacolate 20 mg, bromhexine HCl
2 mg, chlorpheniramine maleate 0.5 mg
Bondi Diacerein
Bonvit Global Health Pharma MSM 300 mg, chondroitin sulfate 200 mg,
glucosamine sulfate 250 mg, vit B1 5 mg, vit B6
25 mg, Mg 0.5 mg, selenium 6 mcg
Boostrix Per 0.5 mL dose Diphtheria toxoid not <2 IU,
tetanus toxoid not <20 IU, Bordetella pertussis
antigens (pertussis toxoid 8 mcg, filamentous
haemagglutinin 8 mcg, pertactin 2.5 mcg)
Brainvit Mahakam Beta Farma Per 5 mL Colostrum bovine 300 mg, DHA 250 mg,
arachidonic acid 50 mg, ß-carotene 4 mg, vit B1
0.5 mg, vit B2 0.5 mg, vit B6 0.5 mg,
nicotinamide 5 mg, vit B12 1 mcg, dexpanthenol
3 mg, vit D 100 IU, Ca citrate 250 mg
Bralin Citicoline
Brenaris Piracetam
Broncholit Carbocisteine
Bronchophylin Theophylline
Bronsolvan Theophylline
Buscopan Hyoscine-N-butylbromide
Buscotica Hyoscine-N-butylbromide
Calbon Global Health Pharma Ca citrate 300 mg, vit D3 50 IU, isoflavone 50 mg,
Zn 5 mg, Mg 15 mg, manganese 2 mg, vit C 25
mg
CalciD Tunggal Idaman Abdi Ca phosphate 333.34 mg, Ca citrate 666.66 mg,
vit D3 400 IU
Calcido Yarindo Farmatama Algas calcareas sp powd (Algaecal) 750 mg, vit D3
CWS 400 IU
Calcidol Per 5 mL Vit B12 5 mcg, vit B1 3 mg, vit B2 1.25
mg, vit B6 0.5 mg, vit C 50 mg, vit A 3,000 iu, vit
D 400 iu, nicotinamide 10 mg, Ca pantothenate 5
mg, Ca 77 mg, phosphorus 25 mg, DHA 10 mg,
lysine 125 mg
Calcit Calcitriol
calciviton Per 6 g sachet Ca 500 mg, vit C 500 mg, vit D 100
iu, vit K 60 mcg, Mg 20 mg, manganese 1 mg, Zn
10 mg
Caldece Sanbe Vit B6 15 mg, vit C 1,000 mg, vit D 300 IU, Ca
carbonate 625 mg (equiv to elemental Ca 250
mg)
Caldetri Global Multi Pharmalab (GMP) Ca hydrogen phosphate anhydrate 500 mg,
cholecalciferol 133 IU
Calmin-AF Vit A 5,000 iu, vit D 400 iu, vit C 100 mg, vit B1 10
mg, vit B2 2.5 mg, vit B6 15 mg, vit B12 4 mcg,
niacinamide 20 mg, Ca pantothenate 7.5 mg,
folic acid 0.4 mg, Fe fumarate 90 mg, Ca lactate
250 mg, iodine 0.1 mg
Calnic Plus Per caplet Ca 400 mg, vit D3 200 IU. Per 5 mL oral
susp Ca 200 mg, vit D3 200 IU
Caloma Plus Novell Pharma Cod liver oil 200 mg, vit A 120 IU, vit D3 17 IU,
omega-3 fatty acids, EPA 16 mg, DHA 14 mg, vit E
5 mg, vit B12 1 mcg, folic acid 0.3 mg, vit B6 0.6
mg, Ca 40 mg, Mg 25 mg, Fe 4.76 mg
Calostrum Meprofarm Per 5 mL Colostrum bovine 300 mg, DHA 200 mg,
cod liver oil 10 mg, lysine HCl 200 mg, vit A 2,000
mg, vit D2 200 IU, vit B1 0.6 mg, vit B2 0.15 mg,
vit B6 0.6 mg, vit B12 1.5 mcg, nicotinamide 5
mg, dexpanthenol 2.5 mg, Zn picolinate 5 mg, Ca
gluconate 300 mg, Ca hypophosphite 20 mg
Calplex Mahakam Beta Farma Coral Ca 500 mg, soy fiber germ (natural soy
isoflavone) 20 mg, vit D3 200 IU, vit K1 25 mcg,
Zn 5 mg, Mg 100 mg, boron 1 mg
Calporosis D 500/Calporosis D Mersifarma TM Calporosis D 500 Ca carbonate 500 mg, vit D 100
800 IU. Calporosis D 800 Ca carbonate 800 mg, vit D
300 IU
Calvitran Per 5 mL Vit A 1,500 iu, vit D 300 iu, Ca 150 mg,
Mg 30 mg, Zn 5 mg, folic acid 100 mcg, fructo-
oligosaccharide 500 mg
Calvonin Isoflavone
Cameloc Meloxicam
Campain Piroxicam
Campto Pfizer Irinotecan HCl trihydrate
Candazole Clotrimazole
Candipar Fluconazole
candyvit-C Vit C
Cantil Mepenzolate Br
Caprol Pantoprazole
Captensin Captopril
Carbloxal Carvedilol
Carbosin Carboplatin
Combiphar/Pharmachemie
Carcan Carboplatin
Cardiavit Vit B6 2 mg, folic acid 400 mcg, vit C 100 mg, vit
E 40 iu, vit B12 100 mcg.
Cardiomin Darya-Varia Vit B6 25 mg, vit B12 25 mcg, folic acid 500 mcg,
natural vit E 400 IU
Carmed Urea
Car-Q100 Kalbe Farma Coenzyme Q10 100 mg, L-carnitine fumarate 500
mg
Carsive Landson Nicardipine HCl
Catalin Pirenoxine Na
Catanac Diclofenac K
CDR Bayer Indonesia Ca (in Ca carbonate 625 mg) 250 mg, vit B6 15
mg, vit C 1,000 mg, vit D 300 iu
CDR Fortos Bayer Indonesia Per tab Ca elemental 600 mg, vit D3 400 iu
Cefaxon Ceftriaxone Na
Cefemet Cefepime
Classic hemophilia A.
Acute hemorrhage, pre- & post-op treatment & prophylaxis in
hemophila A patients (congenital factor VIII deficiency) & in
patients w/ an acquired reduction in factor VIII activity.
HTN.
Acne vulgaris.
Listed in Dosage.
Resp tract infectins, UTI, infections of bones, joints & skin, intra-
abdominal infections, uncomplicated gonorrhea, septicaemia,
peri-op prophylaxis of infections, meningitis.
Listed in Dosage.
Vit supplement.
Infection of lower resp tract, urinary tract, soft tissue, bone &
joint, O & G infection, gonorrhoea, septicaemia & meningitis.
Prophylaxis against infection in abdominal, pelvic, orthopaedic,
cardiac, pulmonary, esophageal & vascular surgery when there is
increased risk from infection.
GUT, resp tract, skin & soft tissue infections due to susceptible
microorganisms.
Upper & lower resp tract, skin & soft tissue, GUT infections, bone
& joint & other infections (septic abortion, peripheral & intra-
abdominal sepsis, post-op infections).
Antidepressant.
Nonspecific diarrhea.
Schizophrenia.
Prevention of venous thromboembolic events (VTE) in patients
undergoing major orthopaedic surgery of the lower limbs eg, hip
fracture including extended prophylaxis, knee or hip replacement
surgery. Prevention of VTE in patients undergoing abdominal
surgery who are at risk of thromboembolic complications.
Prevention of VTE in medical patients who are at risk of
thromboembolic complications due to restricted mobility during
acute illness. Treament of acute deep vein thrombosis (DVT).
Treatment of acute pulmonary embolism (PE). Treatment of
unstable angina or non-ST segment elevation myocardial
infarction (UA/NSTEMI) in patients for whom urgent (<120 min)
invasive management [percutaneous coronary intervention (PCI)]
is not indicated. Adjunctive treatment of ST segment elevation
myocardial infarction (STEMI) in patients who are managed with
thrombolytics or who initially are to receive no other form of
reperfusion therapy.
Listed in Dosage.
Mild to moderate upper & lower resp tract, skin & soft tissue
infections; non-gonococcal urethritis & cervicitis due to Chlamydia
trachomatis.
Upper & lower resp tract infections; bacterial pneumonia; UTI &
pyelonephritis; intra-abdominal infections; bacterial septicaemia;
skin, soft tissue, bone & joint infections, gonococcal infections.
Prophylaxis of post-op infection in patients undergoing abdominal
or pelvic surgery. Prophylaxis of post-op sepsis in termination of
pregnancy or caesarean section.
Listed in Dosage.
Listed in Dosage.
Listed in Dosage.
Diphteria.
Keeps skin moisture; used on face & neck to whiten & brighten
skin; helps conceal smooth lines on the face.
Cutaneous irritations & lesions. Cover acute & chronic wounds
(abrasions, donor sites & post-op incisions, 1st & 2nd degree
burns, vascular & metabolic ulcers & pressure ulcers). Protection
against abrasion, friction, & dessication.
Cutaneous hyperpigmentation.
Essential HTN.
Infant formula for babies 0-6 mth.
Special infant formula for babies 0-6 mth to reduce risk of allergy.
Special infant formula for babies 0-6 mth w/ cow's milk allergy,
lactose intolerance & galactosemia.
Metastatic bone disease; to reduce the risk of skeletal
complications of malignant disease including hypercalcemia, pain,
the need for radiotherapy against painful bone lesions &
impending fractures, & decrease the risk of bone fractures.
Treatment of tumour-induced hypercalcemia.
Listed in Dosage.
Moisten dry & inflamed nasal membrane due to cold, allergy, low
moisture, minor nose bleeds & other minor nasal irritation.
Infection of lower resp tract, urinary tract, bone & joint, intra-
abdominal, skin; gonorrhoea, bacterial septicaemia, peri-op
prophylaxis, if there is a possibility of severe infection
complication.
Epidural block for surgery, field block (minor & major nerve blocks
& infiltration); post-op or labour pain.
HTN. Heart failure & impaired left ventricular systolic function (left
ventricular ejection fraction =40%) when ACE inhibitors are not
tolerated.
Erectile dysfunction.
Listed in Dosage.
HTN, angina.
Listed in Dosage.
Upper & lower resp tract infections, upper & lower UTI,
peritonitis, cholecystitis, cholangitis, other intra-abdominal
infections, skin & soft tissue infections.
For face, neck & hand usage eg, chloasma, freckles, age spots,
hyperpigmentation post-inflammation, pre- & post-laser
intervention, pre- & post-peeling, post liqd nitrogen therapy.
Resp tract, skin & soft tissue & GUT infection, osteomyelitis,
arthritis, septicaemia, peritonitis, puerperal sepsis.
3TC therapy should be initiated by a physician experienced in the management of HIV infection.
3TC can be taken with or without food. To ensure administration of the entire dose, the tablet(s) should ideally be
swallowed without crushing. For patients who are unable to swallow tablets, lamivudine is available as an oral solution.
Alternatively, the tablets may be crushed and added to a small amount of semisolid food or liquid, all of which should be
consumed immediately.
Adults and Adolescents Weighing at least 30 kg: The recommended dose is 300 mg daily. This may be administered as
150 mg (15 ml oral solution or 1 x 150 mg tablet) twice daily or 300 mg (30 ml oral solution or 2 x 150 mg tablet) once
daily.
Children >3 months and Weighing <30 kg: Oral Solution: The recommended dose is 4 mg/kg twice daily up to a
maximum of 300 mg daily.
Tablets: Children Weighing 21-30 kg: The recommended oral dose of lamivudine is ½ tablet (150 mg) taken in the
morning and 1 whole tablet taken in the evening.
Children Weighing 14-21 kg: The recommended oral dose of lamivudine is ½ of a scored tablet taken twice daily.
Since an accurate dosing cannot be achieved with this formulation, dosing according to weight bands is recommended
for 3TC tablets. This dosing regimen for paediatric patients weighing 14-30 kg is based primarily on pharmacokinetic
modelling, with supporting data from clinical studies.
Children <3 months: The limited data available are insufficient to propose specific dosage recommendations (see
Pharmacokinetics under Actions).
Elderly: No specific data are available, however special care is advised in this age group due to age-associated changes
eg, the decrease in renal function and alteration of hematological parameters.
Renal Impairment: Lamivudine plasma concentrations (AUC) are increased in patients with moderate to severe renal
impairment due to decreased clearance (see Pharmacokinetics under Actions). The dosage should therefore be reduced
for patients with a creatinine clearance <50 mL/min. The same percentage reduction in dose applies for pediatric
patients with renal impairment. When doses <150 mg are needed, the use of the oral solution is recommended. (See
Tables 1 and 2.)
Hepatic Impairment: No dose adjustment is necessary in patients with moderate or severe hepatic impairment unless
accompanied by renal impairment (see Pharmacokinetics under Actions).
Mild hemorrhage & prophylaxis 10 IU/kg as single-dose IV. Moderate hemorrhage 15-25 IU/kg IV. If required, repeated
doses of 10-15 IU/kg 8-12 hrly may be given. Severe hemorrhage Initially 40-50 IU/kg IV. Maintenance: 20-25 IU/kg 8-12
hrly. Surgery Pre-op dose: 50 IU/kg IV. To maintain hemostatic levels, repeated infusions may be necessary 6-12 hrly
initially & for 10-14 days until healing is complete.
Individualized dosage.
HTN & angina 5 mg once daily, may be increased to a max of 10 mg once daily.
Abbotic: Filmtab: Usual Recommended Dose: 250 mg twice daily. In more severe infections, the dosage can be increased
to 500 mg twice daily.
The usual duration of therapy is 7-14 days.
Treatment of Legionella pneumophila Infection: 500 mg twice daily for 4 weeks is appropriate.
In Patients with Renal Impairment (CrCl <30 mL/min): Dosage should be reduced by ½ ie, 250 mg once daily or 250 mg
twice daily, in more severe infections. Treatment should not be continued beyond 14 days in these patients.
Administration: Abbotic filmtab may be given with or without meals (see Pharmacokinetics under Actions).
Note: In the treatment of haemolytic streptococcal infections, a therapeutic regimen should be administered at least 10
days.
Abbotic Granule: Dry Syrup: Children: Recommended Daily Dose: 7.5 mg/kg twice daily up to a maximum of 500 mg
twice daily for severe infections. The usual duration of treatment is 5-10 days depending on the pathogen involved and
the severity of the condition. Treatment for streptococcal pharyngitis should be at least 10 days.
Prepared suspension can be taken with or without meals and can be taken with milk.
The following is a guide for determining dosage in children based on body weight in kg: Dosage in standard 5 mL (125
mg/5mL): Children 30-40 kg: 2 tsp; 20-29 kg: 1.5 tsp; 12-19 kg: 1 tsp; 8-11 kg: 0.5 tsp. To be given twice daily.
Dosage in standard 5 mL (250 mg/5mL): Children 30-40 kg: 1 tsp; 20-29 kg: 0.75 tsp; 12-19 kg: 0.5 tsp. To be given twice
daily.
Children <8 kg should be dosed on a per kg basis (approximately 7.5 mg/kg twice daily).
Abbotic XL: Usual Recommended Dose: Adults: 500 mg once daily with food.
More Severe Infections: Dosage may be increased to 1000 mg once daily (2 x 500 mg).
The usual duration of therapy is 7-14 days.
Renal Impairment (CrCl <30 mL/min): Clarithromycin modified-release should not be used in patients with significant
renal impairment (CrCl <30 mL/min). Clarithromycin 500 mg immediate-release tablets may be utilized in this patient
population (see Contraindications).
Usual Dose: Schizophrenia: Adults: Recommended Starting and Target Dose: 10 or 15 mg once daily without regard to
meals.
Abilify Discmelt has been systematically evaluated and shown to be effective in a dose range of 10-30 mg daily. However,
doses higher than 10 or 15 mg daily were not more effective than 10 or 15 mg daily. Dosage increases should not be
made 2 weeks before the time needed to achieve steady state.
Adolescents: Starting Daily Dose: 2 mg titrated to 5 mg after 2 days and to the target dose of 10 mg after 2 additional
days. Subsequent dose increases should be administered in 5 mg increments. The 30 mg daily dose was not shown to be
more efficacious than the 10 mg daily dose.
Bipolar Disorder: Adults: Starting Dose: 30 mg once daily without regard to meals. A dose of 30 mg daily was found to be
effective when administered as the tablet formulation. Approximately 15% of patients had their dose decreased to 15
mg based on tolerability assessment. The safety of doses above 30 mg daily has not been evaluated in clinical trials.
Children and Adolescents: The efficacy of aripiprazole has been established in the treatment of children and adolescent
patients 10-17 years with bipolar I disorder at doses of 10 or 30 mg daily. Recommended Target Dose: 10 mg daily.
Starting Daily Dose: 2 mg daily titrated to 5 mg daily after 2 days and to the target dose of 10 mg after 2 additional days.
Subsequent dose increases should be administered without regard to meals.
Major Depressive Disorder: Adults: Recommended Starting Dose: Adjunctive Treatment for Patients Taking an
Antidepressants: 2-5 mg daily. The efficacy as an adjunctive therapy was established within a dose range of 2-15 mg
daily.
Dose adjustment of up to 5 mg daily should occur gradually at intervals of no less than 1 week.
Pediatric Patients 6-17 years: 5-15 mg daily. The dosage of Abilify Oral Solution should be individualized according to
tolerability and response. Dosing should be initialized at 2 mg daily. The dose should be increased to 5 mg daily with
subsequent increases to 10 or 15 mg daily, if needed. Dose adjustments of up to 5 mg daily should occur gradually at
intervals of no less than 1 week.
Schizophrenia: Recommended Starting and Target Dose: 10 or 15 mg once a day without regard to meals. Abilify has
been systematically evaluated and shown to be effective in a dose range of 10-30 mg/day, when administered as a tablet
formulation; however, doses >10 or 15 mg/day, the lowest doses in these trials, were not more effective than 10 or 15
mg/day. Dosage increases should be made before 2 weeks, the time needed to achieve steady state.
Special Populations: Dosage adjustments are not routinely indicated on the basis of age, gender, race or renal or hepatic
impairment status (see Pharmacokinetics under Actions).
Dosage Adjustments: Patients Taking Aripiprazole Concomitantly with Potential CYP3A4 or CYP2D6 Inhibitors: When
concomitant administration of CYP3A4 inhibitor eg, ketoconazole and potential CYP2D6 inhibitors eg, quinidine,
fluoxetine or paroxetine with aripiprazole occurs, aripiprazole dose should be reduced to ½ of the usual dose. When the
CYP3A4 or CYP2D6 inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased.
Patients Taking Potential CYP3A4 Inducers: When a potential CYP3A4 inducer eg, carbamazepine is added to aripiprazole
therapy, the aripiprazole dose should be doubled (to 20-30 mg). Additional dose increases should be based on clinical
evaluation. When carbamazepine is withdrawn from the combination therapy, the aripiprazole dose should be reduced
to 10-15 mg.
Maintenance Therapy: While there is no body of evidence available to answer the question of how long a patient treated
with aripiprazole should remain on it, systematic evaluation of patients with schizophrenia who had been
symptomatically stable on other antipsychotic medications for periods of =3 months were discontinued from those
medications, and were then administered Abilify 15 mg/day and observed for relapse during a period of up to 26 weeks,
demonstrated a benefit of such maintenance treatment (see Pharmacology under Actions). Patients should periodically
be reassessed to determine the need for maintenance treatment.
Switching From Other Antipsychotics: There are no systematically collected data to specifically address switching patients
with schizophrenia from other antipsychotics to Abilify or concerning concomitant administration with other
antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some
patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of
overlapping antipsychotic administration should be minimized.
Bipolar Disorder: Usual Starting Dose: 30 mg once a day. A dose of 30-mg/day was found to be effective when
administered as the tablet formulation. Approximately 15% of patients had their dose decreased to 15 mg based on
assessment of tolerability. The safety of doses >30 mg/day has not been evaluated in clinical trials.
Special Populations: See Schizophrenia.
Maintenance Therapy: While there is no body of evidence available to answer the question of how long a patient treated
with aripiprazole should remain on it, patients with bipolar I disorder who had been symptomatically stable on Abilify
tablets (15 or 30 mg/day with a starting dose of 30 mg/day) for at least 6 consecutive weeks and then randomized to
Abilify (15 or 30 mg/day) or placebo, and monitored for relapse demonstrated a benefit of such maintenance treatment
(see Pharmacology under Actions). While it is generally agreed that pharmacological treatment beyond an acute
response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes,
there are no systematically obtained data to support the use of aripiprazole in such longer-term treatment (ie, beyond 6
weeks).
Complicated upper & lower UTI, skin & soft tissue infections 1 g. Lower resp tract infections 1 or 2 g.
Bactericaemia/septicaemia & infections in neutropenic patients 2 g. All doses are given 12 hrly.
Cap Adult & childn weighing =30 kg 50-100 mg twice daily. Severe or intractable infections May be increased up to 200
mg twice daily. Dry syr Childn 1.5-3 mg/kg twice daily. Severe or intractable infections May be increased up to 6 mg/kg
twice daily. Cervical/urethral gonorrhea 400 mg as single dose.
Adult and Children Aged 12 Years and Over: The dosage is one 20 mg tablet twice daily. This dosage should not be
exceeded. Higher doses may be associated with elevations of one or more liver enzymes consistent with hepatotoxicity.
Children: There is no clinical experience of the use of ACCOLATE in children under 12 years of age. Until safety
information is available, the use of ACCOLATE in children is contraindicated.
Elderly: The clearance of zafirlukast is significantly reduced in elderly patients (>65 years old), such that Cmax and AUC
are approximately twice those of younger adults. However, accumulation of zafirlukast is no greater than that seen in
multiple-dose trials conducted in adult subjects with asthma, and the consequences of the altered kinetics in the elderly
are unknown. Clinical experience with ACCOLATE in the elderly (>65 years old) is limited and caution is recommended
until further information is available.
Renal Impairment: No dosage adjustment is necessary in patients with mild renal impairment. However, experience is
limited in patients with moderate to severe renal impairment (see Pharmacology: Pharmacokinetics under Actions) so
clear dose recommendations cannot be given; ACCOLATE should be used with caution in this patient group.
Administration: ACCOLATE should be taken continuously. As food may reduce the bioavailability of zafirlukast, ACCOLATE
should not be taken with meals.
Adult & childn Open lesion Apply 3-4 times daily. Closed lesion Apply more frequent. Duration of therapy: Approx 7 days.
Initially 50 mg daily, may be increased to 100 mg daily. To be given 1-2 times daily.
Resp tract 1 tab daily (preferably at night). Paracetamol toxication (accidental or non-accidental) Early dose: 140 mg/kg.
10 hr after toxication: 70 mg/kg every 4 hr for 1-3 days. Uropathy from iso & cyclophosphamide 1 g 4 times daily.
Relief of pain 1-2 tab 4-6 hrly. Max: 8 tab/day. Patient w/ CrCl <30 mL/min Not >2 tab 12 hrly.
Loading dose: 150 mg/kg in 60 min, followed by subsequent dose w/ 50 mg/kg at slow infusion rate every 4 hr for 72-hr
treatment.
Adult Herpes simplex 200 mg 5 times daily 4 hrly w/o night dose for 5 days, may be increased to 400 mg daily.
Suppression of herpes simplex in immunocompetent patient 200 mg 4 times daily 6 hrly. Prophylaxis of herpes simplex in
immunocompromised patient 200 mg 4 times daily 6 hrly. Doses may be increased to 400 mg in severe
immunocompromised patients (post-bone marrow transplant) or indigestion. Herpes zoster 800 mg 5 times daily 4 hrly
w/o night dose for 5 days. Childn Treatment & prophylaxis of herpes simplex in immunocompromised patient Childn =2
yr Adult dose, <2 yr ½ adult dose. Severe renal dysfunction (CrCl 10 mL/min) 200 mg twice daily 12 hrly. Herpes zoster in
patients w/ severe renal dysfunction 800 mg twice daily 12 hrly. Herpes zoster in patient w/ moderate renal dysfunction
(CrCl 10-25 mL/min) 800 mg 3 times daily.
Apply 5 times daily 4 hrly w/o night dose. Duration of treament: 5 days, may be continued until 10 days.
Adult & childn >12 yr 1 caplet 3 times daily. Childn 7-12 yr 2 tsp dry syr or 1 tsp forte dry syr, 3 times daily, 2-7 yr 1 tsp
dry syr or ½ tsp forte dry syr, 3 times daily.
Osteoporosis in postmenopausal women & men; treatment & prevention of glucocorticoid-induced osteoporosis in
women & men 5 mg as a single IV infusion for =15 min once a yr. Patients w/ a recent low-trauma hip fracture Loading
dose of vit D 50,000-125,000 IU orally or IM is recommended prior to 1st Aclasta infusion. Paget's disease 5 mg as single
IV infusion.
1 cap daily.
1 cap daily.
Adult Initially 5 mg 3-4 times daily. Max: 40 mg 3-4 times daily. Childn Initially 0.2 mg/kg in 3-4 times daily, may be
increased to max 0.8 mg/kg/day but not >20 mg daily.
Tab/Caplet Peptic ulcer 150 mg 2 times daily. Zollinger-Ellison syndrome 150 mg 2 times daily. Severe cases Up to 6
g/daily. Amp IM 50 mg/2 mL 6-8 hrly. IV intermittent bolus 50 mg (2 mL) 6-8 hrly.
Hypercalcemia due to malignancy 2,400 or 3,200 mg daily depending on patient's response which may be reduced
gradually to 1,600 mg. Osteolysis due to malignancy 1,600 mg daily, may be increased to max 3,200 mg if necessary.
Single infusion: 1,500 mg diluted in 500 mL of NaCl 9% or glucose 5% soln to be given as IV infusion over a 4-hr period.
Multiple infusion: 300 mg/day diluted in 500 mL soln to be given as IV infusion over a period of 2 hr until normocalcemia
is achieved or to max of 7 days.
Initially =10 mg once daily, adjusted at =4-wk intervals. Max: 80 mg once daily. Primary hypercholesterolemia &
combined or mixed hyperlipidemia 10 mg daily for 2 wk & up to 4 wk for max response. Homozygous familial
hypercholesterolemia 80 mg. Heterozygous familial hypercholesterolemia Childn 10-17 yr 10 mg daily. Max: 20 mg daily.
Initially 5 mg daily, may be increased to 10 mg daily. Elderly & patients w/ hepatic insufficiency Initially 2.5 mg once daily.
Initially 1 mg/day once daily. Daily dose may be increased at stepwise manner w/ 1-2 wk intervals between each step to
1 mg/day-2 mg/day-3 mg/day-4 mg/day & in exceptional cases, 4 mg/day. Max: 6 mg/day.
IV infusion For previously treated patients 350 mg/m2 for 30-90 min every 3 wk in monotherapy. For previously
untreated patients 180 mg/m2 for 30-90 min once every 2 wk in combination w/ 5-FU & FA. Patients w/ a bilirubin level
up to 1.5 times the ULN 350 mg/m2, 1.5-3 times the ULN 200 mg/m2.
Adult & childn >12 yr 1-2 g once daily. Severe infections Up to 4 g daily. Neonate <2 wk 20-50 mg/kg daily. Infant & childn
15 days-12 yr 20-80 mg/kg daily >50 kg Adult dose <50 kg Administer for minimum of 30 min. Meningitis 100 mg/kg
daily. Max: 4 g. Duration: N. meningitis 4 days. H. influenzae 6 days. S. pneumoniae 7 days. Gonorrhoea 250 mg IM as
single dose. Pre-op prophylaxis 1-2 g over 30-90 min.
Adult 0.25-0.5 mg 3 times daily, may be increased at intervals of 3-4 days in divided doses. Max: 4 mg. Elderly &
debilitated patients, severe liver dysfunction 0.25 mg 2-3 times daily, may be increased gradually.
Syrup: Adults and Children >12 years: 5 mL; 6-12 years: 2.5 mL; 2-6 years: 1.25 mL. All doses are to be taken 3 times a
day.
These dilutions should be stored at 25°C.
Adults and Children >12 years: 5 mL; 6-12 years: 2.5 mL; 2-6 years: 1.25 mL. To be taken 3 times daily.
Adults and children >12 years: 5 mL; 6-12 years: 2.5 mL; 2-6 years: 1.25 mL. To be taken 3 times daily.
Treatment & prevention of postmenopausal osteoporosis 5 mg daily or 35 mg once wkly. Treatment & prevention of
glucocorticoid-induced osteoporosis 5 mg once daily.
Monotherapy: Recommended dose: 10 mg. Adults (previously untreated) 400 mg/m2 IV as a single dose administered in
15-60 min. Renal failure CrCl 41-59 mL/min 250 mg/m2 as a single dose, CrCl 16-40 mL/min 200 mg/m2 as a single dose.
Adult: Monotherapy: Starting Dose: 15 or 30 mg once daily. Combination Therapy: In combination with metformin or
sulfonylurea, may be initiated at 15 or 30 mg once daily. The current metformin or sulfonylurea dose can be continued
upon initiation of Actos therapy.
If patients report hypoglycemia, the dose of sulfonylurea should be decreased.
Elderly: No dosage adjustment is necessary for elderly patients.
Renal Impairment: No dosage adjustment is necessary in patients with impaired renal function (creatinine clearance >4
mL/min). No information is available from dialysed patients, therefore, Actos should not be used in such patients.
Hepatic Impairment: Actos should not be used in patients with hepatic impairment.
Administration: Tablets are taken orally, once daily with or without food.
General: The use of Actosmet in the management of type 2 diabetes should be individualized on the basis of
effectiveness and tolerability.
Dosage Recommendations: Usual Starting Dose: 15 mg/850 mg once or twice daily with food to reduce the
gastrointestinal side effects associated with metformin.
After initiation of Actosmet or with dose increase, patients should be carefully monitored for adverse events related to
fluid retention (see Warnings).
The dosage of Actosmet should be gradually titrated, as needed, based on the adequacy of the therapeutic response.
Maximum Daily Dose: 45 mg/2550 mg of pioglitazone/metformin. This maximal dosage should be administered in
divided doses with meals.
No studies have been performed specifically examining the safety and efficacy of Actosmet in patients previously treated
with other oral hypoglycaemic agents and switched to Actosmet. Any change in therapy of type 2 diabetes should be
undertaken with care and appropriate monitoring as changes in glycemic control can occur.
Sufficient time should be given to assess adequacy of therapeutic response. Ideally, the response to therapy should be
evaluated using HbA1c, which is a better indicator of long-term glycemic control than FPG alone. HbA1c reflects glycemia
over the past 2-3 months. In clinical use, it is recommended that patients be treated with Actosmet for a period of time
adequate to evaluate change in HbA1c (8-12 weeks) unless glycemic control as measured by FPG deteriorates.
Actrapid is a fast-acting insulin and may be used in combination with longer-acting insulin products. An injection should
be followed by a meal or a snack containing carbohydrates within 30 min.
Dosage is individualized and determined by the physician in accordance with the needs of the patient. The individual
insulin requirement is usually between 0.3 and 1 IU/kg daily. The daily insulin requirement may be higher in patients
with insulin resistance (eg, during puberty, in the young or due to obesity) and lower in patients with residual,
endogenous insulin production.
In patients with diabetes mellitus, optimized glycemic control delays the onset of late diabetic complications. Optimized
metabolic control, including close blood glucose monitoring, is therefore recommended.
Dosage Adjustment: Renal or hepatic impairment may reduce insulin requirement.
Administration: For SC and IV use.
Actrapid HM/Penfill is usually administered SC into the abdominal wall. The thigh, the gluteal region or the deltoid
region may also be used.
Subcutaneous injection into the abdominal wall ensures faster absorption than from other injection sites.
Injection into a lifted skinfold minimizes the risk of unintended IM injection.
Injection sites should be rotated within an anatomic region in order to avoid lipodystrophy.
Intramuscular administrations are possible under guidance by a physician.
Actrapid HM/Penfill may also be administered IV, which should only be carried out by healthcare professionals.
Actrapid HM: Actrapid HM vials are for single-person use only with insulin syringes with the corresponding unit scale.
Injecting Actrapid HM on Its Own: Disinfect the rubber membrane. Draw the same amount of air into the syringe as the
dose of insulin needed. Inject the air into the vial by pushing the needle through the rubber stopper then press the
plunger.
Turn the vial and syringe upside down and draw the right insulin dose into the syringe. Withdraw the needle and expel
the air from the syringe and check if the dose is correct. Inject immediately.
Mixing Actrapid HM with Long-Acting Insulin: Disinfect the rubber membrane.
Just before use, roll the vial of long-acting insulin between the palms of the hands until the liquid is uniformly white and
cloudy.
Draw into the syringe the same amount of air as the dose of cloudy insulin. Inject the air into the vial containing cloudy
insulin and withdraw the needle.
Draw into the syringe the same amount of air as the dose of Actrapid HM needed. Inject the air into the Actrapid HM
vial. Turn the vial and syringe upside down and draw the right dose of Actrapid HM into the syringe. Withdraw the
needle and expel the air from the syringe and check the dose.
Push the needle into the vial of long-acting insulin, turn the vial and syringe upside down and withdraw the right dose.
Pull the needle out of the vial. Expel any air from the syringe and check the dose. Inject the mixture immediately.
Always mix fast-acting and long-acting insulin in this order.
How to Inject: Inject the insulin under the skin. Keep the needle under the skin for at least 6 sec to make sure the full
dose has been delivered.
Actrapid Penfill: Penfill cartridges are designed to be used with Novo Nordisk insulin delivery systems and NovoFine or
NovoTwist needles.
Acuatim cream should be applied to the lesions twice daily, and in the case of acne vulgaris, Acuatim should be applied
after cleansing the skin.
Route and Method of Administration: Acuatim is intended for topical (dermal) application only and is not intended for
ophthalmological use. Acuatim should not be applied to the cornea or conjunctiva.
Adults: Usually 2 mL once a week for 5 consecutive weeks, administered by injection in the cavity of the knee joint.
Frequency of injection may be adjusted according to condition of the disease.
As Adant Dispo is injected into the joint, injection should be performed according to a strict aseptic procedure.
Administration: How to Use: After Adant Dispo is restored to room temperature, take out the syringe from the blister
pack.
Cut and sever by hand the tips of finger-wing at the central part of the syringe and expand it until it is fixed and firm.
Turn the stopper and pull it away.
Syringe needle (22-23 G size) is fixed by screwing it in.
Push the plunger rod and start administration. Before administration, the site of injection should be cleaned and
disinfected. After administration, separate the components of Adant Dispo kit and discard.
Apply thinly once daily. Duration: Adult Not >12 wk. Childn Not >4 wk.
Tablet: Adults and Children =12 years: Recommended Dose: 5 mg once daily.
Patients with Liver or Renal Impairment: Starting Dose: 1 tab every other day is recommended based on
pharmacokinetic data.
Syrup: Adults and Adolescents =12 years: 10 mL (5 mg) once daily.
Children 6-11 years: 5 mL (2.5 mg) once daily; 1-5 years: 2.5 mL (1.25 mg) once daily. All doses to be taken with or
without meals.
Adults and Adolescents =12 years: One (1) tab 2 times daily regardless of mealtime.
Administration: For oral use. May take with or without food. Do not chew, break or crush tab. Swallow whole.
Adult 75 mg once daily. Unstable angina or non-Q-wave MI 300 mg, then continued to 75 mg once daily.
Tab UTI 100-400 mg twice daily for 1-10 days. Severe & complicated infections Up to 600 mg daily for 20 days. Resp tract
infections 200-400 mg twice daily. Uncomplicated gonococcal urethritis & cervicitis (including PPNG infections) 200-600
mg as single dose. Non-gonococcal urethritis 400 mg daily in single or divided doses for 9 days. Skin & soft tissue, O&G
infections, bacterial enteritis 400 mg daily for 7 days.
IV infusion only. Hypoproteinemia in acutely ill patient Adult 50-75 g at 2 mL/min. Shock Initially 20 g at 2-4 mL/min.
Total dose should not exceed 2 g/kg in the absence of active bleeding. Severe burns Usual dose: 20-80 g daily at 1
mL/min.
Local haemostasis Apply conc directly. Burns 1:3 to 1:8 dilutions of conc. Extensive burns Diluted conc alone or coating of
Albothyl gel or gauze pad over affected area. Vag supp To be inserted into the vagina. Gel Intravag application every
other day.
Individualized dosage.
Individualized dosage.
Alco drops Childn 2-5 yr 0.8 mL 3 times daily. Alco Plus syr/Alco Plus DMP syr Adult & childn >12 yr 5 mL. Childn 6-12 yr
2.5 mL, 2-5 yr 1.25 mL. To be taken 3 times daily.
Adult Initially 5 mg/day in the evening before bedtime for 1 mth then may be increased up to 10 mg once daily.
Adult 1 tab. Childn 6-12 yr ½ tab, 2-6 yr ¼ tab. To be taken 3-4 times daily.
Initially 1-2 drops/hr in the morning & every 2 hr in the evening. Reduce to 1 drop 4 hrly & then to 1 drop 3-4 times daily.
Combination Use with Cisplatin: The recommended dose of Alimta is 500 mg/m2 of body surface area (BSA)
administered as an IV infusion over 10 min on the 1st day of each 21-day cycle. The recommended dose of cisplatin is 75
mg/m2 BSA infused over 2 hrs approximately 30 min after completion of the pemetrexed infusion on the 1st day of each
21-day cycle.
Patients must receive adequate antiemetic treatment and appropriate hydration prior to and/or after receiving cisplatin.
Single Agent Use: Non-Small Cell Lung Cancer (NSCLC): In patients treated for NSCLC after prior chemotherapy, the
recommended dose of Alimta is 500 mg/m2 BSA administered as an IV infusion over 10 min on the 1st day of each 21-
day cycle.
Premedication Regimen: To reduce the incidence and severity of skin reactions, a corticosteroid should be given the day
prior to, on the day of and the day after pemetrexed administration. The corticosteroid should be equivalent to
dexamethasone 4 mg administered orally twice daily (see Precautions). To reduce toxicity, patients treated with
pemetrexed must also receive vitamin supplementation (see Precautions). Patients must take oral folic acid or a
multivitamin containing folic acid (350-1000 mcg) on a daily basis. At least 5 doses of folic acid must be taken during the
7 days preceding the 1st dose of pemetrexed and dosing must continue during the full course of therapy and for 21 days
after the last dose of pemetrexed. Patients must also receive an IM injection of vitamin B12 (1000 mcg) in the week
preceding the 1st dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be
given on the same day as pemetrexed.
Monitoring: Patients receiving pemetrexed should be monitored before each dose with a complete blood count,
including a differential white cell count (WCC) and platelet count. Prior to each chemotherapy administration, blood
chemistry tests should be collected to evaluate renal and hepatic function. Before the start of any cycle of
chemotherapy, patients are required to have the following: Absolute neutrophil count (ANC) should be =1,500 cells/mm3
and platelets should be =100,000 cells/mm3; CrCl should be =45 mL/min.
The total bilirubin should be =1.5 times upper limit of normal. Alkaline phosphatase (AP), aspartate transaminase (AST or
SGOT) and alanine transaminase (ALT or SGPT) should be =3 times upper limit of normal. Alkaline phosphatase, AST and
ALT =5 times upper limit of normal is acceptable if liver has tumour involvement.
Dose Adjustments: Dose adjustments at the start of a subsequent cycle should be based on nadir haematologic counts
or maximum non-haematologic toxicity from the preceding cycle of therapy. Treatment may be delayed to allow
sufficient time for recovery. Upon recovery, patients should be retreated using the guidelines in Tables 4, 5 and 6 (see
Tables 4,5 and 6), which are applicable for Alimta used as a single agent or in combination with cisplatin. (See Tables 4.)
If patients develop non-haematologic toxicities =Grade 3 (excluding neurotoxicity), Alimta should be withheld until
resolution to less than equal to the patient's pre-therapy value. Treatment should be resumed according to the
guidelines in Table 5. (See Table 5.)
In the event of neurotoxicity, the recommended dose adjustment for Alimta and cisplatin is documented in Table 6.
Patients should discontinue therapy if Grade 3 or 4 neurotoxicity is observed. (See Table 6.)
Treatment with Alimta should be discontinued if a patient experiences any haematologic or non-haematologic Grade 3
Alinamin: Usually, 1 tab daily or based on medical instructions.
Alinamin-F: Tablet: 1 tab daily after meals.
Ampoule: 10 mL, 1-2 times daily by slow IV.
Adult 1½-2 tsp. Childn 7-12 yr 1-1½ tsp, 2-6 yr ½-1 tsp. Infant ¼-½ tsp. To be taken 3-4 times daily.
Adult & childn =12 yr 1 tab or 10 mL daily. Childn 2-12 yr >30 kg 10 mg (2 tsp) daily; <30 kg 5 mg (1 tsp) daily.
1 tab once weekly.
Adult & childn >12 yr 900-1,800 mg/day. Day 1: 300 mg once daily. Day 2: 300 mg twice daily. Day 3: 300 mg 3 times
daily. The dose may be increased to 1,200 mg/day in 3 equally divided doses & if necessary, further titration can occur
using increments of 300 mg/day in 3 divided doses. Max: 2,400 mg/day. Patients w/ renal failure CrCl >60 mL/min 400
mg 3 times daily, 30-60 mL/min 300 mg twice daily, 15-30 mL/min 300 mg once daily, <15 mL/min 300 mg every other
day. Hemodialysis patients Initially 300-400 mg daily. Maintenance dose: 200-300 mg 4 hr after hemodialysis.
Anxiety 0.25-0.5 mg 3 times daily. Geriatric patients or in the presence of debilitating disease 0.25 mg 2-3 times daily.
100 mg/day by deep IM but may be increased to 200 mg in severe cases. The duration of administration can range from
5-10 days & may be continued through oral or rectal routes.
Chewable tab 1-2 tab between meals & at bedtime. Susp 1-2 tsp between meals & at bedtime.
Prevention: Single dose & w/in the 1st hr after birth is recommended. Treatment: Administered early in the course of
RDS, preferably <6 hr of age. Max: Should not exceed 216 mg total phospholipids/kg w/in the 1st 2 days of life.
Adult 0.25-0.5 mg 3 times daily. Geriatric or debilitated patients 0.25 mg 3 times daily.
Threatened abortion 1 tab 3 times daily for 5-7 days. May be extended if necessary. Habitual abortion 1-2 tab daily after
pregnancy is diagnosed, continue for =1 mth after the critical period. Threatened premature labour Individualized
dosage. Max: 40 mg daily.
5 mg once daily before bedtime for 1 mth. After 1 mth, doses may be increased to 10 mg once daily. Max daily dose: 10
mg.
1-8 mg daily. Initial dose & dose titration: 1 mg once daily. Daily dose may be increased at intervals of 1-2 wk, & carried
out stepwise as follows: 1 mg-2 mg-3 mg-4 mg-6 mg, & in exceptional cases, 8 mg.
In principle, the dosage of Amaryl is governed by the desired blood sugar level. The dosage of glimepiride must be the
lowest which is sufficient to achieve the desired metabolic control.
Treatment with Amaryl must be initiated and monitored by a physician. Amaryl must be taken at the times and in the
doses prescribed. Mistakes eg, forgetting to take a dose, must never be corrected by subsequently taking a larger dose.
Measures for dealing with such mistakes (in particular, forgetting a dose or skipping a meal) or situations where a dose
cannot be taken at the prescribed time must be discussed and agreed between physician and patient beforehand. A
physician must be notified immediately if the dose taken is too high, or an extra dose has been taken.
The initial and the maintenance doses are set based on the results of regular checks of glucose in blood and urine.
Monitoring of glucose levels in blood and urine also serves to detect either primary or secondary failure of therapy.
Initial Dose and Dose Titration: Usual Initial Dose: 1 mg once daily. If necessary, the daily dose can be increased. Any
increase should be based on regular blood sugar monitoring and should be gradual ie, at intervals of 1-2 weeks, and
carried out stepwise, as follows: 1 mg - 2 mg - 3 mg - 4 mg and in exceptional cases, 8 mg.
Usual Dose Range in Patients with Well-Controlled Diabetes: 1-4 mg daily. Only some patients benefit from daily doses of
>6 mg.
Distribution of Doses: Timing and distribution of doses are decided by the physician, taking into consideration the
patient's current lifestyle. Normally, a single daily dose of Amaryl is sufficient. The dose should be taken immediately
before a substantial breakfast or, if none is taken, immediately before the first main meal. It is very important not to skip
meals after taking Amaryl.
Secondary Dosage Adjustment: As the control of diabetes improves, sensitivity to insulin increases, therefore,
glimepiride requirements may fall as treatment proceeds. To avoid an excessive reduction in blood sugar
(hypoglycaemia), a timely dose reduction or cessation of Amaryl therapy must be considered.
A dose adjustment must also be considered whenever the patient's weight or lifestyle changes, or other factors causing
an increased susceptibility to hypoglycaemia or to an excessive increase in blood sugar levels (hyperglycaemia) arise (see
Precautions).
Duration of Treatment: Treatment with Amaryl is normally a long-term therapy.
Changeover from Other Oral Antidiabetics to Amaryl: There is no exact dosage relationship between Amaryl and other
oral blood sugar-lowering agents. When substituting Amaryl for other such agents, the initial daily dose is 1 mg; this
applies even in changeovers from the maximum dose of another oral blood sugar-lowering agent. Any Amaryl dose
increase should be in accordance with guidelines given previously in Initial Dose and Dose Titration.
Consideration must be given to the potency and duration of action of the previous blood sugar-lowering agent. It may be
necessary to interrupt treatment to avoid additive effects which would increase the risk of hypoglycaemia.
Use in Combination with Metformin: Whenever blood sugar levels cannot be controlled adequately with the maximum
daily dose of either Amaryl or a metformin-containing antidiabetic alone, both medicines may be used concomitantly. In
such cases, the dose of the established medicine remains unchanged. Treatment with the additional medicine is started
at a low dose which, depending on the desired blood sugar level, may then be increased gradually up to the maximum
daily dose. Combined treatment should be initiated under close medical supervision.
Use in Combination with Insulin: Whenever blood sugar levels cannot be controlled adequately with the maximum daily
dose
Dosage of should
Amaryl,be
insulin may be given
individualized basedconcomitantly. In this
on the patient's case,
blood the current
glucose levels. dose of Amaryl
Generally, remains
it should unchanged. Insulin
be recommended to
initiate the lowest effective dose and increase the dose depending on the patient's blood glucose levels. Adequate
monitoring of blood glucose levels should be performed.
Amaryl M should be administered once or twice per day, before or with a meal.
When switching from combination therapy of glimepiride plus metformin as separate tablets, Amaryl M should be
administered on the basis of dosage currently being taken.
Adult & childn >20 kg 250-500 mg 4 times daily. Childn <20 kg 50-100 mg/kg/day in 4 divided doses. Gonococcal
urethritis 3.5 g ampicillin w/ 1 g probenecid as a single dose.
Hypertension and Angina: Adults: Initially 5 mg once daily, may be increased to maximum dose of 10 mg depending on
the individual patient's response and severity.
Small, Fragile or Elderly Patients or Hepatic Insufficiency: May be started on 2.5 mg once daily and this dose may be used
when adding amlodipine to other antihypertensive therapy.
Majority of hypertensive patients taking 5 mg/day, the dose may not necessarily be increased. For those who need
higher dose, amlodipine can be increased to 7.5 mg/day with maximum dose of 10 mg/day.
Chronic Stable or Vasospastic Angina: Recommended Dose: 5-10 mg, with the lower dose suggested in the elderly and in
patients with hepatic insufficiency. No dose adjustment of amlodipine is required upon concomitant administration of
thiazide diuretics, ß-blockers and ACE inhibitors.
Children: No experience is available on the use of amlodipine in children.
Chronic kidney insufficiency GFR 5 & 50 mL/min 4-8 FC caplet 3 times daily.
Adult: Usual Dose: 500 mL/dose via peripheral vein infusion. The usual infusion rate in adults is 500 mL/120 min and
should be slowed in the elderly and critically ill patients. The dosage may be adjusted according to the patient's
condition, body weight and age. Maximum Dosage: 2500 mL/day.
Method of mixing 2 solutions (never fail to mix 2 solutions): Be sure to press the lower chamber to break the center seal
between the 2 chambers. When the upper chamber is pressed, the checker does not open. To open the package: Tear
outer wrap at notch and remove solution container. To break the center seal: Press the lower chamber with both hands
until the center seal breaks immediately after removing the product. The checker opens upon the seal breaking. (Admix
other drugs, when needed, after mixing 2 solutions). To mix: Remove the open checker and press both chambers
alternately to mix the solutions thoroughly.
Adults: Usual Dose: 500-1000 mL/dose by IV drip infusion. Usual Peripheral Infusion Rate: 500 mL over 180-300 min
(approximately 25-40 drops/min) in adults. For total parenteral nutrition, 500-1000 mL of Aminoleban Infusion should be
suitably combined with dextrose solutions and administered over 24 hrs via the central vein. The dosage may be
adjusted depending on the patient's age, symptoms and body weight.
1.5-2.5 g amino acids/kg body wt/day.
Adults: Internal Disorder or Presurgical Protein Deficiency: Usual Dosage: 500 mL by IV drip infusion over 4-6 hrs (20-30
drops/min) simultaneously or followed by a 10% sugar solution 500 mL over 2 hrs (60-80 drops/min). These infusions are
repeated at 12-hr intervals for 5-7 days. The intervals may be prolonged to 24 hrs according to patient's condition and
response.
Postsurgical Impairment of Protein Synthesis: Usual Dosage: 500 mL by IV drip infusion over 4-6 hrs (20-30 drops/min)
following drip infusion of Darrow's solution 1000 mL over 4 hrs (60-100 drops/min) and followed by drip infusion of a
10% sugar solution 500 mL over 2 hrs (60-100 drops/min). These infusions are started on the 3rd postsurgical day and
repeated at 24-hr intervals for 5-7 days.
IM Neonates Initially 10 mg/kg/day, followed by 7.5 mg/kg 12 hrly. Max: 15 mg/kg/day or 1.5 g/day. Duration of therapy:
7-10 days. IV Infusion Adult & childn 500 mg in 100-200 mL of 0.9% NaCl or 5% Dextrose soln infused over 30-60 min.
Infant Adult dose infused over 1-2 hr.
Central Vein Infusion: Usual Adult Dosage: 1000 mL/day by drip infusion via the central vein.
Peripheral Vein Infusion: Usual Adult Dosage: 500 mL/dose by drip infusion via the peripheral vein. The usual peripheral
infusion rate is such a rate as to provide about 10 g of amino acids over 60 min of infusion in order to achieve optimal
physiological utilization of amino acids. A typical infusion rate in adults is 100 mL over 60 min (about 25 drops/min), and
the rate should be adjusted downward in the case of children, elderly patients and severely ill patients.
The dosage may be increased or decreased depending on the patient's age, symptoms and body weight.
Combination of Amiparen with a carbohydrate solution is highly recommended for efficient utilization of amino acids in
the body.
Adult Usual dose: Chronic renal failure 200 mL/day via peripheral vein w/ infusion rate of 100 mL over 60 min (25
drops/min) or 400 mL/day via central vein by TPN. Acute renal failure 600 mL/day via central vein by TPN. >300 kCal of
non-protein cal/g of nitrogen should be administered for efficiency of amino acid utilization. Childn, elderly, seriously ill
patients Individualized dosage via slow infusion.
HTN Initially 5 mg once daily. Max: 10 mg daily. Fragile, elderly patients or patients w/ liver insufficiency Initially 2.5 mg
once daily. Chronic stable & vasospastic angina 5-10 mg once daily.
Adult Internal disorder of presurgical protein deficiency Usual dosage: 500 mL by IV drip infusion over 4-6 hr (20-30
drops/min) simultaneously or followed by drip infusion of Darrow's soln 1000 mL over 4 hr (60-100 drops/ min) &
followed by drip infusion of a 10% sugar soln 500 mL over 2 hr (60-80 drops/min). Post-op impairment of protein
synthesis Usual dosage: 500 mL by IV drip infusion over 4-6 hr (20-30 drops/min) following drip infusion of Darrow's soln
1,000 mL over 4 hr (60-100 drops/min).
Cap/Dispersible tab Adult & childn =20 kg 250-500 mg 8 hrly. Childn <20 kg 20-40 mg/kg 8 hrly in divided doses. Syr
Childn >8 kg 125-250 mg 8 hrly. Paed drops All indications except infections of lower resp tracts, Childn =6 mth 6-8 kg
0.5-1 mL 8 hrly, =6 kg 0.25-0.5 mL 8 hrly. Infections of lower resp tract Childn =6 mth 6-8 kg 1-1.5 mL 8 hrly, =6 kg 0.5-1
mL 8 hrly. Inj Adult 250-500 mg IM 8 hrly. 500 mg-1 g IV/infusion 6 hrly in severe infections. Childn 35-100 mg/kg/day IM
in divided doses or up to 100 mg/kg/day IV/infusion in divided doses 6 hrly over 30-min infusion. Typhoid & paratyphoid
Adult 4 g daily in divided doses for 14-21 days. Childn 100 mg/kg/day in divided doses for 14-21 days. Typhoid carrier
states 3-4 g daily in divided doses for min of 1 mth. Gonorrhea Single dose of 3 g + 1 g probenecid. Uncomplicated UTI
Single dose of 3 g. Syphilis 250 mg 6 hrly for 4 wk up to 5 mth. Severe or recurrent lower resp tract infection 3 g twice
daily. Dental abscess 3 g twice daily 8 hrly. Otitis media Adult & childn 3-10 yr 750 mg 2 times daily for 2 days.
Adult & childn =12 yr 4-48 mg/day. Childn <12 yr 416 mcg-1.7 mg/kg/day.
Adult & Childn =12 yr 4-48 mg/day. Childn <12 yr 416 mcg-1.7 mg/kg/day.
Chronic venous disease 2 caplet daily. Acute hemorrhoidal attacks 6 caplet for the 1st 4 days, then 4 caplet daily for 3
days, 2 caplet thereafter. Chronic hemorrhoids 2 caplet daily.
Adult 1 caplet, if pain persist, followed by 1 cap 6-8 hrly. Max: 4 caplet daily.
Adult & adolescent =16 yr Initially 2 caplet/day & as needed in not <6 hr dose interval. Max dose: 8 caplet/day.
Caplet Adult & childn >12 yr 250 mg 2 times daily, may be increased up to 500 mg 2 times daily. Infant & childn =12 yr
125 mg 2 times daily. Uncomplicated UTI 125-250 mg 2 times daily. Uncomplicated gonococcal urethritis 1 g as a single
dose. Otitis media Childn =2 yr 250 mg, <2 yr 125 mg. To be taken 2 times daily. Inj Adult 750 mg-1.5 g 8 hrly IM or IV for
5-10 days. If necessary, may increase to 3-6 g/day 6 hrly. Childn & infant >3 mth 50-100 mg/kg/day 6-8 hrly, severe &
serious infections: 100 mg/kg/day. Bone & joint infections 150 mg/kg/day 8 hrly (not exceeding max dosage of adult).
Bacterial meningitis 200-240 mg/kg/day IV 6-8 hrly.
Adult 150 mg twice daily, morning & evening. Childn >4 yr 5-8 mg/kg daily in 2 divided doses & not for >10 days.
Adult & childn >40 kg 1-2 g daily in 2 divided doses. Childn <40 kg 25 mg/kg daily in 2 divided doses.
FC tab Adult & childn >12 yr Mild to moderate infections ½ tab 3 times daily. Severe infections 1 tab 3 times daily. Dry
susp Childn 31.25 mg/kg daily in divided doses every 8 hr. >6 yr 5 mL 3 times daily; 1-6 yr 2.5 mL 3 times daily; <1 yr 1 mL
3 times daily.
Folic acid deficiency Initially 0.25-1 mg/day. Maintenance: 0.25-0.5 mg/day. Supplement in pregnancy & lactation 0.5-1
mg/day. Megaloblastic anemia 0.5-1 mg/day.
IM Pre-op med Adult 0.07-0.1 mg/kg. Elderly & debilitated patients 0.025-0.05 mg/kg to be administered 30 min before
induction of anesth. IV Basal sedation Initially 2.5 mg 5-10 min pre-op. Severe illness Initially 1-1.5 mg. Max total dose:
3.5 mg. Induction of anesth & conscious sedation 10-15 mg.
Initially 2.5 mg once daily, may be increased by doubling the dose at intervals of 2-3 wk. Usual maintenance dose is 2.5-5
mg daily, max dose of 10 mg daily.
Cap/caplet Adult & childn >30 kg 50-100 mg twice daily, may be increased to 200 mg twice daily for more severe cases.
Dry syr 1.5-3 mg/kg twice daily. Typhoid fever in childn 10-15 mg/kg/day for 2 wk.
Drag Adult 1 drag. Syr Adult 2 tsp. Childn 6-12 yr 1 tsp. To be taken 3-4 times daily.
Adult Initially 100-150 mg daily in 2-3 divided doses. Pain management & OA Max dose: 150 mg/day. RA Max dose: 225
mg/day. Ankylosing spondylitis Max dose: 125 mg/day. Migraine Initially 50 mg at the 1st signs of an impending attack.
In cases where pain relief w/in 2 hr after the 1st dose is not sufficient, dose may be repeated. Further doses may be
taken 4-6 hrly, if needed. Max dose: 200 mg/day.
Adult 1-2 sugar-coated tab daily. Prevention of motion sickness ½ sugar-coated tab 1 hr before travelling & when
necessary. Childn 6-12 yr ½ adult dose.
Childn 7-12 yr 5 mL 2 times daily, 1-6 yr 5 mL once daily, 6 mth-1 yr 2.5 mL once daily.
Syr Adult & childn >5 yr 1-2 tsp once daily. Childn 2-5 yr 1 tsp once daily. Drops Childn 1-3 yr 0.6 mL once daily, <12 mth
0.3 mL once daily.
Apidra is a recombinant human insulin analogue that has been shown to be equipotent to regular human insulin. It has
more rapid onset and a shorter duration of action than regular human insulin.
Apidra should be given shortly (0-15 min) before or soon after meals. It should be used in regimens that include a longer-
acting insulin or basal insulin analogue and can be used with oral hypoglycemic agents. The dosage of Apidra should be
individually adjusted.
Administration: Apidra should be given by SC injection or by continuous SC pump infusion. Apidra should be
administered SC in the abdominal wall, the thigh or upper arm or by continuous infusion in the abdominal wall. As for all
insulins, injection and infusion sites within an injection area (abdomen, thigh or deltoid) should be rotated from one
injection to the next. As for all insulins, the rate of absorption and consequently, the onset and duration of action, may
be affected by the injection site, exercise and other variables.
Subcutaneous injection in the abdominal wall ensures a slightly faster absorption than other injection sites. Care should
be taken to ensure that blood vessel has not been entered. After administration, the site of injection should not be
massaged. Patients must be educated to use proper injection techniques.
Mixing with Insulins: Apidra must not be mixed with any preparation other than Neutral Protamine Hagedorn (NPH)
human insulin. If Apidra is mixed with NPH human insulin, Apidra should be drawn into the syringe first. Injection should
be given immediately after mixing. No data are available on mixing insulin glulisine with insulin preparations other than
NPH human insulin.
Continuous Subcutaneous Infusion Pump: Apidra may be used for Continuous Subcutaneous Insulin Infusion (CSII) in
pump systems suitable for insulin.
Special Populations: Renal Impairment: The pharmacokinetic properties of insulin glulisine are generally maintained in
patients with renal impairment. However, insulin requirements may be reduced in the presence of renal impairment (see
Pharmacokinetics under Actions).
Hepatic Impairment: The pharmacokinetic properties of insulin glulisine have not been investigated in patients with
decreased liver function. In patients with hepatic impairment, insulin requirements may be diminished due to reduced
capacity for gluconeogenesis and reduced insulin metabolism.
Elderly: Limited pharmacokinetic data are available in elderly patients with diabetes mellitus. Deterioration of renal
function may lead to a decrease in insulin requirements.
Children and Adolescents: There is no adequate clinical information on the use of Apidra in children and adolescents.
Initially 75 mg twice daily. May be increased to 150 mg twice daily at 3-7 daily interval. Max: 300 mg twice daily.
Usual Recommended Initial Maintenance Dose: 150 mg once daily, with or without food. Aprovel, at a dose of 150 mg
once daily generally provides a better 24-hr blood pressure control than 75 mg. However, initiation of therapy with 75
mg could be considered, particularly in haemodialysed patients and in the elderly >75 years.
In patients insufficiently controlled with 150 mg once daily, the dose can be increased to 300 mg or other
antihypertensive agents can be added. In particular, the addition of a diuretic eg, hydrochlorothiazide has been shown to
have an additive effect with Aprovel (see Interactions).
Hypertensive Type 2 Diabetic Patients: Therapy should be initiated at irbesartan 150 mg once daily and titrated up to 300
mg once daily as the preferred maintenance dose for treatment of renal disease.
The demonstration of renal benefit of Aprovel in hypertensive type 2 diabetic patients is based on studies where
irbesartan was used in addition to other antihypertensive agents, as needed, to reach target blood pressure (see
Pharmacology under Actions).
Intravascular Volume Depletion: Volume- and/or sodium-depletion should be corrected prior to administration of
Aprovel.
Children: The safety and efficacy of Aprovel have not been established in children.
Elderly: Although considerations should be given to initiating therapy with 75 mg in patients >75 years, dosage
adjustment is not usually necessary for the elderly.
Renal Impairment: No dosage adjustment is necessary in patients with impaired renal function. A lower starting dose (75
mg) should be considered for patients undergoing haemodialysis.
Hepatic Impairment: No dosage adjustment is necessary in patients with mild to moderate hepatic impairment. There is
no clinical experience in patients with severe hepatic impairment.
Adult 100-150 mg daily. Milder cases & childn >14 yr 75-100 mg daily. Daily dose should be given in 2-3 divided doses.
2 tabs a day.
Adult 250-500 mg. Childn up to 10 yr 125 mg. To be taken 3 times daily.
Adult & childn >12 yr 2 tab/tsp after stool (max 12 tab/tsp daily), 6-12 yr 1 tab/tsp after stool (max 6 tab/tsp daily).
Arcoxia is administered orally. It may be taken with or without food. Recommended Dose: Arthritis/Osteoarthritis: 60 mg
once daily. Analgesia/Acute Pain Associated with Dental Surgery: 120 mg once daily. Arcoxia 120 mg should be used only
for the acute symptomatic period.
Chronic Musculoskeletal Pain: 60 mg once daily.
Doses greater than those recommended for each indication have either not demonstrated additional efficacy or have not
been studied. Therefore, the dose for each indication is the maximum recommended dose.
Hepatic Insufficiency: In patients with mild hepatic insufficiency (Child-Pugh score 5-6), a dose of 60 mg once daily
should not be exceeded. In patients with moderate hepatic insufficiency (Child-Pugh score 7-9), the dose should be
reduced; a dose of 60 mg every other day should not be exceeded. There are no clinical or pharmacokinetic data in
patients with severe hepatic insufficiency (Child-Pugh score >9). (See Precautions.)
Renal Insufficiency: In patients with advanced renal disease (CrCl <30 mL/min), treatment with Arcoxia is not
recommended. No dosage adjustment is necessary for patients with lesser degrees of renal insufficiency (CrCl =30
mL/min). (See Precautions.)
Elderly, Gender, Race: No dosage adjustment in Arcoxia is necessary.
Acute Hemorrhoid: 6 tablets daily for 4 days, then 4 tablets daily for the next 3 days.
Chronic Hemorrhoid and Venous Insufficiency: 2 tablets daily for 2 months.
Dilute 4 mL in 1L of 5% dextrose soln or 5% dextrose-NaCl soln. Initially 2-3 mL/min via IV infusion. Maintenance: 0.5-1
mL/min.
Adult 400 mg 3-4 times daily. Analgesia 200-400 mg 3-4 times daily.
Adult & childn >12 yr 1 tab 3 times daily, childn 6-12 yr 1 tab twice daily (morning & evening). Max duration of therapy: 3
wk.
Adult & elderly Mild to moderate Alzheimer's disease Initially 5 mg/day in the evening (prior to retiring). Dose can be
increased to 10 mg/day after at least 1 mth of clinical assessment of treatment at 5 mg/day. Max: 10 mg/day. Severe
Alzheimer's disease 10 mg/day, only after daily dose of 5 mg for 4-6 wk. If not tolerated, reduce to 5 mg.
OA 7.5 mg once daily, may be increased to 15 mg once daily. RA 15 mg once daily, may be reduced to 7.5 mg once daily.
Patient w/ kidney failure Max: 7.5 mg once daily.
Patients w/ normal kidney function Acute exacerbation of chronic bronchitis 500 mg/day for 7 days. Community-
acquired pneumonia 500 mg/day for 7-14 days. Acute maxillary sinusitis 500 mg/day for 10-14 days. Skin infections 500
mg/day for 7-10 days. Complicated UTI 250 mg/day for 10 days. Acute pyelonephritis 250 mg/day for 10 days. Patient w/
CrCl 20-49 mL/min Initially 500 mg followed by 250 mg/day, CrCl 10-19 mL/min Initially 500 mg followed by 250 mg/48
hr; Haemodialysis Initially 500 mg, followed by 250 mg/2 days; CAPD Initially 250 mg, followed by 250 mg/2 days.
1 cap daily.
Adult 75 mg once daily. Unstable angina 300 mg, then reduce to 75 mg once daily.
Tab Initially 1200 mg daily. Maintenance: 600-800 mg daily. To be taken in 3-4 divided doses. Susp Adult 2 tsp 3-4 times
daily. Childn 8-12 yr 2 tsp, 3-7 yr 1 tsp, 1-2 yr ½ tsp. All doses to be taken 3-4 times daily.
Childn >6 yr 1 tbsp twice daily; <6 yr ½-1 tbsp twice daily.
Adult & childn >14 yr Initially 500 mg, followed by 250 mg 6 hrly.
Adult 1-2 tab 3-4 times daily. Childn ½-1 tab up to 2 times daily.
Adult 0.5- 2 g daily IV/IM.
1 caplet daily.
1 cap daily.
Tab Adult 2-4 mg, childn 6-12 yr 2 mg, 2-6 yr 1-2 mg. Syr Adult 5-10 mL, childn 6-12 yr 5 mL, 2-6 yr 2.5-5 mL. All doses
are to be taken 3-4 times daily.
1 cap daily.
1 softcap daily.
Anxiety 0.25-0.5 mg 3 times daily. Geriatric patients or in the presence of debilitating disease 0.25 mg 2-3 times daily.
Adult 50 mcg twice daily. Childn >6 yr 25 mcg (or 5 mL syr) twice daily; <6 yr 1.125 mcg or 0.2-0.25 mg/kg body wt twice
daily.
Usual dose: 10 mg once daily. Range: 10-80 mg once daily. Primary hypercholesterolemia & combined or mixed
hyperlipidemia 10 mg daily for 2 wk & up to 4 wk for max response. Homozygous familial hypercholesterolemia 80 mg.
Heterozygous familial hypercholesterolemia in ped patients 10-17 yr 10 mg daily. Max: 20 mg daily. Dose adjustment
should be made at =4 wk intervals.
Apply to affected area 3 times daily & massage gently into the skin.
Initially 10 mg once daily at range of 10-80 mg once daily. Primary hypercholesterolemia & combined (mixed)
hyperlipidemia 10 mg once daily for 2 wk & up to 4 wk for max response. Homozygous familial hypercholesterolemia 80
mg. Heterozygous familial hypercholesterolemia Childn 10-17 yr Recommended starting dose: 10 mg daily. Max: 20 mg
daily. Adjust dose at =4 wkly intervals.
General: Before instituting therapy with atorvastatin, an attempt should be made to control hypercholesterolemia with
appropriate diet, exercise and weight reduction in obese patients and to treat underlying medical problems. The patients
should continue on a standard cholesterol-lowering diet during treatment with atorvastatin.
Usual Starting Dose: 10 mg once daily. Dosage Range: 10-80 mg once daily.
Dosage may be given any time of the day, with or without food. Starting and maintenance dosage should be
individualized according to baseline LDL-C levels, the goal of therapy and patients response. After initiation and/or upon
titration of atorvastatin, lipid levels should be analyzed within 2-4 weeks and dosage adjusted accordingly.
Primary Hypercholesterolemia and Combined (Mixed) Hyperlipidemia: The majority of patients are controlled with
atorvastatin 10 mg once daily. A therapeutic response is evident within 2 weeks and the maximum response is usually
achieved within 4 weeks. The response is maintained during chronic therapy.
Homozygous Familial Hypercholesterolemia: In a compassionate-use study of patients with homozygous familial
hypercholesterolemia, most patients responded to 80 mg of atorvastatin.
Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10-17 years): Recommended Starting Dose: 10
mg/day. Maximum Recommended Dose: 20 mg/day (doses >20 mg have not been studied in this population). Doses
should be individualized according to the recommended goal of therapy (see Indications and Pharmacodynamics under
Actions). Adjustment should be made at intervals of =4 weeks.
Hepatic Insufficiency (see Contraindications and Precautions).
Renal Insufficiency: Renal disease has no influence on the plasma concentrations or on the LDL-C of atorvastatin. Thus,
no adjustment of the dose is required.
Children: Treatment experience in a pediatric population is limited to doses of atorvastatin up to 80 mg/day for 1 year in
patients with homozygous FH. No clinical or biochemical abnormalities were reported in these patients.
Elderly: No differences in safety, efficacy or lipid treatment goal attainment were observed between elderly patients and
the overall population (see Actions).
The Following Treatment Guidelines may be Used to Establish Treatment Goals (see Table 1):
After the LDL-C goal has been achieved, if the TG is still =200 mg/dL, non HDL-C (total-C minus HDL-C) becomes a
secondary target of therapy. Non-HDL-C goals are set 30 mg/dL higher than LDL-C goals for each risk category. (See Table
2.)
European Atherosclerosis Society (EAS)/Treatment Goals for Lipid Management: For patients with established coronary
heart disease or other patients at increased risk of ischemic events, the treatment goal is LDL-C <3 mmol/L (or <115
mg/dL) and total cholesterol <5 mmol/L (or <190 mg/dL).
Customary Local Treatment Guidelines (include local guidelines as necessary).
RA 15 mg daily, may be reduced to 7.5 mg daily. OA 7.5 mg daily, may be increased to 15 mg daily. Max: 15 mg/day.
Initially, 7.5 mg daily for patients w/ increased risk of adverse reactions.
Metered-Dose Inhaler/Metered-Aerosol: The dosage should be adapted to the individual requirements. Unless
otherwise prescribed, the following dosages are recommended: Adults and Children =12 years: 2 metered doses (puffs) 4
times daily.
Since a requirement for increasing doses suggests that additional therapeutic modalities may be needed, a total daily
dose of 12 puffs should generally not be exceeded.
If therapy does not produce a significant improvement or if the patient's condition gets worse, medical advice must be
sought in order to determine a new plan of treatment. In the case of acute or rapidly worsening dyspnoea (difficulty in
breathing), a doctor should be consulted immediately.
For acute exacerbations of chronic obstructive pulmonary disease, treatment with Atrovent inhalation solution or unit
dose vials may be indicated.
Because of insufficient information in children, Atrovent metered-aerosol should only be used on medical advice and
under the supervision of an adult.
Inhalation Solution: The dosage should be adapted to the individual requirements of the patient. Patients should also be
kept under medical supervision during treatment. Unless otherwise prescribed, the following doses are recommended:
Adults (Including the Elderly) and Adolescents >14 years: 0.4-2 mL (8-40 drops=0.1-0.5 mg) 3-4 times daily. Children 6-14
years: 0.4-1 mL (8-20 drops=0.1-0.25 mg) 3-4 times daily.
The recommended dose is to be diluted with physiological saline to a final volume of 3-4 mL and nebulised and inhaled
until the solution is consumed. The solution should be rediluted each time before use; any residual diluted solution
should be discarded.
Dosage may be dependent upon the mode of inhalation and the quality of nebulisation. In the case of particle sizes up
to 5 micrometer or with assisted ventilation, dose levels may be reduced to approximately 0.4 mL (8 drops=0.1 mg). The
duration of inhalation can be controlled by the dilution volume.
The dose may be repeated after intervals of at least 4 hrs, if required.
Daily doses exceeding 2 mg should be given under medical supervision.
Patients should be advised to consult a physician or the nearest hospital immediately in the case of acute or rapidly
worsening dyspnoea (difficulty in breathing) if additional inhalations do not produce an adequate improvement. Where
wall oxygen is available, the solution is best administered at a flow rate of 6-8 L/min.
Atrovent inhalation solution is suitable for concurrent inhalation with secretomucolytics and Berotec inhalation
solutions.
Administration: The correct operation of the metered aerosol apparatus is essential for successful therapy.
Depress the valve twice before the apparatus is used for the 1st time.
Before each use, the following rules should be observed: Remove protective cap. Breathe out deeply. Hold the metered
aerosol and close lips over the mouthpiece. The arrow and the base of the container should be pointing upwards.
Breathe in as deeply as possible, pressing the base of the container firmly at the same time; this releases 1 metered
dose. Hold breath for a few seconds, then remove mouthpiece from the mouth and breathe out. The same action should
be repeated for a 2nd inhalation. Replace the protective cap after use.
After not using the metered aerosol for 3 days, the valve has to be actuated once.
The container is not transparent. It is not therefore possible to see when it is empty. The aerosol will deliver 200 doses.
Dosages depends on the age, weight and renal function of the patient and the severity of the infection.
Dosages are expressed throughout in terms of amoxicillin-clavulanate content except when doses are stated in terms of
an individual component.
Adults: Mild to Moderate Infections: 250/125 mg 3 times daily, or 500/125 mg 2 or 3 times daily, or 875/125 mg twice
daily.
Severe Infections (Including Chronic and Recurrent Infections of Urinary Tract and Lower Respiratory Tract): 2 times
250/125 mg 3 times daily, or 1-2 times 500/125 mg 3 times daily, or 875/125 mg 3 times daily.
Two (2) amoxicillin-clavulanate 250/125 mg tablets should not be substituted for 1 amoxicillin-clavulanate 500/125 mg
tablet, since they are not equivalent.
Children: Dosage should be expressed in terms of the age of the child and either in mg/kg/day or mL of suspension/dose
or equivalent for other presentations.
Children Weighing =40 kg: Dosed according to adult recommendations.
Children up to 12 years: Lower Dose: Skin and Soft Tissue and Recurrent Tonsillitis: 20/5 to 40/10 mg/kg/day. Higher
Dose: Otitis Media, Sinusitis, Lower Respiratory Tract and Urinary Tract Infections: 40/10 to 60/15 mg/kg/day. Doses
should be taken 3 times daily.
No clinical data are available on doses of these formulations >40/10 mg/kg/day 3 times daily.
There are no clinical data for the 7:1 (amoxicillin-clavulanate ratio) formulation for patients <2 months. Dosing
recommendation in this population therefore cannot be made.
Premature: No dosage recommendation can be made for this category.
Elderly: No adjustment needed as for adults. If there is evidence of renal impairment, dose should be adjusted as for
renally impaired adults.
Renal Impairment: Dosage adjustments are based on the maximum recommended level of amoxicillin.
Hemodialysis: Adults: 1 time 500/125 mg or 2 times 250/125 mg every 24 hours plus 1 dose during dialysis to be
repeated at the end of dialysis (as serum concentrations of both amoxicillin and clavulanic acid are decreased)+.
Note: +The 875/125-mg presentations should only be used in patients with a creatinine clearance of >30 mL/min.
Children: 15/3.75 mg/kg/day given as a single daily dose.
Prior to hemodialysis, one additional dose of 15/3.75 mg/kg should be administered. In order to restore circulating drug
levels, another dose of 15/3.75 mg/kg should be administered after hemodialysis.
Hepatic Impairment: Dose with caution; monitor hepatic function at regular intervals. There are insufficient data on
which to based a dosage recommendations.
Administration: To minimize potential gastrointestinal intolerance, administer at the start of a meal.
The absorption of amoxicillin-clavulanate is optimized when taken at the start of a meal.
Treatment should not be extended >14 days without review.
Therapy can be started parenterally and continued with oral preparation.
After cleansing the face, apply thoroughly over the face affected by acne; only by then, loose powd may be applied.
For full therapeutic benefit, regular scheduled usage is recommended. Onset of action has been observed as early as 8
hrs after initial administration. It may take several days of treatment to achieve maximum benefit and the patient should
be informed that their symptoms will improve with continuous regular use. The duration of treatment should be
restricted to the period that corresponds to allergenic exposure.
Adults and Adolescents =12 years: The recommended starting dosage is 2 sprays (27.5 mcg/spray) in each nostril once
daily (total daily dose: 110 mcg). Once adequate control of symptoms is achieved, dose reduction to 1 spray in each
nostril once daily (total daily dose: 55 mcg) may be effective for maintenance. The dose should be titrated to the lowest
dose at which effective control of symptoms is maintained.
Children 6-11 years: The recommended starting dosage is 1 spray (27.5 mcg/spray) in each nostril once daily (total daily
dose: 55 mcg). Patients not adequately responding to 1 spray in each nostril once daily (total daily dose: 55 mcg) may
use 2 sprays in each nostril once daily (total daily dose: 110 mcg). Once adequate control of symptoms is achieved, dose
reduction to 1 spray in each nostril once daily (total daily dose: 55 mcg) is recommended.
Children <6 years: The experience in children <6 years is limited. Safety in efficacy in this group has not been well
established.
Elderly: No dosage adjustment is required. (See Pharmacokinetics under Actions.)
Renal Impairment: No dosage adjustment is required. (See Pharmacokinetics under Actions.)
Hepatic Impairment: No dosage adjustment is required in patients with mild to moderate hepatic impairment. There are
no data in patients with severe hepatic impairment (see Pharmacokinetics under Actions and Precautions).
Administration: Avamys nasal spray is for administration by the intranasal route only.
The intranasal device should be shaken before use. The device is primed by pressing the mist release button for at least 6
spray actuations (until a fine mist is seen), whilst holding the device upright. The device should be cleansed after each
use and the cap replaced.
Adult 1-2 sachet daily. May be given before or during cancer treatment (surgery, radio- & chemotherapy).
Avodart can be administered alone or in combination with the a-blocker tamsulosin (0.4 mg).
Recommended Dose: 1 cap (0.5 mg) taken orally once daily.
Although an improvement may be observed at an early stage, it can take up to 6 months before a response to the
treatment can be achieved. No dose adjustment is necessary in the elderly.
Renal Impairment: The effect of renal impairment on dutasteride pharmacokinetics has not been studied. No adjustment
in dosage is anticipated for patients with renal impairment (see Pharmacokinetics under Actions).
Hepatic Impairment: The effect of hepatic impairment on dutasteride pharmacokinetics has not been studied, and
therefore, should be used with caution in patients with mild to moderate hepatic impairment (see Pharmacokinetics
under Actions and Precautions). In patients with hepatic impairment, the use of dutasteride is contraindicated.
Administration: Avodart capsule should be swallowed whole and not chewed or opened as contact with the capsule
contents may result in irritation of the oropharyngeal mucosa. Avodart may be taken with or without food.
Adult & elderly 2 tsp once daily. Childn <12 yr 0.1 mg/kg body wt.
Adult 4 mg. Childn >12 yr 2-4 mg, 6-12 yr 2 mg, 2-6 yr 1-2 mg. To be taken 3-4 times daily.
In women of reproductive age, therapy should begin during menstruation. A sensitive test (eg, ß-subunit test if available)
capable of determining early pregnancy is recommended immediately prior to start of therapy to ensure the patient is
not pregnant. A nonhormonal method of contraception should be recommended.
Endometriosis: 200-600 mg daily in 2 divided doses. Initially 200 mg, if necessary dose may be increased to 600 mg daily.
Continue therapy uninterrupted for 3-6 months, which may be extended to 9 months.
Menorrhagia: 200 mg daily for 12 weeks. An occasional patient may need up to 400 mg daily.
Fibrocystic Breast Disease: Start with 50 mg daily, then the dose can be increased up to 100 mg daily in 2 divided doses,
depending on the severity of symptoms and the patient's response. Therapy should begin during menstruation.
Otherwise, appropriate test should be performed to ensure that the patient is not pregnant while on therapy with Azol
200.
Adult Mild to moderate infection in pulmonary disease, pneumonia, pharyngitis, tonsillitis, skin & soft tissue infections
Day 1: 500 mg as a single dose, Days 2-5: 250 mg once daily. Total dose of 1 g. Non-gonococcal urethritis & cervicitis 1 g
as a single dose.
Cap Upper & lower resp tract, mild & moderate skin infections 500 mg as single dose on the 1st day followed by single
dose of 250 mg for 2.5 days. Non-complicated urethritis & non-gonorrheal cervicitis caused by Chlamydia trachomatis 1
g as single dose. Syr Adult 500 mg/day for 3 days. Alternative dose: For 5 days administration: 1st day: 500 mg/day, 2nd-
5th day: 250 mg/day. Childn 10 mg/kg/day for 3 days. Alternative dose: For 5 days administration: 1st day: 10 mg/kg/day,
2nd-5th day: 5 mg/kg/day.
Initial treatment & prophylaxis: A single dose of 15 mg/kg/day ethambutol w/ 300 mg/day INH. Repeat treatment after
2-mth initial phase: A single dose of 25 mg/kg/day ethambutol w/ 300 mg/day INH.
Tab Adult & childn >30 kg 375-750 mg twice daily. Childn <30 kg 25-50 mg/kg/day in 2 divided dose. Uncomplicated
gonorrhoea 2.25 g as a single dose + probenecid 1 g concomitantly. Inj Adult 1.5-12 g/day in divided doses every 6-8 hr
up to a max of 4 g/day of sulbactam. Childn, infant & neonates 150 mg/kg/day in divided doses every 6-8 hr. Prophylaxis
of surgical infections 1.5-3 g upon induction of anesth. May be repeated every 6-8 hr.
UTI 250 mg twice daily. May be increased to 500 mg twice daily in severe infections. Resp tract, bone & joint, skin & soft
tissue infections 500 mg twice daily, may be increased to 750 mg twice daily. GIT infections 500 mg twice daily. Acute
gonorrhoea 250 mg as a single dose. Acute osteomyelitis 750 mg twice daily.
Complicated upper & lower UTI, skin & soft tissue infections 1 g. Lower resp tract infections 1 or 2 g.
Bacteraemia/septicaemia & infections in neutropenic patients 2 g. All doses are given 12 hrly.
Adults, Children and the Elderly: Apply to the affected area up to 3 times daily, for up to 10 days depending on the
response.
Hepatic and Renal Impairment: No dosage adjustment is necessary.
Administration: Cream: A small quantity of cream should be applied to the affected area with a piece of clean cotton
wool or gauze swab. The treated area may be covered by a dressing.
Ointment: The treated area may be covered with a dressing or occluded if desired.
Epilepsy Adult & childn >12 yr Initially 200 mg 2 times daily. Dosage may be increased at intervals of 1 wk until 200 mg 3-
4 times daily. Childn 12-15 yr Max: 1,000 mg/day, >15 yr Max: 1,200 mg/day. Adult 1,600 mg/day. Maintenance 800-
1,200 mg/day. Childn 6-12 yr Initially 100 mg 2 times daily, increased w/ interval 1 wk to 3-4 times daily until the
optimum dosage is reached. Maintenance 400-800 mg/day. Trigeminal neuralgia Initially 100 mg 2 times daily. Dosage
may be increased to 200 mg 2 times daily until free of pain. Max: 1,200 mg/day. Maintenance: 400-800 mg/day.
Childn 7-12 yr 10 mL, 2-6 yr 5 mL. All doses are to be taken 3 times daily.
Corneal ulcer 1st day: 2 drops every 15 min for 1st 6 hr then 2 drops every 30 min for remainder of the day. 2nd day: 2
drops hrly. 3rd-14th day 2 drops 4 hrly. Conjunctivitis 1-2 drops 2 hrly for 2 days & 1-2 drops 4 hrly for next 5 days.
Oral UTI Mild/moderate: 250 mg twice daily. Severe infections: 500 mg twice daily. Resp tract, skin & soft tissues, bone &
joints infections Mild/moderate: 500 mg twice daily. More severe complications: 750 mg twice daily. GIT infections 500
mg twice daily. Acute osteomyelitis Dosage should not be <750 mg twice daily. IV infusion Uncomplicated renal infection,
lower & upper UTI 100 mg twice daily. Other infections 200 mg twice daily. Acute gonorrhoea & uncomplicated cystitis in
women 100 mg as a single dose in women.
Recommended Dosage: Compensated Liver Disease: Adults and Adolescents =16 years: Chronic Hepatitis B Virus
Infection in Nucleoside-Treatment-Naive: 0.5 mg once daily with or without food.
History of Hepatitis B Viremia while Receiving Lamivudine or Known Lamivudine Resistance Mutations: 1 mg once daily
administered on an empty stomach (at least 2 hrs after a meal and 2 hrs before the next meal).
Decompensated Liver Disease: Adults: 1 mg once daily administered on an empty stomach (at least 2 hrs after a meal
and 2 hrs before the next meal).
Renal Impairment: In subjects with renal impairment, the apparent oral clearance of entecavir decreased as creatinine
clearance decreased. Dosage adjustment is recommended for patients with creatinine clearance <50 mL/min, including
patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), as shown in Table 10. The once-daily
dosing regimens are preferred. (See Table 10.)
Hepatic Impairment: No dosage adjustment is necessary for patients with hepatic impairment.
Duration of Treatment: The optimal duration of treatment with Baraclude for patients with chronic hepatitis B infection
and the relationship between treatment and long-term outcome eg, cirrhosis and hepatocellular carcinoma are
unknown.
Adult Monotherapy Initially 300 mg/day. Maintenance: 600-1,200 mg/day. Polytherapy Initially 300 mg/day.
Maintenance: 900-3,000 mg/day. Childn >5 yr Mono- or polytherapy 10 mg/kg/day. Maintenance: 30 mg/kg/day. Dose
may be increased by 5-10 mg/kg/day if seizures remain uncontrolled.
Adult 2-4 g daily 12 hrly. May be increased up to 8 g daily in severe or refractory infections. Max daily dose: 4 g. Childn
40-80 mg/kg/day in divided doses every 6-12 hr. May be increased up to 160 mg/kg/day in severe or refractory
administered in 2-4 equally divided doses. Neonate May be given in the 1st wk of life 12 hrly. Max: 80 mg/kg/day.
Acute or chronic infection 1-2 cap daily. Supportive treatment of cancer 2 cap 3 times daily.
Reconstitution: 3 scoops to 90 mL water.
Reconstitution: To make 1 glass, add 3 spoonful into 180 mL of water. To be taken 2 glass/day.
Gastric ulcer & gastritis Adult 1 tab 3 times daily in the morning, in the evening & before bedtime.
Tab 1 or more tab daily. Syr 1 tsp once daily.
Consciousness due to head injury or brain surgery 100-500 mg IM/IV 1-2 times daily. Consciousness disturbances in
acute cerebral infarction stage 1,000 mg IV once daily for 2 consecutive wk. Hemiplegia after cerebral apoplexy 1,000 mg
IV once daily for 4 consecutive wk, continue for 4 wk if patient shows clinical improvement.
1 caplet daily.
Childn 1 mL once daily.
2.5 g IV infusion (corresponding to 50 mL/kg/day). Infusion rate: 2-5 mL/kg/hr or 2-5 drops/kg/min (60 drops=1g±0.1 g).
Apply 1-2 times daily. Nipple sore May be applied directly to the nipple after breastfeeding.
Tab Adult & childn >12 yr 1 tab 2-3 times daily. Childn 6-12 yr ½ tab 2-3 times daily. Syr Adult & childn >12 yr 10 mL 2-3
times daily. Childn 6-12 yr 5 mL 2-3 times daily.
The dosage should be adapted to the individual's requirements. Unless otherwise prescribed, the following dosages are
recommended for adults and children >6 years: Acute Asthma Episodes: 2 actuations are sufficient for prompt
symptomatic relief in many cases. In more severe cases, if breathing has not noticeably improved after 5 min, 2 further
actuations may be taken. If an attack has not been relieved by 4 actuations, further actuations may be required. In these
cases, patients should consult the physician or go to the nearest hospital immediately.
Intermittent and Long-Term Treatment: (In asthma, Berodual metered dose aerosol should be used only on an as needed
basis) 1-2 actuations for each administration, up to a maximum of 8 actuations/day (average of 1-2 actuations 3 times
daily).
In children, Berodual metered aerosol should only be used upon medical advice and under the supervision of an adult.
Patients should be instructed in the correct administration of the metered aerosol to ensure successful therapy.
Administration: Before first time use of the metered-dose aerosol, the following rules should be observed: Remove
protective cap and depress the valve twice.
Before each use of the metered dose aerosol, the following rules should be observed: Remove protective cap (if the
metered aerosol has not been used for >3 days, the valve has to be actuated once). Breathe out deeply. Hold the inhaler
between the thumb and forefinger and close lips over the mouthpiece. The arrow and the base of the container should
be pointing upwards. Breathe in as deeply as possible, pressing the base of the container firmly at the same time, this
releases 1-metered-dose. Hold breath for a few secs, then remove the mouthpiece from the mouth and breathe out. The
same action should be repeated for a second inhalation. Replace the protective cap after use.
The container is under pressure and should by no account be opened by force or exposed to temperatures exceeding
50°C. As the container is not transparent, it is impossible to see when the contents are used up, the inhaler will deliver
200 or, if available, 300 doses. When these have all been used, the container may still appear to contain a small amount
of fluid.
The inhaler should, however, be replaced to get the right amount of treatment.
The approximate amount of treatment in your inhaler can be checked as follows: Shaking the container will show if there
is any remaining fluid.
Alternatively, remove the canister from the plastic mouthpiece and put into a container of water. The contents can be
estimated by observing its position in the water. Clean your inhaler at least once a week. It is important to keep the
mouthpiece of your inhaler clean to ensure that medicine does not build up and block the spray. For cleaning, first take
off the dust cap and remove the canister from the inhaler. Rinse with warm water through the inhaler until no
medication build-up and/or dirt is visible. After cleaning, shake out the inhaler and let it air-dry without using any
heating system. Once the mouthpiece is dry, replace the canister and the dust can.
Metered Aerosol: Acute Asthma Episodes: 1 puff is sufficient for prompt symptomatic relief in many cases. If breathing
has not noticeably improved after 5 min, a 2nd dose may be taken.
If an attack has not been relieved by 2 puffs, further puffs may be required. In these cases, patients should consult the
doctor or the nearest hospital immediately.
Prophylaxis of Exercise-Induced Asthma: 1-2 puffs for each administration, up to a maximum of 8 puffs/day.
Bronchial Asthma and Other Conditions with Reversible Airways Narrowing: If repeated dosing is required, 1-2 puffs for
each administration, up to a maximum of 8 puffs/day.
Administration: The correct operation of the metered aerosol is essential for successful therapy.
Depress the valve twice before the apparatus is used for the 1st time.
Before each use, the following rules should be observed: Remove protective cap. Breathe out deeply. Hold the metered
aerosol and close lips over the mouthpiece. The arrow and the base of the container should be pointing upwards.
Breathe in as deeply as possible, pressing the base of the container firmly at the same time, this releases 1 metered
dose. Hold breath for a few seconds, then remove the mouthpiece from the mouth and breathe out. If a 2nd inhalation
is required, the same action should be repeated. Replace the protective cap after use. After not using the metered
aerosol for 3 days, the valve has to be actuated once.
The container is not transparent. It is, therefore, not possible to see when it is empty. The metered-dose aerosol will
deliver 200 doses. When these have all been used, the metered-aerosol may still appear to contain a small amount of
fluid. The metered-dose aerosol should, however, be replaced because it may not get the right amount of treatment.
The amount of treatment in the metered aerosol can be checked as follows: Remove the metered aerosol from the
plastic mouthpiece and put the metered-aerosol into a container of water.
Clean the metered aerosol at least once a week. It is important to keep the mouthpiece of the metered-aerosol clean to
ensure that medicine does not build up and block the spray.
For cleaning, first take off the dust cap and remove the canister from the inhaler. Rinse warm water through the metered
aerosol until no medication build-up and/or dirt is visible. After cleaning, shake the metered aerosol and let it air-dry
without using any heating system. Once the mouthpiece is dry, replace the canister and the dust cap.
Warning: The plastic mouthpiece has been specially designed for use with Berotec 100 mcg to ensure in getting the right
amount of the medicine. The mouthpiece must never be used with any other metered aerosol nor must Berotec 100
mcg be used with any mouthpiece other than the one supplied.
The container is under pressure and should by no account be opened by force or exposed to temperatures above 50°C.
Inhalation Solution: (20 drops=1 mL) (1 drop=50 mcg fenoterol HBr).
The dosage should be adapted to the individual requirements of the patient; patients should also be kept under medical
supervision during treatment.
Unless otherwise prescribed, the following doses are recommended:
Adults (Including the Elderly) and Adolescent >12 years: Acute Asthma Episodes: 0.5 mL (10 drops=0.5 mg fenoterol HBr)
are sufficient for immediate symptomatic relief in many cases.
In severe cases eg, in most patients admitted to the emergency room, higher doses between 1 and 1.25 mL (20-25
drops=1-1.25 mg fenoterol HBr) may be required.
For
Tab particular severedaily.
1 tab 2-3 times cases, up to 2 mL
Dispersible (40
tab drops=2
Adult mg2-3
1-2 tab fenoterol HBr) may
times daily. be6-12
Childn administered
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yr ½ tab 3
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Adult 25 mg 3 times daily, if required 100 mg daily, childn >6 yr 50-100 mg daily divided into 3-4 doses, <6 yr 50 mg daily
divided into 3-4 doses. Sedative Adult 50-100 mg. Childn 0.6 mg/kg/day.
Mild or moderate UTI 250 twice daily. Severe UTI, chonic prostatitis, GIT infections 500 mg twice daily. Mild or moderate
resp tract, bone, joint, skin & soft tissue infections 250-500 mg twice daily. Severe resp tract, bone, joint, skin & soft
tissue infections 500-750 mg twice daily. Acute gonorrhoeae 250 mg as a single dose. Acute osteomyelitis Not <750 mg
twice daily.
1-2 drops 4-6 times daily.
Duodenal ulcer & recurrent gastric ulcer 30 mg once daily for 4-8 wk. Reflux/erosive oesophagitis 30 mg once daily for 8
wk.
Initially 1-2 drops/hr during the day & every 2 hr at night. Reduce to 1 drop 4 hrly & then to 1 drop 3-4 times daily.
Tab Adult & childn =12 yr 10 mg daily. Syr Adult & childn >12 yr 10 mL once daily. Childn 6-12 yr 10 mL once daily or 5 mL
12 hrly, 2-6 yr 5 mL once daily or 2.5 mL 12 hrly. Drops Adult & childn >12 yr 1 mL once daily. Childn 6-12 yr 1 mL once
daily or 0.5 mL 12 hrly, 2-6 yr 0.5 mL once daily or 0.25 mL hrly.
Adults: 24-48 mg per day in divided doses.
8-mg Tablet: 1-2 tablets 3 times daily.
24-mg Tablet: 1 tablet 2 times/day.
The dosage should be individually adapted according to the response.
Improvement can sometimes only be observed after a couple of weeks of treatment. The best results are sometimes
obtained after a few months. There are indications that treatment from onset of the disease prevents the progression of
the disease and/or the loss of hearing in later phases of the disease.
Children: Betaserc is not recommended for use in children below 18 years due to insufficient data on safety and efficacy.
Elderly: No dose adjustment is required in elderly.
Renal Impairment: No dose adjustment is required in renally impaired patients.
Hepatic Impaiment: No dose adjustment is required in hepatically impaired patients.
Apply 2-3 times daily until acute phase is over, then apply once daily.
Adult & childn >12 yr 1-2 g IV once daily. Max: 4 g daily. Peri-op infection prophylaxis 1 g as a single dose ½-2 hr pre-op.
Infant & childn <12 yr 50-75 mg/kg/day in 2 divided doses. Max: 4 g daily. Meningits 100 mg/kg/day in 2 divided doses.
Adult 1 tsp 3 times daily. Childn 6-12 yr 1 tsp 2 times daily, 1-6 yr 1 tsp once daily, 6 mth-1 yr ½ tsp once daily.
Adult 1 caplet daily.
Trichomoniasis Adult 2 g daily in a single dose or 500 mg twice daily for 7 days. To prevent re-infection, the partner
should be treated simultaneously w/ the same dose. Childn 15 mg/kg/day in 3 divided doses for 7-10 days. Intestinal
amoebiasis Adult 750 mg 3 times daily for 5-10 days. Hepatic amoebiasis 500-750 mg 3 times daily for 5-10 days. Childn
35-50 mg/kg/day in 3 times daily for 10 days. Giardiasis Adult 2 g once daily for 3 days or 250-500 mg 3 times daily for 5-
7 days. Childn 15 mg/kg in 3 divided doses for 5-7 days. Anaerobe infection Adult 7.5 mg/kg 6 hrly, (Max: 4 g daily) for 7-
10 days.
Adult 2-3 tab. Up to 6 tab may be taken for complete evacuation of the colon. Childn 1-2 tab.
Pharyngitis/tonsillitis 250 mg 12 hrly for 10 days. Acute maxillary sinusitis 500 mg 12 hrly for 14 days. Lower resp tract
infections 250-500 mg 12 hrly for 7-14 days. Uncomplicated skin & skin structure 250 mg 12 hrly for 7-14 days.
Adult 2-4 g daily IM/IV at 12 hr intervals. Severe infections 6-12 g daily in 2-4 divided doses.
1-3 softcap 3 times/day.
Childn 6 mth to 5 yr 1 tab once daily for 10 days. Infant 2-6 mth ½ tab once daily for 10 days.
After the skin has been cleansed, apply thinly 2 or 3 times a day.
Tab Adult 1 tab once daily. Inj Adult Severe deficiencies: 1 amp IM daily until acute symptoms subside, then 1 amp 2-3
times wkly. Mild deficiencies: 1 amp IM 2-3 times wkly.
Adult Serious infection 150-300 mg 6 hrly. More severe infection 300-450 mg 6 hrly. Childn Serious infection 8-16
mg/kg/day in 3-4 divided doses. More severe infection 16-20 mg/kg/day in 3-4 divided doses.
Adult 1 tsp 3 times daily. Childn 7-12 yr 1 tsp twice daily; 1-6 yr 1 tsp once daily.
Adult 1-2 tab 3 times daily. Childn 7-12 yr 10-15 mL, 2-6 yr 5-10 mL. Infant 2.5-5 mL. To be taken 3-4 times daily.
1 cap daily.
The dose should be individualised according to the patient profile (see Precautions) and blood pressure response.
Hypertension: Bioprexum may be used in monotherapy or in combination with other classes of antihypertensive therapy.
Recommended Dose: 5 mg once daily in the morning.
Patients with a strongly activated renin-angiotensin-aldosterone system (in particular, renovascular hypertension, salt-
and/or volume-depletion, cardiac decompensation or severe hypertension) may experience an excessive drop in blood
pressure following the initial dose. A starting dose of 2.5 mg is recommended in such patients and the initiation of
treatment should take place under medical supervision. The dose may be increased to 10 mg once daily after 1 month of
treatment.
Symptomatic hypotension may occur following initiation of therapy with Bioprexum; this is more likely in patients who
are being treated concurrently with diuretics. Caution is therefore recommended since these patients may be volume-
and/or salt-depleted.
If possible, the diuretic should be discontinued 2-3 days before beginning therapy with Bioprexum (see Precautions).
Hypertensive Patients in Whom the Diuretic Cannot be Discontinued: Therapy with Bioprexum should be initiated with a
2.5-mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of Bioprexum should
be adjusted according to blood pressure response. If required, diuretic therapy may be resumed.
Elderly: Treatment should be initiated at a dose of 2.5 mg which may be progressively increased to 5 mg after 1 month,
then to 10 mg if necessary depending on renal function.
Symptomatic Heart Failure: It is recommended that Bioprexum, generally associated with a nonpotassium-sparing
diuretic and/or digoxin and/or a ß-blocker, be introduced under close medical supervision with a recommended starting
dose of 2.5 mg taken in the morning. This dose may be increased after 2 weeks to 5 mg once daily if tolerated. The dose
adjustment should be based on the clinical response of the individual patient.
In severe heart failure and in other patients considered to be at high risk (patients with impaired renal function and a
tendency to have electrolyte disturbances, patients receiving simultaneous treatment with diuretics and/or treatment
with vasodilating agents), treatment should be initiated under careful supervision (see Precautions).
Patients at high risk of symptomatic hypotension eg, patients with salt depletion with or without hyponatraemia,
patients with hypovolaemia or patients who have been receiving vigorous diuretic therapy, should have these conditions
corrected, if possible, prior to therapy with Bioprexum. Blood pressure, renal function and serum potassium should be
monitored closely, both before and during treatment with Bioprexum (see Precautions).
Stable Coronary Artery Disease: Initially 5 mg once daily for 2 weeks, then increased to 10 mg once daily, depending on
renal function and provided that the 5 mg dose is well tolerated.
Elderly: Elderly patients should receive 2.5 mg once daily for 1 week, then 5 mg once daily the next week, before
increasing the dose up to 10 mg once daily depending on renal function. The dose should be increased only if the
previous lower dose is well tolerated.
Renal Impairment: Dosage in patients with renal impairment should be based on creatinine clearance (CrCl).
CrCl =60 mL/min: 5 mg/day, >30 to <60 mL/min: 2.5 mg/day, >15 to <30 mL/min: 2.5 mg every other day.
Haemodialysed Patients* (CrCl <15 mL/min): 2.5 mg on the day of dialysis.
*Dialysis clearance of perindoprilat is 70 mL/min. For patients on haemodialysis, the dose should be taken after dialysis.
Hepatic Impairment: No dosage adjustment is necessary in patients with hepatic impairment (see Pharmacokinetics
1 tab/day as a single dose, preferably to be taken in the morning and before a meal.
When possible, individual dose titration with the components is recommended.
Elderly: Treatment should be initiated after considering blood pressure response and renal function (see Precautions).
Renal Impairment: In severe renal impairment (CrCl <30 mL/min), treatment is contraindicated (see Contraindications).
In patients with moderate renal impairment (CrCl 30-60 mL/min), it is recommended to start treatment with the
adequate dosage of the free combination (see Precautions).
In patients with CrCl =60 mL/min, no dose modification is required. Usual medical follow-up will include frequent
monitoring of creatinine and potassium.
Hepatic Impairment: In severe hepatic impairment, treatment is contraindicated (see Contraindications).
In patients with moderate hepatic impairment, no dose modification is required (see Pharmacokinetics under Actions
and Precautions).
Children and Adolescents: Bioprexum Plus should not be used in children and adolescents as the efficacy and tolerability
of perindopril in children and adolescents, alone or in combination, have not been established.
Cream Apply twice daily. Forte cream Apply once or twice daily.
1 softcap daily.
1 cap daily.
Depends on severity. Infusion 1st dose of 2% v/v at rate of 40-80 drop/min then repeat dose after 6 hr. If needed, doses
may be given 24 hrly to max of 80-100 mL. Childn Same dose as adult.
Gently massage into skin w/ fingertips using slow circular motion w/ a few pressure points. Apply morning & night.
Apply small dabs to the entire face & neck twice daily, preferably in the morning & night for optimum result. Allow to
penetrate the skin for 5 min before applying make-up.
1 tab daily. Mild case: 1 tab daily, severe case: 2 tab daily.
Rub on the affected area.
1-2 drops to the affected eye 1-2 hrly for 2-3 days, decrease to 1-2 drops 3-4 times daily.
Uterine involution 1 tab 3 times daily for 3-4 days. Control of uterine bleeding in emergency state 0.2 mg IV.
Subinvolution, puerperium & lochiometral bleeding 1-2 tab 3 times daily or 0.5-1 mL IM. Caesarean section 1 mL IM or
0.5-1 mL IV following baby delivery.
Total dose: 300-400 mg. Twice a wk in average cases, should be adjusted according to patient's condition in the range
from once a day to once a wk. Pleural effusion 30-60 mg dissolved in 50-100 mL saline soln to be instilled via needle or
catheter used for aspiration.
Anovulatory infertility 1 tab daily for 5 days starting on the 5th day of the menstrual cycle. If no ovulation occurs, a 2nd
course of 1 tab twice daily for 5 days may be given. Oligospermia 1 tab daily for 40-90 days.
Emergency treatment of acute HTN during surgery 0.01-0.02% IV drip infusion (equiv 0.1-0.2 mg/mL) at a starting rate of
2-10 mcg /kg/min until the desired BP value is reached. Rapid BP reduction 10-30 mcg/kg/min IV inj. Hypertensive
emergency 0.01-0.02% IV drip infusion (equiv 0.1-0.2 mg/mL) at a rate of 0.5 mcg/kg/min until the desired BP value is
reached.
Hypertension: The recommended dose of Blopress is 4 mg once daily. The dose should be titrated according to response
up to 16 mg once daily. The maximum antihypertensive effect is attained within 4 weeks after initiation of treatment.
Children: The safety and efficacy of Blopress have not been established in children.
Elderly: No dosage adjustment is necessary for patients up to 75 year. In patients >75 years, an initial dose of 2 mg once
daily is recommended. The dose may be titrated up according to response.
Impaired Renal Function: No dosage adjustment is necessary in patients with mild renal impairment. In patients with
moderate to severe renal impairment, an initial dose 2 mg once daily is recommended. The dose may be titrated up
according to response.
Impaired Hepatic Function: An initial dose of 2 mg once daily is recommended in patients with mild to moderate hepatic
impairment. The dose may be titrated up according to response. There is no experience in patients with severe hepatic
impairment.
Concomitant Therapy: Blopress may be administered with other antihypertensive agents.
Heart Failure: The usual recommended initial dose of Blopress is 4 mg once daily. Up-titration to the target dose of 32
mg once daily or the highest tolerated dose is done by doubling the dose at intervals of at least 2 weeks.
Special Patient Populations: No initial dose adjustment is necessary for elderly patients or in patients with intravascular
volume depletion, renal impairment or mild to moderate hepatic impairment.
Concomitant Therapy: Blopress can be administered with other heart failure treatment, including ACE-inhibitors, beta-
blockers, diuretics and digitalis or a combination of these medicinal products.
Administration: Blopress should be taken once daily with or without food.
1 tab once daily. Adult Recommended dose: Initially 12.5 mg once daily for the 1st 2 days. Thereafter, 25 mg once daily.
May be subsequently increased at intervals of at least 2 wk up to the recommended max daily dose of 50 mg once daily
or in divided doses (twice daily).
Reconstitution: 1 level scoop (4.3 g) to 30 mL water.
Chronic renal failure & osteoporosis Adult 0.5-1 mcg once daily. Hypoparathyroidism & other diseases associated w/
abnormal vit D metabolism Adult 1-4 mcg once daily. The dose may be adjusted according to patient's age, severity of
symptoms & type of disease.
Ointment: Spread 2-5 g on a piece of gauze or lint sheet and apply to the afflicted areas. Change the gauze or lint sheet
2-3 times daily.
Children: Borraginol-S may be applied by rubbing-in.
Suppository: Remove wrapper and insert 1 supp intrarectally twice daily (morning and evening). In severe cases, also use
another suppository before retiring.
Strabismus For vertical muscles & horizontal strabismus of <20 prism diopters: 1.25-2.5 units in any 1 muscle. For
horizontal strabismus of 20-50 prism diopters: 2.5-5 units in any 1 muscle. For persistent VII nerve palsy of =1 mth: 1.25-
2.5 units in the medial rectus muscle. Max: 25 units as single inj for any muscle. Blepharospasm Initially 1.25-2.5 units
into the medial & lateral pre-tarsal orbicularis oculi of the upper lid & into the lateral pre-tarsal orbicularis oculi of the
lower lid. Glabellar lines 0.1 mL of reconstituted soln into each of 5 sites, 2 in each corrugator muscle & 1 in the procerus
muscle. Total dose: 20 units.
Unconsciousness due to head injury or brain surgery 500 mg drip or IV 1-2 times daily. Unconsciousness in acute cerebral
infarction 1,000 mg IV once daily continuously for 2 wk. Post-apoplectic hemiplegia 1,000 mg IV once daily continuously
for 4 wk. Continue treatment for additional 4 wk if there is tendency of recovery. Tab/caplet/powd 1,000-2,000 mg daily
in divided doses. O-dis tab 500 mg 2 times daily.
Unconsciousness due to head injury or brain surgery 100-500 mg IV drip or IM 1-2 times daily. Unconsciousness in acute
cerebral infarct 1000 mg IV once daily continuously for 2 wk. Post-apoplectic hemiplegia 1000 mg once daily by oral or IV
inj.
Mild to moderate disease 1-2 drops 4 hrly. Severe infections 2 drops hrly until improvement, reduce prior to
discontinuation.
1-2 drops 4-6 hrly. During initial 24-48 hr, dosage may be increased to 1-2 drops 2 hrly.
Recommended initial dose: Anovulation 75-150 IU daily for at least 7 days. Controlled ovarian hyperstimulation 150-225
IU daily for the 1st 5 days of treatment.
Adult 3-4 tab daily. Elderly & debilitated Initially 1-2 tab daily, increase gradually to the effective dose.
Cerebral circulatory disorders & equilibrium disturbances 1 caplet 3 times daily. Peripheral circulatory disorders 2 caplet
3 times daily.
Childn & infant >1 mth Nasal spray 1 spray/day in each nostril. Nasal drops 1-2 drops into each nostril.
Breast cancer Recommended dose: 100 mg/m2 IV over 1 hr 3 wkly. 1st-line treatment: 75 mg/m2 in combination w/
doxorubicin 50 mg/m2. Non-small cell lung cancer Failure of prior platinum-based chemotherapy Recommended dose:
75 mg/m2 IV over 1 hr 3 wkly. Chemotherapy-naive patient Recommended dose: 75 mg/m2 IV over 1 hr immediately
followed by cisplatin 75 mg/m2 over 30-60 min 3 wkly. Ovarian cancer Recommended dose: 100 mg/m2 as 1 hr infusion
3 wkly.
Adults: Tablet: 1-2 tab 2-3 times daily. In most patients, the optimum single dose is 2 tab. In patients being unusually
sensitive to sympathomimetic amines, it is advisable to initiate treatment with 1 tab 2-3 times daily. A total dose of 15
mg in a 24-hr period should not be exceeded.
Injection: Bronchospasm: Intravenous Injection: Adults: 0.25-0.5 mg (0.5-1 ml) is injected slowly intravenously. The
solution for injection is diluted with sterile physiological saline up to 10 ml and is given slowly intravenously during 5
minutes. The dose may have to be repeated with short intervals (a few hours). The dose should not exceed 2 mg in 24
hours.
Intravenous Infusion: Adults: 1-2 mg (2-4 ml) is given during a 24 hour interval as a continuous infusion. An initial loading
dose up to 0.10 mg (0.2 ml) can be given over 10 minutes.
Children: Up to 25 µg/kg bw (0.05 ml/kg bw) is given during a 24 hour interval as a continuous infusion. An initial loading
dose up to 1.5 µg/kg bw (0.003 ml/kg bw) can be given over 10 minutes.
Subcutaneous Injection: Adults: 1-2 mg (2-4) ml) is given during a 24 hour interval, split into at least 4 occasions.
Children: Up to 25 µg/kg bw (0.05 ml/kg bw) is given during a 24 hour interval, split into at least 4 occasions.
Respules: Inhaled bronchodilators should, as initial therapy, be used as required rather than regularly.
BRICASMA solution for nebulization is to be used in nebulizers with or without assisted breathing in acute or subacute
disorders where conventional inhalers prove unsatisfactory and in maintenance therapy in severe broncho-obstructive
conditions.
Dosage should be individual.
Body Weight >25 kg: 5 mg (1 single dose unit, 2 ml) is inhaled 2 up to 4 times in a 24 h period.
Terbuhaler: Dosage of inhaled terbutaline via BRICASMA TURBUHALER should be individualized.
BRICASMA TURBUHALER should, as initially therapy, be used as required rather than regularly.
Adult and children over 12 years: 0.25 mg-0.50 mg as required or, when used as regular maintenance therapy, every 6
hours. In severe cases the single dose may be increased to 1.5 mg. The total dose in 24 hours should not exceed 2 mg.
Children 7-12 years: 0.25 mg-0.5 mg as required or, when used as regular maintenance therapy, every 6 hours. In severe
cases the single dose may be increased to 1.0 mg. The total dose in 24 hours should not exceed 2 mg.
The medication from BRICASMA TURBUHALER is delivered to the lung as patient inhales and therefore it is important to
instruct the patient to breathe in forcefully and deeply through the mouthpiece. When prescribing BRICASMA
TURBUHALER to young children it is necessary to ascertain that they can follow the instructions for use.
The patient may not taste or feel any medication when using BRICASMA TURBUHALER due to the small amount of drug
dispensed.
Administration: Injection: The dose may be given intravenously or subcutaneously. BRICASMA for injection, 1 ml
ampoule, is intended for subcutaneous and intravenous injection. Dosage should be individual.
Terbuhaler: Instruction for correct use of TURBUHALER.
TURBUHALER is inspiratory flow-driven which means that, when the patient inhales through the mouthpiece, the
substance will follow the inspired air into the airways.
NOTE: It is important to instruct the patient: To breathe in forcefully and deeply through the mouthpiece to ensure that
an optimal dose is delivered to the lungs; never to breathe out through the mouthpiece.
The patient may not taste or feel any medication when using TURBUHALER due to the small amount of drug dispensed.
Initiate BRILINTA treatment with a 180 mg (two 90 mg tablets) loading dose and continue treatment with 90 mg twice
daily.
After the initial loading dose of aspirin (usually 325 mg), use Brilinta with a daily maintenance dose of aspirin 75-100 mg.
ACS patients who have received a loading dose of clopidogrel may be started on BRILINTA.
A patient who misses a dose of BRILINTA should take one 90 mg tablet (their next dose) at its scheduled time.
Administration: BRILINTA can be administered with or without food. For patients who are unable to swallow the tablets
whole, Brilinta tablets (90 mg and 2 x 90 mg) can be crushed to a fine powder and mixed in half a glass of water and
drunk immediately. The glass should be rinsed with a further half glass of water and the contents drunk. The mixture can
also be administered via a nasogastric tube (CH8 or greater). It is important to flush the nasogastric tube through with
water after administration of the mixture.
Adult & childn >12 yr 1-2 g once daily depending on type & severity of infection. Max: 4 g daily. Uncomplicated
gonococcal infection 250 mg IM as a single dose. Childn <12 yr & infant For serious infection other than meningitis 50-75
mg/kg daily in equally divided doses 12 hrly. Max: 2 g/day. Meningitis 100 mg/kg daily in divided doses 12 hrly w/ or w/o
a loading dose of 75 mg/kg. Max: 4 g/day. Preop use (surgical prophylaxis) 1 g as a single dose ½-2 hr before surgery. To
be administered by IV, IM or short IV infusion.
Brochifar Adult & childn >12 yr 1 caplet 3-4 times daily, 6-12 yr ½ caplet 3-4 times daily. Brochifar Plus Adult 1 caplet 3
times daily. Childn 6-12 yr ½ caplet 3 times daily.
Caplet & Plus tab Adult & childn >10 yr 1 tab 3 times daily; childn 5-10 yr ½ tab 3 times daily; 2-5 yr ¼ tab twice daily (for
Bromifar caplet) or 3 times daily (for Bromifar Plus tab). Syr Adult & childn >12 yr 10 mL 3 times daily; childn 6-12 yr 5 mL
3 times daily.
Adult 1 tab 3 times daily. In long-term therapy, the dose may be reduced to twice daily. Childn 1.2-1.6 mg/kg/day.
1 cap daily for 10 days/mth for 3 mth.
Susp: Adult: To Relieve Pain: 3-4 times of 10 ml a day. Children: To Relieve Fever and Pain: See table.
Forte tab: Initially 1,200-1,800 mg daily in 3 divided doses. Rheumatic arthritis and osteoarthritis Max dose of 2,400
mg/day in acute exacerbation and may be reduced to max of 1,800 mg/day in stable condition.
Adult 1 cap or 3 tsp. Childn 6-12 yr 1½ tsp. All doses to be taken 3 times daily.
HTN 5 mg once daily. Max: 10 mg/day. Chronic stable or vasospastic angina 5-10 mg daily. Fragile, elderly or patients w/
impaired liver function Initially 2.5 mg once daily.
Adult & childn =12 yr 1 tab 3-4 times daily. Max: 12 mg/day. Childn 6-12 yr Max: 6 mg/day in 3-4 divided doses. Childn 2-
6 yr Max: 3 mg/hr in 3-4 divided doses.
Bufect tab Adult & childn 8-12 yr 1 tab, 3-7 yr ½ tab, 1-2 yr ¼ tab. All doses to be taken 3-4 times daily. Bufect oral susp
Adult 2 tsp 3-4 times daily. Bufect Forte oral susp Adult 1 tsp 3-4 times daily. Childn Relief of pain & reduction of fever 20
mg/kg in divided doses.
Lumbar epidural abdominal, pelvic & lower limb surgery including caesarean section 5 mg/mL (75-150 g). Thoracic
epidural upper abdominal & thoracic surgery 2.5 mg/mL (12.5-37.5 g) or 5 mg/mL (25-50 g). Caudal epidural 2.5 mg/mL
(37.5-100 g) or 5 mg/mL (75-125 g). Other blocks local inflitration 2.5 mg/mL (12.5-150 g) or 5 mg/mL (25-150 g).
Intercostal (per segment) 2.5 mg/mL (10-20 g) or 5 mg/mL (15-25 g). Brachial plexus 5 mg/mL (100-150 g). Sciatic 3 in 1
(femoral, obturator & lateral cutaneous) 5 mg/mL (50-100 g). Pudendal 2.5-5 mg/mL (7.5-100 g). Caudal epidural post-op
pain management 2.5 mg/mL (50-75 mg bolus). Lumbar epidural bolus & continuous (including labour pain
management) 2.5-5 mg/mL (15-60 mg bolus followed by 12.5-18.75 mg/hr. Thoracic epidural continuous infusion for
post-op pain management 1.25 mg/mL (6.25-12.5 mg/hr).
Individualized dosage.
After cleansing & debriding of the wound, the cream is applied w/ a sterile glove to the burned surface 1-2 times daily to
a 2 mm thickness. Therapy is continue until satisfactory healing has occurred or until the burned site is ready for grafting.
1 effervescent tab daily.
1 tab daily.
Adult 1 tsp twice daily. Childn 6-12 yr 1 tsp 1-2 times daily; 1-6 yr 1 tsp once daily; 6 mth-1 yr ½ tsp once daily.
Caplet Adult 1 caplet 1-2 times daily. Adolescent & childn >8 yr ½ caplet 1-2 times daily. Susp Childn 1-3 tsp once daily.
Pregnancy & lactation 2 cap daily. Menopausal period & elderly 2-3 cap daily.
Childn >4 yr 1 tsp 1-2 times daily; <4 yr 1 tsp once daily.
HTN 5 mg once daily. Max: 10 mg. Patients w/ liver dysfunction, elderly & infants Initially 2.5 mg once daily. Chronic
stable or vasospastic (Prinzmetal's) angina 5-10 mg.
CalSource: Children 4-12 years: 6-9 measuring spoons (30-45 mL) daily in divided doses; up to 3 years: 2-5 measuring
spoons (10-15 mL) daily in divided doses.
In severe calcium deficiency states, up to 75 mL may be necessary.
Fast-growing children may require adult doses.
CalSource Forte: The effervescent tab should be dissolved in a glass of water.
Adults: The usual daily dose is 1-2 tabs covering at least 70% of recommended dietary allowance.
In severe cases, up to 4 effervescent tabs may be required during the first few weeks of therapy.
CalSource Plus Vitamin C: Adults and Children of School Age: 1 effervescent tab daily.
Children 3-7 years: ½-1 tab effervescent tab daily.
CalSource Junior Strength: Children: 2 tab daily.
CalSource Junior Growth: >3 years: 2 tabs daily. 1-3 years: 1 tab/day.
1 tab daily.
HTN Initially 4 mg once daily; max: 16 mg/day. Patients w/ moderate & severe renal impairment & mild to moderate
hepatic impairment Initially 2 mg once daily. Heart failure Usual recommended initial dose: 4 mg once daily, may be up-
titrated to target dose 32 mg or to the highest tolerated dose by doubling the dose w/ at least 2-wk interval.
HTN Initially 4 mg daily. Max: 16 mg daily. Elderly (>75 yr) & patients w/ moderate to severe impaired kidney function &
mild to moderate impaired liver function Initially 2 mg once daily. Heart failure 4 mg daily, may be increased to 32 mg or
to the highest tolerated dose by doubling the dose w/ at least 2-wk interval.
Adult 250-500 mg 3-4 times daily. Childn 50 mg/kg/day in 3-4 divided doses. Premature & newborn infant <2 wk 25
mg/kg/day in 4 divided doses.
Adult & elderly Recommended dose: 30 mg once daily. Duration of therapy: Duodenal ulcer & reflux esophagitis 4 wk;
benign gastric ulcer 8 wk. Hepatic & renal impairment Max dose: 30 mg daily.
Adult 50 mg as needed 1 hr before sexual activity. May be taken anywhere from 4 to ½ hr before sexual activity. Dose
may be increased to a max of 100 mg or decreased to 25 mg. Max dosing frequency is once daily.
Adult Pneumonia, UTI, gynecological infections eg, endometritis, skin & skin structure infections 500 mg IV 8 hrly.
Nosocomial pneumonia, peritonitis, septicemia, presumed infections in neutropenic patients 1 g IV 8 hrly. Meningitis 2 g
IV 8 hrly. Renal impairment: CrCl 26-50 mL/min 1 unit dose 12 hrly, 10-25 mL/min ½-1 unit dose 12 hrly, <10 mL/min ½-1
unit dose 24 hrly. Childn >3 mth up to 12 yr 10-20 mg/kg 8 hrly depending on type & severity of infection, susceptibility
of the pathogen & condition of the patient. >50 kg Same as adult dose. Meningitis 40 mg/kg 8 hrly.
Adult Mild to moderate UTI 500 mg-1 g IM/IV. Mild to moderate infections except UTI 1 g IM/IV. Severe infections
including skin & skin structure infections 2 g IV. Doses are given 12 hrly. Very severe or life-threatening infections 2 g IV 8
hrly. IV doses should be given approx over 30 min. Childn 2 mth-<16 yr w/ =40 kg body wt Pneumonia, UTI, skin & skin
structure infections; empiric therapy for febrile neutropenia 50 mg/kg body wt/dose 12 hrly for 7-10 days. Febrile
neutropenic patient 50 mg/kg body wt/dose 8 hrly for 7-10 days.
FC caplet Adult & childn =12 yr 10 mg daily during the evening meal. Childn 6-12 yr 10 mg daily either as single dose or
as divided doses 5 mg (½ caplet) in the morning & in the evening. Patient w/ renal insufficiency Reduce to ½ of the usual
recommended dose. Syr Adult & childn >6 yr 10 mL once daily. Childn 2-6 yr 2.5 mL once daily. May be increased to a
max of 5 mL/day given as 2.5 mL every 12 hr. Childn 6 mth to <2 yr 2.5 mL once daily. Drops Childn 2-6 yr 0.25 mL once
daily. May be increased to a max of 0.5 mL/day, given as 0.25 mL 12 hrly. Childn 6 mth to <2 yr 0.25 mL once daily.
Complicated upper & lower UTI, skin & soft tissue infections 1 g, may be increased to 2 g in very severe cases. Lower resp
tract infections 1-2 g. Infections in neutropenic patient, bacteremia/septicemia 2 g. All doses should be given 12 hrly.
Infections Adult & childn >12 yr 1.2 g inj 8 hrly. Childn 3 mth-12 yr 30 mg/kg 8 hrly. In more serious infections, increase
frequency to 6 hrly. Childn 0-3 mth 30 mg/kg 8 hrly. In more serious infections, increase frequency to 8 hrly. Surgical
prophylaxis 1.2 g inj given after the induction of anesth. Operations where there is a high risk of infections eg, colorectal
surgery, may require 3-4 times daily.
Adult w/ normal renal function 400 mg/m2 IV over 15-60 min. Combination w/ other myelosuppresive agent requires
dosage adjustment; or use target AUC of 5-7 mg/mL.min for single agent, or 4-6 mg/mL·min for combination therapy.
Recommended dose: 60-75 mg/m2 as single IV administration for 21 days. Alternative dose: 20 mg/m2 wkly or 30
mg/m2 each successive days repeated every 4 wk to decrease toxicity. In combination w/ other myelosuppressive drugs
30-40 mg/m2 every 3-4 wk. In combination w/ non-myelosuppressive drugs 60-75 mg/m2 every 3-4 wk.
The dosage is based on the desired effect and on how the patient tolerates Cardace. Therapy is usually long-term. The
physician determines the duration of treatment individually for each patients.
Treatment of Hypertension: Recommended Initial Dose: 2.5 mg once daily. Depending on the response, the dose may be
increased. Any increase should be implemented by doubling the dose at intervals of 2-3 weeks. Usual Maintenance
Dose: 2.5-5 mg daily. Maximum Dose: 10 mg daily.
Renal Impairment: Creatinine Clearance (CrCl) 20-50 mL/min/1.73 m2 Body Surface Area: Initial Dose: Generally, 1.25
mg. Maximum Daily Dose: 5 mg. When CrCl cannot be measured, it can be calculated based on the serum creatinine
level using the following formula (Cockcroft's equation):
In patients with incompletely corrected fluid or salt deficiency, those with severe hypertension, as well as in those for
whom a hypotensive reaction would constitute a particular risk (eg, patients with haemodynamically relevant stenoses
of the coronary arteries or of the blood vessels supplying the brain) and in the elderly, a reduced initial dose of 1.25 mg
daily must be considered.
Patients Pretreated with a Diuretic: Discontinuing the diuretic for at least 2-3 days or longer, depending on the duration
of action of the diuretic, before starting treatment with Cardace, or at least reducing the diuretic dose shoud be
considered. The physician will decide in each individual case whether such discontinuation or dose reduction is possible
and how long it should last. The initial dose in such patients is generally Cardace 1.25 mg.
Hepatic Impairment: Response to treatment may be either increased or decreased. Therefore, treatment must be
initiated only under close medical supervision. Maximum Daily Dose: 2.5 mg.
Treatment of Congestive Heart Failure: Recommended Initial Dose: 1.25 mg once daily. Depending on the response, the
dose may be increased. Any increase should be implemented by doubling the dose at intervals of 1-2 weeks. Maximum
Daily Dose: 10 mg.
The required daily dose, if =25 mg may be taken as a single dose or in 2 separate doses.
In impaired liver or renal function and in patients pretreated with a diuretic, dosage recommendations for Cardace are
identical to those given previously in the treatment of hypertension. The recommendations given there in conjunction
with diuretic pretreatment also apply.
Treatment After Myocardial Infarction: Recommended Initial Dose: 5 mg daily, divided into 2 single doses of 2.5 mg each,
1 in the morning and 1 in the evening. If this dose is not well tolerated, 1.25 mg should be taken twice daily over 2 days.
In either event depending on the response, the dose may then be increased. Any increase should be implemented by
doubling the dose at intervals of 1-3 days. As treatment progresses, the total daily dose may be taken as a single dose.
Maximum Daily Dose: 10 mg.
Sufficient experience is still lacking in the treatment of patients with severe heart failure (NYHA IV) immediately after
myocardial infarction. Treatment, if nevertheless given, should be started with 1.25 mg once daily and increased only
with particular caution.
In patients with impaired liver or renal function, with incompletely corrected fluid or salt deficiency, or with severe
hypertension, and in those for whom a hypotensive reaction would constitute a particular risk (eg, patients with
haemodynamically relevant stenoses of the coronary arteries or of the blood vessels supplying the brain), as well as in
those pretreated with a diuretic and in the elderly, the recommendations are identical to those given prevoiusly in
HTN Initially 5 mg daily may be increased up to 7.5 mg/day w/ max 10 mg/day. Chronic stable or vasospastic angina 5-10
mg. Elderly & hepatically impaired 2.5 mg daily.
1 softcap daily.
Rate of infusion: 2.5-10 mcg/kg/min which may be increased up to 40 mcg/kg/min. Dose adjustment depends on heart
rate & rhythm, BP & diuresis.
5 mg once daily. Max: 10 mg/day. Patients w/ hepatic insufficiency, elderly Initially 2.5 mg.
Adult 1 tab twice daily, if necessary 1 tab up to 3 times daily. Max: 120 mg/day.
Hypertension: Full Dosage Range: 1-16 mg daily. It is recommended that therapy be initiated at 1 mg given once daily for
1 or 2 weeks. The dosage may then be increased to 2 mg once daily for an additional 1 or 2 weeks. If necessary, the daily
dosage should then be increased gradually at similar intervals to 4 mg, 8 mg and a maximum of 16 mg as determined by
patient's response to achieve the desired reduction in blood pressure. The usual dose is 2-4 mg once daily.
Benign Prostatic Hyperplasia: Initial Dosage: 1 mg given once daily. Depending on the individual patient's urodynamics
and BPH symptomatology, dosage may then be increased to 2 mg and thereafter to 4 mg and up to the maximum
recommended dose of 8 mg. The recommended titration interval is 1-2 weeks. The usual recommended dose is 2-4 mg
once daily.
Elderly: Normal adult dosage is recommended.
Children: The safety and efficacy of Cardura in childrena have not been established.
Renally Impaired Patients: Since the pharmacokinetics of Cardura is unchanged in patients with renal insufficiency, and
there is no evidence that Cardura aggravates existing renal dysfunction, the usual dosages may be used in these patients.
Hepatically Impaired Patients: See Precautions.
Adult Pneumonia, UTI, endometritis, gynecological infections, skin & soft tissue infections 500 mg IV 8 hrly. Nosocomial
pneumonia, peritonitis, infections in patient w/ neutropenia, septicemia 1 g IV 8 hrly. Meningitis 2 g IV 8 hrly. Childn 3
mth-12 yr 10-20 mg/kg 8 hrly. Childn >50 kg Adult dose. Meningitis 40 mg/kg 3 times daily.
Essential HTN Adult Initially 25 mg/day, then increased to 100 mg/day as a single dose or in 2 divided doses. Childn 1-2
mg/kg body wt/day in 2 divided doses. Severe HTN 100 mg/day. May be increased at 2 wkly intervals up to 400 mg/day.
Cardiac edema Adult 50-100 mg/day as a single or divided doses. Childn 1 mg/kg body wt 3 times daily. Edema due to
hepatic cirrhosis w/ or w/out ascites Adult 300-600 mg/day. Edema due to nephrotic syndrome Adult 100-200 mg/day.
Idiopathic edema 100 mg/day. Edema in childn 3.3 mg/kg in either divided dose or as a single dose. Diagnosis &
treatment of primary aldosteronism 400 mg/day for 3-4 wk for long test. For short test, 400 mg/day for 4 days.
Adult Males Including the Elderly: Casodex 50 mg/Casodex 150 mg: 1 tab once a day.
Casodex 50 mg: Should be started at least 3 days before commencing treatment with an LHRH analogue, or at the same
time as surgical castration.
Casodex 150 mg: Should be taken continuously for at least 2 years or until disease progression.
Renal Impairment: No dosage adjustment is necessary for patients with renal impairment.
Hepatic Impairment: No dosage adjustment is necessary for patients with mild hepatic impairment. Increased
accumulation may occur in patients with moderate to severe hepatic impairment (see Precautions).
The dosage should be adjusted to the patient's condition and started from the lowest effective dose.
Adults: The recommended initial daily dosage is 100-150 mg. The daily dosage should generally be divided in 2-3 doses.
Dosage should not exceed 150 mg/day (for pain management and osteoarthritis), 225 mg/day (for rheumatoid arthritis)
and 125 mg/day (for ankylosing spondylitis).
Migraine: Initial dose of 50 mg should be taken at the 1st sign of an impending attack. In cases where pain relief within 2
hrs after the 1st dose is not sufficient, a further dose of 50 mg may be taken. If needed, further doses of 50 mg may be
taken at intervals of 4-6 hrs, not exceeding a total dose of 200 mg/day.
Children: Cataflam/Cataflam D is not recommended for use in children.
Administration: Cataflam sugar-coated tablets should be swallowed whole with liquid, preferably before meals and must
not be divided or chewed.
Cataflam D should be dissolved in water.
Adult 1-2 mL 4 times daily. Infant & childn 1 mL 3-4 times daily. Prophylaxis 1 mL once daily.
1 tab daily.
1 tab daily.
Adult 2-4 g daily 12 hrly. Max daily dose: 4 g. Childn 40-80 mg/kg/day 6-12 hrly. Max daily dose: 160 mg/kg/day. Neonate
To be given 12 hrly. Max daily dose: 80 mg/kg/day.
Apply twice daily, may be used by itself or in combination w/ other dermatological treatments.
Apply twice daily, may be used by itself or in combination w/ other dermatological treatments.
Apply twice daily, may be used by itself or in combination w/ other dermatological treatments.
Adult Cedocard 5 tab Angina acute attack 1 tab. Prophylaxis: 1-2 tab 3-4 times daily. Prevention of nocturnal attacks 1-2
tab before sleep. Cedocard 10 tab 1-3 tab 4 times daily. Cedocard 20 tab Prevention of expected attack or of nocturnal
angina 1 tab. General dose: 30-160 mg/day, taken 3-4 times daily. CHF Initially ½ tab. Effective dose: 40-160 mg daily, in
severe cases up to 240 mg daily. Cedocard IV infusion 2-10 mg/hr. Cedocard Retard tab 1 tab 2 times daily.
Adult Usual dose: 50-100 mg twice daily. Renal impairment CrCl >60 mL/min Standard dose, 21-60 mL/min 75% of the
standard dose, <20 mL/min 50% of the standard dose. Uncomplicated gonorrhea 400 mg as single dose. Childn >30 kg
Recommended daily dose: 50-100 mg twice daily. Childn =30 kg 1.5-3 mg/kg body wt twice daily. More severe or
intractable infections Up to 6 mg/kg daily in divided doses as twice daily.
Adult & childn >12 yr Usual dose: 1 g 2 times daily (12 hrly), may be increased to max 12 g in severe cases. Gonorrhoea 1
g IM as a single dose. Uncomplicated infection 1 g IM/IV 12 hrly. Moderate to severe infection 1-2 g IM/IV 8 hrly. High-
level infection 2 g IV 6-8 hrly.
Cap Adult & childn =30 kg 100 mg 1-2 times daily, may be increased to 200 mg 2 times daily in severe infections. Dry syr
Childn 1.5-3 mg/kg body wt 2 times daily, may be increased to 6 mg/kg body wt 2 times daily in severe infection.
Adult 1-2 g daily in 2 divided doses. Cystitis 1-2 g daily as a single dose or in 2 divided doses. Other UTI 2 g daily in 2
divided doses. Skin & soft tissue infections 1 g daily as a single dose or in 2 divided doses. Upper & lower resp tract
infections 1 g daily. The dose may be increased up to 2 g daily in severe infections in 2 divided doses. Pharyngitis &
tonsillitis caused by group A ß-haemolytic streptococci 1 g daily in divided doses for 10 days. Childn 25-50 mg/kg/day in
2 divided doses.
Adult 1 g in 2 equally divided doses, may be increased to 1.5-3 g in 3 divided doses. Childn 20-40 mg/kg in 2 equally
divided doses, may be increased to 100 mg/kg in =3 equally divided doses.
Adult & childn =30 kg 50-100 mg twice daily, may be increased up to 200 mg twice daily. Childn 1.5-3 mg/kg twice daily.
Adult 0.5 g IM/IV in 2-4 divided doses, may be increased to 4 g/day. Childn =6 mth 40-80 mg/kg/day IV in 2-4 divided
doses, may be increased to 120 mg/kg/day.
Adult Mild to moderate UTI 500 mg-1 g IV/IM 12 hrly. Mild to moderate infections except UTI 1 g IV/IM 12 hrly. Severe
infections 2 g IV 12 hrly. Very severe to life-threatening infections 2 g IV 8 hrly. Paed patient 2 mth-16 yr up to 40 kg
Pneumonia & empiric therapy for febrile neutropic patient 50 mg/kg/dose 12 hrly (or 8 hrly in neutropenic patient) for
7-10 days.
Symptoms: Limited data are available on the consequences of May be taken with or without food.
ingestion of acute overdoses in humans. No fatalities
occurred, and the patients recovered. No specific signs or
symptoms have been identified following such overdose.
Treatment: If overdosage occurs, the patient should be
monitored and standard supportive treatment applied as
required. Since lamivudine is dialyzable, continuous
hemodialysis could be used in the treatment of overdosage,
although this has not been studied.
Administration of lamivudine at very high dose levels in acute May be taken with or without food.
animal studies did not result in any organ toxicity. Limited
data are available on the consequences of ingestion of acute
overdoses in humans. No fatalities occurred and the patients
recovered. No specific signs or symptoms have been
identified following such overdose.
If overdosage occurs, the patient should be monitored, and
standard supportive treatment applied as required. Since
lamivudine is dialyzable, continuous hemodialysis could be
used in the treatment of overdosage, although this has not
been studied.
May be taken with or without food.
Symptoms: Reports indicate that the ingestion of large Filmtab/Granule dry syr: May be taken with
amounts of clarithromycin can be expected to produce or without food.; XL filmtab: Should be
gastrointestinal symptoms. One patient who had a history of taken with food: Must be taken w/ meals.
bipolar disorder ingested clarithromycin 8 g and showed Swallow whole, do not chew/crush.
altered mental status, paranoid behavior, hypokalemia and
hypoxemia.
Treatment: Allergic reactions accompanying overdosage
should be treated by the prompt elimination of unabsorbed
drug and supportive measures. As with other macrolides,
clarithromycin serum are not expected to be appreciably
affected by hemodialysis or peritoneal dialysis.
Treatment should be symptomatic and supportive eg, May be taken with or without food.
adequate airway maintenance, cardiovascular monitoring and
close medical supervision. Activated charcoal reduces serum
concentration.
Treatment should be symptomatic and supportive eg, May be taken with or without food.
adequate airway maintenance, cardiovascular monitoring and
close medical supervision. Activated charcoal reduces serum
concentration.
MedDRA terminology has been used to classify the adverse May be taken with or without food.
events.
Human Experience: A total of 76 cases of deliberate or
accidental overdosage with aripiprazole have been reported
worldwide. These include overdoses with aripiprazole alone
and in combination with other substances. No fatality was
reported from these cases. Of the 44 cases with known
outcome, 33 recovered without sequelae and 1 recovered
with sequelae (mydriasis and feeling abnormal). The largest
known acute ingestion with a known outcome involved 1080
mg of aripiprazole (36 times the maximum recommended
daily dose) in a patient who fully recovered. Included in the
76 cases are 10 cases of deliberate or accidental overdosage
in children (=12 years) involving aripiprazole ingestions up to
195 mg with no fatalities.
Symptoms: Common adverse events (reported in at least 5%
of all overdose cases) reported with aripiprazole overdosage
(alone or in combination with other substances) include
vomiting, somnolence and tremor. Other clinically important
signs and symptoms observed in =1 patients with aripiprazole
overdoses (alone or with other substances) include acidosis,
aggression, increased aspartate aminotransferase, atrial
fibrillation, bradycardia, coma, confusional state, convulsion,
increased blood creatine phosphokinase, depressed level of
consciousness, hypertension, hypokalaemia, hypotension,
lethargy, loss of consciousness, prolonged QRS complex,
prolonged QT, aspiration pneumonia, respiratory arrest, status
epilepticus and tachycardia.
Treatment: No specific information is available on the
treatment of overdose with aripiprazole. An
electrocardiogram should be obtained in case of overdosage
and, if QTc interval prolongation is present, cardiac
monitoring should be instituted. Otherwise, management of
overdose should concentrate on supportive therapy,
maintaining an adequate airway, oxygenation and ventilation,
and management of symptoms. Close medical supervision
and monitoring should continue until the patient recovers.
Charcoal: In the event of an overdose of Abilify, an early
Limited information exists with regard to the effects of Should be taken on an empty stomach:
overdosage of ACCOLATE in humans. Take at least 1 hr before or 2 hr after meals.
Management should be supportive. Removal of excess
medication by gastric lavage may be helpful.
May be taken with or without food.
Symptoms: Drowsiness, lethargy, dizziness, ataxia, weakness, May be taken with or without food.
hypotonicity, respiratory depression, dryness of the skin and
mucous membranes, tachycardia, hypertension, hyperpyrexia,
hyperactivity, irritability, convulsions and difficulty with
micturition.
Treatment: Necessary measures should be taken to maintain
and support respiration and control convulsions. Gastric
lavage should be performed up to 3 hrs after ingestion, if
indicated. Catheterisation of the bladder may be necessary. If
desired, the elimination of pseudoephedrine can be
accelerated by acid diuresis or by dialysis.
Pioglitazone Hydrochloride: During controlled clinical trials, 1 Should be taken with food.
case of overdosage with pioglitazone was reported. A male
patient took 120 mg daily for 4 days, then 180 mg daily for 7
days. The patient denied any clinical symptoms during this
period.
In the event of overdosage, appropriate supportive treatment
should be initiated according to patient's clinical signs and
symptoms.
Metformin Hydrochloride: Overdosage of metformin
hydrochloride has occurred, including ingestion of amounts
>50 g. Hypoglycemia was reported in approximately 10% of
cases, but no causal association with metformin
hydrochloride has been established. Lactic acidosis has been
reported in approximately 32% of metformin overdosage
cases (see Metformin Hydrochloride under Warnings).
Metformin is dialyzable with a clearance of up to 170 mL/min
under good hemodynamic conditions. Therefore,
hemodialysis may be useful for removal of accumulated
metformin from patients in whom metformin overdosage is
suspected.
There are no specific overdose definitions for insulins. Should be taken with food: Administer 30
However, hypoglycemia may develop over sequential stages, min before meals. Administration should be
if too high doses relative to the patient's requirements are followed by a meal/snack containing
administered: carbohydrates w/in 30 min.
Mild hypoglycemic episodes can be treated by oral
administration of glucose or sugary products. It is therefore
recommended that the diabetic patient constantly carries
some sugar-containing products.
Severe hypoglycemic episodes, where the patient has become
unconscious, can be treated with glucagon (0.5-1 mg) given
IM or SC by a person who has received appropriate
instruction or glucose given IV by a medical professional.
Glucose must be given IV if the patient does not respond to
glucagon within 10-15 min. Upon regaining consciousness,
administration of oral carbohydrate is recommended for the
patient in order to prevent relapse.
Should be taken with food: Take during or
after meals.
Information regarding acute overdosage is limited to May be taken with or without food.
experience from clinical trials conducted during the
development of Aerius. In a dose-ranging trial, at doses of 10
and 20 mg/day, somnolence was reported.
Single-daily doses of 45 mg were given to normal male and
female volunteers for 10 days. All ECGs obtained in this study
were manually read in a blinded fashion by a cardiologist. In
Aerius-treated subjects, there was an increase in mean heart
rate of 9.2 bpm relative to placebo. The QT interval was
corrected for heart rate (QTc) by both the Bazett and
Fridericia methods.
Using the QTc (Bazett), there was a mean increase of 8.1 msec
in Aerius-treated subjects relative to placebo.
Using QTc (Fridericia), there was a mean increase of 0.4 msec
in Aerius-treated subjects relative to placebo. No clinically
relevant adverse events were reported.
In the event of overdose, consider standard measures to
remove any unabsorbed drug. Symptomatic and supportive
treatment is recommended.
Based on a multiple-dose clinical trial in adults and
adolescents, in which up to 45 mg of desloratadine was
administered (9 times the clinical dose), no clinically relevant
effects were observed.
Desloratadine and 3-hydroxydesloratadine are not eliminated
by hemodialysis; it is not known if it is eliminated by
peritoneal dialysis.
Lethality occurred in rats at oral doses of =250 mg/kg
(estimated desloratadine and desloratadine metabolite
exposures were approximately 120 times the AUC in humans
at the recommended daily oral dose). The oral median lethal
dose in mice was 353 mg/kg (estimated desloratadine
exposures were approximately 290 times the human daily
oral dose on a mg/m2 basis). No deaths occurred at oral
doses up to 250 mg/kg in monkeys (estimated desloratadine
exposures were approximately 810 times the human daily
oral dose on a mg/m2 basis).
Symptoms: Accidental or intentional overdose may cause Should be taken with food: Take
severe and prolonged hypoglycaemia which may be life- immediately before the 1st main meal of
threatening. the day. Do not skip meals. Swallow whole,
Treatment: In case of overdosage with glimepiride, a do not chew/crush.
physician must be notified immediately. At the 1st signs of
hypoglycaemia, the patient must immediately take sugar,
preferably glucose, unless a physician has already started
care.
Since hypoglycaemia and its clinical symptoms may recur
after apparent clinical recovery (even after several days), close
and continued medical supervision and possibly referral to a
hospital are indicated. In particular, significant overdosage
and severe reactions eg, with unconsciousness or other
neurological dysfunctions, are emergency cases and require
immediate care and hospitalization.
If hypoglycaemic coma is diagnosed or suspected, intravenous
infusion of a 20% glucose solution (adults: 40-100 mL) is
indicated. Alternatively, IV, SC or IM administration of
glucagons (adults: 0.5-1 mg) may be considered. In infants,
glucose must be dosed very carefully and close monitoring of
blood glucose is required to minimize the risk of potentially
severe hyperglycaemia. Other symptomatic therapy (eg,
anticonvulsants) should be administered as necessary. After
acute glucose replacement has been completed, it is usually
necessary to give an IV glucose infusion in lower
concentration so as to ensure that hypoglycaemia does not
recur. The patient's blood glucose level should be carefully
monitored for at least 24 hrs. In severe cases with a
protracted course, hypoglycaemia, or the danger of slipping
back into hypoglycaemia, may persist for several days.
In cases of acute intake of large amounts of glimepiride,
detoxification (eg, by gastric lavage and administration of
medicinal charcoal) is indicated.
Because Amaryl M includes glimepiride, overdosage can Should be taken with food: Take
produce hypoglycemia. Mild hypoglycemia without loss of immediately before or together w/ meals.
consciousness or neurological findings should be treated
aggressively with oral glucose and adjustments in drug
dosage and/or meal patterns. Close monitoring should
continue until the physician is assured that the patient is out
of danger. Severe hypoglycemic reactions with coma, seizure
or other neurological impairment occur infrequently, but
constitute medical emergencies requiring immediate
hospitalization. If hypoglycemic coma is diagnosed or
suspected, the patient should be given a rapid IV injection of
concentrated (50%) glucose solution. This should be followed
by a continuous infusion of a more dilute (10%) glucose
solution at a rate that maintain the blood glucose at a level
>100 mg/dL. Patients should be closely monitored for a
minimum of 24-48 hrs, because hypoglycemia may recur after
apparent clinical recovery.
Because Amaryl M includes metformin, lactic acidosis may
occur. Hypoglycemia has not been seen with ingestion of up
to 85 g of metformin HCl. Metformin is dialyzable with a
clearance of up to 170 mL/min under good hemodynamic
conditions. Therefore, hemodialysis may be useful for
removal of accumulated drug from patients in whom
metformin overdosage is suspected.
Should be taken on an empty stomach:
Take 1 hr before or 2 hr after meals.
In humans, experiences with intentional overdose is limited. May be taken with or without food.
Gastric lavage may be worthwhile in some cases. Available
data suggest that gross overdosage could result in excessive
peripheral vasodilatation with subsequent marked and
probably prolonged systemic hypotension. Clinically
significant hypotension due to amlodipine overdosage calls
for active cardiovascular support including frequent
monitoring of cardiac and respiratory function, elevation of
extremities and attention to circulating fluid volume and urine
output. A vasoconstrictor may be helpful in restoring vascular
tone and blood pressure, provided that there is no
contraindication to its use.
Calcium gluconate IV may be beneficial in reversing the
effects of calcium channel blockade. Since amlodipine is
highly protein bound, dialysis is not likely to be of benefit.
Hypoglycemia may occur as a result of an excess of insulin Should be taken with food: Administer w/in
activity relative to food intake and energy expenditure. 15 min before a meal or immediately after
There are no specific data available concerning overdose with a meal.
insulin glulisine. However, hypoglycemia may develop over
sequential stages: Mild hypoglycemia episodes can be treated
by oral administration of glucose or sugary products. It is
therefore recommended that the diabetic patient constantly
carries sugar lumps, sweets, biscuits or sugary fruit juice.
Severe hypoglycemia episodes, where the patient has
become unconscious, can be treated by glucagon (0.5-1 mg)
given IM or SC by a person who has received appropriate
instruction, or by glucose given IV by a medical professional.
Glucose must also be given IV, if the patient does not respond
to glucagon within 10-15 min. Upon regaining consciousness,
administration of oral carbohydrate is recommended for the
patient in order to prevent relapse.
After an injection of glucagon, the patient should be
monitored in a hospital in order to find the reason for this
severe hypoglycemia and prevent other similar episodes.
No overdoses of Arcoxia were reported during clinical trials. May be taken with or without food.
In clinical studies, administration of Arcoxia at single doses up
to 500 mg and multiple doses up to 150 mg/day for 21 days
did not result in significant toxicity.
In the event of an overdose, it is reasonable to employ the
usual supportive measures eg, removing unabsorbed material
from the gastrointestinal tract, employing clinical monitoring,
and instituting supportive therapy, if required.
Etoricoxib is not dialyzable by hemodialysis; it is not known
whether etoricoxib is dialyzable by peritoneal dialysis.
There is limited clinical experience of overdosage. In animal May be taken with or without food:
studies, anastrozole demonstrated low acute toxicity. Clinical Swallow whole, do not chew/crush.
trials have been conducted with various dosages of Arimidex,
up to 60 mg in a single dose given to healthy male volunteers
and up to 10 mg daily given to postmenopausal women with
advanced breast cancer; these dosages were well tolerated. A
single dose of Arimidex that results in life-threatening
symptoms has not been established. There is no specific
antidote to overdosage and treatment must be symptomatic.
In the management of an overdose, consideration should be
given to the possibility that multiple agents may have been
taken. Vomiting may be induced if the patient is alert. Dialysis
may be helpful because Arimidex is not highly protein-bound.
General supportive care, including frequent monitoring of
vital signs and close observation of the patient, is indicated.
Symptoms: Gastrointestinal symptoms and disturbance of the May be taken with or without food: May be
fluid and electrolyte balances may be evident. given w/o regard to meals. Best taken at
Amoxicillin crystalluria, in some cases leading to renal failure, the start of meals for better absorption &
has been observed (see Precautions). to reduce GI discomfort.
Treatment: Gastrointestinal symptoms may be treated
symptomatically, with attention to the water/electrolyte
balance. Amoxicillin-clavulanate can be removed from the
circulations by hemodialysis.
Children: A prospective study of 51 pediatric patients at a
poison control centre suggested that overdosages of <250
mg/kg of amoxicillin are not associated with significant
clinical symptoms and do not require gastric emptying.
Drug Abuse and Dependence: Drug dependency, addiction
and recreational abuse have not been reported as a problem
with this compound.
Symptoms: In a bioavailability study, intranasal doses of up to
24 times the recommended daily adult dose were studied
over 3 days with no adverse systemic effects observed (see
Pharmacokinetics under Actions).
Treatment: Acute overdose is unlikely to require any therapy
other than observation.
In volunteer studies, single doses of dutasteride up to 40 May be taken with or without food:
mg/day (80 times the therapeutic dose) for 7 days have been Swallow whole, do not chew/crush.
administered without significant safety concerns. In clinical
studies, doses of 5 mg daily have been administered to
patients for 6 months with no additional adverse effects to
those seen at therapeutic doses of 0.5 mg.
There is no specific antidote for dutasteride; therefore, in
cases of suspected overdosage, symptomatic and supportive
treatment should be given as appropriate.
Not applicable.
There is limited experience of entecavir overdosage reported Should be taken on an empty stomach:
in patients. Healthy subjects who received single entecavir Take on an empty stomach at least 2 hr
doses up to 40 mg or multiple doses up to 20 mg/day for up after a meal & 2 hr before the next meal.
to 14 days had no increase in or unexpected adverse events.
If overdose occurs, the patient must be monitored for
evidence of toxicity, and standard supportive treatment
applied as necessary.
Following a single 1-mg dose of entecavir, a 4-hr hemodialysis
session removed approximately 13% of the entecavir dose.
Symptoms: Limited data are available for overdosage in Should be taken on an empty stomach:
humans. Symptoms associated with overdosage of ACE Take before meals.
inhibitors may include hypotension, circulatory shock,
electrolyte disturbances, renal failure, hyperventilation,
tachycardia, palpitations, bradycardia, dizziness, anxiety and
cough.
Treatment: The recommended treatment of overdosage is IV
infusion of 0.9% sodium chloride 9 mg/mL solution. If
hypotension occurs, the patient should be placed in the shock
position. If available, treatment with angiotensin II infusion
and/or IV catecholamines may also be considered. Perindopril
may be removed from the general circulation by
haemodialysis (see Precautions). Pacemaker therapy is
indicated for therapy-resistant bradycardia. Vital signs, serum
electrolytes and creatinine concentrations should be
monitored continuously.
Symptoms: The most likely adverse reaction in cases of Should be taken on an empty stomach:
overdose is hypotension, sometimes associated with nausea, Take before meals.
vomiting, cramps, dizziness, sleepiness, mental confusion,
oliguria which may progress to anuria (due to hypovolemia).
Salt and water disturbances (low sodium and potassium
levels) may occur.
Treatment: The first measures to be taken consist of rapidly
eliminating the product(s) ingested by gastric lavage and/or
administration of activated charcoal, then restoring fluid and
electrolyte balance in a specialized center until they return to
normal.
If marked hypotension occurs, this can be treated by placing
the patient in a supine position with the head lowered. If
necessary an IV infusion of isotonic saline may be given or any
other method of volemic expansion may be used.
Perindoprilat, the active form of perindopril, can be dialysed
(see Pharmacokinetics under Actions).
Symptoms: Based on pharmacological considerations, the May be taken with or without food.
main manifestation of an overdose of candesartan cilexetil is
likely to be symptomatic hypotension and dizziness. In 2 case
reports of overdose (candesartan cilexetil 160 and 432 mg),
patient recovery was uneventful.
The main manifestation of an overdose of
hydrochlorothiazide is acute loss of fluid and electrolytes.
Symptoms eg, dizziness, hypotension, thirst, tachycardia,
ventricular arrhythmias, sedation/impairment of
consciousness and muscle cramps can also be observed.
Management: No specific information is available on the
treatment of overdosage with Blopress Plus. The following
measures are, however, suggested in case of overdosage.
When indicated, induction of vomiting or gastric lavage
should be considered. If symptomatic hypotension should
occur, symptomatic treatment should be instituted and vital
signs monitored. The patient should be placed supine with
the legs elevated. If it is not sufficient, plasma volume should
be increased by infusion of isotonic saline solution. Serum
electrolyte and acid balance should be checked and
corrected, if needed. Sympathomimetic drugs may be
administered if the previously mentioned measures are not
sufficient.
Candesartan cannot be removed by haemodialysis. It is not
known to what extent hydrochlorothiazide is removed by
haemodialysis.
Too frequent administration, as with other sympathomimetic May be taken with or without food.
agents, may cause nausea, headaches, changes in blood
pressure, anxiety, tension, insomnia, tremor. The symptoms
and sign are those characteristic of excessive sympathetic
stimulation.
Symptoms: Headache, anxiety, tremor, nausea, tonic muscle
cramps, palpitation, tachycardia and cardiac arrhythmia. A fall
in blood pressure sometimes occurs.
Laboratory Findings: Hyperglycaemia and lactacidosis
sometimes occur. ß2-agonists may cause hypokalemia as a
result of redistribution of potassium.
Treatment: Usually no treatment is required.
If it can be suspected that significant amounts of terbutaline
sulphate have been swallowed, the following measures
should be considered: Gastric lavage, activated charcoal.
Determine acid-base balance, blood sugar and electrolytes.
Monitor heart rate and rhythm and blood pressure. Metabolic
changes should be corrected. A cardio-selective ß-blocker
(e.g. metoprolol) is recommended for the treatment of
arrhythmias causing a hemodynamic deterioration. The ß-
blocker should be used with care because of the possibility of
inducing bronchial obstruction.
If the ß2-mediated reduction in peripheral vascular resistance
significantly contributes to the fall in blood pressure, a
volume expander should be given.
Mild and Moderate Cases: Reduce the dose. Then increase
the dose more slowly if the broncholytic effect is insufficient.
Turbuhaler: There is a potential for progressive accumulation
of dry powder in the mouthpiece of the Bricasma Turbuhaler
that could be released if dropped (for example, see table)
towards the end of inhaler life. To minimize unnecessary
systemic exposure to terbutaline, the patients should be
advised to, when possible, rinse their mouth after each use.
There is currently no known treatment to reverse the effects May be taken with or without food: For
of BRILINTA and ticagrelor is not expected to be dialyzable. patients w/ swallowing difficulties, the tab
Treatment of overdose should follow local standard medical may be crushed to a fine powd & mixed in
practice. Bleeding is the expected pharmacologic effect of a ½ glass of water & drunk immediately.
overdosing. If bleeding occurs, appropriate supportive Rinse the glass w/ ½ glass of water & drink.
measures should be taken. Other effects of overdose may The mixture may also be administered via a
include gastrointestinal effects (nausea, vomiting, diarrhea) or nasogastric tube.
ventricular pauses. Monitor the electrocardiogram (ECG).
There is no human experience of overdosage. There is no May be taken with or without food.
specific antidote; treatment should be symptomatic. Dialysis
may not be helpful since bicalutamide is highly protein bound
and is not recovered unchanged in the urine. General
supportive care, including frequent monitoring of vital signs,
is indicated.
Symptoms: There is no typical clinical picture resulting from Should be taken with food: Take before
diclofenac overdosage. Overdosage can cause symptoms eg, meals.
vomiting, gastrointestinal (GI) haemorrhage, diarrhoea,
dizziness, tinnitus or convulsions. In the event of significant
poisoning, acute renal failure and liver damage are possible.
Treatment: Management of acute poisoning with NSAIDs,
including diclofenac, consists essentially of supportive and
symptomatic measures. Supportive measures and
symptomatic treatment should be given for complications eg,
hypotension, renal failure, convulsions, GI irritation and
respiratory depression.
Specific measures eg, forced diuresis, dialysis, or
haemoperfusion are probably of no help in eliminating
NSAIDs, including diclofenac, due to high protein-binding and
extensive metabolism.
Activated charcoal may be considered after ingestion of a
potentially toxic overdose and gastric decontamination (eg,
vomiting, gastric lavage) after ingestion of a potentially life-
threatening overdose.
Symptoms: Clonidine has a wide therapeutic range. May be taken with or without food.
Manifestations of intoxication are due to generalised
sympathetic depression and include pupillary constriction,
lethargy, bradycardia, hypotension, hypothermia, coma,
apnea. Paradoxic hypertension caused by stimulation of
peripheral a1-receptors may occur.
Treatment: In most cases, symptomatic therapy is sufficient.
Gastric lavage is only worthwhile if it guarantees that the part
taken which has not yet been absorbed, can be removed.
Tolazoline is indicated as a specific antidote (tolazoline 10 mg
IV or 50 mg oral neutralises the effect of Catapres 600 mcg).
Hypersensitivity to dihydropyridine.
Hypesensitivity to aripiprazole.
Hypersensitivity to aripiprazole.
Hypersensitivity.
Hypersensitivity.
Hypersensitivity.
Hypersensitivity.
Hypersensitivity.
Hypersensitivity to penicillins.
Hypersensitivity.
Hypersensitivity to Acuatim.
Patients with history of hypersensitivity to any of
the ingredients of Adant Dispo.
Infection or skin disease at the injection site.
Hypersensitivity.
Hypersensitivity to paracetamol, ibuprofen, or
other NSAIDs. Severe & active peptic ulcer.
Patients in whom acetosal or other NSAIDs
induce symptoms of asthma, rhinitis, or urticaria.
3rd trimester of pregnancy.
Hypersensitivity.
Hypercalcemia.
Patients with hepatic coma or a risk of hepatic
coma (because of inadequate amino acid
metabolism, the patient's clinical condition may
be worsened. Patients with severe renal disorder
or azotemia (the amounts of water and
electrolytes tend to be excessive and the
patient's clinical condition may be worsened.
Urea and other amino acid metabolites may be
retained, which may worsen the patient's clinical
condition). Patient's with congestive cardiac
failure (an increase in the circulating blood
volume may worsen the patient's clinical
condition). Patients with severe acidosis
(hyperlactacidemia, etc) (the patient's clinical
condition may be worsened). Patients with
abnormal electrolyte metabolism: Patients with
hyperpotassemia (oliguria, Addison's disease,
etc), patients with hyperphosphatemia
(hypoparathyroidism, etc), patients with
hypermagnesemia (hypothyroidism, etc),
patients with hypercalcemia (administration may
worsen the patient's clinical condition). Patients
with reduced urine output due to obstructive
uropathy (overload of water and electrolytes
may worsen the patient's clinical condition).
Patients with abnormal amino acid metabolism.
Since the infused amino acids are not adequately
metabolized, the patient's clinical condition may
be worsened.
Hypersensitivity to cephalosporins.
Hypersensitivity to penicillins.
Pernicious anemia.
Hypersensitivity to cephalosporins.
Hypersensitivity.
Hypersensitivity to insulin glulisine or to any of
the exipients of Apidra.
Hypoglycaemia.
Constipation.
Hypersensitivity.
Known hypersensitivity to fondaparinux or to any
of the excipients of Arixtra. Clinically active
significant bleeding; acute bacterial endocarditis;
severe renal impairment (CrCl <20 mL/min).
Hypersensitivity.
Active liver disease or unexplained persistent
serum transaminases elevation =3 x ULN.
Pregnancy, women of childbearing potential &
lactation.
Hypersensitivity to penicillins.
Hypersensitivity. Pregnancy & lactation. Childn,
adolescents.
Hypersensitivity to cephalosporins.
Hypersensitivity. Haemophilia.
Arterial & strong venous bleeding. Known
hypersensitivity to bovine proteins.
Lactation.
Hypersensitivity to the active substance or to any
of the excipients. Betaserc should not be given to
pregnant women and lactation.
Phaeochromocytoma. Children less than 12
years.
Hypersensitivity to cephalosporins.
Liver diseases (except fatty liver), gallbladder
diseases w/ or without cholelithiasis. Severe
renal dysfunction (serum creatinine >6 mg/100
mL or 530 micromole/L for Bezalip or >1.6
mg/100 mL or 136 micromole/L for Bezalip
Retard). Pregnancy, lactation. Nephrotic
syndrome.
Hypersensitivity.
Hypersensitivity to cephalosporins.
Hypersensitivity to Zn.
Hypersensitivity.
Hypersensitivity. Patients w/ kidney failure, AV
block, unless the patients are using pacemaker.
Hypersensitivity.
Hypersensitivity.
Hypersensitivity to terbutaline or to
sympathomimetic amines, or to any of the
components of Bricasma.
Hypersensitivity (eg, angioedema) to ticagrelor
or to any of the components of Brilinta (see
Adverse Reactions).
History of Intracranial Hemorrhage: Patients with
a history of intracranial hemorrhage (ICH)
because of a high risk of recurrent ICH in this
population (see Pharmacology:
Pharmacodynamics: Clinical Studies under
Actions).
Active Bleeding: Patients with active pathological
bleeding eg, peptic ulcer or intracranial
hemorrhage (see Warnings, Precautions and
Adverse Reactions).
Severe Hepatic Impairment: Patients with severe
hepatic impairment because of a probable
increase in exposure and it has not been studied
in these patients. Severe hepatic impairment
increases the risk of bleeding because of
reduced synthesis of coagulation proteins (see
Pharmacology under Actions).
Warnings Bleeding Risk: Brilinta, like other
antiplatelet agents, can cause significant,
sometimes fatal, bleeding.
Do not use Brilinta in patients with active
pathological bleeding or a history of intracranial
hemorrhage.
Do not start Brilinta in patients planned to
undergo urgent coronary artery bypass graft
surgery (CABG). When possible, discontinue
Brilinta at least 5 days prior to any surgery.
Suspect bleeding in any patient who is
hypotensive and has recently undergone
coronary angiography, percutaneous coronary
intervention (PCI), CABG or other surgical
procedures in the setting of Brilinta.
If possible, manage bleeding without
discontinuing Brilinta. Stopping Brilinta increases
the risk of subsequent
Hypersensitivity CV events.
to cephalosporins.
Gastric ulcer.
Hypersensitivity to dihydropiridine.
Hypersensitivity.
Pregnancy, lactation.
Hypercalcemia & hypercalciuria, renal calculi,
severe renal failure.
Hypersensitivity to colostrum-containing
products.
Hypervitaminosis D, hypercalcemia,
hypercalciuria, severe kidney dysfunction.
Hypersensitivity.
Canesten SD Hypersensitivity.
Hypersensitivity.
Hypersensitivity.
Hypersensitivity to hydroxybenzoate.
Myelosuppression due to antitumor therapy or
radiotherapy. Patients w/ preexisting heart
disease, who received previous treatment w/
complete cumulative doses of doxorubicin HCl or
daunorubicin. Pregnancy.
Known hypersensitivity to ramipril, to any other
ACE inhibitor or to any of the excipients of
Cardace (see Description).
History of angioneurotic oedema (risk of
precipitating angioneurotic oedema; see also
Adverse Reactions).
Blood flow reducing and narrowing
(haemodynamically relevant stenosis) of the
renal artery, bilateral or unilateral in the single
kidney (risk of fall in blood pressure and renal
failure).
Patients with low blood pressure or labile
circulatory condition (risk of fall in blood
pressure and renal failure).
Since severe rapid-onset and allergy-like
(anaphylactoid) hypersensitivity reactions may
occur, treatment with ACE inhibitors in
conjunction with extracorporeal treatments
leading to contact of blood with negatively
charged surfaces must be avoided. This latter
include dialysis or haemofiltration with certain
high-flux membranes (eg, polyacrylonitril
membranes) and low-density lipoprotein
apheresis with dextran sulfate.
Use in Pregnancy & Lactation: Cardace must not
be taken during pregnancy. Therefore, pregnancy
must be excluded before starting treatment.
Pregnancy must be avoided where treatment
with ACE inhibitors is indispensable.
If a pregnancy is planned, treatment with ACE
inhibitors must be discontinued ie, replaced by
another form of treatment.
If pregnancy occurs during treatment,
medication with Cardace must be substituted as
soon as possible with a treatment regimen which
excluded ACE inhibitors. Otherwise, there is a
risk of harm to the fetus. Whether the exposure
is limited to the 1st 3 months of pregnancy,
Bleeding disorder.
Hypopigmentation.
Hypersensitivity to cephalosporins.
Hypersensitivity to cephalosporins.
Hypersensitivity.
Special Precautions
Administer only via IV route. When large or frequently repeated doses are required, patients of blood groups A, B or AB
should be monitored for signs of progressive anemia. Pregnancy.
Anaphylactic reaction.
Clarithromycin is principally excreted by the liver and kidney. Therefore, caution should be exercised in administering this
antibiotic to patients with impaired hepatic function. Caution should also be exercised when administering clarithromycin to
patients with moderate to severe renal impairment. Clarithromycin may be administered without dosage adjustment to
patients with hepatic impairment and normal renal function. However, in the presence of severe renal impairment with or
without coexisting hepatic impairment, decreased dosage or prolonged dosing intervals may be appropriate.
Prolonged or repeated use of clarithromycin may result in an overgrowth of nonsusceptible bacteria or fungi. If superinfection
occurs, clarithromycin should be discontinued and appropriate therapy instituted. Attention should also be paid to the
possibility of cross-resistance between clarithromycin and other macrolide drugs, as well as lincomycin and clindamycin.
A pharmacokinetic study demonstrated that the concomitant administration of ritonavir 200 mg every 8 hrs and
clarithromycin 500 mg every 12 hrs resulted in a marked inhibition of the metabolism of clarithromycin. The clarithromycin
Cmax increased by 31%, Cmin increased 182% and AUC increased by 77% with concomitant administration of ritonavir. An
essentially complete inhibition of the formation of 14-(R)-hydroxy clarithromycin was noted. Because of the large therapeutic
window for clarithromycin, no dosage reduction should be necessary in patients with normal renal function. However, for
patients with renal impairment, the following dosage adjustment should be reduced by 50%. For patients with creatinine
clearance 30-60 mL/min, the dose of clarithromycin should be decreased by 75%. Doses of clarithromycin >1 g/day should not
be co-administered with ritonavir.
Carcinogenicity, Mutagenicity & Impairment of Fertility: The following in vitro mutagenicity test have been conducted with
clarithromycin: Salmonella/mammalian microsome test, bacterial-induced mutation frequency tests, in vitro chromosome
aberration test, rat hepatocyte DNA synthesis assay, mouse dominant lethal study, mouse lymphoma assay and mouse
micronucleus test.
All tests had negative results except the in vitro chromosome aberration test, which was weakly positive in one test and
negative in another.
In addition, a bacterial reverse mutation test (Ames test) has been performed on clarithromycin metabolites with negative
results.
Fertility and reproduction studies have shown that daily doses of 150-160 mg/kg/day to male and female rats caused no
adverse effects on the estrous cycle, fertility, parturition or number and viability of offspring. Plasma levels in rats after 150
mg/kg/day were 2 times the human serum levels.
In the 150 mg/kg/day monkey studies, plasma levels were 3 times the human serum levels. When given orally at 150
mg/kg/day, clarithromycin was shown to produce embryonic loss in monkeys. This effect has been attributed to marked
maternal toxicity of the drug at this high dose.
In rabbits, in utero fetal loss occurred at an IV dose of 33 mg/m2, which is 17 times less than the maximum proposed human
oral daily dose of 618 mg/m2. Long-term studies in animals have not been performed to evaluate carcinogenic potential.
Use in pregnancy: Teratogenic Effects: Pregnancy Category C: Four teratogenicity studies in rats (3 with oral doses and 1 with
IV doses up to 160 mg/kg/day administered during the period of major organogenesis) and 2 in rabbits (at oral doses up to
125 mg/kg/day or IV doses of 30 mg/kg/day administered during gestation days 6-18) failed to demonstrate any teratogenicity
from clarithromycin. Two additional oral studies in a different rat strain at similar doses and similar conditions demonstrated a
low incidence of cardiovascular anomalies at doses of 150 mg/kg/day administered during gestation days 6-15. Plasma levels
after 150 mg/kg/day were 2 times the human serum levels. Four studies in mice revealed a variable incidence of cleft palate
Clinical improvement may take several days to some weeks. Monitoring the patient throughout this period is recommended.
Reduce dose or discontinue if signs or symptoms of tardive dyskinesia appear. Discontinue if patient develops signs and
symptoms indicative of neuroleptic malignant syndrome. Caution in patients with a history of seizure.
Effects on the Ability to Drive or Operate Machinery: Until individual patient response is established, caution is advised when
driving or operating machines.
Use in pregnancy & lactation: Do not use in pregnancy unless the benefit outweighs the risk.
Breastfeeding is not advised during treatment.
Clinical improvement may take several days to some weeks. Monitoring of the patient throughout this period is
recommended. Reduce dose or discontinue if signs or symptoms of tardive dyskinesia appear. Discontinue if patient develops
signs and symptoms indicative of neuroleptic malignant syndrome. Caution in patients with a history of seizure.
Effects on the Ability to Drive or Operate Machinery: Until individual patient response is established, caution is advised when
driving or operating machines.
Use in pregnancy & lactation: Do not use in pregnancy unless the benefit outweighs the risk.
Breastfeeding is not advised during treatment.
General: Orthostatic Hypotension: Aripiprazole may be associated with orthostatic hypotension, perhaps due to its a1-
adernergic receptor antagonism. The incidence of orthostatic hypotension-associated events from 5 short-term, placebo-
controlled trials in schizophrenia (n=926) on Abilify included: Orthostatic hypotension (placebo 1%, aripiprazole 1.9%),
orthostatic lightheadedness (placebo 1%, aripiprazole 0.9%), and syncope (placebo 1%, aripiprazole 0.6%). The incidence of
orthostatic hypotension-associated events from short-term, placebo-controlled trials in bipolar mania (n=597) on Abilify
included: Orthostatic hypotension (placebo 0%, aripiprazole 0.7%), orthostatic lightheadedness (placebo 0.5%, aripiprazole
0.5%), and syncope (placebo 0.9%, aripiprazole 0.5%).
The incidence of a significant orthostatic change in blood pressure (defined as a decrease of at least 30 mm Hg in systolic
blood pressure when changing from a supine to standing position) for aripiprazole was not statistically different from placebo
(in schizophrenia: 14% among aripiprazole-treated patients and 12% among placebo-treated patients and in bipolar mania:
3% among aripiprazole-treated patients and 2% among placebo-treated patients).
Aripiprazole should be used with caution in patients with known cardiovascular disease (history of myocardial infarction or
ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease, or conditions which would
predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications).
Seizure: Seizures occurred in 0.1% (1/926) of aripiprazole-treated patients with schizophrenia in short-term, placebo-
controlled trials. In short-term, placebo-controlled clinical trials of patients with bipolar mania, 0.3% (2/597) of aripiprazole-
treated patients and 0.2% (1/436) of placebo-treated patients experienced seizures. As with other antipsychotic drugs,
aripiprazole should be used cautiously in patients with a history of seizures or with conditions that lower the seizure threshold
eg, Alzheimer's dementia. Conditions that lower the seizure threshold may be more prevalent in a population of >65 years.
Potential for Cognitive and Motor Impairment: In short-term, placebo-controlled trials of schizophrenia, somnolence was
reported in 11% of patients on Abilify compared to 8% of patients on placebo; somnolence led to discontinuation in 0.1%
(1/926) of patients with schizophrenia on Abilify in short-term, placebo-controlled trials. In short-term, placebo-controlled
trials of bipolar mania, somnolence was reported in 14% of patients on Abilify compared to 7% of patients on placebo, but did
not lead to discontinuation of any patients with bipolar mania. Despite the relatively modest increased incidence of
somnolence compared to placebo, Abilify, like other antipsychotics, may have the potential to impair judgment, thinking or
motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are
reasonably certain that therapy with Abilify does not affect them adversely.
Body Temperature Regulation: Disruption of the body's ability to reduce core body temperature has been attributed to
antipsychotic agents. Appropriate care is advised when prescribing aripiprazole for patients who will be experiencing
conditions which may contribute to an elevation in core body temperature eg, exercising strenuously, exposure to extreme
heat, receiving concomitant medication with anticholinergic activity or being subject to dehydration.
Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is
a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer's dementia.
Aripiprazole and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia (see Use in
Patients with Concomitant Illness as follows).
Suicide: The possibility of a suicide attempt is inherent in psychotic illnesses and bipolar disorder, and close supervision of
high-risk patients should accompany drug therapy. Prescriptions for Abilify should be written for the smallest quantity
consistent
Monitor renalwithfunction
good patient
duringmanagement
concomitantin order to reduce
treatment the risk of overdose.
w/ aminoglycocides. Pregnancy & lactation.
History of hypersensitivity to other cephem antibiotics & penicillins; allergy eg, bronchial asthma, rash, urticaria; serious renal
dysfunction; poor oral nutrition, receiving parenteral nutrition, debility. Periodic monitoring of renal function is
recommended. Pregnancy & lactation. Childn <6 mth, elderly.
ACCOLATE should be taken regularly to achieve benefit, even during symptom free periods.
ACCOLATE therapy should normally be continued during acute exacerbations of asthma.
ACCOLATE does not allow a reduction in existing steroid treatment.
As with inhaled steroids and cromones (disodium cromoglycate, nedocromil sodium), ACCOLATE is not indicated for use in the
reversal of bronchospasm in acute asthma attacks.
ACCOLATE has not been evaluated in the treatment of labile (brittle) or unstable asthma.
Rarely, patients with asthma on anti-leukotriene medications, including ACCOLATE, may present with systemic eosinophilia,
eosinophilic pneumonia or with clinical features of systemic vasculitis, consistent with Churg-Strauss syndrome. Presentations
may involve various body systems including vasculitic rash, worsening pulmonary symptoms, cardiac complications or
neuropathy. These events have usually, but not always, been associated with reductions and/or withdrawal of steroid therapy.
The possibility that leukotriene-receptor antagonists, including ACCOLATE may be associated with emergence of Churg-
Strauss syndrome can neither be excluded nor established. If a patient develops an eosinophilic condition or a Churg-Strauss
syndrome-type illness, ACCOLATE should be stopped, a rechallenge test should not be performed and treatment should not
be restarted.
Elevations in serum transaminases can occur during treatment with ACCOLATE. These are usually asymptomatic and transient
but could represent early evidence of hepatotoxicity, and have been very rarely associated with more severe hepatocellular
injury, fulminant hepatitis and liver failure, some of which resulted in a fatal outcome. Extremely rarely, case of fulminant
hepatitis and liver failure has been reported in patient in whom no previous clinical sign or symptoms of liver dysfunction
were reported.
If clinical symptoms or signs suggestive of liver dysfunction occur (e.g. anorexia, nausea, vomiting, upper right quadrant pain,
fatigue, lethargy, flu-like symptoms, enlarged liver, pruritus and jaundice), ACCOLATE should be discontinued. The serum
transaminases, in particular serum ALT, should be measured immediately and the patient managed accordingly.
Physicians may consider the value of routine liver function testing. Periodic serum transaminase testing has not been proven
to prevent serious injury but is generally believed that early detection of drug-induced hepatic injury along with immediate
withdrawal of the suspect drug may enhance the likelihood of recovery. If liver function testing shows evidence of
hepatotoxicity, ACCOLATE should be discontinued immediately and the patient managed accordingly.
Patients in whom ACCOLATE was withdrawn because of hepatotoxicity cause should not be re-exposed to ACCOLATE.
Effects on Ability to Drive and Use Machines: There is no evidence that ACCOLATE affects the ability to drive and use
machinery.
Use In Pregnancy & Lactation The safety of ACCOLATE in human pregnancy has not been established. In animal studies,
zafirlukast did not have any apparent effect on fertility and did not appear to have any teratogenic or selective toxic effect on
the foetus. The potential risks should be weighed against the benefits of continuing therapy during pregnancy and ACCOLATE
should be used during pregnancy only if clearly needed.
Zafirlukast is excreted in human breast milk. ACCOLATE should not be administered to mothers who are breast-feeding.
Avoid contact w/ eyes. May increase the risk of sensitization & bacterial resistance. If possible, avoid use during the last mth
of pregnancy. May cause kernicterus in babies during the 1st mth of age.
Administer after food intake in patients with gastritis. Not recommended for DM patients until blood glucose level is
controlled at normal level.
Anaphylactic reactions. Patients w/ bronchial asthma or w/ a history of asthma. Monitor coagulation factors in case of liver
transplantation. May interfere w/ the determination of salicylates & plasma, & urinary ketones. Pregnancy & lactation. Childn.
Do not apply to mucous membrane. Not for prevention of recurrent herpes simplex infection. Pregnancy & lactation, childn.
Babies born of mother hypersensitive to penicillins. Previous hypersensitivity reactions to cephalosporins or to other
allergens. Superinfections. Pregnancy, lactation.
Ensure appropriate hydration prior to administration esp in elderly & in patients on diuretics. Adequate Ca & vit D intake prior
to Aclasta therapy in patients w/ preexisting hypocalcemia & for 10 days following Aclasta in patients w/ Paget's disease of
bone. Should not be used in severe renal impairment (CrCl <35 mL/min); monitor serum creatinine. Dental examination prior
to treatment in patients w/ cancer, under chemotherapy or corticosteroids, w/ poor oral hygiene; avoid invasive dental
procedures for those who develop osteonecrosis of the jaw. 5-mg dose must be administered over at least 15 min.
Arrhythmias, ventricular tachycardia, ventricular fibrillation, Torsade de pointes, QT interval prolongation; history of heart
disease including serious ventricular arrhythmia, ischaemic heart disease, CHF, renal impairment, hypocalcaemia,
hypomagnesemia, resp disorders.
Renal insufficiency; patient w/ concomitant risk factors eg, cancer, chemotherapy, radiotherapy, corticosteroids, poor oral
hygiene. Monitor hydration status, renal function & serum Ca. Avoid invasive dental procedures.
Perform liver function test prior to initiation 12 wk after treatment initiation, during dose evaluation & periodically thereafter.
Alcohol consumption or history of liver disease. Promptly report unexplained muscle pain, tenderness or weakness, especially
if accompanied w/ malaise or fever. Discontinue use in case of markedly elevated CPK levels, diagnosed or suspected
myopathy or w/ risk factor to development of renal failure secondary to rhabdomyolysis.
Impaired hepatic & renal function. Heart failure. Lactation. Elderly.
Regular hepatic & hematological monitoring; undernutrition, irregular meal times, missed meals, diet alteration, imbalance
between physical exertion & carbohydrate intake, alcohol consumption; impaired renal function, serious liver dysfunction,
endocrine system disorders affecting carbohydrate metabolism; galactose intolerance, Lapp-lactase deficiency or glucose-
galactose malabsorption. Childn.
WHO performance status = 2. Patients may have cholinergic symptoms. Extravasation may occur. Discontinue if neutropenic
fever occurs or if the absolute neutrophil count drops <1000/mm3. Late diarrhea (generally occurs >8 hr after administration
of irinotecan) can be prolonged, may lead to dehydration, electrolyte imbalance or sepsis & may be life-threatening. Patients
must not be treated w/ irinotecan until resolution of the bowel obstruction. Nausea & vomiting can be severe & usually
occurs during or shortly after infusion. Increase in serum creatinine or BUN. Monitor patients w/ risk factors for resp
symptoms before & during therapy. Unsuitable in hereditary fructose intolerance. Increased risk of myelosuppression for
patients who have previously received pelvic/abdominal irradiation & patients w/ gastric cancer. May impair ability to drive or
operate machinery. Renal & hepatic insufficiency. Elderly.
History of anaphylactic shock & diarrhea. Monitor blood count during prolonged treatment. Hepatic & renal dysfunction.
Pregnancy & lactation. Hyperbiliruminemic neonates especially prematures.
Chronic renal & hepatic disorders, resp disorder, muscle weakness, history of drug or alcohol abuse, marked personality
disorders, chronic pulmonary insufficiency. May cause dependence. Avoid single dose treatment in depression or combined
anxiety-depression. Avoid long-term therapy. May affect the ability to drive or operate machinery. Pregnancy & lactation.
Severe hypertension, over weight. Discontinue treatment if insomnia, palpitation and dizziness occur. Impaired liver and
kidney function, glaucoma, prostate hypertrophy, hyperthyroid.
Concomitant use with other central nervous system (CNS) suppressants. Caution is recommended in pregnancy and lactation
and in the elderly.
Dextromethorphan: Debility and hypoxia. May cause respiratory depression and CNS depression in large dose usage or in
patients with impaired respiratory function (eg, asthma, emphysema).
Effects on the Ability to Drive or Operate Machinery: May impair ability to drive or operate machinery.
Use in children: Not recommended for children <2 years.
Hypertension, over weight, impaired liver and kidney function, glaucoma, prostate hypertrophy, hyperthyroid, heart disease,
diabetes mellitus.
Concomitant use with other central nervous system suppressants. Discontinue treatment if insomnia, palpitation and
dizziness occur.
Caution is recommended in pregnancy and lactation and in the elderly.
Effects on the Ability to Drive or Operate Machinery: May impair ability to drive or operate machinery.
Use in children: Not recommended for children <2 years.
Actilyse should be used by physicians experienced in the use of thrombolytic treatment and with facilities to monitor the use.
As with other thrombolytics, it is recommended that when Actilyse is administered, standard resuscitation equipment and
medication be available in all circumstances.
General: Bleeding: The most common complication encountered during Actilyse therapy is bleeding. The concomitant use of
heparin anticoagulant may contribute to bleeding. As fibrin is lysed during Actilyse therapy, bleeding from recent puncture
sites may occur. Therefore, thrombolytic therapy requires careful attention to all possible bleeding sites (including those
following catheter insertion, arterial and venous puncture cut down and needle puncture). The use of rigid catheters, IM
injections and non-essential handling of the patient should be avoided during treatment with Actilyse.
Should serious bleeding occur, in particular cerebral haemorrhage, the fibrinolytic therapy must be discontinued and
concomitant heparin administration should be terminated immediately. Administration of protamine should be considered if
heparin has been administered within 4 hrs before the onset of bleeding. In the few patients who fail to respond to these
conservative measures, judicious use of transfusion products may be indicated. Transfusion of cryoprecipitate, fresh frozen
plasma and platelets should be considered with clinical and laboratory re-assessment after each administration. A target
fibrinogen level of 1 g/L is desirable with cryoprecipitate infusion. Antifibrinolytic agents should also be considered.
A dose >100 mg of Actilyse should not be given in acute myocardial infarction as well as pulmonary embolism and 90 mg in
acute ischaemic stroke because it has been associated with an increase in intracranial bleeding.
No sustained antibody formation to the recombinant human tissue-type plasminogen activator molecule has been observed
after treatment. There is no systemic experience with re-administration of Actilyse. If an anaphylactoid reaction occurs, the
infusion should be discontinued and appropriate treatment should be initiated. Monitoring is recommended particularly for
patients receiving angiotensin-converting enzyme (ACE) inhibitors concomitantly (see Adverse Reactions). As with all
thrombolytics, the use of Actilyse therapy has to be carefully evaluated in order to balance the potential risks of bleeding with
expected benefits under the following conditions: Recent IM injection or small recent traumas eg, biopsies, puncture of major
vessels, cardiac massage for resuscitation; conditions with an increased risk of haemorrhage which are not mentioned under
Contraindications.
For the treatment of acute myocardial infarction and acute pulmonary embolism, caution should be exercised in patients with
systolic blood pressure >160 mmHg; advanced age, which may increase the risk of intracerebral haemorrhage. As the
therapeutic benefit is also increased in elderly patients, the risk-benefit evaluation should be carried out carefully.
For the treatment of acute myocardial infarction, the following precautions apply:
Arrhythmias: Coronary thrombolysis may result in arrhythmia associated with reperfusion.
Glycoprotein IIb/IIIa Antagonists: There is no experience with the use of GP IIb/IIIa antagonists within the first 24 hrs after
start of treatment.
Thromboembolism: The use of thrombolytics can increase the risk of thromboembolic events in patients with left heart
thrombus eg, mitral stenosis or atrial fibrillation.
For the treatment of acute ischaemic stroke, the following precautions apply:
Treatment must be performed only by a physician trained and experienced in neurological care. Compared to other
indications, patients with acute ischaemic stroke treated with Actilyse have a markedly increased risk of intracranial
haemorrhage as the bleeding occurs predominantly into the infarcted area. This applies in particular in the following cases: All
situations listed in Contraindications and in all general situations involving a high risk of haemorrhage; small asymptomatic
Treat hypocalcaemia & other disturbances of bone & mineral metabolism before starting therapy. Maintain adequate Ca & vit
D intake. Severe renal impairment, preexisting GI disease. Pregnancy & lactation.
Additional, specific therapy required in bacterial &/or fungal infections. Avoid contact w/ eyes. Avoid extensive application to
large areas of the body. Glaucoma may develop after large-dosed or extensive application over a prolonged period, occlusive
dressing techniques or application to the skin around the eyes. Childn. Elderly.
Aerius syrup should be used with caution in patients with severe renal insufficiency.
Aerius syrup contains sucrose and sorbitol, thus, patients with rare hereditary problems of fructose intolerance, glucose-
galactose malabsorption or sucrose-isomaltose insufficiency should not take Aerius syrup.
Drug Abuse and Dependence: There is no information to indicate that abuse or dependency occurs with Aerius.
Information for Patients: Patients should be instructed to use Aerius tablets as directed. As there are no food effects on
bioavailability, patients can be instructed that Aerius tablets may be taken without regard to meals. Patients should be advised
not to increase the dose or the dosing frequency as studies have not demonstrated increased effectiveness at higher doses
and somnolence may occur.
Effects on the Ability to Drive or Operate Machinery: No effects on the ability to drive and use machines have been observed.
Carcinogenicity, Mutagenicity & Impairment of Fertility: The carcinogenic potential of desloratadine was assessed using
loratadine studies. In an 18-month study in mice and a 2-year study in rats, loratadine was administered in the diet at doses
up to 40 mg/kg/day in mice (estimated desloratadine and desloratadine metabolite exposures were approximately 3 times the
AUC in humans at the recommended daily oral dose) and 25 mg/kg/day in rats (estimated desloratadine and desloratadine
metabolite exposures were approximately 30 times the AUC in humans at the recommended daily oral dose). Male mice given
loratadine 40 mg/kg/day had a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas)
than concurrent controls. In rats, a significantly higher incidence of hepatocellular tumors (combined adenomas and
carcinomas) was observed in males given 10 mg/kg/day and in males and females given 25 mg/kg/day. The estimated
desloratadine and desloratadine metabolite exposures of rats given loratadine 10 mg/kg were approximately 7 times the AUC
in humans at the recommended daily oral dose. The clinical significance of these findings during long-term use of
desloratadine is not known. In genotoxicity studies with desloratadine, there was no evidence of genotoxic potential in a
reverse mutation assay (Salmonella/E. coli mammalian microsome bacterial mutagenicity assay) or in 2 assays for
chromosomal aberrations (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus
assay).
There was no effect on female fertility in rats at desloratadine doses up to 24 mg/kg/day (estimated desloratadine and
desloratadine metabolite exposures were approximately 130 times the AUC in humans at the recommended daily oral dose).
A male-specific decrease in fertility, demonstrated by reduced female conception rates, decreased sperm numbers and
motility, and histopathologic testicular changes occurred at an oral desloratadine dose of 12 mg/kg in rats (estimated
desloratadine exposures were approximately 45 times the AUC in humans at the recommended daily oral dose).
Desloratadine had no effect on fertility in rats at an oral dose of 3 mg/kg/day (estimated desloratadine and desloratadine
metabolite exposures were approximately 8 times the AUC in humans at the recommended daily oral dose).
Use in pregnancy: Pregnancy Category C: Desloratadine was not teratogenic in rats at doses up to 48 mg/kg/day (estimated
desloratadine and desloratadine metabolite exposures were approximately 210 times the AUC in humans at the
recommended daily oral dose) or in rabbits at doses up to 60 mg/kg/day (estimated desloratadine exposures were
approximately 230 times the AUC in humans at the recommended daily oral dose). In a separate study, an increase in pre-
implantation loss and a decreased number of implantations and fetuses were noted in female rats at 24 mg/kg (estimated
desloratadine and desloratadine metabolite exposures were approximately 120 times the AUC in humans at the
recommended daily oral dose).
Reduced body weight
Patients should and slow
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be discontinued in caseofof=9hypertension,
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tachycardia, palpitationsand
or
cardiac arrhythmias, nausea or any other neurological sign (eg, headache or increased headache).
Central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension may be
produced by sympathomimetic amines. These effects may be more likely to occur in children, elderly patients or in cases of
overdose.
Caution should be exercised in patients receiving digitalis, patients with cardiac arrhythmias, hypertension and with history of
myocardial infarction, diabetes mellitus, bladder neck obstruction or positive anamnesis of bronchospasm.
Use with caution in patients with stenosing peptic ulcer, pyloroduodenal and vesical cervix obstruction.
Patients being treated with other sympathomimetics including decongestants, anorexogenics or amphetamine-type
psychostimulants, antihypertensive agents, tricyclic antidepressants and other antihistamines.
Patients suffering from migraine who are currently being treated with ergot alkaloid vasoconstrictors. Pseudoephedrine
sulfate carries the risk of abuse. Increased doses may ultimately produce toxicity. Continuous use can lead to tolerance
resulting in an increased risk of overdosing. Depression may follow rapid withdrawal.
Perioperative acute hypertension can occur if volatile halogenated anaesthetics are used during treatment with indirect
sympathomimetic agents. Therefore, if surgery is scheduled, it is preferable to discontinue treatment 24 hrs before
anesthesia.
Athletes should be informed that treatment with pseudoephedrine could lead to positive doping test.
The administration of Aerius D-12 should be discontinued at least 48 hrs before skin tests since antihistamines may prevent or
reduce the other.
Use in pregnancy & lactation: There have been no reproduction studies conducted with the combination of desloratadine and
pseudoephedrine. There are no adequate and well-controlled studies in pregnant women.
Desloratadine and pseudoephedrine both pass into breast milk, therefore, a decision should be made whether to discontinue
nursing or to discontinue Aerius D-12 tab taking into account the importance of the drug to the mother.
Patients who may be at risk of increased bleeding from trauma, surgery or other pathological conditions; moderate hepatic
disease who may have bleeding diatheses; renal impairment. Acute ischaemic stroke (<7 days). Patients w/ rare hereditary
problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Pregnancy.
Possibility of lesions or erosions of cartilage in wt bearing joints & other signs of arthropathy.
Avoid a high dose.
A history of upper GI disorders (peptic ulcer). Impaired kidney function. Heart diseases, HTN, or other conditions causing fluid
retention. Blood coagulation disorders. Asthma. SLE. Concomitant use w/ acetosal or other drugs which contain paracetamol
& ibuprofen, or warfarin anticoagulants. Pregnancy & lactation.
Patients requiring Na restriction. Patients w/ cardiac failure, renal insufficiency or chronic anemia at special risk of developing
circulatory overload, dehydration. Monitor BP, MI, serum K, platelet count & prothrombin times. Pregnancy.
IV route only. Monitor central venous pressure, blood coagulation parameters & hematocrit during treatment. Potency of
heart failure. Pregnancy & lactation. Elderly.
Glaucoma, peptic ulcer stenosis, pyloroduodenal obstruction, CV disease, prostatic hypertrophy, HTN, increased IOP or DM.
Elderly.
Sinus syndrome or other supraventricular cardiac conditions; history of ulcer disease, asthma or obstructive pulmonary
disease. Concurrent treatment w/ NSAIDs. Pregnancy & lactation. May impair ability to drive or operate machinery.
Prolonged use may cause posterior subcapsular cataract, glaucoma & increase secondary fungal & viral ocular infections;
suppress body resistance to infections. Avoid abrupt w/drawal. Patients w/ history of psychotic disorder, HTN, gastric ulcer,
diabetes, osteoporosis, fresh diverticulitis & intestinal anastomosis, myasthenia gravis, narrow-angle glaucoma,
pyloroduodenal obstruction, prostate hypertrophy, renal insufficiency. May impair ability to drive or operate machinery.
Pregnancy & lactation.
Severe renal insufficiency. Pregnancy & lactation. Childn <1 yr.
Pemetrexed can suppress bone marrow function as manifested by neutropenia, thrombocytopenia and anaemia (or
pancytopenia) (see Adverse Reactions). Myelosuppression is usually the dose-limiting toxicity. Patients should be monitored
for myelosuppression during therapy and pemetrexed should not be given to patients until absolute neutrophil count (ANC)
returns to =1,500 cells/mm3 and platelet count returns to =100,000 cells/mm3. Dose reductions for subsequent cycles are
based on nadir ANC, platelet count and maximum non-haematologic toxicity seen from the previous cycle (see Dosage &
Administration).
Less toxicity and reduction in Grade 3/4 haematologic and non-haematologic toxicities eg, neutropenia, febrile neutropenia
and infection with Grade 3/4 neutropenia were reported when pre-treatment with folic acid and vitamin B12 was
administered. Therefore all patients treated with pemetrexed must be instructed to take folic acid and vitamin B12 as a
prophylactic measure to reduce treatment-related toxicity (see Dosage & Administration).
Skin reactions have been reported in patients not pre-treated with a corticosteroid. Pre-treatment with dexamethasone (or
equivalent) can reduce the incidence and severity of skin reactions (see Dosage & Administration).
An insufficient number of patients has been studied with CrCl of <45 mL/min. Therefore, the use of pemetrexed in patients
with CrCl of <45 mL/min is not recommended (see Dosage & Administration).
Patients with mild to moderate renal insufficiency (CrCl 45-79 mL/min) should avoid taking nonsteroidal anti-inflammatory
drugs (NSAIDs) eg, ibuprofen, aspirin (>1.3 g daily) for 2 days before, on the day of and 2 days following pemetrexed
administration (see Interactions).
In patients with mild to moderate renal insufficiency eligible for pemetrexed therapy NSAIDs with long elimination t½ should
be interrupted for at least 5 days prior to, on the day of, and at least 2 days following pemetrexed administration (see
Interactions).
Serious renal events, including acute renal failure, have been reported with pemetrexed alone or in association with other
chemotherapeutic agents. Many of the patients in whom these occurred had underlying risk factors for the development of
renal events including dehydration or preexisting hypertension or diabetes.
The effect of third space fluid, eg pleural effusion or ascites, on pemetrexed is not fully defined. A phase 2 study of
pemetrexed in 31 solid tumour patients with stable 3rd space fluid demonstrated no difference in pemetrexed dose
normalized plasma concentrations or clearance compared to patients without 3rd space fluid collections. Thus, drainage of
3rd space fluid collection prior to pemetrexed treatment should be considered, but may not be necessary.
Due to the gastrointestinal toxicity of pemetrexed given in combination with cisplatin, severe dehydration has been observed.
Therefore, patients should receive adequate antiemetic treatment and appropriate hydration prior to and/or after receiving
treatment.
Serious cardiovascular events, including myocardial infarction and cerebrovascular events have been uncommonly reported
during clinical studies with pemetrexed, usually when given in combination with another cytotoxic agent. Most of the patients
in whom these events have been observed had preexisting cardiovascular risk factors (see Adverse Reactions).
Immunodepressed status is common in cancer patients. As a result, concomitant use of live attenuated vaccines is not
recommended (see Contraindications and Interactions).
Cases of radiation pneumonitis have been reported in patients treated with radiation either prior, during or subsequent to
their pemetrexed therapy. Particular attention should be paid to these patients and caution exercised with use of other
radiosensitising agents.
Alinamin-F: Ampoule: Sometimes, anaphylactic shock may occur.
Cardiac disease; diabetes; glaucoma; pregnancy. May impair ability to drive or operate machinery.
Inspect dressing frequently. Not to be used with oxidising agents eg, hypochlorite soln or hydrogen peroxide.
Sick-sinus syndrome, supraventricular cardiac conductions, history of ulcer disease, asthma or obstructive pulmonary disease.
Discontinue gradually over a min of 1 wk. May affect ability to drive or operate machinery. Pregnancy & lactation. Childn <12
yr.
Avoid single dose treatment in depression or combined anxiety-depression. Pregnancy & lactation, chronic renal & liver
disorders, resp disorder, atrophy & patients who are prone to abuse drugs. Childn <10 yr, geriatric & debilitated patients.
Avoid long-term treatment. May impair ability to drive or operate machinery.
Renal insufficiency.
May impair the process of granulocytic defense cells (macrophages, leukocytes) phagocyte lipid emulsions in the presence of
pneumonia &/or sepsis. Monitor arterial blood gases, inspired oxygen fraction & ventilatory change to ensure appropriate
adjustments. Episodes of bradycardia & decreased oxygen saturation may occur during the dosing procedure.
Abuse-prone individuals. Renal or hepatic dysfunction. Patients whose primary diagnosis is schizophrenia. Depressed or
suicidal patients. Pregnancy, lactation. Childn <18 yr. Avoid abrupt discontinuation. May affect ability to drive or operate
machinery.
Diabetes.
Sick sinus syndrome, conduction defects, asthma, COPD, pregnancy, lactation. Patients receiving NSAIDs.
Regular monitoring of glucose levels in blood & urine. Milder or absent symptoms of hypoglycaemia eg in patients w/
autonomic neuropathy or taking ß-blockers, clonidine, reserpine, guanethidine or other sympatholytics. Temporary
changeover to insulin in exceptional stress situations (trauma, surgery, febrile infections).
To achieve optimal control of blood sugar, a correct diet, regular and sufficient physical exercise and if necessary, reduction of
body weight are just as important as regular intake of Amaryl. Clinical signs of hyperglycaemia are increased urinary
frequency, intense thirst, dryness of the mouth and dry skin.
When starting treatment, the patient must be informed about the effects and risks of Amaryl and about its role in conjunction
with dietary measures and physical exercise; the importance of adequate cooperation must also be stressed.
In the initial weeks of treatment, the risk of hypoglycaemia may be increased and necessitates especially careful monitoring.
Factors favouring hypoglycaemia include: Unwillingness or (more commonly in older patients) incapacity of the patient to
cooperate; undernutrition, irregular mealtimes or skipped meals; imbalance between physical exertion and carbohydrate
intake; alterations of diet; consumption of alcohol, especially in combination with skipped meals; impaired renal function;
severe impairment of liver function; overdosage with Amaryl; certain uncompensated disorders of the endocrine system
affecting carbohydrate metabolism or counter-regulation of hypoglycaemia (eg, in certain disorders of thyroid function and in
anterior pituitary or adrenocortical insufficiency); concurrent administration of certain other medicines (see Interactions).
The physician must be informed about such factors and about hypoglycaemic episodes, since these require particularly careful
monitoring.
If such risk factors for hypoglycaemia are present, it may be necessary to adjust the dosage of Amaryl or the entire therapy.
This also applies whenever illness occurs during therapy or the patient's lifestyle changes.
Those symptoms of hypoglycaemia which reflect the body's adrenergic counter-regulation (see Adverse Reactions) may be
milder or absent in those situations where hypoglycaemia develops gradually in the elderly and in patients with a certain type
of nervous disease (autonomic neuropathy) or those receiving concurrent treatment with ß-blockers, clonidine, reserpine,
guanethidine or other sympatholytic drugs.
Hypoglycaemia can almost always be promptly controlled by immediate intake of sugar eg, in the form of glucose, sugar cubes
or sugar-sweetened beverages. Patients should always carry at least 20 g of glucose with them for this purpose (food or
beverages containing artificial sweeteners eg, diet foods or drinks, are ineffective in controlling hypoglycaemia). They may
require the assistance of other persons to avoid complications.
It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycaemia may recur. Therefore,
continued close observation is necessary. Severe hypoglycaemia requires, in addition, immediate treatment and follow-up by
a physician and, in some circumstances, hospitalization.
If treated by different physicians (eg, upon admission to hospital after an accident, illness while on holiday), the patients must
inform them of their diabetic condition and previous treatment.
In exceptionally stressful situations (eg, trauma, surgery, infections with fever), blood sugar control may deteriorate and a
temporary change to insulin may be necessary.
During treatment with Amaryl, fasting glucose levels in blood and urine must be checked regularly, as should, additionally, the
proportion of glycosylated haemoglobin. Usually every 3-6 months to more precisely assess long-term glycaemic control.
Effects on the Ability to Drive or Operate Machinery: Alertness and reactions may be impaired due to hypo- or
hyperglycaemia, especially when beginning or after altering treatment or when Amaryl is not taken regularly. Such
impairment may for example, affect the ability to operate a vehicle or machinery.
Use in Children: Safety and effectiveness in paediatric patients have not been established.
Adequate blood glucose levels should be maintained concomitantly by diet and exercise, if necessary by weight loss as well as
by taking Amaryl M regularly. Clinical signs of not adequately controlled blood glucose levels include oliguria, thirst, dipsia, dry
skin, etc.
Patients should be informed of the potential risks and advantage of Amaryl M. They should also be informed about the
importance of adherence to dietary instructions and of a regular exercise program. It should be emphasized that patient's
positive cooperation is important.
Hypoglycemia can almost always be promptly controlled by immediate intake of carbohydrates (glucose or sugar eg, lump
sugar, fruit juice and tea including sugar, etc). Patients should carry approximately at least 20 g of sugar for this. Others help
may be necessary to avoid complications. Artificial sweeteners have no effect.
It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycemia may recur. Patients
must, therefore, remain under close observation. Severe hypoglycemia further requires immediate treatment and follow-up
by a physician in some circumstances, inpatient hospital care.
If a patient receives a treatment from other physician or pharmacist (eg, hospitalization, accident, needed to see a doctor,
etc), he should inform him of his current diabetic situation and previous treatment.
In exceptional stress-situations (eg, trauma, surgery, febrile infections) blood glucose regulation may deteriorate and a
temporary change to insulin may be necessary to maintain good metabolic control.
The dosage of Amaryl M must be the lowest. Treatment requires regular monitoring of glucose levels in blood and urine. (In
addition, determination of the proportion of glycosylated hemoglobin is recommended.) The effectiveness of therapy should
be assessed and if not satisfactory, switch to another therapy should be promptly made.
Alertness and reactions may be impaired due to hypo- or hyperglycemia, especially when beginning or after altering
treatment or when Amaryl M is not taken regularly. This may affect the ability to drive or to operate machinery.
Monitoring of Renal Function: Amaryl M is known to be substantially excreted by the kidney, and the risk of metformin
accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum
creatinine levels above the upper limit of normal for their age should not receive this drug. In patients with advanced age,
Amaryl M should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is
associated with reduced renal function. In elderly patients, renal function should be monitored regularly and generally,
Amaryl M should not be titrated to the maximum dose.
Use of Concomitant Medications that may Affect Renal Function or Metformin Disposition: Concomitant medication(s) that
may affect renal function or result in significant hemodynamic change or may interfere with the disposition of Amaryl M eg,
cationic drugs that are eliminated by renal tubular secretion, should be used with caution.
Radiologic studies involving the use of intravascular iodinated contrast materials (eg, IV urogram, IV cholangiography,
angiography and computed tomography (CT) scans with contrast materials): Intravascular contrast studies iodinated materials
can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving this drug (see
Contraindications). Therefore, in patients in whom any such study is planned, Amaryl M should be discontinued at the time of
or prior to the procedure, and withheld for 48 hrs, subsequent to the procedure and reinstituted only after renal function has
been re-evaluated and found to be normal.
Hypoxic States: Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, acute myocardial
infarction and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause pre-
Hypersensitivity to cephalosporins. Renal impairment. Prolonged treatment requires assessment of renal, hepatic &
hematopoietic function.
Hepatic Impairment: As with all calcium antagonists, amlodipine half-life is prolonged in patients with impaired liver function
and dosage recommendations have not been established. Amcor should therefore be administered with caution in these
patients.
Renal Failure: Amlodipine is extensively metabolized to inactive metabolites with 10% excreted as unchanged drug in the
urine. Changes in amlodipine plasma concentrations are not correlated with the degree of renal impairment. Amlodipine may
be used in such patients at normal doses. Amlodipine is not dialyzable.
Congestive Heart Failure: In general, calcium-channel blockers should be used with caution in patients with heart failure.
Use in pregnancy & lactation: Safety of amlodipine in human pregnancy or lactation has not been established. Amlodipine
does not demonstrate toxicity in animal reproductive studies other than to delay parturition and prolong labor in rats at a
dose level 50 times the maximum recommended dose in humans. Accordingly, use in pregnancy and lactation is
recommended only when there is no safer alternative and when the disease itself carries greater risk for the mother and
fetus.
Use in the elderly: The time to reach peak plasma concentrations of amlodipine is similar in elderly and younger subjects.
Amlodipine clearance tends to be decreased with resulting increases in area under the curve (AUC) and elimination half-life in
elderly patients. Increases in AUC and elimination half-life in patients with congestive heart failure were as expected for the
patient age group studied. Amlodipine, used at a similar doses in elderly or younger patients, is equally well tolerated.
Therefore, normal dosage regimens are recommended.
Ensure adequate calorie intake (35-40 kCal/kg/day). Monitor serum Ca level periodically. Pregnancy & lactation. Childn.
Careful administration of Aminofluid should be observed in the following patients: Patients with hepatic disorder (water and
electrolyte metabolism may be worsened).
Patients with renal disorder (since the patients have reduced water and electrolyte control, the solution should be
administered with care).
Patients with cardiovascular dysfunction (an increase in the circulating blood volume may worsen the patient's clinical
condition).
Patients with acidosis (the patient's clinical condition may be worsened).
Patients with diabetes mellitus (inhibited uptake of glucose into the tissues may cause hyperglycemia, which may worsen the
patient's clinical condition).
Important Precaution: Aminofluid contains amino acids 15 g (nitrogen 2.35 g) and 150 kCal in 500 mL. However, daily calorie
requirements cannot be met by only administering this solution as the sole source of nutrition. Thus, this solution should be
used for short-term nutrition therapy.
When used as a nutritional supplement in patients whose oral intake is inadequate, the solution should be used based on the
overall assessment of the patient's nutritional requirements and oral intake.
When this solution is used alone postoperatively, its use shoud be limited to 3-5 days and oral/enteral nutrition or other
regimens should be started as soon as it is feasible to do so.
Use in pregnancy & lactation: The safety in pregnant women has not been established. Aminofluid should be used in pregnant
women and women who may possibly be pregnant only if the therapeutic benefits outweigh the possible risks associated
with treatment.
Use in children: The safety in children has not been established (no clinical experience).
Use in the elderly: Since elderly patients often have reduced physiological function and associated hepatic, renal or cardiac
dysfunction, it is advisable to take such measures as reducing the dose by decreasing the infusion rate under careful
supervision.
Careful administration in patients with severe acidosis and congestive heart failure.
Use with electrolyte solution and administration of the solution in large doses require careful supervision of electrolyte
balance.
Use in children: The safety of Aminoleban Infusion in children has not been established.
Careful checking should be done for urine volume not less than 60-70 mL/hr and re-examination of dosage schedule is
necessary when the volume falls below the level.
Caution For Usage Take special care in handling instruments for injection as these preparations are liable to propagate
microorganisms.
Use immediately after breaking the seal and do not use the remaining solution.
Patients w/ impaired kidney function. Adjust or discontinue use if renal impairment, vestibular or hearing disturbances occur.
Prolonged use. Pregnancy & lactation.
Acetic acid is formulated in an amount of about 120 mEq/L. Concomitant use of the solution with electrolyte solutions and
administration of the solution in large doses require careful supervision of electrolyte balance.
Administer by slow infusion.
Careful Administration: Patients with severe acidosis, congestive heart failure and hyponatremia.
Use in children: The safe use of Amiparen in immature infants, newborns and infants has not yet been established.
Cerebrovascular dysfunction, hepatic disorder or GI bleeding, severe acidosis or electrolyte imbalance or abdominal acid-base
balance. Pregnancy. Childn. Elderly.
Liver dysfunction, kidney failure. Pregnancy & lactation. Elderly.
Check for urine vol not <60-70 mL/hr & re-examine dosage schedule when vol falls below the level.
Periodically assess renal, hepatic & haematopoietic functions during prolonged therapy. Maintain adequate fluid intake &
urinary output during high-dose treatment. Check indwelling catheters regularly for patency. Pregnancy & lactation.
HTN, ocular herpes simplex, cirrhosis, hypothyroidism, nonspecific ulcerative colitis, DM.
HTN, ocular herpes simplex, cirrhosis, hypothyroidism, nonspecific ulcerative colitis, DM.
Lactation.
Hepatic & renal dysfunction, severely depressed patients, blood disorders.
Moderate or severe renal/resp insufficiency, moderate or severe hepatic impairment, patients susceptible to seizure, opioid
dependence, cranial trauma, convulsive disorder, biliary tract disorder, under altered state of conciousness, resp center
problem. May affect ability to drive or operate machinery. Childn <16 yr.
Hypersensitivity to penicillins, renal impairment & colitis, prolonged use, superinfections. Pregnancy & lactation.
Moderate or severe renal impairment, severe hepatic dysfunction, prolonged use. Pregnancy (especially 1st trimester) &
lactation.
Avoid contact w/ eyes or mucous membranes. Burning sensation or efflorescence, chickenpox or morbilli. Childn. Prolonged
use may cause skin irritation.
Should not be used as monotherapy for megaloblastic anemia associated w/ vit B12 deficiency.
Elderly or debilitated patients w/ chronic renal failure, CHF. Impaired hepatic function, myasthenia gravis. May affect ability to
drive or operate machinery at least 12 hr after IV administration. Pregnancy & lactation. Infant & neonate. Childn <18 yr.
Angioedema unrelated to ACE inhibitor therapy; CHF w/ or w/o associated renal insufficiency.
Controlled epilepsy, renal & hepatic impairment, acute cardiac failure, may impair ability to drive or operate machinery.
Cardiac disease, diabetes; glaucoma; impaired kidney or liver function; pregnancy; may impair ability to drive or operate
machinery. Childn <6 yr.
CV thrombotic events, HTN, CHF, prior history of ulcer disease or GI bleeding & toxicity, impaired renal function, heart failure,
liver dysfunction, taking diuretics & ACE inhibitors. Monitor renal function & blood count. Concomitant use w/ systemic
NSAIDs including COX-2 selective inhibitors; rare hereditary problems of fructose intolerance, glucose-galactose
malabsorption or sucrose-isomaltase insufficiency; ulcerative colitis or Crohn's disease; impaired hepatic function; hepatic
porphyria. May impair female fertility. May affect ability to drive or operate machinery. Elderly.
Rare hereditary problems of galactose intolerance Lapp lactase deficiencies, glucose-galactose malabsorption. May affect the
ability to drive or operate the machinery. Pregnancy & lactation. Childn <12 yr. Elderly >65 yr.
Intravascular Volume Depletion: Symptomatic hypotension, especially after the 1st dose, may occur in patients who are
volume- and/or sodium-depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions
should be corrected before the administration of Aprovel.
Renovascular Hypertension: There is an increased risk of severe hypotension and renal insufficiency when patients with
bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with drugs that affect the
renin-angiotensin-aldosterone system. While this is not documented with Aprovel, a similar effect should be anticipated with
angiotensin II receptor antagonists.
Renal Impairment and Kidney Transplantation: When Aprovel is used in patients with impaired renal function, a periodic
monitoring of potassium and creatinine serum levels is recommended. There is no experience regarding the administration of
Aprovel in patients with a recent kidney transplantation.
Hypertensive Patients with Type 2 Diabetes and Renal Disease: The effects of irbesartan both on renal and cardiovascular
events were not uniform across all subgroups, in an analysis carried out in the study with patients with advanced renal
disease. In particular, they appeared less favourable in women and non-white subjects (see Pharmacology under Actions).
Hyperkalemia: As with other drugs that affect the renin-angiotensin-aldosterone system, hyperkalemia may occur during the
treatment with Aprovel, especially in the presence of renal impairment, overt protenuria due to diabetic renal disease and/or
heart failure. Close monitoring of serum potassium in patients at risk is recommended (see Interactions).
Lithium: The combination of lithium and Aprovel is not recommended (see Interactions).
Aortic and Mitral Valve Stenosis, Obstructive Hypertrophic Cardiomyopathy: As with other vasodilators, special caution is
indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Primary Aldosteronism: Patients with primary aldosteronism generally will not respond to antihypertensive drugs acting
through inhibition of the renin-angiotensin-aldosterone system. Therefore, the use of Aprovel is not recommended.
General: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-
aldosterone system (eg, patients with severe congestive heart failure or underlying renal disease, including renal artery
stenosis), treatment with ACE inhibitors or angiotensin II receptor antagonists that affect this system has been associated with
acute hypotension, azotaemia, oliguria or rarely, acute renal failure. As with any antihypertensive agent, excessive blood
pressure decrease in patients with ischaemic cardiopathy or ischaemic cardiovascular disease could result in a myocardial
infarction or stroke.
As observed for ACE inhibitors, irbesartan and the other angiotensin antagonists are apparently less effective in lowering
blood pressure in Black people than in non-Blacks, possibly because of higher prevalence of low-renin states in the Black
hypertensive population (see Pharmacology under Actions).
Lactose: Aprovel contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency
or glucose-galactose malabsorption should not take this medicinal product.
Effects on the Ability to Drive or Operate Machinery: The effects of irbesartan on the ability to drive and use machines has not
been studied, but based on its pharmacodynamic properties, irbesartan is unlikely to affect this ability. When driving vehicles
or operating machines, it should be taken into account that dizziness or weariness may occur during treatment.
Use in Pregnancy: Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued
AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive
treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with
GI disorders, severe hepatic impairment; impaired cardiac or renal function; patients treated w/ diuretics; extracellular vol
depletion. Pregnancy. Elderly.
Use in pregnancy: No fetal toxicity or malformation has been reported. However, follow-up of women exposed to
sulbutiamine during pregnancy is insufficient to exclude such a risk. Therefore, as a precautionary measure, it is preferable not
to use this drug during pregnancy.
Use in lactation: In the absence of data concerning the diffusion into breast milk, breastfeeding is not recommended during
treatment.
Hypersensitivity to cephalosporins. Renal impairment.
Clinical trial suggests that the selective COX-2 inhibitor class of drugs may be associated with an increased risk of thrombotic
events (especially MI and stroke), relative to placebo and some NSAIDs (naproxen). As the cardiovascular risks of selective
COX-2 inhibitors may increase with dose and duration of exposure, the shortest duration possible and the lowest effective
daily dose should be used. The patients need symptomatic relief and response to therapy should be re-evaluated periodically.
Patients with significant risk factors for cardiovascular events (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking) or
peripheral arterial disease should only be treated with etoricoxib after careful consideration.
Selective COX-2 inhibitors are not a substitute for aspirin for cardiovascular prophylaxis because of their lack of effect on
platelets. Because etoricoxib does not inhibit platelet aggregation, antiplatelet therapies should not be discontinued.
There is a further increase in the risk of GI adverse effects (GI ulceration or other GI complications) for etoricoxib, other
selective COX-2 inhibitors and NSAIDs, when taken concomitantly with acetylsalicylic acid (even at low doses). The relative
differences in gastrointestinal safety between selective COX-2 inhibitors + acetylsalicylic acid vs NSAIDs + acetylsalicylic acid
has not been adequately evaluated in long term clinical trials.
In patients with advanced renal disease, treatment with Arcoxia is not recommended. Clinical experience in patients with
estimated CrCl of <30 mL/min is very limited. If therapy with Arcoxia must be initiated in such patients, close monitoring of
the patient's renal function is advisable.
Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore, under conditions of
compromised renal perfusion, administration of Arcoxia may cause a reduction in prostaglandin formation and secondarily, in
renal blood flow and thereby impair renal function. Patients at greatest risk of this response are those with preexisting
significantly impaired renal function, uncompensated heart failure or cirrhosis. Monitoring of renal function in such patients
should be considered. As with other drugs known to inhibit prostaglandin synthesis, discontinuation of therapy with Arcoxia
would be expected to be followed by recovery to the pre-treatment state.
Caution should be used when initiating treatment with Arcoxia in patients with considerable dehydration. It is advisable to
rehydrate patients prior to starting therapy with Arcoxia.
As with other drugs known to inhibit prostaglandin synthesis, fluid retention, edema and hypertension have been observed in
some patients taking Arcoxia. The possibility of fluid retention, edema or hypertension should be taken into consideration
when Arcoxia is used in patients with preexisting edema, hypertension or heart failure.
Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs and selective COX-2
inhibitors, particularly at high doses. Therefore, special attention should be paid to blood pressure monitoring during
treatment with etoricoxib. If blood pressure rises significantly, alternative treatment should be considered.
Caution should be exercised in patients with a medical history of ischemic heart disease because of the pharmacodynamic
profile of COX-2 selective inhibitors noted previously.
Physicians should be aware that individual patients may develop upper GI ulcer complications irrespective of treatment. In
clinical studies, the risk of endoscopically detected upper GI ulcers was lower in patients treated with Arcoxia 120 mg once
daily than in patients treated with nonselective NSAIDs. While the risk of endoscopically detected ulcers was lower in patients
treated with Arcoxia 120 mg than in patients treated with placebo. Upper GI ulcer complications have occurred in patients
treated with Arcoxia. Independent of treatment, patients with a prior history of GI perforation, ulcers and bleeding (PUB) and
patients >65 years are known to be at a higher risk for a PUB.
Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately =3 times the upper limit
Lactation.
May cause a variety type of allergic reactions, including anaphylaxis or asthma in patients w/ sensitivity.
Avoid use w/ occlusive dressing & intensive prolonged treatment, superinfection may occur. Pregnancy & lactation. Childn <2
yr.
Sick sinus syndrome, supraventricular cardiac conduction conditions; history of ulcer disease, asthma or obstructive
pulmonary disease.
Underlying cardiac condition abnormalities, history of ulcer disease or those receiving concurrent NSAIDs, history of asthma
or obstructive pulmonary disease. May impair ability to drive or operate machinery. Pregnancy & lactation.
History of upper GI diseases, liver or kidney dysfunction, CHF, hypovolemia, dehydration, receiving anticoagulants or diuretic
therapy.
The menopause should be defined biochemically [luteinizing-hormone (LH), follicle stimulating hormone (FSH) and/or
estradiol levels] in any patient where there is doubt about hormonal status. There are no data available for the use of
Arimidex with luteinizing hormone releasing hormone (LHRH) analogues. This combination should not be used outside clinical
trials.
There are no data to support the safe use of Arimidex in patients with moderate or severe hepatic impairment, or patients
with severe impairment of renal function (CrCl <20 mL/min).
As Arimidex lowers circulating estrogen levels, it may cause a reduction in bone mineral density with a possible consequent
increase risk of fractures. This possible increased risk should be managed according to treatment guidelines for managing
bone health in postmenopausal women.
Women with osteoporosis or at risk of osteoporosis should have their bone mineral density formally assessed by bone
densitometry at the commencement of treatment and at regular intervals thereafter. Treatment or prophylaxis for
osteoporosis should be initiated as appropriate and carefully monitored.
Arimidex contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp-lactase deficiency or glucose-
galactose malabsorption should not take Arimidex.
Effects on the Ability to Drive or Operate Machinery: Arimidex is unlikely to impair the ability of patients to drive and operate
machinery. However, asthenia and somnolence have been reported with the use of Arimidex and caution should be observed
when driving or operating machinery while such symptoms persist.
Use in children: Arimidex is not recommended for use in children as safety and efficacy have not been established in this
group of patients.
Orthostatic hypotension, CV disease (history of MI or ischemic heart disease, heart failure or conduction abnormalities),
cerebrovascular disease, dehydration & hypovolemia. Seizure, alzheimer's disease. May impair judgement, thinking.
Reduction of core body temp. Dysphagia. Heat exposure & dehydration. Neuroleptic malignant syndrome (NMS). Tardive
dyskinesia. May impair ability to drive or operate machinery. Pregnancy & lactation. Childn. Elderly.
Route of Administration: Arixtra must not be administered IM (see Dosage & Administration).
Percutaneous Coronary Intervention (PCI) and Risk of Guiding Catheter Thrombus: In STEMI patients undergoing primary PCI
for reperfusion, the use of Arixtra prior to and during PCI is not recommended. Similarly, in UA/NSTEMI patients with life-
threatening conditions that require urgent revascularization, the use of Arixtra prior to and during PCI is not recommended.
These are patients with refractory or recurrent angina associated with dynamic ST deviation, heart failure, life-threatening
arrhythmias or haemodynamic instability. In UA/NSTEMI and STEMI patients undergoing non-primary PCI, the use of Arixtra
as the sole anticoagulant during PCI is not recommended, therefore UFH should be used according to local practice (see
Dosage & Administration).
There are limited data on the use of UFH during non-primary PCI in patients treated with Arixtra (see Clinical Studies under
Actions).
In those patients who underwent non-primary PCI 6-24 hrs after the last dose of Arixtra, the median dose of UFH was 8000 IU
and the incidence of major bleeding was 2% (2/98). In those patients who underwent non-primary PCI <6 hrs after the last
dose of Arixtra, the median dose of UFH was 5000 IU and the incidence of major bleeding was 4.1% (2/49).
Clinical trials have shown a low but increased risk of guiding catheter thrombus in patients treated with Arixtra for
anticoagulation during PCI compared to control. Incidences in non-primary PCI in UA/NSTEMI were 1% versus 0.3% (Arixtra vs
enoxaparin) and in primary PCI in STEMI were 1.2% versus 0% (Arixtra vs control).
Haemorrhage: Arixtra, like other anticoagulants should be used with caution in conditions with an increased risk of
hemorrhage (eg, congenital or acquired bleeding disorders, active ulcerative gastrointestinal disease, recent intracranial
hemorrhage; shortly after brain, spinal or ophthalmic surgery).
Agents that may enhance the risk of hemorrhage should not be administered concomitantly with fondaparinux. These agents
include desirudin, fibrinolytic agents, GPIIb/IIIa receptor antagonists, heparin, heparinoids or Low Molecular Weight Heparin
(LMWH). Other antiplatelet medicinal products (acetylsalicylic acid, dipyridamole, sulfinpyrazone, ticlopidine or clopidogrel)
and NSAIDs should be used with caution. If co-administration is essential, close monitoring is necessary.
Prevention of VTE: Other medicinal products enhancing the risk of haemorrhage, with the exception of vitamin K antagonists
used concomitantly for treatment of VTE, should not be administered with Arixtra. If co-administration is essential, close
monitoring is recommended (see Interactions).
Prevention of VTE Following Surgery (Timing of 1st Arixtra Injection): The timing of the 1st injection requires strict adherence.
The 1st dose should be given no earlier than 6 hrs following surgical closure and only after haemostasis has been established.
Administration before 6 hrs has been associated with an increased risk of major bleeding. Patient groups at particular risk are
those =75 years, body weight of <50 kg or renal impairment with CrCl <50 mL/min.
Treatment of UA/NSTEMI and STEMI: Arixtra should be used with caution in patients who are being treated concomitantly
with other medicinal products that increase the risk of haemorrhage (eg, GPIIb/IIIa inhibitors or thrombolytics).
Spinal/Epidural Anaesthesia/Spinal Puncture: Epidural or spinal haematomas that may result in long-term or permanent
paralysis can occur with the use of anticoagulants and spinal/epidural anaesthesia or spinal puncture. The risk of these rare
events may be higher with postoperative use of indwelling epidural catheters or the concomitant use of other medicinal
products affecting haemostasis.
Low Body Weight: Patients with body weight <50 kg are at increased risk of bleeding. Elimination of Arixtra decreases with
weight decrease.
Tachycardia, Arixtra should
thyrotoxicosis, be used with caution
MI, hyperpyrexia, renal & in thesedisease.
hepatic patientsChildn.
(see Dosage & Administration).
Elderly.
Not for women w/ premenopausal endocrine status. Postmenopausal status ascertained by assessment of LH, FSH &
oestradiol levels. Assess bone mineral density in women w/ osteoporosis or at risk of osteoporosis. Consider routine
assessment of 25 hydroxy vit D levels prior to start of aromatase inhibitor treatment. Reduction in bone mineral density.
Hepatic or renal impairment. May impair ability to drive or operate machinery. Childn.
In combination w/ other ophth soln, instil as last w/ an interval of at least 10 min following instillation of other ophth soln.
Patients at risk of increased bleeding from trauma, surgery or other pathological conditions. Moderate hepatic disease,
bleeding diatheses; renal impairment.
Hepatic or renal impairment. Patients w/ SLE. Asthma. History of upper GI diseases. Peptic ulcer. History of heart failure. CV
diseases, HTN, other diseases which can cause fluid retention. Bleeding disorders. Elderly. Pregnancy & lactation. Childn <1 yr.
History of upper GI disease (peptic ulcer), kidney dysfunction, blood coagulation disorders, heart failure, HTN, other diseases
which lead to fluid retention, SLE. Lactation. Childn <12 yr.
Pregnancy & lactation.
Clinical evaluation eg, periodical monitoring of serum ionogram, water and acid-base balance should be done in long-term
use. Caution should be taken when administering to children, elderly, hypertensive patients and pregnancy toxemia. Do not
administer together with blood transfusion as it may cause precipitation.
Patients in whom aspirin & other NSAIDs precipitate symptoms of bronchospasm, allergic rhinitis or urticaria. Pregnancy.
Childn <14 yr.
Patients w/ hypoxemia, renal & hepatic disorder. Pregnancy, lactation. Childn & elderly.
Esophageal passage disturbance. Penicillin allergy. Pregnancy, lactation.
Thyrotoxicosis, HTN, CV dysfunction, hyperthyroidism & DM. Pregnancy & lactation. Childn <2 yr.
Avoid single-dose treatment in depression or combined anxiety-depression. Chronic renal & liver disorders, resp disorder,
atrophy & patients who are prone to abuse drugs. Childn <10 yr, geriatric & debilitated patients. Avoid long-term treatment.
May impair ability to drive or operate machinery. Pregnancy & lactation.
Hyperthyroidism, HTN, heart disease, DM. Pregnancy & lactation. Elderly, childn.
Perform liver function test prior initiation, 12 wk after, during evaluation of dose & periodically thereafter; patient w/ diffuse
myalgias, muscle tenderness or weakness &/or marked elevation of CPK. Promptly report unexplained muscle pain,
tenderness or weakness, especially if accompanied w/ malaise or fever. Discontinue use in case of markedly elevated CPK
levels, diagnosed or suspected myopathy or w/ risk factor to development of renal failure secondary to rhabdomyolysis.
Perform liver function test prior to initiation, 12 wk after treatment initiation, during dose evaluation & periodically thereafter.
Alcohol consumption, active or history of liver disease, unexplained persistent transaminases elevation; diffuse myalgia,
muscle tenderness or weakness &/or marked CPK elevation. Discontinue use in case of markedly elevated CPK levels,
diagnosed or suspected myopathy or w/ risk factor predisposing to development of renal failure secondary to rhabdomyolysis.
Hepatic Effects: As with other lipid-lowering agents of the same class, moderate [>3 x upper limit of normal (ULN)] elevations
of serum transaminases have been reported following therapy with atorvastatin. Liver function was monitored during pre-
marketing as well as post-marketing clinical studies of atorvastatin given at doses of 10, 20, 40, and 80 mg.
Persistent increases in serum transaminases (>3 x ULN on =2 occasions) occurred in 0.7% of patients who received
atorvastatin in these clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% for 10, 20, 40 and 80
mg respectively. One (1) patient in clinical trials developed jaundice.
Increases in liver function tests (LFT) in other patients were not associated with jaundice or other clinical signs or symptoms.
When the dosage of atorvastatin was reduced or drug treatment interrupted or discontinued, transaminase levels returned to
pretreatment levels. Most patients continued treatment on a reduced dose of atorvastatin without sequelae. LFT elevation
continued treatment with a reduced dose of atorvastatin.
Liver function tests should be performed before the initiation of treatment and periodically thereafter. Patients who develop
any signs or symptoms suggesting liver injury should have liver function test performed. Patients who develop increased
transaminase levels should be monitored until the abnormality (ies) resolve(s). Should an increase in ALT or AST of >3 times
the ULN persist, reduction of dose or withdrawal of atorvastatin is recommended.
Atorvastatin can cause an elevation in transaminases (see Adverse Reactions).
Atorvastatin should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of
liver disease. Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of
atorvastatin (see Contraindications).
Skeletal Muscle Effects-Myalgia has been reported in atorvastatin-treated patients (see Adverse Reactions). Myopathy, defined
as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values >10 x ULN, should
be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK.
Patients should be advised to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied
by malaise of fever. Atorvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is
diagnosed or suspected.
The risk of myopathy during treatment with drugs in this class is increased with concurrent administration of cyclosporine,
fibric acid derivatives, erythromycin, niacin or azole antifungals. Many of these drugs inhibit cytochrome P-450 and 3A4
metabolism and/or drug-transport. Atorvastatin is biotransformed by CYP 3A4. Physicians considering combined therapy with
atorvastatin and fibric acid derivatives, erythromycin, immunosuppressive drugs, azole antifungals or lipid-lowering doses of
niacin should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and
symptoms of muscle pain, tenderness or weakness, particularly during the initial months of therapy and during any periods of
upward dosage titration of either drug. Periodic creatine phosphokinase (CPK) determinations may be considered in such
situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy (see Interactions).
Atorvastatin may cause an elevation of CPK (see Adverse Reactions).
As with other drugs in this class, rare cases of rhabdomyolysis with acute renal failure, secondary to myoglobinuria has been
reported.
Atorvastatin therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition
suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis
(eg, severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders and
History of upper GI diseases; patients receiving antihemostatic therapy or diuretic. Discontinue if peptic ulcer or GI bleeding
occurs. Patients w/ dehydration, CHF, liver cirrhosis, nephrotic syndrome, kidney diseases. Post-op patients w/ tendency of
hypovolemia. Debilitated patients & elderly.
Atrovent 0.025% inhalant solution contains the (antimicrobial) preservative benzalkonium chloride and the stabiliser disodium
edetate. It has been shown that these components may cause bronchoconstriction in some patients.
Atrovent should be used with caution in patients predisposed to narrow-angle glaucoma or with prostatic hyperplasia or
bladder-neck obstruction.
Patients with cystic fibrosis may be more prone to gastrointestinal motility disturbances.
Immediate hypersensitivity reactions may occur after administration of Atrovent as demonstrated by rare cases of urticaria,
angioedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis.
Ocular Complications: There have been isolated reports of ocular complications (ie, mydriasis, increased intraocular pressure,
narrow-angle glaucoma, eye pain) when aerosolised ipratropium bromide either alone or in combination with an adrenergic
ß2-agonist has come into contact with the eyes. Thus, patients must be instructed in the correct administration of Atrovent
metered aerosol.
Eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion
and corneal edema may be signs of acute narrow-angle glaucoma. Should any combination of these symptoms develop,
treatment with miotic drops should be initiated and specialist advice sought immediately.
Patients must be instructed of the correct administration of Atrovent solution for inhalation. Care must be taken not to allow
the solution or mist to enter into the eyes. It is recommended that the nebulised solution is administered via a mouth piece. If
this is not available and a nebuliser mask is used, it must fit properly. Patients who may be predisposed to glaucoma should be
warned specifically to protect their eyes.
Use in pregnancy & lactation: The safety of Atrovent during human pregnancy has not been established. The benefits of using
Atrovent during a confirmed or suspected pregnancy must be weighed against possible hazards to the unborn child.
Preclinical studies have shown no embryotoxic or teratogenic effects following inhalation or intranasal application at doses
considerably higher than those recommended in man.
It is not known whether Atrovent is excreted in breast milk. Although lipid-insoluble quaternary cations pass into breast milk,
it is unlikely that Atrovent would reach the infant to an important extent, when administered by inhalation. However, because
many drugs are excreted in breast milk, caution should be exercised when Atrovent is administered to nursing mothers.
Use in children: Safety and effectiveness in children <12 years have not been established.
Side Effects The most frequent nonrespiratory adverse events reported in clinical trials were GI motility disorders (eg,
constipation, diarrhea and vomiting), dryness of the mouth and headache.
Further, the following side effects have been observed with Atrovent: Increased heart rate, palpitations, supraventricular
tachycardia and atrial fibrillation, ocular accommodation disturbances, nausea and urinary retention. These side effects have
been reversible. The risk of urinary retention may be increased in patients with preexisting outflow tract obstruction.
Ocular side effects have been reported (see Precautions).
As with other inhaled therapy including bronchodilators, cough, local irritation and inhalation-induced bronchoconstriction
have been observed.
Allergic-type reactions eg, skin rash, angioedema of the tongue, lips and face, urticaria (including giant urticaria),
laryngospasm and anaphylactic reactions have been reported, with positive rechallenge in some cases.
Before initiating therapy with amoxicillin-clavulanate, careful enquiry should be made concerning previous hypersensitivity
reactions to penicillin, cephalosporins or other allergens.
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy.
These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity. If an allergic reaction occurs,
amoxicillin-clavulanate therapy should be discontinued and appropriate alternative therapy instituted. Serious anaphylactoid
reactions require immediate emergency treatment with adrenaline. Oxygen IV steroids and airway management, including
intubation may also be required.
Amoxicillin-clavulanate should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash
has been associated with this condition following the use of amoxicillin.
Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
In general, amoxicillin-clavulanate is well tolerated and possesses the characteristic low toxicity of the penicillin group of
antibiotics. Periodic assessment of organ system functions, including renal, hepatic and hematopoietic function is advisable
during prolonged therapy.
Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin-clavulanate. Appropriate
monitoring should be undertaken when anticoagulants are prescribed concomitantly.
Changes in liver function tests have been observed in some patients receiving Augmentin. The clinical significance of these
changes is uncertain but Augmentin should be used with caution in patients with evidence of hepatic dysfunction.
In patients with renal impairment, dosage should be adjusted according to the degree of implement (see Renal Impairment
under Dosage & Administration).
In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy.
During the administration of high doses of amoxicillin. It is advisable to maintain adequate fluid intake and urinary output in
order to reduce the possibility of amoxicillin crystalluria (see Overdosage).
Amoxicillin-clavulanate suspensions, contains aspartame, which is a source of phenylalanine; and so should be used with
caution in patients with phenylketonuria.
Erythematous rashes have been associated with glandular fever in patients receiving amoxicillin. Augmentin should be
avoided if glandular fever is suspected.
Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely, signs and symptoms may not
become apparent for several weeks after treatment has ceased.
Effects on the Ability to Drive or Operate Machinery: Adverse effects on the ability to drive or operate machinery have not
been observed.
Use in pregnancy: Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and
parenterally administered Augmentin have shown no teratogenic effects. In a single study in women with preterm, premature
rupture of the fetal membrane (pPROM), it was reported that prophylactic treatment with amoxicillin-clavulanate may be
associated with an increased risk of necrotizing enterocolitis in neonates. As with all medicines, use should be avoided in
pregnancy, unless considered essential by the physician.
Use in lactation: Amoxicillin-clavulanate may be administered during the period of lactation. With the exception of the risk of
sensitization, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the
breastfed infant.
Fluticasone furoate undergoes extensive first-pass metabolism by the liver enzyme CYP3A4, therefore the pharmacokinetics of
fluticasone furoate in patients with severe liver disease may be altered (see Pharmacokinetics under Actions and Interactions).
Based on data with another glucocorticoid metabolized by CYP3A4, co-administration with ritonavir is not recommended
because of the potential risk of increased systemic exposure to fluticasone furoate (see Pharmacokinetics under Actions and
Interactions).
Systemic effects of nasal corticosteroid may occur, particularly at high doses prescribed for prolonged periods. These effects
vary between patients and different corticosteroids. Treatment with higher than the recommended doses of nasal
corticosteroids may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses
being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.
Fluticasone furoate 110 mcg once daily was not associated with hypothalamic-pituitary-adrenal (HPA) axis suppression in
adult, adolescent or pediatric subjects. However, the dose of intranasal fluticasone furoate should be reduced to the lowest
dose at which effective control of the symptoms of rhinitis is maintained. As with all intranasal corticosteroids, the total
systemic burden of corticosteroids should be considered whenever other forms of corticosteroid treatment are prescribed
concurrently.
Growth retardation has been reported in children receiving some nasal corticosteroids at licensed doses. It is recommended
that the height of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. If growth is
slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid if possible, to the lowest dose at
which effective control of symptoms is maintained.
In addition, consideration should be given to referring the patient to a pediatric specialist. If there is any reason to believe that
adrenal function is impaired, care must be taken when transferring patients from systemic steroid treatment to fluticasone
furoate.
Nasal or inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is
warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma and/or cataracts.
Avamys nasal spray contains benzalkonium chloride. It may cause irritation of the nasal mucosa.
Effects on the Ability to Drive or Operate Machinery: Based on the pharmacology of fluticasone furoate and other intranasally
administered steroids, there is no reason to expect an effect on the ability to drive or to operate machinery with Avamys nasal
spray.
Impairment of Fertility: There are no data in humans (see Toxicology under Actions).
Use in pregnancy & lactation: Adequate data are not available regarding the use of Avamys nasal spray during pregnancy and
lactation in humans. Avamys nasal spray should be used in pregnancy only if the benefits to the mother outweigh the
potential risks to the fetus.
Following intranasal administration of fluticasone furoate at the maximum recommended human dose (110 mcg/day), plasma
fluticasone furoate concentrations were typically non-quantifiable and therefore potential for reproductive toxicity is expected
to be very low (see Toxicology under Actions).
The excretion of fluticasone furoate into human breast milk has not been investigated. Administration of fluticasone furoate to
women who are breastfeeding should only be considered if the expected benefit to the mother is greater than any possible
risk to the child.
Combination therapy should be prescribed after careful benefit risk assessment due to the potential increased risk of adverse
events and after consideration of alternative treatment options including monotherapies (see Dosage & Administration).
In two 4-year clinical studies, the incidence of cardiac failure (a composite term of reported events, primarily cardiac failure
and congestive cardiac failure) was higher among subjects taking the combination of Avodart and an a-blocker, primarily
tamsulosin, than it was among subjects not taking the combination. In these two trials, the incidence of cardiac failure was
low (=1%) and variable between the studies. No imbalance was observed in the incidence of cardiovascular adverse events
overall in either trial. No causal relationship between Avodart (alone or in combination with an alpha blocker) and cardiac
failure has been established (See Clinical Studies under Actions).
Digital rectal examination, as well as other evaluations for prostate cancer, must be performed on patients with BPH prior to
initiating therapy with Avodart and periodically thereafter.
Dutasteride is absorbed through the skin; therefore, women, children and adolescents must avoid contact with leaking
capsules (see Use in pregnancy & lactation under Contraindication). If contact is made with leaking capsules, the contact area
should be washed immediately with soap and water.
Dutasteride was not studied in patients with liver disease. Caution should be used in the administration of dutasteride to
patients with mild to moderate hepatic impairment (see Dosage & Administration, Contraindications, and Pharmacokinetics
under Actions).
Serum prostate-specific antigen (PSA) concentration is an important component in the detection of prostate cancer. Generally,
a total serum PSA concentration >4 ng/mL (Hybritech) requires further evaluation and consideration of prostate biopsy.
Physicians should be aware that a baseline PSA <4 ng/mL in patients taking Avodart does not exclude a diagnosis of prostate
cancer. Avodart causes a decrease in serum PSA levels by approximately 50% after 6 months, in patients with BPH, even in the
presence of prostate cancer. Although there may be individual variation, the reduction in PSA by approximately 50% is
predictable as it was observed over the entire range of baseline PSA values (1.5-10 ng/mL). Therefore, to interpret an isolated
PSA value in a man treated with Avodart for =6 months, PSA values should be doubled for comparison with normal ranges in
untreated men. This adjustment preserves the sensitivity and specificity of the PSA assay and maintains its ability to detect
prostate cancer.
Any sustained increases in PSA levels while on Avodart should be carefully evaluated, including consideration of non-
compliance to therapy with Avodart.
Total serum PSA levels return to baseline within 6 months of discontinuing treatment.
The ratio of free to total PSA remains constant even under the influence of Avodart. If clinicians elect to use percent-free PSA
as an aid in the detection of prostate cancer in men undergoing Avodart therapy, no adjustment to its value is necessary.
Effects on the Ability to Drive or Operate Machinery: Based on the pharmacokinetic and pharmacodynamic properties of
dutasteride, treatment would not be expected to interfere with the ability to drive or operate machinery.
Impairment of Fertility: The effects of dutasteride 0.5 mg/day on semen characteristics were evaluated in normal volunteers
18-52 years (n=27 dutasteride, n=23 placebo) throughout 52 weeks of treatment and 24 weeks of post-treatment follow-up.
At 52 weeks, the mean percent reduction from baseline in total sperm count, semen volume and sperm motility were 23%,
26% and 18%, respectively, in the dutasteride group when adjusted for changes from baseline in the placebo group. Sperm
concentration and morphology were unaffected. After 24 weeks of follow-up, the mean percentage change in total sperm
count in the dutasteride group remained 23% lower than baseline. While mean values for all semen parameters at all time
Impaired liver or kidney function, patients taking other hepatotoxic agents. Reduced visual acuity. Gout. Convulsive disorders,
DM, chronic alcoholism.
Overgrowth of nonsusceptible organisms. Check periodically for organ system dysfunction eg renal, hepatic & haematopoietic
system. Neonates.
CNS disorders, renal impairment.
Monitor renal function during concomitant treatment w/ aminoglycosides. Pregnancy & lactation.
Avoid contact w/ eyes, moderate to severe renal impairment. Prolonged use. Pregnancy, lactation.
Cream: In the rare event of a possible sensitization reaction or severe local irritation occurring with the use of Bactroban
cream, treatment should be discontinued, Bactroban cream should be washed off and appropriate alternative therapy for the
infection should be instituted. As with other antibacterial products, prolonged use may result in overgrowth of nonsusceptible
organisms.
For intranasal use, a separate presentation as Bactroban nasal ointment is available. Avoid contact with eyes.
Ointment: When Bactroban ointment is used on the face, care should be taken to avoid contact with eyes. Polyethylene glycol
can be absorbed from open wounds and damaged skin and is excreted by the kidneys.
In common with other polyethylene glycol-based ointments, Bactroban ointment should be used with caution if there is
evidence of moderate or severe renal impairment.
Bactroban ointment is not suitable for ophthalmic or intranasal use.
Effects on the Ability to Drive or Operate Machinery: No adverse effects on the ability to drive or operate machinery have
been observed.
Use in pregnancy: Adequate human and animal data on use during pregnancy are not available. Therefore, there is
inadequate evidence of safety to recommend the use of Bactroban during pregnancy. However, experimental animal studies
have shown that mupirocin has no teratogenic effect.
Mupirocin should only be used in pregnancy when the potential benefits outweigh the potential risks associated with
treatment.
Use in lactation: Cream: Adequate human and animal data on use during lactation are not available. If a cracked nipple is to
be treated, it should be thoroughly washed prior to breastfeeding.
Ointment: Adequate human data on use during lactation is not available.
Severe CV disease, hepatic or renal disorders, elderly patients, history of haematological disorders.
Heart & thyroid disease, HTN, diabetes, difficulty in urination due to enlargement of prostate gland; chronic cough due to
asthma, smoking, emphysema or accompanied by excessive phlegm, fever, drowsiness, debile & hypoxia. Childn <2 yr.
Prolonged use may result in overgrowth of nonsusceptible organisms. Discontinue use at first appearance of skin rash or other
signs of hypersensitivity reactions.
General: Renal Impairment: Dosage adjustment of Baraclude is recommended for patients with a creatinine clearance <50
mL/min, including patients on hemodialysis or CAPD (see Renal Impairment under Dosage & Administration).
Post-Liver Transplant Recipients: The safety and efficacy of Baraclude in liver transplant recipients are unknown. However, in a
small pilot study of entecavir use in HBV-infected liver transplant recipients on a stable dose of cyclosporine A (n=5) or
tacrolimus (n=4), entecavir exposure was approximately 2-fold healthy subjects with normal renal function. Altered renal
function contributed to the increased in entecavir exposure in these subject. The potential of pharmacokinetic interactions
between entecavir and cyclosporine A or tacrolimus was not formally evaluated. Renal function must be carefully monitored
both before and during treatment with Baraclude in liver transplant recipients who have received or are receiving an
immunosupresant that may affect renal function eg, cyclosporine or tacrolimus. (See Pharmacokinetics: Special Population
under Action, and Renal Impairment under Dosage & Administration).
Information for Patients: Patients should remain under the care of a physician while taking Baraclude. The patient should
discuss any new symptoms or concurrent medications with their physician.
Lamivudine-refractory patients receiving the 1-mg daily dose should be advised to take Baraclude on an empty stomach (at
least 2 hrs after a meal and 2 hrs before the next meal).
Patients should be informed that deterioration of liver disease may occur in some cases if treatment is discontinued, and that
the patient should discuss any change in regimen with the physician.
Patient should be offered HIV antibody testing before starting Baraclude therapy. The patient should be informed that if the
patient have HIV infection and are not receiving effective HIV treatment, Baraclude may increase the chance of HIV resistance
to HIV medication (see Patient Co-Infected with HIV and HBV under Warnings).
Patients should be advised that treatment with Baraclude has not been shown to reduce the risk of transmission of HBV to
others through sexual contact or blood contamination (see Labor and Delivery).
Carcinogenicity, Mutagenicity & Impairment of Fertility: Long-term oral carcinogenicity studies of entecavir in mice and rats
were carried out at exposures up to approximately 42 times (mice) and 35 times (rats) those observed in humans at the
highest recommended dose of 1 mg/day. In mouse and rat studies, entecavir was positive for carcinogenic findings.
In mice, lung adenomas were increased in males and females at exposures 3 times and 40 times those in humans. Lung
carcinomas in both male and female mice were increased at exposures 40 times those in humans. Combined lung adenomas
and carcinomas were increased in male mice at exposures 3 times and in female mice at exposures 40 times those in humans.
Tumor development was preceded by pneumocyte proliferation in the lung, which was not observed in rats, dogs, or monkeys
administered entecavir, supporting the conclusion that lung tumors in mice may be a species-specific event. Hepatocellular
carcinomas were increased in males and combined liver adenomas and carcinomas were also increased at exposures 42 times
those in humans. Vascular tumors in female mice (hemangiomas of ovaries and uterus and hemangiosarcomas of spleen)
were increased at exposures 40 times those in humans. In rats, hepatocellular adenomas were increased in females at
exposures 24 times those in humans; combined adenomas and carcinomas were also increased in females at exposures 24
times those in humans. Brain gliomas were induced in both males and females at exposures 35 and 24 times those in humans.
Skin fibromas were induced in females at exposures 4 times those in humans.
It is not known how predictive the results of rodent carcinogenicity studies may be for humans.
Entecavir was clastogenic to human lymphocyte cultures. Entecavir was not mutagenic in the Ames bacterial reverse mutation
assay using S. typhimurium and E. coli strains in the presence or absence of metabolic activation, a mammalian-cell gene
Pregnancy, lactation. Monitor serum Na levels & blood counts. Renal, hepatic or cardiac dysfunction. Abrupt discontinuation
of treatment. Cross-allergy to carbamazepine. Alcohol consumption. Elderly. May affect ability to drive or operate machinery.
Vit K deficiency in patient w/ poor diet, malabsorption states (cystic fibrosis) & prolonged IV alimentation regimen. Monitor
prothrombin time & those receiving anticoagulant therapy. Overgrowth of nonsusceptible organism in prolonged use. Periodic
monitoring for organ system dysfunction during extended therapy eg, renal, hepatic & hematopoietic system. May impair
ability to drive or operate machinery. Pregnancy & lactation. Childn.
Pregnancy & lactation. Childn. Elderly.
Should be given concomitantly w/ brain pressure-decreasing agent or antihemorrhagic; maintain body temp at low level in
acute & serious situation. Slow IV administration; IM administration only when no side effect & limited in min requirements;
avoid repeated inj at same site. Hypersensitivity. Childn, premature, neonates, infant.
Not for patients who are receiving repeated blood transfusion or anemia that are not caused by iron deficiency.
Decompensated cardiac insufficiency; shock, acid-base balance disturbances, pre-renally-induced oliguria. Treat anuria before
commencing parenteral nutrition. Ensure adequate renal function.
GI disturbances, skin allergy, facial edema, dyspnea, fever.
When using Berodual metered-dose aerosol HFA for the first time, some patients may notice that the taste is slightly different
from that of the CFC-containing metered-dose aerosol formulation. Patients should be made aware of this when changing
from one formulation to the other. They should also be told that the formulations have been shown to be interchangeable for
all practical purposes and that the difference in taste has no consequences in terms of the safety or the efficacy.
In the case of acute, rapidly worsening dyspnea (difficulty in breathing), a physician should be consulted immediately.
Prolonged Use: In patients with bronchial asthma, Berodual should be used only on an as needed basis. In patients with mild
COPD, on demand treatment (symptom-oriented) may be preferable to use regularly. The addition or the increase of anti-
inflammatory therapy to control airway inflammation and to prevent the deterioration of disease control should be
considered for patients with bronchial asthma and steroid-responsive COPD.
The use of increasing amounts of ß2-agonists-containing products eg, Berodual on a regular basis to control symptoms of
bronchial obstruction may suggest declining disease control. If bronchial obstruction deteriorates, it is inappropriate and
possibly hazardous to simply increase the use of ß2-agonist-containing products eg, Berodual beyond the recommended dose
over extended periods of time. In this situation, the patient's therapy plan and in particular, the adequacy of anti-
inflammatory therapy with inhaled corticosteroids, should be reviewed to prevent potentially life-threatening deterioration of
disease control.
Other sympathomimetic bronchodilators should only be used with Berodual under strict medical supervision.
In the following conditions, Berodual should only be used after careful risk-benefit assessment, especially when doses higher
than recommended are used: Insufficiently controlled diabetes mellitus, recent myocardial infarction, severe organic heart or
vascular disorders, hyperthyroidism and pheochromocytoma.
Cardiovascular effects may be seen with sympathomimetic drugs, including Berodual. There is some evidence from post-
marketing data and published literature of rare occurrences of myocardial ischaemia associated with ß-agonists. Patients with
underlying severe heart disease (eg, ischaemic heart disease, arrhythmia or severe heart failure) who are receiving Berodual,
should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease,
attention should be paid to the assessment of symptoms eg, dyspnoea and chest pain, as they may be of either respiratory or
cardiac origin. Potentially serious hypokalemia may result from ß2-agonist therapy.
Berodual should be used with caution in patients predisposed to narrow-angled glaucoma, or with preexisting urinary outflow
tract obstruction (eg, prostatic hyperplasia or bladder-neck obstruction).
There have been isolated reports of ocular complications (ie, mydriasis, increased intraocular pressure, narrow-angle
glaucoma, eye pain) when aerosolized ipratropium bromide, either alone or in combination with an adrenergic ß2-agonist,
has come in contact with. Thus, patients must be instructed in the correct administration of Berodual metered aerosol.
Eye pain or discomfort, blurred vision, visual halos or coloured images in association with red eyes from conjunctival
congestion and corneal oedema may be signs of acute narrow-angle glaucoma. Should any combination of these symptoms
develop, treatment with miotic drops should be initiated and specialist advice sought immediately.
Patients with cystic fibrosis may be more prone to gastrointestinal motility disturbances.
Immediate hypersensitivity reactions may occur after administration of Berodual as demonstrated by rare cases of urticaria,
angiooedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis.
The use of Berodual may lead to positive result with regard to fenoterol in tests for nonclinical substance abuse eg, in the
context of athletic performance enhancement (doping).
Metered-Dose Aerosol: When using the new formulation of Berotec HFA 100 mcg for the first time, some patients may notice
that the taste is different from that of the CFC-containing formulation. Patients should be made aware of this when changing
from one formulation to the other. They should also be told that the formulations have been shown to be interchangeable for
all practical purposes and that the difference in taste have no consequences in terms of the safety or the efficacy of the new
formulation.
Other sympathomimetic bronchodilators should only be used with Berotec HFA 100 mcg/Berotec Solution 0.1% under strict
medical supervision. Anticholinergic bronchodilators may, however, be inhaled at the same time.
In the following conditions, Berotec HFA 100 mcg/Berotec Solution 0.1% should only be used after careful risk/benefit
assessment, especially when doses higher than recommended are used: Insufficiently controlled diabetes mellitus, recent
myocardial infarction, severe organic heart or vascular disorders, hyperthyroidism and phaeochromocytoma.
In the case of acute, rapidly worsening dyspnea (difficulty in breathing), a physician should be consulted immediately.
Prolonged Use: On demand (symptom-oriented) treatment is preferable to regular use. Patients must be evaluated for the
addition or the increase of anti-inflammatory therapy (eg, inhaled corticosteroids) to control airway inflammation and to
prevent long-term lung damage.
If bronchial obstruction deteriorates, it is inappropriate and possibly hazardous to simply increase the use of ß2-agonist-
containing drugs eg, Berotec HFA 100 mcg/Berotec Solution 0.1% beyond the recommended dose over extended periods of
time. The use of increasing amounts of ß2-agonist-containing products like Berotec HFA 100 mcg/Berotec Solution 0.1% on
regular basis to control symptoms of bronchial obstruction may suggest declining disease control. In this situation, the
patient's therapy plan and, in particular, the adequacy of anti-inflammatory therapy, should be reviewed to prevent
potentially life-threatening deterioration of disease control.
Potentially serious hypokalemia may result from ß2-agonist therapy. Particular caution is advised in severe asthma, as this
effect may be potentiated by concomitant treatment with xanthine derivatives, glucocorticosteroids and diuretics.
Additionally, hypoxia may aggravate the effects of hypokalemia on cardiac rhythm. Hypokalaemia may result in an increased
susceptibility to arrhythmias in patients receiving digoxin.
It is recommended that serum potassium levels are monitored in such situations.
Cardiovascular effects may be seen with sympathomimetic drugs, including Berotec. There is some evidence from post-
marketing data and published literature of rare occurrences of myocardial ischaemia associated with ß-agonists.
Patients with underlying severe heart disease (eg, ischaemic heart disease, arrhythmia or severe heart failure) who are
receiving Berotec should be warned to seek medical advice if they experience chest pain or other symptoms of worsening
heart disease.
Attention should be paid to the assessment of symptoms eg, dyspnoea and chest pain, as they may be of either respiratory or
cardiac origin.
Solution 0.1% for Inhalation: Berotec solution for inhalation contains the (antimicrobial) preservative benzalkonium chloride
and the stabiliser disodium edetate. It has been shown that these components may cause bronchoconstriction in some
patients.
The use of Berotec may lead to positive results on fenoterol in tests for nonclinical substance abuse eg, in the context of
athletic performance enhancement (doping).
Effects on the Ability to Drive or Operate Machinery: No studies on the effect on the ability to drive and use machines have
Discontinue therapy if pain, swelling or inflammation of tendon or tendon rupture occur. Patients w/ impaired kidney
function, epilepsy or history of CNS disorders. Avoid excessive sunlight exposure. May impair ability to drive of operate
machinery. Elderly.
Use of contact lenses, prolonged use. Childn <6 yr. Pregnancy. Discontinue use if eye irritation, sensitivity or superinfection
occurs. May lead to overgrowth of nonsusceptible organisms.
Allergy to seafood.
Childn, pregnancy.
Renal impairment.
Patients w/ megaloblastic anemia. May mask subacute symptoms of bone marrow degeneration or true pernicious anemia.
Monitor serum K during early phase treatment of pernicious anemia.
Not for upper resp tract infections. History of GI diseases esp colitis. Severe liver & kidney dysfunction. Liver & kidney function
should be monitored in long-term use. Pregnancy & lactation. Newborn. Elderly.
Renal & hepatic failure.
Black stool.
Stable Coronary Artery Disease: If an episode of unstable angina pectoris (major or not) occurs during the 1st month of
perindopril treatment, a careful appraisal of the benefit/risk should be performed before treatment continuation.
Hypotension: ACE inhibitors may cause a fall in blood pressure. Symptomatic hypotension is seen rarely in uncomplicated
hypertensive patients and is more likely to occur in patients who have been volume-depleted eg, by diuretic therapy, dietary
salt restriction, dialysis, diarrhoea or vomiting, or who have severe renin-dependent hypertension (see Adverse Reactions and
Interactions). In patients with symptomatic heart failure, with or without associated renal insufficiency, symptomatic
hypotension has been observed. This is most likely to occur in those patients with more severe degrees of heart failure, as
reflected by the use of high doses of loop diuretics, hyponatraemia or functional renal impairment. In patients at increased
risk of symptomatic hypotension, initiation of therapy and dose adjustment should be closely monitored (see Dosage &
Administration and Adverse Reactions). Similar considerations apply to patients with ischaemic heart or cerebrovascular
disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.
If hypotension occurs, the patient should be placed in the supine position and if necessary, should receive an IV infusion of
0.9% sodium chloride 9 mg/mL solution. A transient hypotensive response is not a contraindication to further doses, which
can be given usually without difficulty once the blood pressure has increased after volume expansion.
In some patients with congestive heart failure who have normal or low blood pressure, additional lowering of systemic blood
pressure may occur with Bioprexum.
This effect is anticipated and is usually not a reason to discontinue treatment. If hypotension becomes symptomatic, a
reduction of dose or discontinuation of Bioprexum may be necessary.
Aortic and Mitral Valve Stenosis/Hypertrophic Cardiomyopathy: As with other ACE inhibitors, Bioprexum should be given with
caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle eg, aortic stenosis or
hypertrophic cardiomyopathy.
Renal Impairment: In cases of renal impairment (CrCl <60 mL/min), the initial perindopril dosage should be adjusted according
to the patient's CrCl (see Dosage & Administration) and then as a function of the patient's response to treatment. Routine
monitoring of potassium and creatinine are part of normal medical practice for these patients (see Adverse Reactions).
In patients with symptomatic heart failure, hypotension following the initiation of therapy with ACE inhibitors may lead to
some further impairment in renal function. Acute renal failure, usually reversible, has been reported in this situation.
In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, who have been treated with
ACE inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy, have been
seen. This is especially likely in patients with renal insufficiency. If renovascular hypertension is also present, there is an
increased risk of severe hypotension and renal insufficiency. In these patients, treatment should be started under close
medical supervision with low doses and careful dose titration. Since treatment with diuretics may be a contributory factor to
the above, they should be discontinued and renal function should be monitored during the 1st weeks of Bioprexum therapy.
Some hypertensive patients with no apparent preexisting renal vascular disease have developed increases in blood urea and
serum creatinine, usually minor and transient, especially when Bioprexum has been given concomitantly with a diuretic. This
is more likely to occur in patients with preexisting renal impairment. Dosage reduction and/or discontinuation of the diuretic
and/or Bioprexum may be required.
Haemodialysis Patients: Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes and
treated concomitantly with an ACE inhibitor. In these patients, consideration should be given to using a different type of
Perindopril and Indapamide: Renal Impairment: In cases of severe renal impairment (CrCl <30 mL/min), treatment is
contraindicated.
In certain hypertensive patients without preexisting apparent renal lesions and for whom renal blood tests show functional
renal insufficiency, treatment should be stopped and possibly restarted either at a low dose or with 1 constituent only.
In these patients, usual medical follow-up will include frequent monitoring of potassium and creatinine, after 2 weeks of
treatment and then every 2 months during therapeutic stability period. Renal failure has been reported mainly in patients
with severe heart failure or underlying renal failure including renal artery stenosis.
Bioprexum Plus is usually not recommended in case of bilateral renal artery stenosis or a single functioning kidney.
Hypotension and Water and Electrolyte Depletion: There is a risk of sudden hypotension in the presence of preexisting
sodium depletion (particularly in individuals with renal artery stenosis). Therefore systematic testing should be carried out for
clinical signs of water and electrolyte depletion, which may occur with an intercurrent episode of diarrhea or vomiting.
Regular monitoring of plasma electrolytes should be carried out in such patients.
Marked hypotension may require the implementation of an IV infusion of isotonic saline.
Transient hypotension is not a contraindication to continuation of treatment. After re-establishment of a satisfactory blood
volume and blood pressure, treatment can be started again either at a reduced dose or with only 1 of the constituents.
Potassium Levels: The combination of perindopril and indapamide does not prevent the onset of hypokalaemia particularly in
diabetic patients or in patients with renal failure. As with any antihypertensive agent containing a diuretic, regular monitoring
of plasma potassium levels should be carried out.
Bioprexum Plus should not be administered to patients with rare hereditary problems of galactose intolerance, Lapp-lactase
deficiency or glucose-galactose malabsorption.
Perindopril: Cough: A dry cough has been reported with the use of ACE inhibitors. It is characterized by its persistence and
disappearance when treatment is withdrawn. An iatrogenic etiology should be considered in the event of this symptom. If the
prescription of an ACE inhibitor is still preferred, continuation of treatment may be considered.
Patients with Known Atherosclerosis: The risk of hypotension exists in all patients but particular care should be taken in
patients with ischaemic heart disease or cerebral circulatory insufficiency, with treatment being started at a low dose.
Renovascular Hypertension: The treatment for renovascular hypertension is revascularization. Nonetheless, ACE inhibitors can
be beneficial in patients presenting with renovascular hypertension who are awaiting corrective surgery or when such a
surgery is not possible.
If Bioprexum Plus is prescribed to patients with known or suspected renal artery stenosis, treatment should be started in a
hospital setting at a low dose and renal function and potassium levels should be monitored, since some patients have
developed a functional renal insufficiency which was reversed when treatment was stopped.
Other Populations: In patients with severe cardiac insufficiency (grade IV) or in patients with insulin-dependent diabetes
mellitus (spontaneous tendency to increased levels of potassium), treatment should be started under medical supervision
with a reduced initial dose. Treatment with ß-blockers in hypertensive patients with coronary insufficiency should not be
stopped, the ACE inhibitor should be added to the ß-blocker.
Diabetic Patients: The glycaemia levels should be closely monitored in diabetic patients previously treated with oral
antidiabetic drugs or insulin, namely during the 1st month of treatment with an ACE inhibitor.
Ethnic Differences: As with other ACE inhibitors, perindopril is apparently less effective in lowering blood pressure in Black
Avoid use around eyes or on open wounds. Avoid exposure to sunlight. Childn <12 yr. For Bioquin Forte: Pregnancy &
lactation.
Perform sensitivity test prior treatment. Not effective to snake bites caused by snakes from Eastern Indonesia. May be given in
patients w/ history of severe asthma who shown symptoms of systemic toxicity.
Premature & newborn infants. Pregnancy & lactation.
Bronchospasm, bronchial asthma, other chronic obstructive lung disease; concomitant treatment w/ inhalational anesth, DM
w/ large fluctuations in blood glucose values, strict fasting, ongoing desensitization therapy, 1st degree AV block, Prinzmetal's
angina, psoriasis; may mask symptoms of thyrotoxicosis & increase sensitivity to allergens & severity of anaphylactic
reactions. May impair ability to drive or operate machinery. Pregnancy.
Avoid contact w/ eyes & open skin lesions.
Avoid prolonged use >7 days. Not to be applied on open wounds or damaged skin. Infants & small childn. Hypersensitivity to
streptomycin (neomycin, paromomycin, kanamycin).
Undiagnosed red eye. Avoid prolonged use >7 days. Not to be applied on open wounds or damaged skin. Infants & small
childn. Hypersensitivity to streptomycins (neomycin, paramomycin, kanamycin).
HTN, sepsis, vascular stricture; heart or kidney impairment. If inverse, methylergometrine is not allowed until the birth over. If
twins, then wait until the last baby birth is over.
Acute, severe & progressive consciousness disturbance; concomitant therapy w/ hemostatic or intracranial pressure-relieving
drugs or use of measures to keep body temp low. Avoid high doses in intracranial bleeding. Patients w/ phenylketonuria &
pregnant women w/ high phenylalanine. Pregnancy & lactation. Childn.
Acute, severe & progressive consciousness disturbance; concomitant therapy w/ hemostatic or intracranial pressure-relieving
drugs or use of measures to keep body temp low. Avoid high doses in intracranial bleeding.
Regularly monitor ovarian response w/ ultrasound, alone or preferably in combination w/ measurement of serum estradiol
levels. Administer 1st inj under direct medical supervision.
Discontinue if irritation occurs. Not for ophth use. Avoid contact w/ eye. Systemic absorption of topical corticosteroid may
cause reversible hypothalmic pituitary adrenal, Cushing's syndrome, hypoglycemia, glycosuria. Long-term use may cause
superinfections. Pregnancy & lactation.
Long-term & prophylactic use; avoid abrupt w/drawal. Avoid contact w/ eyes. Excessive skin damage.
Pregnancy.
All patients should be premedicated w/ oral corticosteroids for 3 days starting 1 day prior to docetaxel therapy. Hepatic
impairment. Contraceptive measures must be taken during & for at least 3 mth after therapy. Avoid contact w/ plasticized PVC
equipment. Childn <16 yr. Elderly.
If a previously effective dosage regimen no longer gives the same symptomatic relief, the patient should seek medical care as
soon as possible as this could be sign of worsening asthma and repeated inhalations of ß2-agonists must then not delay
reassessment of the asthma therapy.
As for all ß2-agonists, caution should be observed in patients with thyrotoxicosis. Cardiovascular effects may be seen with
sympathomimetic drugs, including Bricasma. There is some evidence from post-marketing data and published literature of
myocardial ischaemia associated with ß-agonists.
Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are
receiving Bricasma should be warned to seek medical advice if they experience chest pain or other symptoms of worsening
heart disease. Attention should be paid to assessment of symptoms eg, dyspnoea and chest pain, as they may be of either
respiratory or cardiac origin.
Due to the hyperglycemic effect of ß2-agonist, additional blood glucose controls are recommended initially in diabetic
patients.
Due to the positive inotropic effect of ß2-agonist these drugs should not be used in patients with hypertrophic
cardiomyopathy.
As terbutaline sulphate is largely excreted in urine, caution should be exercised in patients with renal impairment.
Increased tendency to uterine bleeding has been reported in connection with Caesarean section. However, this can be
effectively stopped by propranolol 1-2 mg injected intravenously.
Terbutaline is not indicated and should not be used for the management of preterm labor. Serious adverse reactions have
been reported following administration of terbutaline sulphate to women in labor.
These reports have included transient hypokalemia, pulmonary edema (sometimes after delivery) and hypoglycemia in the
mother and/or neonatal child. Maternal death has been reported with terbutaline sulphate and other drugs of this class.
There have been rare reports of seizures occurring in patients receiving terbutaline, which do not recur when the drug is
discontinued and have not been explained on any other basis.
Terbutaline sulphate is a sympathomimetic amine and such should be used with caution in patients with cardiovascular
disorders (including arrhythmias, coronary insufficiency and hypertension), in patients with hyperthyroidism or diabetes
mellitus, history of seizures, or in patients who are unusually responsive to sympathomimetic amines.
Potentially serious hypokalemia may result from ß2-agonist therapy. Particular caution is recommended in acute severe
asthma as the associated risk may be augmented by hypoxia. The hypokalemic effect may be potentiated by concomitant
treatment (see Interactions). It is recommended that serum potassium levels are monitored in such situations. Patients
susceptible to hypokalemia should be monitored because transient early falls in serum potassium levels have been reported
with ß-agonist.
Immediate hypersensitivity reactions and exacerbation of bronchospasm have been reported after terbutaline administration.
Lactic acidosis has been reported in association with high therapeutic doses of parenteral and nebulised short-acting beta-
agonist therapy, mainly in patients being treated for an acute asthma exacerbation (see Overdosage and Adverse Reactions).
In patients not adequately responding to acute Bricasma therapy, consideration should be given to the presence of lactic
acidosis as a possible contributing factor to ongoing respiratory symptoms.
Tablet: Terbutaline should not be given together with non-selective ß-blocker.
Respules: The patient's inhalation technique should be checked regularly, and the optimal dose of Bricasma should be
General Risk of Bleeding: Drugs that inhibit platelet function including Brilinta increase the risk of bleeding. Brilinta increased
the overall risk of bleeding (major + minor) to a somewhat greater extent than did clopidogrel. The increase was seen for non-
CABG-related bleeding, but not for CABG-related bleeding. Fatal and life-threatening bleeding rates were not increased (see
Adverse Reactions).
In general, risk factors for bleeding include older age, a history of bleeding disorders, performance of percutaneous invasive
procedures and concomitant use of medications that increase the risk of bleeding [eg, anticoagulant and fibrinolytic therapy,
higher doses of aspirin, and chronic nonsteroidal anti-inflammatory drugs (NSAIDs)].
When possible, discontinue Brilinta five days prior to surgery. Suspect bleeding in any patient who is hypotensive and has
recently undergone coronary angiography, PCI, CABG, or other surgical procedures, even if the patient does not have any signs
of bleeding.
If possible, manage bleeding without discontinuing Brilinta. Stopping Brilinta increases the risk of subsequent cardiovascular
events (see Precautions and Adverse Reactions).
Concomitant Aspirin Maintenance Dose: In PLATO, use of BRILINTA with maintenance doses of aspirin >100 mg decreased the
effectiveness of Brilinta. Therefore, after the initial loading dose of aspirin (usually 325 mg), use Brilinta with a maintenance
dose of aspirin 75-100 mg (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions, and Dosage &
Administration).
Moderate Hepatic Impairment: BRILINTA has not been studied in patients with moderate hepatic impairment. Consider the
risks and benefits of treatment, noting the probable increase in exposure to ticagrelor.
Dyspnea: Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of patients taking clopidogrel. Dyspnea
was usually mild to moderate in intensity and often resolved during continued treatment. If a patient develops new,
prolonged, or worsened dyspnea during treatment with BRILINTA, exclude underlying diseases that may require treatment. If
dyspnea is determined to be related to BRILINTA, no specific treatment is required; continue BRILINTA without interruption.
In a substudy, 199 patients from PLATO underwent pulmonary function testing irrespective of whether they reported dyspnea.
There was no significant difference between treatment groups for FEV1. There was no indication of an adverse effect on
pulmonary function assessed after 1 month or after at least 6 months of chronic treatment.
Discontinuation of BRILINTA: Avoid interruption of BRILINTA treatment. If BRILINTA must be temporarily discontinued (eg, to
treat bleeding or for elective surgery), restart it as soon as possible. Discontinuation of BRILINTA will increase the risk of
myocardial infarction, stent thrombosis and death.
Strong Inhibitors of Cytochrome CYP3A: Ticagrelor is metabolized by CYP3A4/5. Avoid use with strong CYP3A inhibitors eg,
atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and
voriconazole (see Pharmacology under Actions and Interactions).
Cytochrome CYP3A Potent Inducers: Avoid use with potent CYP3A inducers eg, rifampin, dexamethasone, phenytoin,
carbamazepine, and phenobarbital (see Pharmacology under Actions and Interactions).
Hepatic Impairment: BRILINTA has not been studied in the patients with moderate or severe hepatic impairment. Ticagrelor is
metabolized by the liver and impaired hepatic function can increase risks for bleeding and other adverse events. Hence,
BRILINTA is contraindicated for use in patients with severe hepatic impairment and its use should be considered carefully in
patients with moderate hepatic impairment. No dosage adjustment is needed in patients with mild hepatic impairment (see
Pharmacology under
Penicillin-sensitive Actions,Pregnancy
patients. Contraindications and Precautions).
& lactation.
HTN, overwt. Liver & kidney dysfunction, glaucoma, prostate hypertrophy, hyperthyroid, urinary retention, alcohol
consumption, resp disorders, debilitated patients, hypoxia. May impair ability to drive or operate machinery. Pregnancy &
lactation. Childn <6 yr. Elderly.
Pregnancy, lactation.
Pregnancy & lactation. Childn <6 mth.
Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to control
symptoms (see Dosage & Administration). As with other NSAIDs, ibuprofen may mask the signs of infection.
Caution on the use in geriatric use; gastrointestinal bleeding, ulceration and perforation; respiratory disorder; cardiac, renal
and hepatic impairment. BRUFEN has also been reported to be associated with dermatological effects; renal effects;
hematological effects; and aseptic meningitis.
Use In Pregnancy & Lactation While no teratogenic effects have been demonstrated in animal toxicology studies, the use of
ibuprofen during pregnancy should be avoided. In the limited studies so far available, ibuprofen appears in the breast milk in
very low concentrations. Ibuprofen is not recommended for use in nursing mothers.
TB, HTN, DM, osteoporosis, peptic ulcer, glaucoma, cataract, family history of diabetes or glaucoma, hepatic impairment.
Pregnancy & lactation.
Hypoxemia, HTN, hepatic failure, chronic resp disease. Pregnancy & lactation. Elderly, infants & childn.
Avoid contact w/ open wound (muscle layer), eye or mucous membrane. Avoid concomitant use w/ oral prep to avoid active
toxicity. Extensive & prolonged use may cause systemic side effects. Pregnancy & lactation.
Hypersensitivity to cephalosporins. Renal impairment. Lymphatic leukemia. Pregnancy & lactation.
Close-angle glaucoma, urinary retention, prostate hyperplasia, pyloroduodenal obstructions, kidney disorders. May impair the
ability to drive the vehicle or operate the machinery. Lactation.
History of upper GI diseases (peptic ulceration); heart failure, renal & liver impairment, lupus erythematosus; HTN or other
conditions predisposing to fluid retention; coagulation defect, asthma. 1st & 2nd trimester pregnancy & lactation. Childn <1
yr.
Careful & constant monitoring of CV & resp vital signs & patient's state of consciousness should be accomplished after each
local anaesth inj. Patients w/ impaired CV function. Risk of developing an epidural or spinal haematoma which can result in
long-term or permanent paralysis in patients anti-coagulated or scheduled to be anti-coagulated w/ LMWH or heparinoids.
Frequently monitor for signs & symptoms of neurological impairment. Patients w/ epilepsy, impaired cardiac conduction,
bradycardia, severe shock or digitalis intoxication. Stokes-Adams syndrome or Wolff-Parkinson-White syndrome. Myasthenia
gravis. Epidural, caudal & spinal anaesth when there are serious CNS disease. Severe hepatic disease. Reduced plasma protein
conc, hyperthyroidism. Careful monitoring of the fetal heart rate is necessary. Drug sensitivities. May impair ability to drive or
operate machinery. Pregnancy other than labour & lactation. Childn <12 yr.
Prolonged or extensive use. Avoid contact w/ eyes. Pregnancy. Occlusive dressing of large areas of skin. Infected skin lesions.
Severe hypotension; close monitoring of dialysis patients w/ malignant HTN; heart failure, severe aortic stenosis, diabetes.
Renal impairment.
Vitamins are taken as supplement when nutritional intake from diet is inadequate.
Consult the physician if currently taking or has recently used prescribed medicines.
Vitamins are taken as supplement when nutritional intake from diet is inadequate.
Consult the physician if currently taking or has recently used prescribed medicines.
Excessive dose may cause diarrhoea & kidney dysfunction. Patients w/ impaired kidney function & receiving levodopa therapy.
Patients whose vascular tone & renal function depend predominantly on the activity of the renin-angiotensin-aldosterone
system, severe CHF; renal impairment; haemodialysis; unilateral or bilateral renal artery stenosis; patients w/ vol- & salt-
depletion secondary to salt restriction, prolonged diuretic therapy, heart failure or dialysis; surgery/anaesth; aortic & mitral
valve stenosis (obstructive hypertrophic cardiomyopathy); primary hyperaldosteronism; CHF; history of angioedema
associated w/ or unrelated to ACE or angiotensin II receptor therapy; galactose intolerance, Lapp-lactase deficiency or
glucose-galactose malabsorption. Avoid concomitant use w/ ACE inhibitor in heart failure patients & K-sparing diuretics.
Monitor BP, serum creatinine K levels periodically. May affect ability to drive or operate machinery. Childn & adolescents <18
yr. Elderly >75 yr.
Serum K & creatinine level should be examined regularly in patients w/ kidney failure. Patients receiving hemodialysis.
Patients w/ bilateral or unilateral renal artery. Patients using diuretics in high-dose. Patients w/ primary hyperaldosteronism.
Patients receiving coumarin (warfarin) anticoagulants, DM. Avoid taking high doses. Pregnancy.
Perform periodic hematological test on long-term treatment. Renal impairment. Avoid prolonged use. Pregnancy & lactation.
Hepatic disorders, exclude possibility of malignancy in suspected gastric ulcer. Pregnancy & lactation. Childn. Elderly.
Serious CV events eg, MI, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage, transient ischemic
attack. Stroke, life-threathening arryhtmia w/in the last 6 mth, hypotension (BP <90/50), HTN (BP >170/110), cardiac failure or
CAD causing unstable angina, retinitis pigmentosa. Patients w/ bleeding disorders & active peptic ulceration. Patients w/
anatomical deformation of the penis eg, angulation, cavernosal fibrosis or Peyronie's disease or in patients who have
conditions which may predispose them to priapism eg, sickle cell anemia, multiple myeloma or leukemia. Combinations w/
other drug for treatment of erectile dysfunction is not recommended. Patients w/ regular &/or intermittent use of organic
nitrates.
Hypersensitivity to ß-lactams. Do not use for infections due to MRSA. Monitor serum hepatic levels in patients w/ hepatic
disease. Consider diagnosis of pseudomembranous colitis in patients who develop diarrhea. May impair ability to drive &
operate machinery. Pregnancy & lactation. Infant <3 mth.
Impaired renal function (CrCl =50 mL/min); superinfection. Discontinue in case of allergic reactions or mild case of
pseudomembranous colitis. Elderly. Pregnancy & lactation.
May impair ability to drive or operate machinery. Pregnancy. Childn <6 mth.
Liver impairment; maintain liver function monitoring; renal impairment. Prolonged use may result in overgrowth of
nonsusceptible organisms. Hypersensitivity to penicillin. In high doses administration, fluid intake & urine excretion should be
ensure in excessive amount, to reduce the possibility of crystalluria. Patients using catheter should be in closed monitoring.
Pregnancy & lactation.
Monitor peripheral blood counts, renal & neurological functions. Carboplatin should not come in contact w/ Al.
Do not inject IM or SC. Reduced dosage in patients w/ hepatic impairment. Perform laboratory test eg SGOT, SGPT, alkaline
phosphate, bilirubin. Severe myelosuppression. Monitor ECG, before & after treatment hematological, blood uric level. It
causes red coloration to urine 1-2 days after administration.
Treatment with Cardace requires regular medical supervision.
If angioneurotic oedema occurs during treatment (see Adverse Reactions), Cardace must be discontinued immediately and
emergency measures must be taken especially if the tongue, glottis or larynx are involved.
Patients with a hyperstimulated rennin-angiotensin system must be treated with particular caution. ACE inhibition puts such
patients at risk of an acute pronounced fall in blood pressure and deterioration of renal function, especially when an ACE
inhibitor in combination with a diuretic, a medicine that promotes fluid excretion, is given for the 1st time or for the 1st time
at an increased dose.
Therefore, at the start of treatment with Cardace or after the 1st dose of an additional diuretic, as well as after every 1st
increased dose thereof, blood pressure must be closely monitored until such time as no further acute reduction in blood
pressure is expected.
Significant activation of the rennin-angiotensin system is to be expected eg, patients with severe and particularly malignant
hypertension. The initial phase of treatment requires special medical supervision).
Patients with heart failure particularly if severe or if treated with other potential blood pressure-lowering medicines in severe
heart failure, the initial phase of treatment requires special medical supervision.
Patients with blood flow-reducing (haemodynamically relevant) left-ventricular inflow or outflow impediment (eg, narrowing
of the aortic or mitral valve); patients with blood flow reducing and narrowing (haemodynamically relevant stenosis) of the
renal artery. The initial phase of treatment requires special medical supervision and concomitant treatment with a diuretic
may have to be discontinued.
Patients pretreated with diuretics, where discontinuation or reduction of diuretic dose is not possible, the initial phase of
treatment requires special medical supervision.
Patients in whom fluid or salt deficiency exists or may develop as a result of inadequate fluid or salt intake, or as a result of eg,
diarrhea, vomiting or excessive sweating in cases where salt and fluid replacement is inadequate. Generally, dehydration,
reduced blood volume (hypovolaemia) or salt deficiency should be corrected before initiating treatment in patients with heart
failure; however, such corrective action must be carefully weighed against the risk of volume overload. When such conditions
have become clinically relevant, treatment with Cardace must be started or continued only if appropriate steps are taken
concurrently to prevent an excessive fall in blood pressure and deterioration of renal function (see Dosage & Administration).
Also, at particular risk from a pronounced fall in blood pressure are eg, patients with haemodynamically relevant stenoses of
the coronary arteries or of the blood vessels supplying the brain. Such patients require special medical supervision in the
initial phase of treatment as well.
In patients with impaired liver function, response to treatment with Cardace may either be increased or decreased. In
addition, the renin-angiotensin system may be significantly activated; therefore, in patients with severe liver cirrhosis with
oedema and/or ascites; therefore, particular caution must be exercised in treating such patients (see Dosage &
Administration).
Renal function should be monitored, particularly, in the initial weeks of treatment. Particularly, careful monitoring is required
in patients with heart failure, renovascular disease (including those with haemodynamically relevant unilateral renal artery
stenosis in whom even a small increase in serum creatinine may be indicative of unilateral loss of renal function), in renal
impairment, or in kidney transplant patients.
Serum potassium should be monitored regularly. More frequent monitoring of serum potassium is required in patients with
Severe aortic stenosis, CHF, impaired liver function, heart failure. Pregnancy & lactation.
Not suitable for treating attacks of acute angina pectoris. severe hepatic or renal impairment; hypothyroidism, malnutrition,
or hypothermia; recent history of MI. Pregnancy & lactation.
Postural Hypotension/Syncope: As with all a-blockers, a very small percentage of patients have experienced postural
hypotension evidenced by dizziness and weakness, or rarely loss of consciousness (syncope), particularly with the
commencement of therapy (see Dosage & Administration).
When instituting therapy with any effective a-blocker, the patient should be advised how to avoid symptoms resulting from
postural hypotension and what measures to take should they develop. The patient should be cautioned to avoid situations
where injury could result should dizziness or weakness occur during the initiation of doxazosin mesylate therapy.
Use with PDE-5 Inhibitors: Concomitant administration of doxazosin with a PDE-5 inhibitor should be used with caution as it
may lead to symptomatic hypotension in some patients.
Hepatic Impairment: As with any drug wholly metabolized by the liver, Cardura should be administered with caution to
patients with evidence of impaired hepatic function (see Pharmacokinetics under Actions).
Effects on the Ability to Drive or Operate Machinery: The ability to engage in activities eg, operating machinery or a motor
vehicle, may be impaired, especially when initiating therapy.
Use in pregnancy & lactation: Although no teratogenic effects were seen in animal testing, reduced fetal survival was
observed in animals at extremely high doses. These doses were approximately 300 times the maximum human recommended
dose. Animal studies have shown that doxazosin mesylate accumulates in breast milk. As there are no adequate and well-
controlled studies in pregnant or nursing women, the safety of Cardura during pregnancy or lactation has not yet been
established. Accordingly, during pregnancy or lactation, Cardura should be used only when, in the opinion of the physician,
potential benefit outweighs the risk.
Use in children: No experience is available on usage of Cardura in children.
Monotherapy in patients w/ critical illness & known or suspected Pseudomonas aeruginosa infection; cross-allergy to
penicillins & cephalosporins. Monitor transaminase & bilirubin level in patients w/ liver disease. History of GI disease
especially colitis; concomitant use w/ other nephrotoxic drugs. May affect the ability to drive vehicle or operate machinery.
Pregnancy & lactation. Childn <3 mth.
Patients using warfarin. Discontinue use if hypersensitivity reactions occur. Pregnancy & lactation.
Initiation of treatment should be under the direct supervision of a specialist. Bicalutamide is extensively metabolised in the
liver. Data suggest that its elimination may be slower in subjects with severe hepatic impairment and this could lead to
increased accumulation of bicalutamide. Therefore, Casodex should be used with caution in patients with moderate to severe
hepatic impairment.
Periodic liver function testing should be considered due to the possibility of hepatic changes. The majority of changes are
expected to occur within the first 6 months of Casodex therapy.
Severe hepatic changes and hepatic failure have been observed rarely with Casodex and fatal outcomes have been reported
(see Adverse Reactions). Casodex therapy should be discontinued if changes are severe.
Bicalutamide has been shown to inhibit cytochrome P-450 (CYP3A4), as such, caution should be exercised when co-
administered with drugs metabolised predominantly by CYP3A4 (see Contraindications and Interactions).
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose
malabsorption should not take Casodex.
50 mg: A reduction in glucose tolerance has been observed in males receiving LHRH agonist. This may manifest as diabetes or
loss of glycaemic control in those with preexisting diabetes. Consideration should therefore, be given to monitoring blood
glucose in patients receiving Casodex in combination with LHRH agonist.
150 mg: For patients who have an objective progression of disease together with elevated PSA, cessation of Casodex therapy
should be considered.
Lactose-sensitive patients should be aware that each Casodex 150 mg contains lactose monohydrate 183 mg.
Effects on the Ability to Drive or Operate Machinery: Casodex is unlikely to impair the ability of patients to drive or operate
machinery. However, it should be noted that occasionally somnolence may occur. Any affected patients should exercise
caution.
General: The concomitant use of Cataflam/Cataflam D with systemic NSAIDs including COX-2 selective inhibitors, should be
avoided due to the absence of any evidence demonstrating synergistic benefits and the potential for additive undesirable
effects.
Cataflam tablets contain sucrose and therefore are not recommended for patients with rare hereditary problems of fructose
intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
Preexisting Asthma: In patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (ie, nasal polyps), chronic
obstructive pulmonary diseases or chronic infections of the respiratory tract (especially if linked to allergic rhinitis-like
symptoms), reactions on NSAIDs eg, asthma exacerbations (so-called intolerance to analgesics/analgesics-asthma), Quincke's
oedema or urticaria are more frequent than in other patients. Therefore, special precaution is recommended in such patients
(readiness for emergency). This is applicable as well for patients who are allergic to other substances eg, with skin reactions,
pruritus or urticaria.
Gastrointestinal Effects: As with all NSAIDs, including diclofenac, close medical surveillance is imperative and particular
caution should be exercised when prescribing Cataflam/Cataflam D in patients with symptoms indicative of GI disorders or
with a history suggestive of gastric or intestinal ulceration, bleeding or perforation (see Adverse Reactions). The risk of GI
bleeding is higher with increasing NSAID doses and in patients with a history of ulcer (particularly if complicated with
haemorrhage or perforation) and in the elderly.
To reduce the risk of GI toxicity in patients with a history of ulcer (particularly if complicated with haemorrhage or perforation)
and in the elderly, the treatment should be initiated and maintained at the lowest effective dose.
Combination therapy with protective agents (eg, proton-pump inhibitors or misoprostol) should be considered for these
patients and also for patients requiring concomitant use of medicinal products containing low-dose acetylsalicylic acid
(ASA)/aspirin or other medicinal products likely to increase GI risk.
Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI
bleeding). Caution is recommended in patients receiving concomitant medications which could increase the risk of ulceration
or bleeding eg, systemic corticosteroids, anticoagulants, antiplatelet agents or selective serotonin re-uptake inhibitors (see
Interactions).
Close medical surveillance and caution should also be exercised in patients with ulcerative colitis or Crohn's disease, as their
condition may be exacerbated (see Adverse Reactions).
Hepatic Effects: Close medical surveillance is required when prescribing Cataflam/Cataflam D to patients with impaired
hepatic function, as their condition may be exacerbated.
As with other NSAIDs, including diclofenac, values of 1 or more liver enzymes may increase. During prolonged treatment with
Cataflam/Cataflam D, regular monitoring of hepatic function is indicated as a precautionary measure. If abnormal liver
function tests persist or worsen, if clinical signs or symptoms consistent with liver disease develop, or if other manifestations
occur (eg, eosinophilia, rash), Cataflam/Cataflam D should be discontinued. Hepatitis may occur with the use of diclofenac
without prodromal symptoms.
Caution is called for when using Cataflam/Cataflam D in patients with hepatic porphyria, since it may trigger an attack.
Renal Effects: As fluid retention and oedema have been reported in association with NSAID therapy, including diclofenac,
particular caution is called for in patients with impaired cardiac or renal function, history of hypertension, the elderly, patients
receiving concomitant treatment with diuretics or medicinal products that can significantly impact renal function, and in
Catapres should be used with caution in patients with mild to moderate bradyarrhythmia eg, low sinus rhythm, with disorders
of cerebral or peripheral perfusion, depression, polyneuropathy and constipation. In hypertension caused by
phaeochromocytoma, no therapeutic effect of Catapres can be expected.
As with other antihypertensive drugs, treatment with Catapres should be monitored particularly carefully in patients with
heart failure or severe coronary heart disease.
Patients should be instructed not to discontinue therapy without consulting the physician. Following sudden discontinuation
of Catapres after prolonged treatment with high doses, restlessness, palpitations, rapid rise in blood pressure, nervousness,
tremor, headache or nausea have been reported. When discontinuing therapy with Catapres, the physician should reduce the
dose gradually over 2-4 days.
If long-term treatment with a ß-receptor blocker has to be interrupted, the ß-receptor blocker should first be phased out
gradually and then clonidine.
Effects on the Ability to Drive or Operate Machinery: The ability to drive or operate machinery may be impaired by Catapres.
Use in pregnancy & lactation: During pregnancy, Catapres, as any drug, should only be administered if clearly needed.
Careful monitoring of mother and child is recommended.
Clonidine passes the placental barrier and may lower the heart rate of fetus. Postpartum and transient rise in blood pressure
in the newborn cannot be excluded.
During pregnancy, the oral forms of Catapres should be preferred. IV injection of clonidine should be avoided.
There is no adequate experience regarding the long-term effects of prenatal exposure.
The use of Catapres during lactation is not recommended due to a lack of supporting information.
Side Effects Most side effects are mild and tend to diminish with continued therapy.
Frequent side effects are dryness of the mouth and sedation.
Occasionally constipation, nausea and vomiting, headache, malaise, impotence, decreased libido, gynaecomastia, orthostatic
complaints, paresthesia of the extremities, Raynaud's phenomenon, pain in the parotid gland, drying out of the nasal mucosa
and reduced lacrimal flow (contact lens wearers should be cautioned) as well as skin reactions with symptoms eg, rash,
urticaria, pruritus and alopecia have been observed. Sleep disturbances, nightmares, depression, perceptual disorders,
hallucinations, confusion and disturbances of accommodation may occur.
In very rare cases, pseudo-obstruction of the large bowel has been observed in predisposed patients.
Clonidine may cause or potentiate bradyarrhythmic conditions eg, sinus bradycardia or AV block.
Rarely, transient elevations of blood sugar levels have been reported.
Do not w/draw prior to treatment completion. Pregnancy.
Liver dysfunction. May cause vit K deficiency in patients w/ poor diet, malabsorption (cystic fibrosis), patients w/ prolonged IV
alimentation regimen. Periodic monitoring for organ system dysfunction during extended therapy eg, renal, hepatic &
hematopoietic system. Pregnancy & lactation.
Glaucoma. May develop tolerance & cross-tolerance to other nitrates & nitrites.
Sensitivity to penicillin; history of allergy eg, bronchial asthma, rash, urticaria; impaired renal function; patient w/ poor oral
nutrition or under therapy w/ parenteral nutrition; history of GI disease eg, colitis. Childn w/ otitis media should be treated w/
syr only. Discontinue if superinfection occurs. Pregnancy, lactation, childn <6 mth, elderly or debilitated patients.
Cross-allergic reaction may occur in patients hypersensitive to penicillin or other ß-lactam antibiotics. Monitor kidney function
in patients receiving aminoglycosides. Monitor haematologic effects in long-term use (>10 days). Prolonged use may cause
resistance. Pregnancy, lactation.
History of hypersensitivity to penicillin & other cephalosporins, personal or familial history of allergy eg, bronchial asthma,
rash, urticaria, severe kidney function impairment, low oral nutrition; concomitant therapy w/ parenteral nutrition. Pregnancy,
lactation. Elderly, debilitated patients. Childn <6 mth (including newborn & premature infants).
Hypersensitivity to penicillins. Impaired renal function. Patients receiving potent diuretics & nephrotoxic antibiotics.
Penicillin allergy, severe renal impairment. Pregnancy & lactation.
History of hypersensitivity to penicillins or cephems. Bronchial asthma, rash or urticaria; serious renal function disorder; poor
oral nutrition. Elderly or debilitated states. Pregnancy.
Impaired renal function (CrCl =50 mL/min); developed pseudomembranous colitis or diarrhea during therapy; long-term
usage. Pregnancy & lactation. Elderly.
Hypersensitivity to penicillins.
Adverse Reactions
The following events have been reported during therapy for HIV disease with 3TC alone and in combination with other anti-
retroviral agents. With many still unclear whether they are related to the medicinal products or are as a result of the underlying
disease process.
The following convention has been utilized for the classification of undesirable effects: Very common (>1/10); common (>1/100,
<1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/1000); very rare (<1/10,000).
Blood and Lymphatic Systems Disorders: Uncommon: Neutropenia, anemia, thrombocytopenia. Very Rare: Pure red cell aplasia.
Metabolism and Nutrition Disorders: Common: Hyperlactatemia. Rare: Lactic acidosis (see Precautions).
Redistribution/Accumulation of Body Fat (see Precautions): The incidence of this event is dependent on multiple factors
including the particular antiretroviral drug combination.
Nervous System Disorders: Common: Headache. Very Rare: Paresthesia. Peripheral neuropathy has been reported although a
causal relationship to treatment is uncertain.
Gastrointestinal Disorders: Common: Nausea, vomiting, upper abdominal pain, diarrhea. Rare: Pancreatitis, although a causal
relationship to treatment is uncertain. Rises in serum amylase.
Hepatobiliary Disorders: Uncommon: Transient rises in liver enzymes (AST, ALT).
Skin and Subcutaneous Tissue Disorders: Common: Rash, alopecia.
Musculoskeletal and Connective Tissue Disorders: Common: Arthralgia, muscle disorders. Rare: Rhabdomyolysis.
General Disorders and Administration Site Conditions: Common: Fatigue, malaise, fever.
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3TC-HBV appears to be well-tolerated. In clinical studies of patients treated for chronic hepatitis B infection, the incidence of
adverse events were similar between placebo and the different doses of lamivudine studied. The most commonly reported
adverse events were symptoms associated with upper respiratory tract infection, headache, nausea, malaise, abdominal pain
and diarrhea.
The incidence of laboratory abnormalities were similar in the lamivudine- and placebo-treated groups. The most commonly
reported laboratory abnormalities were associated with hepatic dysfunction and were more likely to be due to the underlying
disease.
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Allergic reactions, tingling in the arm, ear & face, blurred vision, headache, nausea, stomachache, jittery feeling.
Mild reaction eg urticaria (treated w/ antihistamies & corticosteroids). Discontinue in case of more severe reactions (eg,
anaphylactic shock), treat w/ high dose corticosteroids & then w/ adrenaline, slowly administered.
Headache, edema, fatigue, somnolence, nausea, abdominal pain, flushing, palpitations, dizziness.
The most frequently reported adverse effects of clarithromycin in clinical studies in adults were gastrointestinal-related
complaints ie, tongue discolouration, oral moniliasis, hepatic abnormalities, nausea, dyspepsia, abdominal pain, vomiting and
diarrhea, stomatitis and glossitis have been reported. Other side effects included headache, taste perversion and transient
elevations of liver enzymes. The safety profile of the paediatric formulation is similar to that of the 250-mg tablet in adult
patients.
Metabolic/Nutritional: Increased serum creatinine and increased glutaryl transferase (GGT).
Immunocompromised Patients: In adult patients, the most frequently reported adverse events by patients treated with total
doses of clarithromycin 1000 mg and 2000 mg were nausea, vomiting, altered taste, abdominal pain, diarrhea, rash, flatulence,
headache, constipation, hearing disturbance, and SGOT and SGPT elevations. Additional low-frequency events included
dyspepsia, insomnia and dry mouth. The incidences were comparable for patients treated with 1000 and 2000 mg, but were
generally about 3-4 times as frequent for those patients who received total daily doses of clarithromycin 4000 mg.
Post-Marketing Experience: Hepatic dysfunction, including increased liver enzymes and hepatocellular and/or cholestatic
hepatitis, with or without jaundice, has been infrequently reported with clarithromycin. This hepatic dysfunction may be severe
and is usually reversible. In very rare instances, hepatic failure and fatal outcome has been reported and generally has been
associated with serious underlying diseases and/or concomitant medications.
Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis and Stevens-Johnson syndrome have occurred
with orally administered clarithromycin.
There have been reports of transient central nervous system side effects including anxiety, dizziness, insomnia, hallucinations,
bad dreams, confusion and psychosis. However, a cause-and-effect relationship has not been established.
There have been reports of hearing loss with clarithromycin, which is usually reversible upon withdrawal of therapy. Reports of
alteration of the sense of smell, usually in conjunction with altered taste have also been reported.
Glossitis, stomatitis, oral monilia and tongue discoloration have been reported with clarithromycin therapy. There have been
reports of tooth discolouration in patients treated with clarithromycin. Tooth discolouration is usually reversible with
professional dental cleaning.
There have been rare reports of hypoglycemia, some of which have occurred in patients on concomitant oral hypoglycemic
agents or insulin.
Isolated cases of thrombocytopenia have been reported. Rarely, erythromycin has been associated with ventricular arrhythmias,
including ventricular tachycardia and Torsade de pointes, individuals with prolonged QT intervals.
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Adverse events occurred in =10% of patients treated with Abilify Discmelt are headache, nausea, vomiting, constipation, anxiety,
insomnia, lightheadedness, somnolence, akathisia, dyspepsia, agitation.
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Adverse events occurred in =10% of patients treated with Abilify Oral Solution are headache, nausea, vomiting, constipation,
anxiety, insomnia, lightheadedness, somnolence, akathisia, dyspepsia, agitation.
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Aripiprazole has been evaluated for safety in 7951 patients who participated in multiple-dose, premarketing trials in
schizophrenia, bipolar mania and dementia of the Alzheimer's type, and who had approximately 5235 patient-years of exposure.
A total of 2280 aripiprazole-treated patients were treated for at least 180 days and 1558 aripiprazole-treated patients had at
least 1 year of exposure.
The conditions and duration of treatment with aripiprazole included (in overlapping categories) double-blind, comparative and
noncomparative open-label studies, inpatient and outpatient studies, fixed- and flexible-dose studies, and short- and longer-
term exposure.
Adverse events during exposure were obtained by collecting volunteered adverse events, as well as results of physical
examinations, vital signs, weights, laboratory analyses and ECG. Adverse experiences were recorded by clinical investigators using
terminology of their own choosing. In the tables and tabulations that follow, modified COSTART dictionary terminology has been
used initially to classify reported adverse events into a smaller number of standardized event categories, in order to provide a
meaningful estimate of the proportion of individuals experiencing adverse events.
The stated frequencies of adverse events represent the proportion of individuals who experienced at least once, a treatment-
emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or
worsened while receiving therapy following baseline evaluation. There was no attempt to use investigator causality assessments
ie, all reported events are included.
The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side
effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in
the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations
involving different treatment, uses and investigators. The cited figures, however, do provide the prescribing physician with some
basis for estimating the relative contribution of drug and nondrug factors to the adverse event incidence in the population
studied.
Adverse Findings Observed in Short-Term, Placebo-Controlled Trials of Patients with Schizophrenia: The following findings are
based on a pool of 5 placebo-controlled trials (four 4-week and one 6-week) in which aripiprazole was administered in doses
ranging from 2-30 mg/day.
Adverse Events Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials: Overall, there was no
difference in the incidence of discontinuation due to adverse events between aripiprazole-treated (7%) and placebo-treated (9%)
patients. The types of adverse events that led to the discontinuation were similar between the aripiprazole- and placebo-treated
patients.
Adverse Findings Observed in Short-Term, Placebo-Controlled Trials of Patients with Bipolar Mania: The following findings are
based on a pool of 3-week, placebo-controlled, bipolar mania trials in which aripiprazole was administered at doses of 15 or 30
mg/day.
Adverse Events Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials: Overall, in patients with
bipolar mania, there was no difference in the incidence of discontinuation due to adverse events between aripiprazole-treated
(11%) and placebo-treated (9%) patients. The types of adverse events that led to discontinuation were similar between the
aripiprazole and placebo-treated patients.
Commonly Observed Adverse Events in Short-Term, Placebo-Controlled Trials of Patients with Bipolar Mania: Commonly
observed adversereactions,
Hypersensitivity events associated withrenal
GI disorders, the use of aripiprazole
& liver in patients
function disorders, with bipolar
changes in bloodmania (incidence
constituent, localofreactions,
=5% and neurogical
effects, superinfection.
Rash, urticaria, erythema, pruritus or fever; granulocytopenia or eosinophilia; increased SGOT, SGPT or alkaline phosphatase;
vomiting, diarrhea, abdominal pain, stomach discomfort, heartburn or anorexia.
Adverse reactions, which have been associated with ACCOLATE treatment, are given in the table (see table).
Hepatic Effects: Elevated serum transaminase levels have been observed in clinical trials with ACCOLATE. The changes usually
resolved during continued treatment or following cessation of therapy. Rarely the transaminase profile has been consistent with
a drug-induced hepatitis, which resolved following cessation of ACCOLATE therapy.
Hyperbilirubinemia without elevated liver function tests has also been associated with the use of ACCOLATE.
During post-marketing experience there have been rare reports of symptomatic hepatitis, with and without hyperbilirubinemia,
associated with the use of ACCOLATE. These cases have usually resolved following cessation of therapy with ACCOLATE. The
predominate majority of cases have been reported in females. Very rarely, fulminant hepatitis and hepatic failure have been
reported, sometimes with a fatal outcome (see Precautions).
Infection: In placebo-controlled clinical trials, an increased incidence of infection has been observed in elderly patients given
ACCOLATE. Infections were usually mild, predominantly affecting the respiratory tract.
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Skin rash, urticaria, irritation.
Asthenia, fatigue, edema, abdominal pain, chest pain, headache, pharyngitis, angina pectoris, 2nd degree AV block, CVA,
hypotension, MI, liver function abnormalities.
Hypersensitivity reactions eg, bronchospasm, angioedema, rashes & pruritus. Nausea & vomiting, fever, syncope, sweating,
arthralgia, blurred vision, liver function disturbances.
Skin rash, reversible neurological reactions, GI disturbances, increased bilirubin & liver enzymes, increased BUN & creatinine,
lowering of haematological index, headache & fatigue.
Rarely, GI upsets.
Zn supplementation may cause GI upset, nausea, vomiting & diarrhea if taken on an empty stomach (particularly w/ Zn sulfate).
Dizziness, nausea, pharyngitis, chest pain, fatigue, lower back pain, depression, dehydration, myalgia; abdominal cramps,
borborygmi, diarrhoea; rash, pruritus, urticaria, angioedema, bronchospasm.
Mild GI disturbances; skin hypersensitivity reactions; renal dysfunction; reversible elevations of serum creatinine, parathyroid
hormone, lactic acid dehydrogenase, transaminase & alkaline phosphatase.
Insomnia; headache; nausea, diarrhea, abdominal pain, dyspepsia, constipation, flatulence; myalgia; asthenia; hypo- &
hyperglycemia, anorexia; peripheral neuropathy, paresthesia; pancreatitis, vomiting; hepatitis, cholestatic jaundice; rash,
pruritus, alopecia; myopathy, myositis, muscle cramps; impotence; angioneurotic edema.
Dizziness, headache, facial redness, flushing, somnolence, muscle fatigue, peripheral oedema (ankles), palpitations, abdominal
pain, nausea, drowsiness.
Early & late diarrhea, nausea, vomiting, abdominal cramping/pain, anorexia, stomatitis, mucositis. Leukopenia, anemia,
neutropenia, thrombocytopenia. Asthenia, fever, pain. Decreased wt, dehydration, hypovolemia. Alopecia. Infection.
Thromboembolic events includes angina pectoris, arterial thrombosis, cerebral infarct, CVA, deep thrombophlebitis, lower
extremity embolus, heart arrest, MI, myocardial ischemia, peripheral vascular disorder, pulmonary embolus, sudden death,
thrombophlebitis, thrombosis, vascular disorder. Bilirubinemia. Dyspnea.
Drowsiness, muscle weakness, ataxia, amnesia, depression, lightheadedness, confusion, hallucinations, blurred vision.
Central nervous system depression or excitation may occur, drowsiness being reported most frequently. Sleep disturbance and,
rarely, hallucinations have been reported.
Skin rashes, with or without irritation, tachycardia and dryness of the mouth, nose and throat, have occasionally been reported.
Urinary retention has been reported occasionally in men receiving pseudoephedrine; prostatic enlargement could have been an
important predisposing factor.
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Drowsiness, gastrointestinal disturbances, psychomotor disturbance, tachycardia, arrhythmia, dry mouth, palpitation, urinary
difficulties.
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Drowsiness, gastrointestinal disturbances, headache, insomnia, excitation, tremor, tachycardia, arrhythmia, dry mouth,
palpitation, urinary difficulties.
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The following adverse events which may be causally related to the administration of Actilyse have been reported. The most
frequent adverse reaction associated with Actilyse is bleeding resulting in a fall in haematocrit and/or haemoglobin values. The
type of bleeding associated with thrombolytic therapy can be divided into 2 broad categories: Superficial or surface bleeding,
normally from punctures or damaged blood vessels; and internal bleedings into the gastrointestinal or urogenital tract,
retroperitoneum or CNS or bleeding of parenchymatous organs.
Death and permanent disability are reported in patients who have experienced stroke (including intracranial bleeding) and other
serious bleeding episodes.
The frequencies given as follows are based on corresponding occurrences in a clinical trial involving 8299 patients treated with
Actilyse for myocardial infarction.
The classification of cholesterol crystal embolisation which was not observed in the clinical trial population was based on
spontaneous reporting.
The number of patients treated in clinical trials with pulmonary embolism and stroke (within the 0-3 hrs time window) is very
small in comparison to the number in the trial for myocardial infarction described previously. Therefore, small numerical
differences observed in comparison with the number in myocardial infarction were presumably attributable to the small sample
size. Except for intracranial haemorrhage as an adverse reaction in stroke as well as for reperfusion arrhythmias in myocardial
infarction, there is no medical reason to assume that the qualitative and quantitative adverse reaction profile of Actilyse in
pulmonary embolism and acute ischaemic stroke is different from the profile in myocardial infarction.
Myocardial Infarction: Cardiac Disorders: Very Common: Reperfusion arrhythmias which can be life threatening and may require
the use of conventional antiarrhythmic therapies.
Myocardial Infarctions and Pulmonary Embolism: Nervous System Disorders: Uncommon: Intracranial haemorrhage.
Acute Ischaemic Stroke: Nervous System Disorders: Common: Intracranial haemorrhage. Symptomatic intracerebral
haemorrhages represent the major adverse event (up to 10% of patients). However, this had not shown an increased overall
morbidity or mortality.
Myocardial Infarction, Pulmonary Embolism and Acute Ischaemic Stroke: Gastrointestinal Disorders: Common: Gastrointestinal
tract bleeding, nausea, vomiting. Nausea and vomiting can also occur as symptoms of myocardial infarction. Uncommon:
Retroperitonium and gingival bleeding.
General Disorders and Administration Site Conditions: Very Common: Superficial bleeding, normally from punctures or damaged
blood vessels.
Injury and Poisoning and Procedural Complications: Uncommon: Anaphylactoid reactions which are usually mild, but can be life
threatening in isolated cases. They may appear as rash, urticaria, bronchospasm, angioedema, hypotension, shock or any other
symptom associated with allergic reactions. If they occur, conventional antiallergic therapy should be initiated. In such cases, a
relatively larger proportion of patients were receiving concomitant ACE inhibitors. No definite anaphylactic (IgE-mediated)
reactions to Actilyse are known. Transient antibody formation to Actilyse has been observed in rare cases and with low titres, but
a clinical relevance of this finding could not be established. Rare: Cholesterol crystal embolisation which may lead to
corresponding consequences in the organs concerned.
Investigations: Very Common: Drop in blood pressure. Common: Increased temperature.
Reproductive System and Breast Disorders: Common: Urogenital tract bleeding.
Respiratory, Thoracic and Mediastinal Disorders: Common: Epistaxis.
GI disturbances, infection, musculoskeletal pain, HTN, depression, dizziness, rash, cataract, UTI.
Thrombocytopenia, leucopenia, neutropenia, myelosuppression, increased blood or serum creatinine levels, nausea, vomiting,
diarrhea, constipation, abdominal pain, wt loss, decrease of hearing acuity, tinnitus, paresthesias, deep tendon reflexes,
cutaneous erythematous eruption, itching, fever; liver function test, alkaline phosphatase, transaminases & total bilirubin
abnormalities; taste alteration, alopecia, chills, fever & hemolytic uremic syndrome.
Adverse reactions reported in excess (0.5%) of placebo and as more than as isolated case in patients receiving piogliatazone in
double-blind studies are listed as follows as MedRA preferred term by system organs class and absolute frequency.
Frequency are defined as: Common >1/100; uncommon >1/1000, <1/100; rare >1/10,000, <1/1000; very rare >1/10,000; not
known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Monotherapy: Eye Disorder: Common: Visual disturbance.
Infectious and Infestations: Common: Upper respiratory tract infection. Uncommon: Sinusitis.
Investigations: Common: Increased weight, increased CK.
Nervous System Disorders: Common: Hypoaesthesia. Uncommon: Insomnia.
Plioglitazone in Combination with Metformin: Blood and Lymphatic System Disorder: Common: Anemia.
Eye Disorder: Common: Visual disturbances.
Gastrointestinal Disorders: Common: Flatulence.
Investigations: Common: Increased weight.
Musculoskeletal System and Connective Tissue Disorders: Common: Arthralgia.
Nervous System Disorders:Common: Headache.
Renal and Urinary Disorders: Common: Hematuria.
Reproductive System and Breast Disorders: Common: Erectile dysfunction.
Plioglitazone in Combination with Sulfonylurea Metformin: Blood and Lymphatic System Disorder: Common: Anemia.
Eye Disorder: Common: Visual disturbances.
Gastrointestinal Disorders: Common: Flatulence.
Investigations: Common: Increased weight.
Musculoskeletal System and Connective Tissue Disorders: Common: Arthralgia.
Nervous System Disorders: Common: Headache.
Renal and Urinary Disorders: Common: Hematuria.
Reproductive System and Breast Disorders: Common: Erectile dysfunction.
In Combination with Sulfonylurea: Weight gain, glycosuria, hypoglycaemia, increase of lactose dehydrogenase, increase of
appetite, dizziness, headache, vertigo, visual disorder, sweating, proteinuria, fatigue.
In double-blind studies, oedema occurred in 5.9% of patients treated with Actos + sulfonylurea (sulfonylurea alone 1.9%) and in
6 of patients treated with Actos + metformin (metformin alone 2.5%). The reports of oedema were generally mild to moderate
and usually did not require discontinuation of treatment.
During treatment with Actos there was a small increase in total cholesterol which was mostly accounted for by an increase in the
HDL-cholesterol.
In clinical trials with Actos, the incidence of elevations of ALT >3 times the upper limit of normal was equal to placebo (0.2%).
But less than that seen in metformin or sulfonylurea comparator groups. The incidence of all adverse events relating to liver and
biliary systems was also low (Actos 1.1%, placebo 0.9%). Isolated cases of elevated liver enzymes and hepatocellular dysfunction
have occurred in post-marketing experience, although causal relationship has not been established.
Heart failure was not reported as an adverse event during double-blind clinical studies of Actos in combination with sulfonylurea
or
Overmetformin, but was
8500 patients withreported with an incidence
type 2 diabetes have beenoftreated
1.1% during studies of Actos
with pioglitazone in combination
in randomized, with insulin.
double-blind, After 60clinical
controlled weeks of
trials. This includes 2605 high-risk patients with type 2 diabetes treated with pioglitazone from the PROactive clinical trial. Over
6000 patients have been treated for =6 months and over 4500 patients for 1 year or longer. Over 3000 patients have received
pioglitazone for at least 2 years.
The most common adverse events reported in at least 5% of patients in the controlled 16-week clinical trial between placebo
plus metformin and pioglitazone 30 mg plus metformin were upper respiratory tract infection (15.6% and 15.5%), diarrhea (6.3%
and 4.8%), combined edema/peripheral edema (2.5% and 6%) and headache (1.9% and 6%), respectively.
The incidence and type of adverse events reported in at least 5% of patients in any combined treatment group from the 24-week
study comparing pioglitazone 30 mg plus metformin, and pioglitazone 45 mg plus metformin are shown in Table 2; the rate of
adverse events resulting in study discontinuation between the 2 treatment groups was 7.8% and 7.7%, respectively.
Most clinical adverse events were similar between groups treated with pioglitazone in combination with metformin and those
treated with pioglitazone monotherapy. Other adverse events reported in at least 5% of patients in controlled clinical trials
between placebo and pioglitazone monotherapy included myalgia (2.7% and 5.4%), tooth disorder (2.3% and 5.3%), diabetes
mellitus aggravated (8.1% and 5.1%) and pharyngitis (0.8% and 5.1%), respectively.
In US, double-blind studies, anemia was reported in =2% of patients treated with pioglitazone plus metformin (see General:
Piogliitazone Hydrochloride under Precautions).
In monotherapy studies, edema was reported for 4.8% (with doses from 7.5-45 mg) of patients treated with pioglitazone versus
1.2% of placebo-treated patients. Most of these events were considered mild or moderate in intensity (see General: Pioglitazone
Hydrochloride under Precautions).
Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive): In PROactive, 5238 patients with type 2 diabetes and
a prior history of macrovascular disease were treated with Actos (n=2605), force-titrated up to 45 mg daily, or placebo (n=2633),
in addition to standard of care. Almost all subjects (95%) were receiving cardiovascular medications (ß-blockers, ACE inhibitors,
ARBs, calcium-channel blockers, nitrates, diuretics, aspirin, statins, fibrates). Patients had a mean age of 61.8 years, mean
duration of diabetes 9.5 years and mean HbA1c 8.1%. Average duration of follow-up was 34.5 months. The primary objective of
this trial was to examine the effect of Actos on mortality and macrovascular morbidity in patients with type 2 diabetes mellitus
who were at high risk for macrovascular events. The primary efficacy variable was the time to the first occurrence of any event in
the cardiovascular composite endpoint (see Table 3). Although there was no statistically significant difference between Actos and
placebo for the 3-year incidence of a first event within this composite, there was no increase in mortality or in total
macrovascular events with Actos.
Post-marketing reports of new onset or worsening diabetic macular edema with decreased visual acuity have also been received
(see General: Pioglitazone Hydrochloride under Precautions).
Laboratory Abnormalities: Hematologic: Pioglitazone may cause decreases in hemoglobin and hematocrit. The fall in hemoglobin
and hematocrit with pioglitazone appears to be dose related. Across all clinical studies, mean hemoglobin values declined by 2%
to 4% in patients treated with pioglitazone. These changes generally occurred within the first 4-12 weeks of therapy and
remained relatively stable thereafter.
These changes may be related to increased plasma volume associated with pioglitazone therapy and have rarely been associated
Adverse drug reactions observed in patients using Actrapid HM/Penfill are mainly dose-dependent and due to the
pharmacologic effect of insulin. As for other insulin products, hypoglycemia, in general, is the most frequent adverse reactions. It
may occur if the insulin dose is too high in relation to the insulin requirement. The symptoms of hypoglycemia usually occur
suddenly. They may include cold sweats, cool pale skin, nervousness or tremor, anxiety, unusual tiredness or weakness,
confusion, difficulty in concentration, dizziness, hunger, blurred vision, headache, nausea and palpitation.
In clinical trials and during market use, the frequency varies with patient population and dose regimens, therefore no specific
frequency can be presented. Severe hypoglycemia may lead to unconsciousness and/or convulsions and may result in temporary
or permanent impairment of brain function or even death. During clinical trials, the overall rates of hypoglycemia did not differ
between patients treated with human insulin compared to insulin aspart.
Frequencies of adverse drug reactions from clinical trials, which by an overall judgment are considered related to Actrapid
HM/Penfill are as follows. The frequencies are defined as: Uncommon (>1/1000, <1/100). Isolated spontaneous cases presented
as very rare are defined as <1/10,000.
Immune System Disorder: Uncommon: Urticaria, rash. Very Rare: Anaphylactic reactions. Symptoms of generalized
hypersensitivity may include generalized skin rash, itching, sweating, gastrointestinal upset, angioneurotic edema, difficulty in
breathing, palpitation, reduction in blood pressure and fainting/loss of consciousness. Generalized hypersensitivity reactions are
potentially life threatening.
Nervous System Disorder: Very Rare: Peripheral neuropathy. Fast improvement in blood glucose control may be associated with a
condition termed "acute painful neuropathy", which is usually reversible.
Eye Disorders: Uncommon: Refraction disorders. Refraction anomalies may occur upon initiation of insulin therapy. These
symptoms are usually of transitory nature. Very Rare: Diabetic retinopathy. Long-term improved glycemic control decreases the
risk of progression of diabetic retinopathy. However, intensification of insulin therapy with abrupt improvement in glycemic
control may be associated with temporary worsening of diabetic retinopathy.
Skin and Subcutaneous Tissue Disorders: Uncommon: Lipodystrophy may occur at the injection site as a consequence of failure
to rotate injection sites within an area.
General Disorders and Administration Site Conditions: Uncommon: Injection site reactions (redness, swelling, itching, pain and
hematoma at the injection site) may occur during treatment with insulin. Most reactions are transitory and disappear during
continued treatment. Edema may occur upon initiation of insulin treatment. These symptoms are usually of transitory nature.
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Adverse reactions were reported in 60 of total 4174 patients (1.44%) treated with Acuatim cream. (The total cases reported from
the time of approval and completion of re-examination are as follows.)
Skin: <1%: Pruritus, irritation, redness/flushing, feeling of facial warmth, papules, contact dermatitis, dry skin and hot flushes.
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Transient pain, swelling. Rarely, oedema, rash, flushing, sensation of heat, hypersensitivity reactions, shock.
GI disorders.
Itching, burning, erythema or vesiculation, skin atrophy, telangiectasia, striae or acneform changes of skin & systemic effects.
Allergic Rhinitis: In multiple-dose, placebo-controlled trials, 2834 patients received Aerius tablets at doses of 2.5-20 mg daily, of
whom 1655 patients received the recommended daily dose of 5 mg. In patients receiving 5 mg daily, the rate of adverse events
was similar between Aerius- and placebo-treated patients. The percent of patients who withdrew prematurely due to adverse
events was 2.4% in the Aerius group and 2.6% in the placebo group. There were no serious adverse events in these trials in
patients receiving desloratadine. All adverse events that were reported by =2% of patients who received the recommended daily
dose of Aerius tablets (5 mg once daily), and that were more common with Aerius tablet than placebo, are listed in Table 5. (See
Table 5.)
The frequency and magnitude of laboratory and electrocardiographic abnormalities were similar in Aerius- and placebo-treated
patients.
There were no differences in adverse events for subgroups of patients as defined by gender, age or race.
Chronic Idiopathic Urticaria: In multiple-dose, placebo-controlled trials of chronic idiopathic urticaria, 211 patients received
Aerius tablets and 205 received placebo. Adverse events that were reported by =2% of patients who received Aerius tablets and
that were more common with Aerius than placebo were (rates for Aerius and placebo, respectively): Headache (14%, 13%),
nausea (5%, 2%), fatigue (5%, 1%), dizziness (4%, 3%), pharyngitis (3%, 2%), dyspepsia (3%, 1%) and myalgia (3%, 1%).
The following spontaneous adverse events have been reported during the marketing of desloratadine: Tachycardia, and rarely
hypersensitivity reactions (eg, rash, pruritus, urticaria, edema, dyspnea and anaphylaxis), hepatitis and elevated liver enzymes
including bilirubin.
In clinical trials in a pediatric population, Aerius syrup was administered to a total of 246 children 6 months to 11 years. The
overall incidence of adverse events in children 2-11 years was similar for Aerius syrup and the placebo groups. In infants and
toddlers 6-23 months, the most frequent adverse events reported in excess of placebo were diarrhea (3.7%), fever (2.3%) and
insomnia (2.3%).
In clinical trials in a range of indications including seasonal allergic rhinitis and chronic idiopathic urticaria, at the recommended
dose of 5 mg daily, undesirable effects with Aerius tablets were reported in 3% of patients in excess of those treated with
placebo. The most frequent adverse events were reported in excess of placebo were fatigue (1.2%), dry mouth (0.8%) and
headache (0.6%). Other undesirable effects reported very rarely during the post-marketing period are as follows: Cardiac
Disorders: Tachycardia, palpitations, psychomotor hyperactivity, seizures.
Gastrointestinal Disorders: Abdominal pain, nausea, vomiting, dyspepsia, diarrhea.
Hepatobiliary Disorders: Hepatitis, elevations of liver enzymes, increased bilirubin.
General Disorders: Hypersensitivity reactions (eg, anaphylaxis, angioedema, pruritus, rash and urticaria).
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Common adverse reactions (=1/100, <1/10) reported during clinical trials involving 414 adult for Aerius D-12 are tachycardia,
mouth dry, dizziness, psychomotoric hyperactivity, pharyngitis, anorexia, constipation, headache, fatigue, insomnia, somnolence,
sleep disorder and nervousness.
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Burn sensation, stinging, sneezing, headache, insomnia, palpitation, dry nose.
Impaired liver function, nausea, vomiting, gastric pain, heartburn, diarrhea, constipation, gastric bleeding; skin rash, dizziness,
bronchospasm, thrombocytopenia, lymphopenia, impaired kidney & liver function; blurred vision.
Fever, urticaria, flushing, nausea, headache, dyspnea, rigors, hypotension, chills, malaise, vomiting, HTN, tachycardia,
bradycardia.
Muscle weakness, loss of muscle mass, steroid myopathy, osteoporosis, vertebral compression fracture, pathological fracture of
long bone, osteonecrosis. GI effects. Impaired wound healing, thin fragile skin, facial erythema, sweating. CNS disturbances,
electrolyte imbalance, endocrine disorders. Posterior subcapsular cataract, increased intraocular pressure, glaucoma,
exophthalmus. Rarely, anaphylaxis.
Diarrhea, dry mouth, abdominal pain, nausea, vomiting, dyspepsia. Dizziness, fatigue, insomnia, psychomotor hyperactivity,
seizures. Tachycardia, palpitations. Fever, hepatitis, elevation of liver enzymes, increased bilirubin, anaphylaxis, angioedema,
pruritus, rash & urticaria.
Summary of the Safety Profile: The most commonly reported adverse reactions related to pemetrexed, whether used as
monotherapy or in combination, are bone marrow suppression manifested as anaemia, neutropenia, leukopenia,
thrombocytopenia and gastrointestinal toxicities, manifested as anorexia, nausea, vomiting, diarrhoea, constipation, pharyngitis,
mucositis and stomatitis. Other adverse reactions include renal toxicities, increased aminotransferase, alopecia, fatigue,
dehydration, rash, infection/sepsis and neuropathy. Rarely seen events include Stevens-Johnson syndrome and toxic epidermal
necrolysis.
Table 7 provides the frequency and severity of adverse reactions that have been reported in >5% of 168 patients with
mesothelioma who were randomised to receive cisplatin and pemetrexed and 163 patients with mesothelioma randomised to
receive the single agent cisplatin. In both treatment arms, these chemo-naive patients were fully supplemented with folic acid
and vitamin B12.
Frequency Estimate: Very common (=1/10); common (=1/100 and <1/10); uncommon (=1/1000 and <1/100); rare (=1/10,000
and <1/1000); very rare (<1/10,000) and not known (cannot be estimated from available data-spontaneous reports).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 7.)
Clinically relevant circular tumor cell (CTC) toxicities that were reported in =1% and =5% (common) of the patients that were
randomly assigned to receive cisplatin and pemetrexed include: Renal failure, infection, pyrexia, febrile neutropenia, increased
AST, ALT and gamma-glutamyl transpeptidase (GGT), urticaria and chest pain.
Clinically relevant CTC toxicities that were reported in <1% (uncommon) of the patients that were randomly assigned to receive
cisplatin and pemetrexed include arrhythmia and motor neuropathy.
Table 8 provides the frequency and severity of adverse reactions that have been reported in >5% of 265 patients randomly
assigned to receive single agent pemetrexed with folic acid and vitamin B12 supplementation and 276 patients randomly
assigned to receive single agent docetaxel. All patients were diagnosed with locally advanced or metastatic NSCLC and received
prior chemotherapy. (See Table 8.)
Clinically relevant CTC toxicities that were reported in =1% and =5% (common) of the patients that were randomly assigned to
pemetrexed include: Infection without neutropenia, febrile neutropenia, allergic reaction/hypersensitivity, increased creatinine,
motor neuropathy, sensory neuropathy, erythema multiforme and abdominal pain.
Clinically relevant CTC toxicities that were reported in <1 % (uncommon) of the patients that were randomly assigned to
pemetrexed include supraventricular arrhythmias.
Clinically relevant Grade 3 and Grade 4 laboratory toxicities were similar between integrated Phase 2 results from 3 single agent
pemetrexed studies (n=164) and the phase 3 single agent pemetrexed study described in the previous text, with the exception of
neutropenia (12.8% vs 5.3%, respectively) and ALT elevation (15.2% vs 1.9%, respectively). These differences were likely due to
differences in the patient population, since the phase 2 studies included both chemo-naive and heavily pre-treated breast cancer
patients with preexisting liver metastases and/or abnormal baseline liver function tests.
The table as follows provides the frequency and severity of adverse reactions considered possibly related to study drug that have
been reported in >5% of 839 patients with NSCLC who were randomized to receive cisplatin and pemetrexed and 830 patients
with NSCLC who were randomized to receive cisplatin and gemcitabine. All patients received study therapy as initial treatment
for locally advanced or metastatic NSCLC and patients in both treatment groups were fully supplemented with folic acid and
Drowsiness, dizziness; dry mouth; epileptiform seizures (high doses).
Abdominal pain & distention, diarrhoea or constipation, flatulence, musculoskeletal pain & headache.
Diarrhea, muscle cramps, fatigue, nausea, vomiting, insomnia, dizziness, psychiatric disturbances.
Somnolence, dizziness, ataxia, fatigue, nystagmus, headache, tremor, nausea, vomiting, diplopia, amblyopia, rhinitis.
Drowsiness, musculoskeletal weakness, amnesia, depression, lightheadedness, confusion, hallucinations, blurred vision,
headache, insomnia, paradoxical reactions, trembling, hypotension, GI disorder, rash, changes in libido, menstrual irregularities,
urine retention, blood dyscrasias & jaundice.
GI disorders eg, gastralgia, nausea or vomiting, diarrhoea. Rarely, anaphylactic shock have been reported w/ IM administration.
Constipation, dyspepsia, abdominal pain, headache, dizziness, vertigo, insomnia, hemorrhage, perforation, rash, liver & renal
impairment, thrombocytopenia.
Drowsiness, lightheadedness, blurred vision, coordination defects, GI discomfort, autonomic effects, dependence, w/drawal
symptoms.
Hypoglycaemia, temporary visual impairment, GI disturbances, liver impairment. Rarely, thrombopenia, leucopenia & haemolytic
anaemia; itching, urticaria, rashes.
Based on experience with Amaryl and on what is known of other sulfonylureas, the following adverse effects must be
considered.
Hypoglycaemia: As a result of the blood sugar-lowering action of Amaryl, hypoglycaemia may occur and may also be prolonged.
Possible symptoms of hypoglycaemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered
sleep, restlessness, aggressiveness, impaired concentration, alertness and reactions, depression, confusion, difficulty in speaking
and even speech loss, visual disorders, tremor, pareses, sensory disturbances, dizziness, helplessness, loss of self-control,
delirium, cerebral convulsions, somnolence and loss of consciousness up to and including coma, shallow respiration and slow
heart rate (bradycardia). In addition, signs of adrenergic counter-regulation may be present eg, sweating, clammy skin, anxiety,
rapid heart rate (tachycardia), hypertension, palpitations, angina pectoris and cardiac arrhythmias. The clinical picture of a
severe hypoglycaemic attack may resemble that of a stroke. The symptoms of hypoglycaemia nearly always subside when
hypoglycaemia is corrected.
Eyes: Especially at the start of treatment, temporary visual impairment may occur due to the change in blood sugar levels.
Digestive Tract: Occasionally, gastrointestinal symptoms may occur eg, nausea, vomiting, sensations of pressure or fullness in the
epigastrium, abdominal pain and diarrhoea.
In rare cases, liver enzyme levels may increase. In isolated cases, impairment of liver function (eg, with cholestasis and jaundice)
and hepatitis may develop, leading to liver failure.
Blood: Severe changes in blood picture may occur. Rarely, thrombopenia and in isolated cases, leucopenia, haemolytic anaemia
or eg, erythrocytopenia, granulocytopenia, agranulocytosis and pancytopenia (eg, due to myelosuppression) may develop.
Others: Occasionally, allergic or pseudoallergic reactions may occur eg, itching, urticaria or rashes (eg, erythema, morbilliform or
maculopapular eruptions), if skin reactions persist, Amaryl should be discontinued. Such reactions may be mild, but also may
become more serious and may be accompanied by dyspnoea and a fall in blood pressure, sometimes progressing to shock. If
urticaria occurs, a physician must be notified immediately.
In isolated cases, a decrease in serum sodium, inflammation of blood vessels (allergic vasculitis) and hypersensitivity of the skin
to light may occur.
Consult the physician if any of the adverse effects listed previously or any other undesired effects or unexpected changes occur.
Since some adverse effects (eg, severe hypoglycaemia, certain changes in blood picture, severe allergic or pseudoallergic
reactions or liver failure) may, under certain circumstances, become life-threatening, it is essential that, if sudden or severe
reactions do occur, inform a physician at once and, on no account, continue taking the drug without a physician's express
guidance.
Further to the previously mentioned adverse effects of Amaryl, the following events have been reported with sulfonylureas:
Porphyria cutanea tarda, hepatic porphyria reaction, disulfiram-like reaction, syndrome of inappropriate antidiuretic hormone
(SIADH) secretion. It has been suggested that these sulfonylureas may augment the peripheral action of ADH and/or increase the
release of ADH.
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Glimepiride: Based on experience with Amaryl M and on what is known of other sulfonylureas, the following adverse reactions
must be considered.
Hypoglycemia: As a result of the blood glucose-lowering action of Amaryl M, hypoglycemia may occur and may also be
prolonged.
Possible symptoms of hypoglycemia include headache, ravenous hunger, nausea, vomiting, lassitude, sleepiness, disordered
sleep, restlessness, aggressiveness, impaired concentration, alertness and reactions, depression, confusion, speech disorders,
aphasia, visual disorders, tremor, pareses, sensory disturbances, dizziness, helplessness, loss of self-control, delirium, cerebral
convulsions, somnolence and loss of consciousness up to and including coma, shallow respiration and bradycardia. In addition,
signs of adrenergic counter-regulation may be present eg, sweating, clammy skin, anxiety, tachycardia, hypertension,
palpitations, angina pectoris and cardiac arrhythmias.
The clinical picture of a severe hypoglycemic attack may resemble that of a stroke. The symptoms nearly always subside when
hypoglycemia is corrected.
Eyes: Temporary visual impairment may occur due to the change in blood sugar levels especially at the start of treatment.
Digestive Tract: Occasionally, GI symptoms eg, nausea, vomiting, sensations of pressure or fullness in the epigastrium, abdominal
pain and diarrhea may occur.
Hepatobiliary: In cases, liver enzyme elevation and liver impairment (eg, cholestasis and jaundice) may occur, as well as hepatitis
which may progress to liver failure.
Blood: Changes in the blood picture may occur. Rarely, thrombopenia and in isolated cases, leucopenia, or hemolytic anemia,
erythrocytopenia, granulocytopenia, agranulocytosis or pancytopenia may develop. Because it is reported that aplastic anemia
and pancytopenia may occur in sulfonylureas, careful monitoring should be performed. If these occur, Amaryl M should be
discontinued and adequate treatment taken.
Hypersensitivity: Occasionally, allergic or pseudoallergic reactions (eg, itching, urticaria or rashes) may occur. These reactions are
almost mild but may develop into serious reactions with dyspnea and a fall in blood pressure, sometimes progressing to shock.
In the event of urticaria, a physician must be notified immediately.
Others: In isolated cases, allergic vasculitis, skin hypersensitivity to light or a decrease in serum sodium concentration may occur.
Metformin: Lactic Acidosis: See Warnings and Overdosage.
Hypoglycemia.
Gastrointestinal: GI symptoms (diarrhea, nausea, vomiting, abdominal bloating, flatulence and anorexia) are the most common
reactions to Amaryl M and are approximately 30% more frequent in patients on monotherapy than in placebo-treated patients,
particularly during therapy initiation. These symptoms are generally transient and resolve spontaneously during continued
treatment. Occasionally, temporary dose reduction may be useful. In clinical trials, Amaryl M was discontinued due to GI
reactions in approximately 4% of patients.
Because GI symptoms during therapy initiation appear to be dose-related, they may be decreased by gradual dose escalation
and by having patients take Amaryl M with meals.
Because significant diarrhea and/or vomiting may cause dehydration and prerenal azotemia, under such circumstances, Amaryl
M should be temporarily discontinued.
For patients who have been stabilized on Amaryl M, nonspecific GI symptoms should not be attributed to therapy unless
intercurrent illness or lactic acidosis has been excluded.
Hypersensitivity reactions, GI disturbances, blood disorders.
Amlodipine is well tolerated. In placebo-controlled clinical trials involving patients with hypertension or angina, the most
commonly observed side effects were headache, edema, fatigue, somnolence, nausea, abdominal pain, flushing, palpitations
and dizziness. In these clinical trials, no pattern of clinically significant laboratory test abnormalities related to amlodipine has
been observed.
Less commonly observed adverse effects in marketing experience include altered bowel habits, arthralgia, asthenia, dyspepsia,
dyspnea, gingival hyperplasia, gynecomastia, impotence, increased urinary frequency, mood changes, muscle cramps, myalgia,
pruritus, rash, visual disturbance and rarely, erythema multiforme.
Jaundice and hepatic enzyme elevations have been reported very infrequently (mostly consistent with cholestasis). Some cases
severe enough to require hospitalization have been reported in association with the use of amlodipine. In many instances, causal
association is uncertain.
As with other calcium-channel blockers, the following adverse events have been rarely reported and cannot be distinguished
from the natural history of the underlying disease: MI, arrhythmia (including ventricular tachycardia and atrial fibrillation) and
chest pain.
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Hypercalcemia.
Reactions: Hypersensitivity: =5% or frequency unknown: [Rash, etc].
Gastrointestinal: 0.1%-<5%: Nausea and vomiting.
Cardiovascular: =5% or frequency unknown: [Chest discomfort, palpitation, etc].
Hepatic: 0.1%-<5%: Increases in AST (SGOT), ALT (SGPT), ALP or total bilirubin.
Large Dose and Rapid Administration: (Cerebral, pulmonary and peripheral edema; hyperpotassemia, acidosis, water
intoxication), [acidosis].
Other: =5% or frequency unknown: Vascular pain, phlebitis, [chills, fever, feeling of warmth, headache].
[ ]: Common adverse reactions in amino acid injections.
( ): Common adverse reactions in maintenance solutions.
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Caution For Usage Instructions for Use, Handling and Disposal: Admixture: Open the outer wrap just before use, break the center
seal between the 2 chambers, and mix the 2 solutions thoroughly. The solution in 1 chamber should not be administered alone
without mixing with the solution in the other chamber.
At the Time of Preparation: Physical changes of the solution such as precipitation may occur when Aminofluid is combined with
the following drugs: Drugs which are stable in alkaline or acidic conditions and drugs which are not soluble in water.
The solution should not be mixed with drugs containing calcium salt or phosphate, since this will cause the solution to
precipitate.
Since the solution contains calcium salt, hemopexis may occur when mixed with citrated blood.
After opening the outer wrap and mixing the 2 solutions, the mixed solution should be used promptly.
Before Administration: When administering Aminofluid, it is recommended to maintain urine output of >500 mL/day or >20
mL/hr.
To prevent infection, carry out all procedures under aseptic conditions.
Use the solution after warming to near body temperature during cold environmental conditions.
Use the solution immediately after opening the container. After use, discard all unused solution.
During Administration: When vascular pain occurs, use an alternate site or discontinue the administration.
Extravasation of the solution may result in skin necrosis and ulceration. Discontinue the administration promptly after confirming
clinical signs of extravasation (eg, redness, infiltration or swelling) at injection site.
Precautions for Handling: Since an oxygen absorbent is enclosed between the bag and the outer wrap to maintain stability of the
product, do not remove the outer wrap until immediately before use.
A crystalline precipitate may form in the upper chamber solution (amino acid solution) due to changes in environmental
temperature. Shake the solution at temperatures of 15°-25°C to dissolve precipitates before use.
Do not use the solution if the outer wrap covering the product has been damaged, the solution is discolored, or a precipitate
that cannot be dissolved by shaking has formed.
If the 2 solutions packaged in the chambers have already been mixed for any reason or if the center seal between the 2
chambers looks white in color (the sealed area appears white in color when it is peeled off), do not use the product.
Puncture rubber stopper vertically with a needle in the marked circle. If the stopper is not pierced vertically, the needle may pass
through the neck of the container and cause leakage of the contents.
Since the bag product may not be infused in tandem using a connection tube, use a Y-type infusion set when 2 bag products are
Hypersensitivity: Skin rashes or other hypersensitivity reactions have been rarely reported and administration should be
discontinued if such signs develop.
Digestive: Nausea and vomiting may infrequently occur.
Cardiovascular: Chest discomfort and palpitations may infrequently occur.
Carbohydrate Metabolism: Hypoglycemia rarely occurs.
Large Dose and Rapid Administration: Acidosis may occur after a rapid and large dose of Aminoleban Infusion.
Others: Chills, fever, headache and vascular pains may infrequently occur.
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Caution For Usage Crystals may precipitate in a cool place. Warm the container at 15°-25°C to dissolve the precipitates and use
the solution after cooling at near body temperature.
Since sodium and chloride are formulated in respective volumes of approximately 14 and 94 mEq/L, concomitant use with
electrolyte solutions and the administration of Aminoleban Infusion in large doses require careful supervision of the electrolyte
balance.
Slow IV infusion is recommended.
Local reactions consisting of erythema, phlebitis & thrombosis at the infusion site can occur w/ peripheral infusion. Generalized
flushing, vomiting & fever furing infusion of amino acid soln.
Neurotoxicity, ototoxicity, nephrotoxicity; skin rash, drug fever, headache, paresthesia, tremor, nausea & vomiting, eosinophilia,
arthralgia, anemia, hypotension; acute muscular paralysis, apnea.
Hypersensitivity: Rare eruption or other hypersensitivity reactions were reported. If such reactions occur, the solution should be
discontinued.
Cardiovascular: Occasional chest discomfort and palpitation were reported.
Gastrointestinal: Occasional nausea and vomiting were reported.
Hepatic: An occasional increase in SGOT, SGPT and total bilirubin levels was reported.
Renal: An occasional increase in blood urea nitrogen was reported.
Large and Acute Administration: Acidosis was reported after large and acute administration of Amiparen.
Others: Occasional chills, fever, hot flush, headache and vascular pain were reported.
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Caution For Usage Crystals may precipitate at cool temperature. Warm the container at 50°-60°C to dissolve the precipitates and
use the solution after cooling to near body temperature.
The Amiparen container is not equipped with an air tube, so it should be punctured with an air needle immediately before to
prevent leakage of solution.
Hypersensitivity reactions, nausea, vomiting, chest discomfort, palpitations, increased BUN or creatinine & liver enzymes,
acidosis, chills, fever, flushing, headache, vascular pain, lower extremities edema, hyperkalemia & dry mouth. Increased GOT,
GPT, ?-GTP, ALP, LDH, LAP, total bilirubin or ammonia.
Headache, edema, fatigue, somnolence, nausea, abdominal pain, flushing, palpitation, dizziness. Rarely joint pain, dyspepsia,
gingival hyperplasia, gynecomastia, impotence, frequent urination, mood changes, muscle cramps & pain, pruritus, skin rash,
visual disturbances.
Occasionally nausea & vomiting; acidosis & CHF (large doses & rapid administration).
Hypersensitivity, haematological & anaphylactoid reactions, GI disturbances.
Fluid & electrolyte disturbance, steroid myopathy, muscle weakness, peptic ulcer, osteoporosis, purpura, striae,
hyperpigmentation.
Fluid & electrolyte disturbance, steroid myopathy, muscle weakness, peptic ulcer, osteoporosis, purpura, striae,
hyperpigmentation.
Minor GI disturbance.
Agranulocytosis, hypersensitivity reactions, skin reactions, drowsiness, dizziness, constipation, depression, hypotension, nausea,
tremor, urinary retention, vertigo.
Nausea, dizziness, somnolence. Asthenia, fatigue, hot flushes; headache, tremor; abdominal pain, constipation, diarrhea,
dyspepsia, flatulence, dry mouth, vomiting; anorexia, anxiety, confusion, euphoria, insomnia, nervousness; pruritus, rash,
increased sweating.
Hypersensitivity, GI disturbances including very rarely pseudomembranous colitis. Haematological changes. Occasionally,
thrombophlebitis (IV inj).
Nausea, vomiting, abdominal pain, diarrhea; skin allerg; possible transient rise of ASAT/ALAT transaminase &/or alkalline
phosphatase.
Diarrhoea, pseudomembranous colitis, dyspepsia, nausea, vomiting, candidiasis, rash, urticaria, hypersensitivity reactions.
Transient hepatitis, cholestatic jaundice, Stevens-Johnson syndrome, exfoliative dermatitis.
Skin sensitization.
Allergy or hypersensitivity reactions.
Arterial BP, pulse rate & breathing changes; nausea, vomiting, headache, hiccups, laryngospasm, dyspnea, hallucination, ataxia,
skin rash, paradoxical reactions, amnesic episodes, resp depression, apnea.
Excessive reduction in BP; dry (non-productive) tickling cough. Uncommonly/rarely, headache, tachycardia, drowsiness,
peripheral edema, psychiatric symptoms, renal impairment, hyperkalemia, angioneurotic edema.
Anxiety, nervousness, insomnia, drowsiness, fatigue, asthenia, tremor, sweating, anorexia, nausea, diarrhea, dizziness or
lightheadedness.
Drowsiness, dizziness, dry mouth; epileptiform seizures (large doses); skin rashes.
Headache, dizziness; vertigo; nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia; increased
transaminases; rash.
Drowsiness.
Hypoglycemia, the most frequent undesirable effect of insulin therapy, may occur if the insulin dose is too high in relation to the
insulin requirement.
The following related adverse reactions from clinical investigations were listed by system organ class and in order of decreasing
incidence (Very common: >1/10; common: >1/100, <1/10; uncommon: >1/1,000, <1/100; rare: >1/10,000, <1/10,000; very rare:
<1/10,000).
Metabolism and Nutrition Disorders: Very Common: Hypoglycemia. Symptoms of hypoglycemia usually occur suddenly. They
may include cold sweats, cool pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion,
difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.
Hypoglycemia can become severe and may lead to unconsciousness and/or convulsions and may result in temporary or
permanent impairment of brain function or even death.
Skin and Subcutaneous Tissue Disorders: Common: Injection site and local hypersensitivity reactions.
Local hypersensitivity reactions (redness, swelling and itching at the injection site) may occur during treatment with insulin.
These reactions are usually transitory and normally disappear during continued treatment.
Rare: Lipodystrophy. It may occur at the injection site as a consequence of failure to rotate injection sites within an area.
General Disorders: Uncommon: Systemic hypersensitivity reactions may include uticaria, chest tightness, dyspnea, allergic
dermatitis and pruritus. Severe cases of generalized allergy, including anaphylactic reaction, may be life-threatening.
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Blood & lyphatic system disorders, metabolism & nutrition disorders, nervous system, eye, ear & labyrinth, cardiac, vascular,
resp, throracic & mediastinal, GI, skin & SC tissue, musculoskeletal & connective tissue, renal & urinary disorders, & reproductive
system & breast disorders; fatigue, peripheral edema, edema, gait abnormalities, asthenia, thirsty, chest tightness, pain,
exacerbated anasarca, pyrexia, rigors; increased alanine aminotransferase, blood creatinine, phosphokinase, aspartate
aminotransferase; decreased platelet count; increased blood glucose.
In placebo-controlled trials in patients with hypertension, the overall incidence of adverse events did not differ between the
irbesartan (56.2%) and the placebo groups (56.5%). Discontinuation due to any clinical or laboratory adverse events was less
frequent for irbesartan-treated patients (3.3%) than for placebo-treated patients (4.5%). The incidence of adverse events was
not related to dose (in the recommended dose range), gender, age, race, or duration of treatment.
In diabetic hypertensive patients with microalbuminuria and normal renal function, orthostatic dizziness and orthostatic
hypotension were reported in 0.5% of the patients (i.e. uncommon) but in excess of placebo.
The following table presents the adverse drug reactions that were reported in placebo-controlled trials in which 1,965
hypertensive patients received irbesartan. Terms marked with a star (*) refer to the adverse reactions that were additionally
reported in >2% of diabetic hypertensive patients with chronic renal insufficiency and overt proteinuria and in excess of placebo.
The frequency of adverse reactions listed below is defined using the following convention: Very common (= 1/10), common (=
1/100, <1/10), uncommon (= 1/1,000, < 1/100), rare (= 1/10,000, < 1/1,000), very rare (<1/10,000). Within each frequency
grouping, undesirable effects are presented in order of decreasing seriousness.
Adverse reactions additionally reported from post-marketing experience are also listed. These adverse reactions are derived
from spontaneous reports and therefore, the frequency of these adverse reactions is "not known" (cannot be estimated from
the available data).
Immune system disorders: Not known: Hypersensitivity reactions such as angiodema, rash, urticaria.
Metabolism and Nutrition Disorders: Not known: Hyperkalaemia.
Nervous System Disorders: Common: Dizziness, orthostatic dizziness*. Not known: vertigo, headache.
Ear and Labyrinth Disorder: Not known: tinnitus.
Cardiac Disorders: Uncommon: Tachycardia.
Vascular Disorders: Common: Orthostatic hypotension*. Uncommon: Flushing.
Respiratory, Thoracic and Mediastinal Disorders: Uncommon: Cough.
Gastrointestinal Disorders: Common: Nausea/vomitting. Uncommon: Diarrhoea, dyspepsia/heartburn. Not known: Dysgeusia.
Hepato-biliary disorders: Not known: Hepatitis, abnormal liver function.
Skin and Subcutaneous Tissue Disorders: Not known: Leukocytoclastic vasculitis.
Musculoskeletal, Connective Tissue and Bone Disorders: Common: Musculoskeletal pain*. Not known: Myalgia, arthralgia (in
some cases associated with increased plasma creatine kinase levels), muscle cramps.
Renal and Urinary Disorders: Not known: Impaired renal function including isolated cases of renal failure in patients at risk (see
Precautions.)
Reproductive System and Breast Disorders: Uncommon: Sexual dysfunction.
General Disorders and Administration Site Conditions: Common: Fatigue. Uncommon: Chest pain.
Investigation: Very common: Hyperkalaemia* occurred more often in diabetic patients treated with irbesartan than with
placebo.
In diabetic hypertensive patients with microalbuminuria and normal renal function, hyperkalaemia (=5.5 mEq/L) occurred in
29.4% of the patients in the irbesartan 300 mg group and 22% of the patients in the placebo group. In diabetic hypertensive
patients with chronic renal insufficiency and overt proteinuria, hyperkalemia (=5.5 mEq/L) occurred in 46.3% of the patients in
the irbesartan group and 26.3% of the patients in the placebo group.
Common: Significant increases in plasma creatine kinase were commonly observed (1.7%) in irbesartan treated subjects. None
Epigastric pain, nausea, vomiting, diarrhea, abdominal cramps, dyspepsia, flatulence, anorexia, headache, dizziness or vertigo,
drowsiness, sensation disturbances (paresthesia, rashes, skin eruptions); asthma, anaphylactic/anaphylactoid systemic reactions
(hypotension).
Occasionally mild agitation in the elderly subject and allergic skin reaction.
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GI disturbances, allergic reactions, anaphylaxis, blood disorders.
In clinical trials, Arcoxia was evaluated for safety in approximately 4800 individuals, including approximately 3400 patients with
OA, RA or chronic low back pain (approximately 600 patients with OA or RA were treated for 1 year or longer).
The following drug-related adverse experiences were reported in clinical studies in patients with OA, RA or chronic low back pain
treated for up to 12 weeks. These occurred in =1% of patients treated with Arcoxia and at an incidence greater than placebo:
Asthenia/fatigue, dizziness, lower extremity edema, hypertension, dyspepsia, heartburn, nausea, headache, increased ALT and
AST.
The adverse experience profile was similar in patients with OA or RA treated with Arcoxia for 1 year or longer.
Seven thousand one hundred eleven (7111) patients were enrolled in an additional study in OA that compared the GI tolerability
of etoricoxib 90 mg once daily (1.5 times above the dose recommended for OA) and diclofenac sodium 50 mg 3 times daily over
a mean period of 9 months. The adverse experience profile on Arcoxia was generally similar to that reported in the Phase IIb/III
placebo-controlled clinical studies; however, hypertension adverse experiences occurred at a higher rate on Arcoxia than on
diclofenac.
In the initial clinical development program, approximately 3100 patients were treated with etoricoxib 60 mg daily for 12 weeks
or longer. There was no discernible difference in the rate of serious thrombotic cardiovascular events between patients receiving
etoricoxib 60 mg or non-naproxen NSAIDs. However, the rate of these events was higher in patients receiving etoricoxib
compared with those receiving naproxen 500 mg twice daily.
In a clinical study for ankylosing spondylitis, patients were treated with Arcoxia 90 mg once daily for up to 1 year (n=126). The
adverse experience profile in this study was generally similar to that reported in chronic studies in OA, RA and chronic low back
pain.
In a clinical study for acute gouty arthritis, patients were treated with Arcoxia 120 mg once daily for 8 days.
In clinical studies for acute analgesia, patients were treated with Arcoxia 120 mg once daily for 1-7 days. The adverse experience
profile in these studies was generally similar to that reported in the combined OA, RA and chronic low back pain studies.
Post-Marketing Experience: The following adverse reactions have been reported in post-marketing experience: Immune System
Disorders: Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.
Psychiatric Disorders: Anxiety, insomnia, confusion, hallucinations.
Nervous System Disorders: Dysgeusia, somnolence.
Cardiac Disorders: Congestive heart failure.
Vascular Disorders: Hypertensive crisis.
Respiratory, Thoracic and Mediastinal Disorders: Bronchospasm.
Gastrointestinal Disorders: Abdominal pain, oral and peptic ulcers including perforation and bleeding (mainly in elderly patients),
vomiting, diarrhea.
Hepatobiliary Disorders: Hepatitis.
Skin and Subcutaneous Tissue Disorders: Angioedema, pruritus, rash, Stevens-Johnson syndrome, urticaria.
Renal and Urinary Disorders: Renal insufficiency, including renal failure, usually reversible upon discontinuation of therapy (see
Precautions).
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Nausea, vomiting, diarrhea, constipation, abdominal pain or transient burning of the upper stomach, skin rashes,
bronchospasms or thrombocytopenia.
Burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis,
allergic contact dermatitis, secondary infection, skin atrophy, striae, miliaria.
Abdominal pain, nausea, diarrhea; slight gum bleeding or epistaxis; skin rash, urticaria, itching. Very rarely, serious
hypersensitivity reaction w/ edema, dyspnea & hypotension.
Diarrhoea, muscle cramps, fatigue, nausea, vomiting, insomnia, dizziness, psychiatric disturbances.
Diarrhea, muscle cramps, fatigue, nausea, vomiting, insomnia, headache, anorexia, hallucination, agitation, aggressive behavior,
depression, abnormalities, somnolence, syncope, dizziness, abdominal disturbance, rash, pruritus, urinary incontinence, pain,
decreased wt, ecchymosis, infection.
Dyspepsia, nausea, vomiting, abdominal pain, diarrhea; anemia, leucopenia, thrombocytopenia; pruritus, skin rash; headache,
vertigo, tinnitus, drowsiness; edema, increased BP.
Unless specified, the following frequency categories were calculated from the number of adverse events reported in a large
phase III study conducted in 9366 post-menopausal women with operable breast cancer treated for 5 years and unless specified,
no account was taken of the frequency within the comparative treatment group or whether the investigator considered it to be
related to study medication.
Very Common (=10%): Vascular: Hot flushes, mainly mild or moderate in nature.
General: Asthenia, mainly mild or moderate in nature.
Musculoskeletal and Connective Tissue Disorders: Arthralgia/joint stiffness, arthritis.
Nervous System: Headache, mainly mild or moderate in nature.
Gastrointestinal: Nausea, mainly or mild to moderate in nature.
Skin and Subcutaneous Tissue: Rash, mainly or mild to moderate in nature.
Common (=1% and <10%): Skin and Subcutaneous Tissue: Hair thinning (alopecia), mainly mild or moderate in nature, allergic
reactions.
Gastrointestinal: Diarrhoea, mainly mild or moderate in nature, vomiting, mainly mild or moderate in nature.
Nervous System: Somnolence, mainly mild or moderate in nature, carpal tunnel syndrome*, sensory disturbances (including
paraesthesia, taste loss and taste perversion).
Hepatobiliary Disorders: Increased alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase.
Reproductive System and Breast: Vaginal dryness, mainly mild or moderate in nature; vaginal bleeding, mainly mild or moderate
in nature**.
Metabolism and Nutrition: Anorexia, mainly mild in nature; hypercholesterolemia, mainly mild or moderate in nature.
Musculoskeletal and Connective Tissue Disorders: Bone pain, myalgia.
Uncommon (=0.1% and <1%): Metabolism and Nutrition: Hypercalcaemia (with or without an increase in parathyroid hormone).
Hepatobiliary Disorders: Increased ?-GT and bilirubin. Hepatitis.
Skin and Subcutaneous Tissue: Urticaria.
Musculoskeletal and Connective Tissue Disorders: Trigger finger.
Rare (=0.01% and <0.1%): Skin and Subcutaneous Tissue: Erythema multiform, anaphylactoid reaction. Cutaneous vasculitis
(including some reports of Henoch-Schonlein purpura).
Very Rare (<0.01%): Skin and Subcutaneous Tissue: Stevens-Johnson syndrome, angioedema.
*Events of carpal tunnel syndrome have been reported in patients receiving Arimidex treatment in clinical trials in greater
numbers than those receiving treatment with tamoxifen. However, the majority of these events occurred in patients with
identifiable risk factors for the development of the condition.
**Vaginal bleeding has been reported commonly, mainly in patients with advanced breast cancer, during the 1st few weeks after
changing from existing hormonal therapy to treatment with Arimidex. If bleeding persists, further evaluation should be
considered.
As Arimidex lowers circulating estrogen levels, it may cause a reduction in bone mineral density placing some patients at a higher
risk of fracture (see Precautions).
In a large phase III study conducted in 9366 postmenopausal women with operable breast cancer treated for 5 years, ischaemic
cardiovascular events were reported more frequently in patients treated with Arimidex compared to those treated with
tamoxifen, although the
Headache, asthenia, difference
fever. Nausea, was not statistically
vomiting, significant.
constipation. Anxiety,The observed
insomnia, difference wassomnolence,
lightheadedness, mainly due toakathisia,
more reports of
tremor.
Rhinitis, coughing, rash, blurred vision.
The safety of fondaparinux 2.5 mg has been evaluated in: 3595 patients undergoing major orthopaedic surgery of the lower
limbs treated up to 9 days, 327 patients undergoing hip fracture surgery treated for 3 weeks following an initial prophylaxis of 1
week, 1407 patients undergoing abdominal surgery treated up to 9 days, 425 medical patients who are at risk for
thromboembolic complications treated up to 14 days, 10,057 patients undergoing treatment of UA or NSTEMI acute coronary
syndrome (ACS), 6036 patients undergoing treatment of STEMI ACS.
Adverse reactions are listed as follows by system organ class and frequency and indication. Frequencies are defined as: Very
common (=1/10); Common (=1/100, <1/10); Uncommon (=1/1000, <1/100); Rare (=1/10,000, <1/1000); Very rare (=1/10,000).
These adverse reactions should be interpreted within the surgical or medical context of the indications.
Clinical Trial Data: Undesirable Effects in Patients Undergoing Major Orthopaedic Surgery of Lower Limbs and/or Abdominal
Surgery: Infections and Infestations: Rare: Postoperative wound infections.
Blood and Lymphatic System Disorders: Common: Anaemia, bleeding (various sites including rare cases of
intracranial/intracerebral and retroperitoneal bleedings), purpura. Uncommon: Thrombocytopenia, thrombocythaemia,
abnormal platelets, coagulation disorder.
Immune System Disorders: Rare: Allergic reaction.
Metabolism and Nutrition Disorders: Rare: Hypokalaemia.
Nervous System Disorders: Uncommon: Headache. Rare: Anxiety, confusion, dizziness, somnolence, vertigo.
Vascular Disorders: Rare: Hypotension.
Respiratory, Thoracic and Mediastinal Disorders: Rare: Dyspnoea, coughing.
Gastrointestinal Disorders: Uncommon: Nausea, vomiting. Rare: Abdominal pain, dyspepsia, gastritis, constipation, diarrhoea.
Hepatobiliary Disorders: Uncommon: Abnormal liver function tests, increased hepatic enzymes. Rare: Bilirubinaemia.
Skin and Subcutaneous Tissue Disorders: Uncommon: Rash, pruritus, wound secretion.
General Disorders and Administration Site Conditions: Common: Oedema. Uncommon: Fever, wound secretion, peripheral
oedema. Rare: Injection site reaction, chest and leg pain, fatigue, genital oedema, flushing, syncope.
Undesirable Effects in Medical Patients: Blood and Lymphatic System Disorders: Common: Bleeding (haematoma, haematuria,
haemoptysis, gingival bleeding). Uncommon: Anaemia.
Respiratory, Thoracic and Mediastinal Disorders: Uncommon: Dyspnoea.
Skin and Subcutaneous Tissue Disorders: Uncommon: Rash, pruritus.
General Disorders and Administration Site Conditions: Uncommon: Chest pain.
In other studies or in post-marketing experience, rare cases of intracranial/intracerebral and retroperitoneal bleedings have been
reported.
The adverse event profile reported in the ACS program is consistent with the adverse drug reactions identified for VTE
prophylaxis.
Bleeding was a commonly reported event in patients with UA/NSTEMI and STEMI. The incidence of adjudicated major bleeding
was 2.1% (fondaparinux) versus 4.1% (enoxaparin) up to and including day 9 in the Phase III UA/NSTEMI study and the incidence
of adjudicated severe haemorrhage by modified TIMI criteria was 1.1% (fondaparinux) versus 1.4% [control (UFH/placebo)] up to
and including day 9 in the Phase III STEMI study.
In the Phase III UA/NSTEMI study, the most commonly reported non-bleeding adverse events (reported in at least 1% of subjects
on fondaparinux)glaucoma,
GI disturbances; were headache, chest
mydriasis; pain and
urinary atrial fibrillation.
retention, mental disturbances, excitement.
Mild headache, hallucination, restlessness, insomnia, allergic reactions, photophobia, nausea, vomiting, constipation, diarrhoea,
abdominal pain, flatulence, anorexia, dyspepsia, drowsiness, tremor, depression.
Hot flushes, arthralgia, nausea, fatigue, increased sweating, dizziness, headache, insomnia, pain, abdominal pain, anorexia,
vomiting, depression, alopecia, peripheral oedema, constipation, dyspepsia, joint & musculoskeletal pain, increased hepatic
enzyme, blood bilirubin, blood alkaline phosphatase, carpal tunnel syndrome, diarrhea, rash, fracture, osteoporosis, asthenia.
Asthmatic attacks, syncope, ocular pemphigoid, AV block, cardiac arrest, CHF.
GI reactions including nausea, vomiting, diarrhea, constipation, gastric pain & bleeding. Peptic ulceration. Rarely, insomnia,
irritability, agitation, minor hearing disorders, edema, skin rashes, palpitations. Bronchospasm, thrombocytopenia, lymphopenia,
visual disturbances.
Nausea, epigastric pain, heartburn, dizziness, sleeplessness, headache, rash, itching, tinnitus, edema.
Fever, infection on the injection site, venous thrombosis or phlebitis on the injection site, hypervolemia.
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Peptic ulceration, GI disturbances, increased bleeding time, hypothrombinemia, hypersensitivity reaction, dizziness, tinnitus.
Drowsiness, musculoskeletal weakness, amnesia, depression, lightheadedness, confusion, hallucinations, blurred vision,
headache, insomnia, paradoxical reactions, trembling, hypotension, GI disorder, rash, changes in libido, menstrual irregularities,
urine retention, blood dyscrasias & jaundice.
Palpitations, tachycardia; tremor & headache; nausea & vomiting; skin rash.
Insomnia; headache; nausea, diarrhea, abdominal pain, dyspepsia, constipation, flatulence; myalgia; asthenia.
Insomnia; headache; nausea, diarrhea, abdominal pain, dyspepsia, constipation, flatulence; myalgia; asthenia; hypo- &
hyperglycemia, anorexia; peripheral neuropathy, paresthesia; pancreatitis, vomiting; hepatitis, cholestatic jaundice; rash,
pruritus, alopecia; myopathy, myositis, muscle cramps; impotence; angioneurotic edema; angina.
Atorvastatin is generally well-tolerated. Adverse reactions have usually been mild and transient. <2% of patients were
discontinued from clinical trials due to side effects attributed to atorvastatin.
The most frequent (=1%) adverse effects associated with atorvastatin therapy, in patients participating in controlled clinical
studies were: Psychiatric Disorders: Insomnia.
Nervous System Disorders: Headache.
Gastrointestinal Disorders: Nausea, diarrhea, abdominal pain, dyspepsia, constipation, flatulence.
Musculoskeletal and Connective Tissue Disorders: Myalgia.
General Disorders and Administration Site Conditions: Asthenia.
The Following Additional Adverse Effects Have Been Reported in Atorvastatin Clinical Trials: Metabolism and Nutrition Disorders:
Hypoglycemia, hyperglycemia, anorexia.
Nervous System Disorders: Peripheral neuropathy, paresthesia.
Gastrointestinal Disorders: Pancreatitis, vomiting.
Hepatobiliary Disorders: Hepatitis, cholestatic jaundice.
Skin and Subcutaneous Tissue Disorders: Alopecia, pruritus, rash.
Musculoskeletal and Connective Tissue Disorders: Myopathy, myositis, muscle cramps.
Reproductive System and Breast Disorders: Impotence.
Not all effects listed above have been causally associated with atorvastatin therapy.
Children (ages 10-17 years): Patients treated with atorvastatin has an adverse experience profile generally similar to that of
patients treated with placebo, the most common adverse experiences observed in both groups, regardless of causality
assessment, were infections.
In post-marketing experience, the following additional undersirable effects have been reported: Blood and Lymphatic System
Disorders: Thromboctytopenia.
Immune System Disorders: Allergic reactions (including anaphylaxis).
Metabolism and Nutrition Disorders: Weight gain.
Nervous System Disorders: Hypoesthesia, amnesia, dizziness.
Ear and Labyrinth Disorders: Tinnitus.
Skin and Subcutaneous Tissue Disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, bullous
rashes, urticarial.
Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis, arthralgia, back pain.
General Disorders and Administration Site Conditions: Chest pain, peripheral edema, malaise.
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GI effects, kidney or liver functions abnormality, hematological changes, CV effects, resp & CNS disorders.
GI motility disorders, dry mouth, headache, tachycardia, palpitations, supraventricular tachycardia, atrial fibrillation, ocular
accommodation disturbances, nausea, urinary retention, cough, local irritation, inhalation-induced bronchospasm, allergic
reactions.
Data from large clinical trial was used to determine the frequency of very common to rare undesirable effects. The frequencies
assigned to all other undesirable effects (ie, those occurring at <1/10,000) were mainly determined using post-marketing data
and refer to a reporting rate rather than a true frequency.
The following convention has been used for the classification of frequency: Very Common: >1/10; common: >1/100 and <1/10;
uncommon: >1/1000 and <1/100; rare: >1/10,000 and <1/1000; very rare: <1/10,000.
Infections and Infestations: Common: Mucocutaneous candidiasis.
Blood and Lymphatic System Disorders: Rare: Reversible leucopenia (including neutropenia) and thrombocytopenia. Very Rare:
Reversible agranulocytosis and hemolytic anemia. Prolongation of bleeding time and prothrombin time (see Precautions).
Immune System Disorders: Very Rare: Angioneurotic edema, anaphylaxis, serum sickness-like syndrome, hypersensitivity
vasculitis, interstitial nephritis.
Nervous System Disorders: Uncommon: Dizziness, headache. Very Rare: Reversible hyperactivity and convulsions. Convulsions
may occur in patients with impaired renal function or in those receiving high doses.
Gastrointestinal Disorders: Adults: Very Common: Diarrhea. Common: Nausea, vomiting. Children: Common: Diarrhea, nausea,
vomiting.
All Populations: Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be
reduced by taking amoxicillin-clavulanate at the start of a meal. Uncommon: Indigestion. Very Rare: Antibiotic-associated colitis
(including pseudomembranous colitis and hemorrhagic colitis). Superficial tooth discoloration has been reported very rarely in
children. Good oral hygiene may help to prevent tooth discoloration as it can usually be removed by brushing*.
Note: *This statement is core safety for the syrup, suspension and chewable tablet formulations.
Hepatobiliary Disorders: Uncommon: A moderate rise in AST and/or ALT has been noted in patients treated with ß-lactam class
antibiotics, but the significance of these findings is unknown. Very Rare: Hepatitis and cholestatic jaundice. These events have
been noted with other penicillins and cephalosporins.
Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged
treatment.
Children: These events have been rarely reported in children. All Populations: Signs and symptoms usually occur during or
shortly after treatment but in some cases may be not become apparent until several weeks after treatment has ceased. These
are usually reversible. Hepatic events may be severe and in extremely rare circumstances, deaths have been reported. These
have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the
potential for hepatic effects.
Skin and Subcutaneous Tissue Disorders: Uncommon: Skin rash, pruritus, urticaria. Rare: Erythema multiforme. Very Rare:
Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalized exanthematous
pustulosis (AGEP). If any hypersensitivity dermatitis occurs, treatment should be discontinued.
Renal and Urinary Disorders: Very Rare: Interstitial nephritis, crystalluria (see Overdosage).
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Data from large clinical trials were used to determine the frequency of adverse reactions. The following convention has been
used for the classification of frequency: Very common (>1/10); common (>1/100 and <1/10); uncommon (>1/1000 and <1/100);
rare (>1/10,000 and <1/1000); very rare (<1/10,000).
Clinical Trial Data: Respiratory, Thoracic and Mediastinal Disorders: Very Common: Epistaxis.
In adults and adolescents, the incidence of epistaxis was higher in longer-term use (>6 weeks) than in short-term use (up to 6
weeks). In paediatric clinical studies of up to 12-weeks duration, the incidence of epistaxis was similar between Avamys nasal
spray and placebo.
Common: Nasal ulceration.
Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods.
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Headache, somnolence, dry mouth, fatigue.
Clinical Trial Data: Avodart Monotherapy: Approximately 19% of the 2167 patients who received dutasteride in the 2-year Phase
III placebo-controlled trials developed adverse reactions during the 1st year of treatment. The majority of events were mild to
moderate and occurred in the reproductive system. No change to the adverse event profile was apparent over a further 2 years
in open-label extension studies.
Table 1 shows adverse reactions from controlled clinical trials and post-marketing experience. The listed adverse events from
clinical trials are investigator-judged drug-related events (with incidence =1%) reported with a higher incidence in patients
treated with dutasteride compared with placebo during the 1st year of treatment. Adverse events from post-marketing
experience were identified from spontaneous post-marketing reports, therefore, the true incidence is unknown.
Avodart and Tamsulosin Combination Therapy for BPH: The following investigator-judged drug-related adverse events (with a
cumulative incidence of =1%) have been reported in the CombAT (combination of Avodart and tamsulosin) study, a comparison
of Avodart 0.5 mg and tamsulosin 0.4 mg once daily for 4 years in combination or as monotherapy. (See Table 2.)
Post-Marketing Data: Adverse drug reactions are listed by system organ class and frequency. Frequencies are defined as: Very
common (=1/10), common (=1/100 and <1/10), uncommon (=1/1000 and <1/100), rare (=1/10,000 and <1/1000) and very rare
(<1/10,000) including isolated reports. Frequency categories determined from post-marketing data refer to reporting rate rather
than true frequency.
Immune System Disorders: Very Rare: Allergic reactions, including rash, pruritus, urticaria, localised oedema and angioedema.
Skin and Subcutaneous Tissue Disorders: Rare: Alopecia (primary body hair loss), hypertrichosis.
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Nausea, vomiting, diarrhea or abdominal pain; vertigo, dizzines, headache; skin rash, photosensitivity, angioedema; palpitation,
chest pain; monilia, vaginitis, nephritis; fatigue.
Diarrhoea, vomiting, abdominal discomfort, flatulence, nausea, gastric distension, gastric pain, dyspepsia, cholestatic jaundice.
Skin rash, GUT disturbances, headache, vertigo, somnolence, fatigue.
Retrobulbar neuritis w/ a reduction of visual acuity, central scotoma & green-red color blindness. Allergic rashes. GI
disturbances. CNS effects. Hyperuricemia. Peripheral neuritis. Liver damage. Blood disorders.
Retrobulbar neuritis w/ reduced visual acuity, central scotoma, green-red colour blindness. Allergic rashes. GI disturbances.
Rarely, jaundice & peripheral neuritis. CNS effects. Hyperuricaemia.
Hypersensitivity reactions, GI disorders, renal & liver functions disorders, changes in blood constituent, local reactions,
neurological effects, superinfection.
Cream: The following convention has been used for the classification of frequency: Common (>1/100 and <1/10).
Skin and Subcutaneous Tissue Disorders: Cutaneous hypersensitivity reactions.
Ointment: Adverse reactions are listed as follows by system organ class and frequency. Frequencies are defined as: Very common
(=1/10), common (=1/100, <1/10), uncommon (=1/1000, <1/100), rare (=1/10,000, <1/1000), very rare (<1/10,000), including
isolated reports. Common and uncommon adverse reactions were determined from pooled safety data from a clinical trial
population of 1573 treated patients encompassing 12 clinical studies. Very rare adverse reactions were primarily determined
from post-marketing experience data and therefore, refer to reporting rate rather than true frequency.
Immune System Disorders: Very Rare: Systemic allergic reactions have been reported with Bactroban ointment.
Skin and Subcutaneous Tissue Disorders: Common: Burning localized to the area of application. Uncommon: Itching, erythema,
stinging and dryness localized to the area of application; cutaneous sensitization reactions to mupirocin or the ointment base.
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Loss of appetite, dry mouth, nausea, diarrhoea or constipation, headache, dizziness, somnolence, ataxia, confusion, agitation,
visual accommodation disorders. Rarely, allergic skin reactions, fever, haematological effects.
High dose may cause nervousness, fatigue, drowsiness, nausea, headache, resp & CNS depressions.
GI disturbances; dizziness, headache, insomnia, hallucinations, tremor, tiredness, visual disturbances; skin reactions; temporary
increase in liver enzyme values.
Clinical Trial Experience: Because clinical trial are conducted under widely varying conditions, adverse reaction rates observed in
the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates
observed in practice.
Compensated Liver Disease: Assessment of adverse reactions is based on 4 studies (AI463014, AI463022, AI463026, and
AI463027) in which 1720 subjects with chronic hepatitis B infection and compensated liver disease received double-blind
treatment with Baraclude 0.5 mg/day (n=679), Baraclude 1 mg/day (n=183) or lamivudine (n=858) for up to 2 years. Median
duration of therapy was 69 weeks for Baraclude-treated subjects and 63 weeks for lamivudine-treated subjects in studies
AI463022 and AI463027 and 73 weeks for Baraclude-treated subjects and 51 weeks for lamivudine-treated subjects in studies
AI463026 and AI463014. The safety profiles of Baraclude and lamivudine were comparable in these studies. The safety profile of
Baraclude 1 mg (n=51) in HIV/HBV co-infected subjects enrolled in study AI463038 was similar to that of placebo (n=17) through
24 weeks of blinded treatment and similar to that seen in non-HIV infected patients.
The most common adverse events of any severity with at least a possible relation to study drug for Baraclude-treated subjects
were headache, fatigue, dizziness and nausea. The most common adverse events among lamivudine-treated subjects were
headache, fatigue and dizziness. One percent of Baraclude-treated subjects in these 4 studies compared with 4% of lamivudine-
treated subjects discontinued for adverse events or abnormal laboratory test results (see Warnings and Precautions).
Clinical Adverse Events: Selected clinical adverse events of moderate to severe intensity and considered at least possibly related
to treatment occurring during therapy in 4 clinical studies in which Baraclude was compared with lamivudine are presented in
Table 11. (See Table 11.)
Laboratory Abnormalities: Frequencies of selected treatment-emergent laboratory abnormalities reported during therapy in 4
clinical trials of Baraclude compared with lamivudine are listed in Table 12. (See Table 12.)
Among Baraclude-treated subjects in these studies, on-treatment ALT elevations >10 x ULN and >2 x baseline generally resolved
with continued treatment. A majority of these exacerbations were associated with a =2 log10/mL reduction in viral load that
preceded or coincided with the ALT elevation. Periodic monitoring of hepatic function is recommended during treatment.
Exacerbations of Hepatitis After Discontinuation of Treatment: An exacerbation of hepatitis or ALT flare was defined as ALT >10 x
ULN and >2 x the subject's reference level (minimum baseline or last measurement at end of dosing). For all subjects who
discontinued the treatment, regardless of reason, Table 12 presents the proportion of subjects in each study who experienced
post-treatment ALT flares. In these studies, a subset of subjects was allowed to discontinue treatment at or after 52 weeks if they
achieved a protocol-defined response to therapy. If Baraclude is discontinued without regard to treatment response, the rate of
post-treatment flares could be higher (see Warnings and Precautions). (See Table 13.)
Decompensated Liver Disease: Study AI463048 was a randomized, open-label study of Baraclude 1 mg once daily versus adefovir
dipivoxil 10 mg once daily given for up to 48 weeks in adult subjects with chronic HBV infection and evidence of hepatic
decompensation, defined as a Child-Turcotte-Pugh (CTP) score of 7 or higher (see Microbiology: Clinical Studies under Actions).
Among the 102 subjects receiving Baraclude, the most common treatment emergent adverse events of any severity, regardless
of causality, occurring through week 48 were peripheral edema (16%), ascites (15%), pyrexia (14%), hepatic encephalophathy
(10%), and upper respiratory infection (10%). Clinical adverse reactions not listed in Table 11 that were observed through week
Diarrhea, nausea, vomiting, maculopapular rash, urticaria, drug fever, reversible neutropenia, decreased Hb or hematocrit,
transient eosinophilia, thrombocytopenia, hypoprothrombinemia, haemolytic anemia, headache, fever, inj pain, chills, transient
elevation of SGOT, SGPT, alkaline phosphatase, & bilirubin level.
Hypersensitivity reactions; constipation, feeling of abdominal enlargement, diarrhea, nausea, vomiting, heartburn, abdominal
pain, belching, taste abnormality; increase in transaminase levels; hematologic reactions.
Hypersensitivity (rash); insomnia, headache, dizziness, convulsion; nausea, anorexia; diplopia; warm sensation; abnormal liver
function.
GI disturbances, black stool.
Renal losses due to rapid infusion; nausea & flushing in susceptible patients; febrile response, inj site infection, venous
thrombosis or phlebitis extending from inj site, extravasation & hypervolemia.
Allergy.
Rarely, allergic-anaphylactic reactions.
Many of the listed undesirable effects can be assigned to the anticholinergic and ß-adrenergic properties of Berodual. As with all
inhalation therapy, Berodual may show symptoms of local irritation. Adverse drug reactions were identified from data obtained
in clinical trials and pharmacovigilance during post approval use of the drug.
The most frequent side effects reported in clinical trials were cough, dry mouth, headache, tremor, pharyngitis, nausea,
dizziness, dysphonia, tachycardia, palpitations, vomiting, hypersensitivity, anaphylactic reactions, hypokalemia, nervousness,
agitation, mental disorder, glaucoma, increased intraocular pressure, accommodation disorder, mydriasis, blurred vision, eye
pain, corneal oedema, conjunctival hyperaemia, halo vision, increased heart rate, arrhythmia, atrial fibrillation, supraventricular
tachycardia, myocardial ischaemia, cough, pharyngitis, bronchospasm, throat irritation, pharyngeal oedema, laryngospasm,
paradoxical dry throat, stomatitis, glossitis, gastrointestinal motility disorder, diarrhoea, constipation, mouth oedema, urticaria,
rash, pruritus, angioedema, hyperhidrosis, muscular weakness, muscle spasms, myalgia, urinary retention, systolic increased
blood pressure, diastolic decreased blood pressure.
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As with other ß-agonists, Berotec may cause the following adverse reactions including serious hypokalaemia. As with all
inhalation therapy, Berotec may show symptoms of local irritation.
Immune System Disorders: Hypersensitivity.
Metabolism and Nutrition Disorders: Hypokalaemia.
Psychiatric Disorders: Agitation, nervousness.
Nervous System Disorders: Tremor, headache, dizziness.
Cardiac Disorders: Myocardial ischaemia, arrhythmia, tachycardia, palpitations.
Respiratory, Thoracic and Mediastinal Disorders (Only Applicable to Inhalative Formulations): Paradoxical bronchospasm, cough,
throat irritation.
Gastrointestinal Disorders: Nausea, vomiting.
Skin and Subcutaneous Tissue Disorders: Hyperhidrosis; skin reaction eg, rash, pruritus, urticaria.
Musculoskeletal, Connective Tissue and Bone Disorders: Muscle spasm, myalgia, muscular weakness.
Investigations: Increased systolic blood pressure, decreased diastolic blood pressure.
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Sedation.
Nausea, vomiting, diarrhea, abdominal pain, indigestion, flatulence, anorexia, dysphagia, dyspepsia; dizziness, headache, fatigue,
insomnia, agitation, tremor; drug eruption of the skin, macula erythema, Stevens-Johnson syndrome, anaphylaxis/anaphylactoid
reactions, dyspnea; hypersensitivity reactions; eosinophilia, leucocytopenia, leukocytosis, granulositopenic anemia; laboratory or
urine deposite effects; transient increase of transaminase & alkaline phosphatase conc in the blood, cholestatic jaundice,
transient increase of blood urea, creatinine, bilirubin, hyperglycemia; tendonitis; interstitial nephritis, kidney failure, polyuria,
urinary retention, urethral bleeding, vaginitis & acidosis; hepatitis, tachycardia, palpitation, atrial flutter, ventricular ectopy,
syncope, angina pectoris, HTN, MI, cardiopulmonary arrest, cerebral thrombosis, flushing, migraine, syncope; joint & muscle
pain, malaise, tendovaginitis, mild photosensitivity, tinnitus, hearing disturbances, epistaxis, laryngeal or pulmonary oedema,
hemoptysis, bronchospasm, pulmonary embolism.
Irritation, hypersensitivity, rise in IOP, blurred vision, subcapsular cataract, corneal thinning & perforation.
Constipation, diarrhea, dry mouth, abdominal distention, headache, nausea, vomiting, urticaria, rash. Rarely, hepatic enzyme &
hematologic changes.
Rise in IOP, hypersensitivity reactions, blurred vision, posterior subcapsular cataracts formation.
Nausea, anorexia, epigastric pain, metallic taste, vomiting, GI disturbances, urticaria, skin redness, pruritus, angioedema,
anaphylaxis.
Abdominal discomfort.
Skin reactions, fever, hematological changes, increased hepatic enzyme function, diarrhea, nausea, vomiting,
pseudomembranous colitis, pain at the inj site, phlebitis.
Zn toxicity (>150 mg/day). Prolonged use & high-dose of Zn may reduce lipoprotein conc & copper absorption.
Anaphylactic shock; serum sickness; fever w/ trembling; pain at inj site after high dose of antisera inj.
Itching, exanthema, cold sensation, fever, hot flushes, nausea, dizziness, anaphylactic shock.
Nausea, vomiting, diarrhea, pseudomembranous colitis, icterus, oliguria, proteinuria, allergic reactions (urticaria, maculopapular
rash, SJS) & hypotension.
Hematological, skin reactions, other allergic reactions.
The following adverse reactions have been observed during treatment with perindopril and ranked under the following
frequencies: Very common (1/10); common (1/100, <1/10); uncommon (1/1000, <1/100); rare (1/10,000, <1/1000); very rare
(<1/10,000); not known (cannot be estimated from the available data).
Blood and Lymphatic System Disorders: Decreases in haemoglobin and haematocrit, thrombocytopenia, leucopenia/neutropenia
and cases of agranulocytosis or pancytopenia, have been reported very rarely. In patients with a congenital deficiency of G6PDH,
very rare cases of haemolytic anaemia have been reported (see Precautions).
Metabolism and Nutrition Disorders: Not Known: Hypoglycaemia (see Precautions and Interactions).
Psychiatric Disorders: Uncommon: Mood or sleep disturbances.
Nervous System Disorders: Common: Headache, dizziness, vertigo, paraesthesia. Very Rare: Confusion.
Eye Disorders: Common: Visual disturbance.
Ear and Labyrinth Disorders: Common: Tinnitus.
Cardiac Disorders: Very Rare: Arrhythmia, angina pectoris and myocardial infarction, possibly secondary to excessive hypotension
in high-risk patients (see Precautions).
Vascular Disorders: Common: Hypotension and effects related to hypotension. Very Rare: Stroke, possibly secondary to excessive
hypotension in high-risk patients (see Precautions). Not Known: Vasculitis.
Respiratory, Thoracic and Mediastinal Disorders: Common: Cough, dyspnoea. Uncommon: Bronchospasm. Very Rare:
Eosinophilic pneumonia, rhinitis.
Gastrointestinal Disorders: Common: Nausea, vomiting, abdominal pain, dysgeusia, dyspepsia, diarrhoea, constipation.
Uncommon: Dry mouth. Very Rare: Pancreatitis.
Hepatobiliary Disorders: Very Rare: Hepatitis either cytolytic or cholestatic (see Precautions).
Skin and Subcutaneous Tissue Disorders: Common: Rash, pruritus. Uncommon: Angioedema of face, extremities, lips, mucous
membranes, tongue, glottis and/or larynx, urticaria (see Precautions). Very Rare: Erythema multiforme.
Musculoskeletal and Connective Tissue Disorders: Common: Muscle cramps.
Renal and Urinary Disorders: Uncommon: Renal insufficiency. Very Rare: Acute renal failure.
Reproductive System and Breast Disorders: Uncommon: Impotence.
General Disorders and Administration Site Conditions: Common: Asthenia. Uncommon: Sweating.
Investigations: Increases in blood urea and plasma creatinine, hyperkalaemia reversible on discontinuation may occur, especially
in the presence of renal insufficiency, severe heart failure and renovascular hypertension. Elevation of liver enzymes and serum
bilirubin have been reported rarely.
Clinical Trials: During the randomised period of the EUROPA study, only serious adverse events were collected. Few patients
experienced serious adverse events: 16 (0.3%) of the 6122 perindopril patients and 12 (0.2%) of the 6107 placebo patients. In
the perindopril-treated patients, hypotension was observed in 6 patients, angioedema in 3 patients and sudden cardiac arrest in
1 patient. More patients withdrew for cough, hypotension or other intolerance on perindopril than on placebo, 6.0% (n=366)
versus 2.1% (n=129) respectively.
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The administration of perindopril inhibits the renin-angiotensin-aldosterone axis and tends to reduce the potassium loss caused
by indapamide. Four percent (4%) of the patients on treatment with Bioprexum Plus experience hypokalemia (potassium level
<3.4 mmol/L).
The following undesirable effects could be observed during treatment and ranked under the following frequency: Very common
(>1/10); common (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/1000), very rare (<1/10,000) and not
known (cannot be estimated from the available data).
Blood and Lymphatic System Disorders: Very Rare: Thrombocytopenia, leucopenia/neutropenia, agranulocytosis, aplastic
anaemia, hemolytic anaemia.
Anaemia has been reported with ACE inhibitors in specific circumstances (patients who have had kidney transplants, patients
undergoing hemodialysis). (See Precautions.)
Psychiatric Disorders: Uncommon: Mood or sleep disturbances.
Nervous System Disorders: Common: Paraesthesia, headache, asthenia, feelings of dizziness, vertigo. Very Rare: Confusion.
Eye Disorders: Common: Visual disturbance.
Ear and Labyrinth Disorders: Common: Tinnitus.
Vascular Disorders: Common: Hypotension, whether orthostatic or not (see Precautions).
Cardiac Disorders: Very Rare: Arrhythmia including bradycardia, ventricular tachycardia, atrial fibrillation, angina pectoris and
myocardial infarction possibly secondary to excessive hypotension in high-risk patients (see Precautions).
Respiratory, Thoracic and Mediastinal Disorders: Common: A dry cough has been reported with the use of ACE inhibitors. It is
characterised by its persistence and disappearance when treatment is withdrawn. An iatrogenic etiology should be considered in
the presence of this symptom. Dyspnea. Uncommon: Bronchospasm. Very Rare: Eosinophilic pneumonia, rhinitis.
Gastrointestinal Disorders: Common: Constipation, dry mouth, nausea, epigastric pain, anorexia, vomiting, abdominal pain, taste
disturbance, dyspepsia, diarrhea. Very Rare: Pancreatitis.
Hepatobiliary Disorders: Very Rare: Hepatitis either cytolytic or cholestatic (see Precautions). Not Known: In case of hepatic
insufficiency, there is a possibility of onset of hepatic encephalopathy (see Contraindications and Precautions).
Skin and Subcutaneous Tissue Disorders: Common: Rash, pruritus, maculopapular eruptions. Uncommon: Angioedema of face,
extremities, lips, mucous membranes, tongue, glottis and/or larynx, urticaria (see Precautions). Hypersensitivity reactions,
mainly dermatological, in subjects with a predisposition to allergic and asthmatic reactions; purpura. Possible aggravation of
preexisting acute disseminated lupus erythematosus. Very Rare: Erythema multiforme, toxic epidermal necrolysis, Stevens-
Johnson syndrome. Cases of photosensitivity reactions have been reported (see Precautions).
Musculoskeletal, Connective Tissue and Bone Disorders: Common: Cramps.
Renal and Urinary Disorders: Uncommon: Renal insufficiency. Very Rare: Acute renal failure.
Reproductive System and Breast Disorders: Uncommon: Impotence.
General Disorders and Administration Site Conditions: Common: Asthenia. Uncommon: Sweating.
Investigations: Potassium depletion with particularly serious reduction in levels of potassium in some at risk populations (see
Precautions). Reduced sodium levels with hypovolemia causing dehydration and orthostatic hypotension. Increase in uric acid
levels and in blood glucose levels during treatment. Slight increase in urea and in plasma creatinine levels, reversible when
treatment is stopped. This increase is more frequent in cases of renal artery stenosis, arterial hypertension treated with
diuretics, renal insufficiency. Increased levels of potassium, usually transitory. Rare: Raised plasma calcium levels.
Anaphylactic shock; serum sickness; fever w/ trembling; pain at inj site after high dose of antisera inj.
Anaphylactic shock; serum sickness; fever w/ trembling, pain at inj site after high dose of antisera inj.
Blood dyscrasias; anaphylaxis, urticaria; GI disturbances, Gray syndrome.
Feeling of coldness or numbness in the extremities; nausea, vomiting, diarrhea, constipation; tiredness, exhaustion, dizziness,
headache; muscular weakness & cramps; AV stimulus disturbances, worsening of heart failure, orthostatic hypotension; sleep
disturbances, depression; bronchospasm in patient w/ bronchial asthma or history of obstructive airways disease; nightmares,
hallucination; hypersensitivity reactions; increased ALAT, ASAT, triglycerides; hepatitis, potency disorders; hearing impairment,
allergic rhinitis, reduced tear flow; conjunctivitis; dyspnea, cardiomyopathy, tachycardia, viral infection, pneumonia, fatigue.
Hypersensitivity reaction including contact dermatitis.
Increased IOP, perforation in conditions causing thinning of the cornea, local allergic reactions.
HTN, nausea, vomiting, headache, hypotension, hallucination, diarrhea, chest pain/transient chest pain; tinnitus, diaphoresis,
palpitation, dyspnea, thrombophlebitis, hematuria, leg cramp, nasal congestion, taste disturbance, allergic reaction, severe
arrhythmia, cerebrovascular attack & disturbance, skin eruption, CV reactions.
Pneumonitis, occasionally progresssing to pulmonary fibrosis; pyrexia, thickening of vein wall; nausea & vomiting. Very rarely,
anaphylaxis.
Reversible ovarian enlargement, abdominal discomfort or pain, nausea, vomiting, transient visual disturbances, headache,
abnormal uterine bleeding, dizziness, fatigue, insomnia, vertigo.
Candesartan Cilexetil-Hydrochlorothiazide: Blopress Plus has been evaluated for safety in >2800 patients treated for
hypertension. More than 750 of these patients were studied for at least 6 months and >500 patients were treated for at least 1
year. Adverse experiences have generally been mild and transient in nature and have only infrequently required discontinuation
of therapy. The overall incidence of adverse events reported with Blopress Plus was comparable to placebo. The overall
frequency of adverse experiences was not related to dose, age, gender or race.
In placebo-controlled trials that included 1089 patients treated with various combinations of candesartan cilexetil (doses of 2-32
mg) and hydrochlorothiazide (doses of 6.25-25 mg) and 592 patients treated with placebo, adverse events, whether or not
attributed to treatment, occurring in >2% of patients treated with Blopress Plus and that were more frequent for Blopress Plus
than placebo were: Respiratory System Disorder: Upper respiratory tract infections (3.6% vs 3%).
Body as a Whole: Back pain (3.3% vs 2.4%), influenza-like symptoms (2.5% vs 1.9%).
Central/Peripheral Nervous System: Dizziness (2.9% vs 1.2%).
The frequency of headache was >2% [2.9% in patients treated with Blopress Plus but was less frequent than the rate in patients
treated with placebo (5.2%)].
Other adverse events have been reported whether or not attributed to treatment, with an incidence of =0.5% from >2800
patients worldwide treated with Blopress Plus included: Body as a Whole: Inflicted injury, fatigue, pain, peripheral oedema,
asthenia.
Central and Peripheral Nervous System: Vertigo, paresthesia, hypesthesia.
Respiratory System Disorders: Bronchitis, sinusitis, pharyngitis, coughing, rhinitis, dyspnea.
Musculoskeletal System Disorders: Arthralgia, myalgia, arthrosis, arthritis, leg cramps, sciatica.
Gastrointestinal System Disorders: Nausea, abdominal pain, diarrhea, dyspepsia, gastritis, gastroenteritis, vomiting.
Metabolic and Nutritional Disorders: Hyperuricaemia, hyperglycemia, hypokalemia, increased BUN, increased creatinine
phosphokinase.
Urinary System Disorder: Urinary tract infection, hematuria, cystitis.
Liver/Biliary System Disorders: Abnormal hepatic function, increased transaminase levels.
Heart Rate and Rhythm Disorders: Tachycardia, palpitation, extrasystoles, bradycardia.
Psychiatric Disorders: Depression, insomnia, anxiety.
Cardiovascular Disorders: Abnormal ECG.
Skin and Appendages Disorders: Eczema, increased sweating, pruritus, dermatitis, rash.
Platelet/Blood Clotting Disorders: Epistaxis.
Resistance Mechanism Disorders: Infection, viral infection.
Vision Disorder: Conjunctivitis.
Hearing and Vestibular Disorders: Tinnitus.
Reported events seen less frequently than 0.5% included angina pectoris, myocardial infarction and angioedema.
Candesartan Cilexetil: Other adverse experiences that have been reported without regard to causality are as follows: Body as a
Whole: Fever.
Metabolic and Nutritional Disorders: Hypertriglyceridemia.
Psychiatric Disorders: Somnolence.
Urinary System
Occassional Disorders:
dizziness, Albuminuria.
headaches, fatigue, bradycardia, postural HTN, GI upset, flare-like syndrome, reduced lacrimations.
Hypocalcemia, bone pain, myalgia, pyrexia, influenza, rigors, osteonecrosis of the jaw.
Localised ocular toxicity & hypersensitivity including itching, swelling & conjunctival erythema.
Localized ocular toxicity & hypersensitivity including lid itching, swelling & conjunctival erythema. Secondary infection.
Headache, abdominal pain, nausea, vag hemorrhage, OHSS, abdominal distention, inj site reaction.
Hypersensitivity reactions. May cause collagen loss & SC atrophy.
Drowsiness, ataxia, confusion, dryness of the mouth, blurring of vision, urinary hesitancy & constipation.
Rarely, somnolence & GI disturbances. Aggravation or manifestation of extrapyramidal symptoms (prolonged use in elderly).
Rash, itching or swelling (especially of the face, tongue or throat), severe dizziness, trouble in breathing.
Myelosuppression, hypersensitivity, cutaneous & infusion site reactions, fluid retention, neuropathy, GI symptoms (including
stomatitis, nausea & vomiting), hypotension, elevation of liver enzymes.
The intensity of the adverse reactions depends on dosage and route of administration. An initial dose titration will often reduce
the adverse reactions. Most of the adverse reactions are characteristic of sympathomimetic amines. The majority of these
effects have reversed spontaneously within the first 1-2 weeks of treatment. (see table.)
Annualized rates of bleeding are summarized in Table 2. About half of the bleeding events were in the first 30 days. (See Table 2.)
As shown in Table 2, BRILINTA was associated with a somewhat greater risk of non-CABG bleeding than was clopidogrel. No
baseline demographic factor altered the relative risk of bleeding with BRILINTA compared to clopidogrel.
In PLATO, 1,584 patients underwent CABG surgery. The percentages of those patients who bled are shown in Table 3. Rates were
very high but similar for BRILINTA and clopidogrel. (See Table 3.)
Although the platelet inhibition effect of Brilinta has a faster offset than clopidogrel in in vitro tests and Brilinta is a reversibly
binding P2Y12 inhibitor, PLATO did not show an advantage of BRILINTA compared to clopidogrel for CABG-related bleeding.
When antiplatelet therapy was stopped 5 days before CABG, major bleeding occurred in 75% of BRILINTA treated patients and
79% on clopidogrel.
No data exists with Brilinta regarding a hemostatic benefit of platelet transfusions.
Drug Discontinuation: In PLATO, the rate of study drug discontinuation attributed to adverse reactions was 7.4% for BRILINTA and
5.4% for clopidogrel. Bleeding caused permanent discontinuation of study drug in 2.3% of BRILINTA patients and 1.0% of
clopidogrel patients. Dyspnea led to study drug discontinuation in 0.9% of BRILINTA and 0.1% of clopidogrel patients.
Common Adverse Events: A variety of non-hemorrhagic adverse events occurred in PLATO at rates of =3%. These are shown in
Table 4. In the absence of a placebo control, whether these are drug related cannot be determined in most cases, except where
they are more common on BRILINTA or clearly related to the drug's pharmacologic effect (dyspnea). (See Table 4.)
Post-Marketing Experience: The following adverse reactions have been identified during post-approval use of BRILINTA. Because
these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their
frequency or establish
Nausea, vomiting a causalstomatitis,
& diarrhea, relationship to drug
glottis; exposure.
headache & dizziness; skin reactions; eosinophilia, thrombocytosis, leukopenia,
granulocytopenia & hemolytic anemia; transient elevations of SGOT or SGPT, BUN. Rarely, inflammatory reactions at inj site.
Drowsiness, indigestion, psychomotor disorder, tachycardia, arrhythmia, palpitation, urinary retention, liver damage (high dose &
prolonged use).
Nausea, diarrhea, indigestion, bloating, headache, vertigo, increased sweating, skin, rash, increased serum transaminase.
Mild GI disturbances.
Nausea, abdominal pain, vomiting; rash, urticaria, & coughing; dyspnea, asthma; fever, fatigue, allergic reactions.
The pattern of adverse events reported for ibuprofen is similar to that for other NSAIDs. Immune system disorder, i.e.
hypersensitivity reaction has been reported following treatment with ibuprofen. The most commonly observed adverse events
are gastrointestinal in nature. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena,
hematemesis, ulcerative stomatitis, gastrointestinal hemorrhage and exacerbation of colitis and Crohn's disease (see
Contraindications) have been reported following ibuprofen administration.
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Allergic exanthema, red striae, petechiae, ecchymosis, steroid acne, delayed wound healing, contact dermatitis, muscle
weakness, osteoporosis, aseptic necrosis of the bone, glaucoma, cataract, depression, irritability, euphoria, GI discomfort,
duodenal ulcer, pancreatitis, Cushing's syndrome, HTN, increased risk of thrombosis & vasculitis, delayed immune response.
Nausea, vomiting, diarrhea, headache, insomnia, palpitation, tachycardia, ventricular arrhythmia, tachypnea, skin rash,
hyperglycemia.
Headache, edema, fatigue, insomnia, nausea, abdominal pain, vomiting, palpitation, dizziness, pruritus, rash, dyspnea, asthenia,
muscle cramps, dyspepsia, gingival hyperplasia, erythema multiforme.
Adrenal suppression, change of glucose metabolism, protein catabolism, gastric ulcer activation.
Local irritation, erythema, eczema, allergic or non-allergic contact dermatitis (symptoms: Itching, redness, edema, papul, vesicle,
bullae or flaky skin). Systemic reactions eg, skin rash, hypersensitivity reactions (eg, asthma, angioderma) & photosensitivity.
GI disturbances, allergic reactions, anaphylaxis, haematologic disorders, nausea, vomiting.
Drowsiness, CV, hematology, neurological, GIT, GUT, resp tract reactions. Skin redness, dry mouth.
Nausea, vomiting, diarrhea, constipation, abdominal pain or transient burning on the upper stomach, skin rashes,
bronchospasm, thrombocytopenia, lymphopenia, blurred or diminished vision.
Maternal hypotension, backache, headache, neuropathy, peripheral nerve injury & arachnoiditis, cutaneous lesions, urticaria,
oedema or anaphylactoid reactions. CNS, CV effects.
Irritation.
Mild & transient vasodilation, HTN, feeling of warmth, nausea, dizziness, SC oedema & palpitation.
Hypercalcemia & hypercalciuria.
Mild GI disturbances.
Back pain, dizziness, upper resp tract infections, pharyngitis & rhinitis.
GI disturbances.
Hypotension, hyperkalemia, kidney disorders; increase of creatinine, urea, or K; leucopenia, neutropenia, agranulocytosis;
hyponatremia; headache, dizziness; nausea; increase of liver enzyme, impaired liver function or hepatitis; angioedema, skin rash,
urticaria, pruritus; back pain, arthralgia, myalgia.
Erythema, stinging, blistering, peeling, edema, pruritus, urticarial, burning, & irritation of the skin.
Rarely, mild local skin reactions.
Blood dyscrasias, GI & hypersensitivity reactions; headache, mental depression, optic neuritis & Gray syndrome.
Diarrhea, headache, nausea, skin allergy, abdominal pain, constipation, flatulence & vomiting.
Face edema, photosensitivity reaction, shock, asthenia, pain, chills, accidental fall, abdominal pain, allergic reaction, chest pain,
accidental injury, angina pectoris, AV block, migraine, syncope, tachycardia, palpitation, hypotension, postural hypotension,
myocardial ischemia, cerebral thrombosis, cardiac arrest, heart failure, abnormal ECG, cardiomyopathy, vomiting, glossitis, colitis,
dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, dry mouth, abnormal liver function tests, rectal hemorrhage,
gingivitis, anemia, leukopenia, thirst, edema, gout, unstable diabetes, hyperglycemia, peripheral edema, hyperuricemia,
hypoglycemic reaction, hypernatremia, arthritis, arthrosis, myalgia, tendon rupture, tenosynovitis, bone pain, myasthenia,
synovitis, ataxia, hypertonia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, somnolence, abnormal
dreams, decreased reflexes, hypesthesia, asthma, dyspnea, laryngitis, pharyngitis, sinusitis, bronchitis, increased sputum,
increased cough, urticaria, herpes simplex, pruritus, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis, mydriasis,
conjunctivitis, photophobia, tinnitus, eye pain, deafness, ear pain, eye hemorrhage, cataract, dry eyes, cystitis, nocturia, urinary
frequency, breast enlargement, urinary incontinence, abnormal ejaculation, genital edema, & anorgasmia.
Inflammation, thrombophlebitis, inj site pain; pruritic rash, urticaria; abdominal pain, nausea, vomiting, diarrhea,
pseudomembranous colitis; reversible thrombocythemia, eosinophilia, thrombocytopenia, leucopenia, neutropenia; increased
serum conc eg, bilirubin, transaminases, alkaline phosphatase & lactic dehydrogenase alone or combination; headache,
paresthesia, convulsion; oral & vag candidosis.
Rash, pruritus, urticaria, nausea, vomiting, oral moniliasis, diarrhea, colitis, headache, fever, vaginitis, erythema; abdominal pain,
constipation, vasodilation, dyspnea, dizziness, paresthesia, genital pruritus, taste perversion, chills & unspecified moniliasis;
phlebitis & inflammation at inj site; transient BUN &/or serum creatinine elevations, thrombocytopenia, leucopenia,
neutropenia; Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, toxic nephropathy, aplastic anemia,
hemolytic anemia, hemorrhage.
Drowsiness, dizziness, headache, agitation, dry mouth & GI discomfort; hypersensitivity reactions, including skin reactions &
angioedema.
Hypersensitivity reactions; GI disturbances; increased liver enzymes, ?-glutamyl transferase, LDL &/or bilirubin;
thrombocytopenia, eosinophilia; irritation, inflammation & pain at inj site; reversible encephalopathy (at high dose especially in
patients w/ renal insufficiency); secondary infections; taste &/or smell disturbances after inj, headache & fever.
Diarrhea, nausea, vomiting, indigestion, pseudomembranous colitis, candidiasis, hepatitis, cholestatic jaundice, urticarial &
erythematous rashes, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis,
angioedema, anaphylaxis, interstitial nephritis, transient leucopenia, thrombocytopenia & hemolytic anemia.
Diarrhea, nausea, vomiting, indigestion, pseudomembranous colitis & candidiasis; hepatitis & cholestatic jaundice; phlebitis at
inj site; urticaria & erythematous rashes; erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis &
exfoliative dermatitis; angioedema & anaphylaxis; transient leucopenia, thrombocytopenia & hemolytic anemia.
GI disturbances, leucopenia, thrombocytopenia, anemia, peripheral neuropathy, dysgeusia, ototoxicity, allergic reactions,
alopecia, flu-like symptoms.
Reversible alopecia, hyperpigmentation of nailbeeds & dermal creases especially in childn; nausea, vomiting, stomatitis w/c
begins as a burning sensation w/ erythema of the oral mucosa leading to ulceration, anorexia, diarrhoea; phlebosclerosis;
vesication, tissue necrosis, severe cellulitis, erythematous streaking; fever, chills, urticaria, anaphylaxis.
Cardiovascular and Nervous System: An excessive reduction in blood pressure may occur particularly after initial or increased
doses of Cardace, or of an additional diuretic (see Precautions), and may sometimes progress to shock.
Uncommonly, mild symptoms and reactions eg, headache, disorders of balance, rapid heart rate (tachycardia), weakness,
drowsiness, lightheadedness or impaired reactions may occur.
Rarely, mild symptoms and reactions eg, peripheral oedema, flushing, dizziness, noises in the ears (tinnitus), fatigue,
nervousness, depressed mood, tremor, restlessness, visual and sleep disturbances, confusion, feeling of anxiety, transient
erectile impotence, palpitations, sweating, disturbed hearing, extreme sleepiness (somnolence) or feeling faint on standing or
standing up (disturbed orthostatic regulation), as well as severe reactions eg, angina pectoris, cardiac arrhythmias and temporary
loss of consciousness (syncope) may also occur.
In isolated cases, insufficient supply of blood to the heart muscle or to the brain (myocardial or cerebral ischaemia), myocardial
infarction, transient reduced blood flow in the brain (transient ischaemic attack), ischaemic stroke, worsening of circulatory
disturbances due to vascular stenoses, precipitation or intensification of attacks of circulatory disturbances characterized by eg,
whiteness of fingers or toes (Raynaud's phenomenon), or abnormal sensations (paraesthesiae) may occur.
Kidney and Electrolyte Balance: Uncommonly, an increase in serum urea and creatinine (particularly and likely in combination
with diuretics). In isolated case, progression of renal function impairment to acute renal failure may develop.
Rarely, an increased in serum potassium may occur. In isolated cases, a decrease in serum sodium may develop, as preexisting
pronounced urinary excretion of proteins (proteinuria) may deteriorate (although ACE inhibitors usually reduce proteinuria), or
urinary output may increase in conjunction with an improvement in cardiac performance.
Respiratory Tract, Anaphylactic/Anaphylactoid and Skin Reactions: Commonly, a dry (nonproductive) tickling cough occurs. This
cough is often worse at night and during periods of recumbency (ie, while reclining), and occurs more frequently in women and
non-smokers. It may necessitate complete discontinuation of treatment with ACE inhibitors. Rarely, nasal congestion,
inflammation of the nasal sinuses (sinusitis), bronchitis, spasmodic narrowing of the bronchia (bronchospasm) and difficulty in
breathing (dyspnoea) may develop.
Uncommonly, the desired ACE inhibition may lead to mild angioneurotic oedema. Swelling of the facial region (eg, lips, eyelids)
or of the tongue, throat, or larynx (noticeable, eg, as difficulty in swallowing or breathing) may be signs and symptoms of such a
condition. If such signs and symptoms occurs, please inform the physician immediately and stop taking the next scheduled dose
of Cardace. Other ACE inhibitors must not be used as an alternative. Serious forms of angioneurotic oedema and other
anaphylactic or anaphylactoid reactions, not attributable to the desired effect, to ramipril or to any of the excipients of Cardace
are rare. Angioneurotic oedema in conjunction with ACE inhibitors appears to occur more frequently in Black patients ie, Afro-
Caribbean than in non-Black patients. Cutaneous or mucosal reactions eg, rash, itching or urticaria may uncommonly occur.
In isolated cases, maculopapular rash, pemphigus, worsening of psoriasis, psoriasiform, pemphigoid or lichenoid exanthema and
enanthema, erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, pronounced hair loss (alopecia),
loosening of the nails (onycholysis), or hypersensitivity of the skin to light (photosensitivity) may occur.
The likelihood and severity of anaphylactic and anaphylactoid reactions to insect venoma is increased under ACE inhibition. It is
assumed that this effect may also occur in connection with other allergens.
Digestive Tract: Uncommonly, nausea, increases in hepatic enzymes and/or serum bilirubin, and jaundice due to impaired
excretion of bile pigment (cholestatic jaundice) may occur. Rarely, dryness of the mouth, inflammation of the tongue (glossitis),
inflammatory reactions of the oral cavity and gastrointestinal tract, abdominal discomfort, gastric (including gastritis-like) pain,
Headache, edema, fatigue, somnolence, nausea, abdominal pain, flushing, palpitations, dizziness.
Increased heart rate, BP, hypotension, phlebitis, headache, unspecified chest pain, palpitation, dyspnea.
Throbbing headache, flushing, dizziness, postural hypotension, tachycardia (but paradoxical bradycardia has occurred).
Hypertension: In controlled hypertension clinical trials, the most common reactions associated with Cardura were of postural
type (rarely associated with syncope) or nonspecific and included dizziness, headache, fatigue, malaise, postural dizziness,
vertigo, edema, asthenia, somnolence, nausea and rhinitis.
The following additional adverse events have been reported in marketing experience among patients treated for hypertension
but these, in general, are not distinguishable from symptoms that might have occurred in the absence of exposure to doxazosin:
Tachycardia, bradycardia, palpitation, chest pain, angina pectoris, myocardial infarction, cerebrovascular accidents and cardiac
arrhythmias.
Benign Prostatic Hyperplasia: Experience in controlled clinical trials in BPH indicates a similar adverse event profile to that seen
in hypertension.
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Mild GI symptoms eg, transient nausea & vomiting, abdominal cramps, diarrhea.
Inflammation, thrombophlebitis & inj site pain. Skin rash, pruritus, urticaria. Abdominal pain, nausea, vomiting, diarrhea,
pseudomembranous colitis. Reversible thrombocytopenia, eosinophilia, neutropenia, leucopenia, +ve result in direct or indirect
Coombs' test, headache, paresthesia, oral & vag candidiasis.
Gynecomastia, cramping, diarrhea, drowsiness, lethargy, rashes, headache, maculopapular or erythematous cutaneous
eruptions, urticaria, mental confusion, drug fever, ataxia, impotence, disturbances in erection, menstrual irregularities. Rarely
agranulocytosis, post-menopausal bleeding.
Adverse reactions are defined as follows: Very common (=1/10); common (=1/100 to <1/10); uncommon (=1/1,000 to =1/100);
rare (=1/10,000 to =1/1,000); very rare (=1/10,000); not known (cannot be estimated from the available data).
Blood and the Lymphatic System Disorders: Very Common: Anaemia (50 mg). Common: Anaemia (150 mg).
Immune System Disorders: Uncommon: Hypersensitivity, angioedema, urticaria.
Metabolism and Nutrition Disorders: Common: Decreased appetite.
Psychiatric Disorders: Common: Decreased libido, depression.
Nervous System Disorders: Very Common: Dizziness (50 mg). Common: Dizziness (150 mg), somnolence.
Cardiac Disorders: Common: Myocardial infarction (fatal outcomes have been reported)5 and cardiac failure5 (50 mg).
Vascular Disorders: Very Common: Hot flush (50 mg). Common: Hot flush (150 mg).
Respiratory, Thoracic and Mediastinal Disorders: Uncommon: Interstitial lung disease (fatal outcomes have been reported).
Gastrointestinal Disorders: Very Common: Abdominal pain, constipation, nausea (50 mg). Common: Dyspepsia, flatulence (50
mg); abdominal pain, constipation, dyspepsia, flatulence, nausea (150 mg).
Hepatobiliary Disorders: Common: Hepatotoxicity, jaundice, hypertransaminasaemia1. Rare: Hepatic failure2 (fatal outcomes
have been reported).
Skin and Subcutaneous Tissue Disorders: Very Common: Rash (150 mg). Common: Alopecia, hirsutism/hair re-growth, dry skin,
pruritus; rash (50 mg).
Renal and Urinary Disorders: Very Common: Haematuria (50 mg). Common: Haematuria (150 mg).
Reproductive System and Breast Disorders: Very Common: Gynaecomastia and breast tenderness3,4. Common: Erectile
dysfunction.
General Disorders and Administration Site Conditions: Very Common: Asthenia; oedema (50 mg). Common: Chest pain; oedema
(150 mg).
Investigations: Common: Increased weight.
1Hepatic changes are rarely severe and were frequently transient, resolving or improving with continued therapy or following
cessation of therapy.
2Hepatic failure has occurred rarely, in patients treated with Casodex, but a casual relationship has not been established with
certainty. Periodic liver function testing should be considered (see Warnings and Precautions).
3May be reduced by concomitant castration.
4The majority of patients receiving Casodex 150 mg as monotherapy experience gynaecomastia and/or breast pain. In studies
these symptoms were considered to be severe in up to 5% of the patients. Gynaecomastia may not resolve spontaneously
following cessation of therapy, particularly after prolonged treatment (=1/10,000), not known (cannot be estimated from the
available data).
5Observed in a pharmaco-epidemiology study of LHRH agonist and antiandrogens used in the treatment of prostate cancer. The
risk appeared to be increased when Casodex 50 mg was used in combination with LHRH agonist but no increase in risk was
evident when Casodex 150 mg was used as a monotherapy to treat prostate cancer.
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Adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: Common
(=1/100, <1/10); uncommon (=1/1000, </100); rare (=1/10,000, <1/1000); very rare (<1/10,000), including isolated reports.
The adverse reactions listed as follows include those reported with Cataflam/Cataflam D and/or other pharmaceutical forms of
diclofenac, with either short-term or long-term use.
Blood and Lymphatic System Disorders: Very Rare: Thrombocytopenia, leukopenia, anaemia (including haemolytic and aplastic
anaemia), agranulocytosis.
Immune System Disorders: Rare: Hypersensitivity, systemic anaphylactic and anaphylactoid reactions (including hypotension and
shock). Very Rare: Angioneurotic oedema (including facial oedema).
Psychiatric Disorders: Very Rare: Disorientation, depression, insomnia, nightmare, irritability, psychotic disorder.
Nervous System Disorders: Common: Headache, dizziness. Rare: Somnolence. Very Rare: Paraesthesia, memory impairment,
convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, cerebrovascular accident.
Eye Disorders: Very Rare: Visual disturbance, blurred vision, diplopia.
Ear and Labyrinth Disorders: Common: Vertigo. Very Rare: Tinnitus, impaired hearing.
Cardiac Disorders: Very Rare: Palpitations, chest pain, congestive cardiac failure, myocardial infarction.
Vascular Disorders: Very Rare: Hypertension, vasculitis.
Respiratory, Thoracic and Mediastinal Disorders: Rare: Asthma (including dyspnoea). Very Rare: Pneumonitis.
Gastrointestinal Disorders: Common: Nausea, vomiting, diarrhoea, dyspepsia, abdominal pain, flatulence, anorexia, epigastric
pain. Rare: Gastritis, GI haemorrhage, haematemesis, melaena, haemorrhagic diarrhoea, GI ulcer (with or without bleeding or
perforation). Very Rare: Colitis (including haemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease),
constipation, stomatitis, glossitis, oesophageal disorder, diaphragm-like intestinal strictures, pancreatitis.
Hepatobiliary Disorders: Common: Increased transaminases. Rare: Hepatitis, jaundice, liver disorder. Very Rare: Fulminant
hepatitis, hepatic necrosis, hepatic failure.
Skin and Subcutaneous Tissue Disorders: Common: Rash. Rare: Urticaria. Very Rare: Bullous eruptions, eczema, erythema,
erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, loss of
hair, photosensitivity reaction, purpura, allergic purpura, pruritus.
Renal and Urinary Disorders: Very Rare: Acute renal failure, haematuria, proteinuria, nephrotic syndrome, interstitial nephritis,
renal papillary necrosis.
General Disorders and Administration Site Conditions: Rare: Oedema.
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Diarrhea, nausea, vomiting, maculopapular rash, urticarial, eosinophilia, drug fever, slight decrease of neutrophil, reversible
neutropenia (due to extended therapy), positive result in Coomb's test, eosinophilia, temporary thrombocytopenia,
hypoprothrombinemia, hemolytic anemia, headache, fever, inj pain, chills.
Thrombocytopenia, eosinophilia, leucopenia, granulocytosis, haemolytic anemia; increased SGOT, SGPT, ?-GT, alkaline
phosphatase, LDH, bilirubin; nausea, vomiting, abdominal spasm, diarrhea, urticaria, rash, pruritus, Stevens-Johnson syndrome,
toxic epidermal necrolysis; headache.
Shock, hypersensitivity reactions, haematological changes, increased SGOT/SGPT/alkaline phosphatase, kidney dysfunction, GI
effects, interstitial pneumonia, stomatitis or candidiasis, vit K or vit B deficiency, headache, +ve direct Coombs' test.
Diarrhea, hypersensitivity reactions, eosinophilia, genital & oral candidiasis. Rarely, pseudomembranous colitis, anaphylaxis,
neutropenia, thrombocytopenia, leukopenia.
Hypersensitivity, GI & resp disorders, shock, renal impairment, granulocytopenia or eosinophilia, stomatitis, candidiasis, vit K
deficiencies.
The likelihood of interactions is low due to limited metabolism and plasma protein-binding and
almost complete renal elimination of unchanged lamivudine.
Lamivudine is predominantly eliminated by active organic cationic secretion. The possibility of
interactions with other medicinal products administered concurrently should be considered,
particularly when their main route of elimination is active renal secretion via the organic cationic
transport system eg, trimethoprim. Other active substances (eg, ranitidine, cimetidine) are
eliminated only in part by this mechanism and were shown not to interact with lamivudine.
Active substances shown to be predominately excreted either via the active organic anionic
pathway or by glomerular filtration are unlikely to yield clinically significant interactions with
lamivudine.
Zidovudine: A modest increase in Cmax (28%) was observed for zidovudine when administered with
lamivudine; however, overall exposure (AUC) was not significantly altered. Zidovudine had no effect
on the pharmacokinetics of lamivudine (see Pharmacokinetics under Actions).
Trimethoprim/Sulfamethoxazole: Administration of trimethoprim/sulfamethoxazole 160 mg/800 mg
(co-trimoxazole) causes a 40% increase in lamivudine exposure because of the trimethoprim
component. However, unless the patient has renal impairment, no dosage adjustment of 3TC is
necessary (see Dosage & Administration). Lamivudine has no effect on the pharmacokinetics of
trimethoprim or sulfamethoxazole. The effect of co-administration of 3TC with higher doses of co-
trimoxazole for the treatment of Pneumocystis carinii pneumonia and toxoplasmosis has not been
studied.
Zalcitabine: Lamivudine may inhibit the intracellular phosphorylation of zalcitabine when the 2
medicinal products are used concurrently. 3TC is therefore not recommended to be used in
combination with zalcitabine.
Interaction studies have shown that the potential for metabolic drug interactions is low.
Lamivudine is predominantly eliminated by active organic cationic secretion. The potential for
interactions with concurrently administered drugs sharing this pathway as a major elimination route
(eg, trimethoprim) should be considered, particularly if the patient has renal impairment. Other
drugs (eg, ranitidine, cimetidine) are eliminated only in part by this mechanism and were shown not
to interact with lamivudine.
Drugs shown to be predominantly excreted either via the active organic anionic pathway, or by
glomerular filtration (eg, ganciclovir, foscarnet) are unlikely to yield clinically significant interactions
with lamivudine.
Administration of trimethoprim, a constituent of co-trimoxazole, causes an increase in lamivudine
exposure of about 40%. Lamivudine has a high therapeutic ratio and this increase is not considered
clinically relevant unless the patient has renal impairment. Lamivudine has no effect on the
pharmacokinetics of co-trimoxazole.
There is no known adverse interaction with a-interferon. There are no observed clinically significant
adverse interactions in patients taking 3TC-HBV concurrently with commonly used
immunosuppressant drugs (eg, cyclosporin A). However, formal interaction studies have not been
performed.
Results of clinical studies indicate that there was a modest but statistically significant (p=0.05)
increase of circulating theophylline or carbamazepine levels when either of these drugs are
administered concomitantly with clarithromycin.
Clarithromycin use in patients who are receiving theophylline may be associated with an increase of
serum theophylline concentrations. Monitoring of serum theophylline concentrations should be
considered for patients receiving high doses of theophylline or with baseline concentrations in the
upper therapeutic range. In 2 studies in which theophylline was administered with clarithromycin (a
theophylline sustained-release formulation was dosed at either 6.5 or 12 mg/kg together with
clarithromycin 250 or 500 mg every 12 hrs), the steady-state levels of Cmax, Cmin and area under
the serum concentration-time curve (AUC) increased about 20%.
Single-dose administration of clarithromycin has been shown to result in increased concentrations
of carbamazepine. Blood level monitoring of carbamazepine may be considered strain.
As with other macrolide antibiotics, the use of clarithromycin in patients concurrently taking drugs
metabolized by the cytochrome P-450 system (eg, digoxin, cyclosporine, disopyramide, ergot
alkaloids, lovastatin, midazolam, phenytoin, triazolam and warfarin) may be associated with
elevations in serum levels of these other drugs.
Elevated cisapride levels have been reported in patients receiving clarithromycin and cisapride
concomitantly. This may result in QT prolongation and cardiac arrhythmias including ventricular
tachycardia, ventricular fibrillation and Torsade de pointes. Similar effects have been observed in
patients taking clarithromycin and pimozide concomitantly. (See Contraindications.)
Macrolides have been reported to alter the metabolism of terfenadine resulting in increased levels
of terfenadine which has occasionally been associated with cardiac arrhythmias eg, QT
prolongation, ventricular tachycardia, ventricular fibrillation and Torsade de pointes (see
Contraindications). In 1 study in 14 healthy volunteers, the concomitant administration of
clarithromycin and terfenadine resulted in a 2- to 3-fold increase in the serum level of the acid
metabolites of terfenadine and in prolongation of the QT interval, which did not lead to any
clinically detectable effect. Similar effects have been observed with concomitant administration of
astemizole and other macrolides.
Simultaneous oral administration of clarithromycin tablets and zidovudine to HIV-infected adult
patients may result in decreased steady-state zidovudine concentrations. Because clarithromycin
appears to interfere with the absorption of simultaneously administered oral zidovudine, this
interaction can be largely avoided by staggering the doses of clarithromycin and zidovudine. This
interaction does not appear to occur in pediatric HIV-infected patients taking clarithromycin
suspension with zidovudine or dideoxyinosine.
The following drug interactions have not been reported in clinical trials with clarithromycin;
however, they have been observed with erythromycin products: There have been reports of
increased anticoagulant effects when erythromycin and oral anticoagulants were used
concomitantly.
Both CYP3A4 and CYP2D6 are responsible for Abilify Discmelt metabolism. Agents that induce
CYP3A4 (eg, carbamazepine) could cause an increase in Abilify Discmelt clearance and lower blood
levels. Inhibitors of CYP3A4 (eg, ketoconazole) or CYP2D6 (eg, quinidine, fluoxetine or paroxetine)
can inhibit Abilify Discmelt elimination and cause increased blood levels.
Both CYP3A4 and CYP2D6 are responsible for Abilify Oral Solution metabolism. Agents that induce
CYP3A4 (eg, carbamazepine) could cause an increase in Abilify Oral Solution clearance and lower
blood levels. Inhibitors of CYP3A4 (eg, ketoconazole) or CYP2D6 (eg, quinidine, fluoxetine or
paroxetine) can inhibit Abilify Oral Solution elimination and cause increased blood levels.
Given the primary CNS effects of aripiprazole, caution should be used when Abilify is taken in
combination with other centrally acting drugs and alcohol. Due to its a1-adrenergic receptor
antagonism, aripiprazole has the potential to enhance the effect of certain antihypertensive agents.
Potential for Other Drugs to Affect Abilify: Aripiprazole is not a substrate of CYP1A1, CYP1A2,
CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or CYP2E1 enzymes. Aripiprazole also does not
undergo direct glucuronidation. This suggests that an interaction of aripiprazole with inhibitors or
inducers of these enzymes, or other factors eg, smoking is unlikely.
Both CYP3A4 and CYP2D6 are responsible for aripiprazole metabolism. Agents that induce CYP3A4
(eg, carbamazepine) could cause an increase in aripiprazole clearance and lower blood levels.
Inhibitors of CYP3A4 (eg, ketoconazole) or CYP2D6 (eg, quinidine, fluoxetine or paroxetine) can
inhibit aripiprazole elimination and cause increased blood levels.
Ketoconazole: Co-administration of ketoconazole (200 mg/day for 14 days) with a 15-mg single dose
of aripiprazole increased the AUC of aripiprazole and its active metabolite by 63% and 77%,
respectively. The effect of a higher ketoconazole dose (400 mg/day) has not been studied. When
concomitant administration of ketoconazole with aripiprazole occurs, aripiprazole dose should be
reduced to ½ of its normal dose. Other strong inhibitors of CYP3A4 (itraconazole) would be
expected to have similar effects and need similar dose reductions; weaker inhibitors (erythromycin,
grapefruit juice) have not been studied. When the CYP3A4 inhibitor is withdrawn from the
combination therapy, aripiprazole dose should then be increased.
Quinidine: Co-administration of a 10-mg single dose of aripiprazole with quinidine (166 mg/day for
13 days), a potent inhibitor of CYP2D6, increased the AUC of aripiprazole by 112% but decreased
the AUC of its active metabolite, dehydro-aripiprazole, by 35%. Aripiprazole dose should be reduced
to ½ of its normal dose when concomitant administration of quinidine with aripiprazole occurs.
Other significant inhibitors of CYP2D6 eg, fluoxetine or paroxetine, would be expected to have
similar effects and, therefore, should be accompanied by similar dose reductions. When the CYP2D6
inhibitor is withdrawn from the combination therapy, aripiprazole dose should then be increased.
Carbamazapine: Co-administration of carbamazapine (200 mg 2 times a day), a potent CYP3A4
inducer, with aripiprazole (30 mg 4 times a day) resulted in an approximate 70% decrease in Cmax
and AUC values of both aripiprazole and its active metabolite, dehydro-aripiprazole. When
carbamazapine is added to aripiprazole therapy, aripiprazole dose should be doubled. Additional
dose increases should be based on clinical evaluation. When carbamazapine is withdrawn from the
combination therapy, aripiprazole should then be reduced.
No clinically significant effect of famotidine, valproate, or lithium was seen on the pharmacokinetics
of aripiprazole (see Pharmacokinetics under Actions).
Potential for Abilify to Affect Other Drugs: Aripiprazole is unlikely to cause clinically important
pharmacokinetic interactions with drugs metabolized by cytochrome P-450 enzymes. In in vivo
studies, 10- to 30-mg/day doses of aripiprazole had no significant effect on metabolism by CYP2D6
(dextromethorphan),
Aminoglycocides, loopCYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin) and CYP3A4
diuretics.
ACCOLATE may be administered with other therapies routinely used in the management of asthma
and allergy. Inhaled steroids, inhaled and oral bronchodilator therapy, antibiotics and antihistamines
are examples of agents which have been co-administered with ACCOLATE without adverse
interaction.
ACCOLATE may be administered with oral contraceptives without adverse interaction.
Co-administration with warfarin results in an increase in maximum prothrombin time by
approximately 35%. It is therefore recommended that if ACCOLATE is co-administered with warfarin,
prothrombin time should be closely monitored. The interaction is probably due to an inhibition by
zafirlukast of the cytochrome P450 2C9 isoenzyme system.
In clinical trials, co-administration with theophylline resulted in decreased plasma levels of
zafirlukast, by approximately 30%, but with no effect on plasma theophylline levels. However,
during post-marketing surveillance, there have been rare cases of patients experiencing increased
theophylline levels when co-administered ACCOLATE.
Co-administration with terfenadine resulted in a 54% decrease in AUC for zafirlukast, but with no
effect on plasma terfenadine levels.
Co-administration with acetylsalicylic acid ("aspirin", 650 mg four times a day) may result in
increased plasma levels of zafirlukast, by approximately 45%.
Co-administration with erythromycin will result in decreased plasma levels of zafirlukast, by
approximately 40%.
Co-administration with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased plasma
levels of zafirlukast, by approximately 60%. The clinical significance of this interaction is unknown.
Co-administration with itraconazole, a strong CYP3A4 inhibitor, caused no change in plasma levels
of zafirlukast.
The clearance of zafirlukast in smokers may be increased by approximately 20%.
At concentrations of 10 microgram/ml and above, zafirlukast causes increases in the assay value for
bilirubin in animal plasma. However, zafirlukast has not been shown to interfere with the 2,5-
dichlorophenyl diazonium salt method of bilirubin analysis of human plasma.
K-sparing diuretics. May have additive effects w/ other antihypertensives.
Increased t½ w/ probenecid.
Anticoagulants & other broad-spectrum antibiotics.
Increased plasma conc w/ concomitant administration of azole antifungals, HIV protease inhibitors,
nefazodone. Increased risk of arrhythmia & prolongation of QT interval w/ antiarrhythmics, tricyclic
& tetracyclic antidepressants, antipsychotics, astemizole, sparfloxacin. Enhances the effects of
anticoagulants. Increased absorption w/ cimetidine & ranitidine. Effects antagonised by
anticholinergics.
Concomitant use of Actifed with other sympathomimetic agents eg, decongestants, tricyclic
antidepressants, appetite suppressants and amphetamine-like psychostimulants or with MAOIs
which interfere with the catabolism of sympathomimetic amines, may occasionally cause a rise in
blood pressure (see Contraindications and Precautions).
Because of its pseudoephedrine content, Actifed may partially reverse the hypotensive action of
drugs which interfere with sympathetic activity, including bretylium, bethanidine, guanethidine,
debrisoquine, methyldopa and a- and ß-adrenergic-blocking agents (see Precautions).
The antibacterial agent furazolidone is known to cause a dose-related inhibition of monoamine
oxidase. Although there are no reports of hypertensive crises caused by the concurrent
administration of Actifed and furazolidone, they should not be taken together.
Storage Store below 25°C. Protect from light. Actifed should not be refrigerated. The tablets should
be kept dry.
No formal interaction studies with Actilyse and medicinal products commonly administered in
patients with acute myocardial infarction have been performed.
Medicinal products that affect coagulation or those that alter platelet function may increase the risk
of bleeding prior to, during or after Actilyse therapy.
Concomitant treatment with ACE inhibitors may enhance the risk of suffering an anaphylactoid
reaction, as in the cases describing such reactions a relatively larger proportion of patients were
receiving ACE inhibitors concomitantly.
Incompatibilities: The reconstituted solution may be diluted further with sterile physiological saline
solution (0.9%) up to a minimal concentration of alteplase 0.2 mg/mL. It may not, however, be
diluted further with water for injections or carbohydrate infusion solutions eg, dextrose.
Actilyse must not be mixed with other drugs, neither in the same infusion vial nor via the same
venous line (not even with heparin).
Concomitant administration w/ Ca, antacids or oral medications containing divalent cations will
decrease absorption.
Pioglitazone Hydrochloride: In vivo drug-drug interaction studies have suggested that pioglitazone
may be a weak inducer of CYP450 isoform 3A4 substrate.
An enzyme inhibitor of CYP2C8 (eg, gemfibrozil) may significantly increase the area under the
concentration-time curve (AUC) of pioglitazone and an enzyme inducer of CYP2CB (eg, rifampin)
may significantly decrease the AUC of piogJitazone. Therefore. if an inhibitor or inducer of CYP2CB is
started or stopped during treatment with pioglitazone, changes in diabetes treatment may be
needed based on clinical response (see Drug-Drug Interactions: Pioglitazone Hydrochloride under
Actions).
Metformin Hydrochloride: Glyburide: In a single-dose interaction study in type 2 diabetes patients,
co-administration of metformin and glyburide did not result in any changes in either metformin
pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and Cmax were observed, but
were highly variable. The single-dose nature of this study and the lack of correlation between
glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this
interaction uncertain.
Furosemide: A single-dose, metformin-furosemide drug interaction study in healthy subjects
demonstrated that pharmacokinetic parameters of both compounds were affected by co-
administration. Furosemide increased the metformin plasma and blood Cmax by 22%, and blood
AUC by 15%, without any significant change in metformin renal clearance. When administered with
metformin, the Cmax and AUC of furosemide were 31% and 12% smaller, respectively, than when
administered alone and the terminal half-life was decreased by 32%, without any significant change
in furosemide renal clearance. No information is available about the interaction of metformin and
furosemide when co-administered chronically.
Nifedipine: A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers
demonstrated that co-administration of nifedipine increased plasma metformin Cmax and AUC by
20% and 9%, respectively, and increased the amount excreted in the urine. Maximum plasma
concentration (Tmax) and half-life were unaffected. Nifedipine appears to enhance the absorption
of metformin. Metformin had minimal effects on nifedipine.
Cationic Drugs: Cationic drugs (eg, amiloride, digoxin, morphine, procainamide, quinidine, quinine,
ranitidine, triamterene, trimethoprim and vancomycin) that are eliminated by renal tubular
secretion theoretically have the potential for interaction with metformin by competing for common
renal tubular transport systems. Such interaction between metformin and oral cimetidine has been
observed in normal healthy volunteers in both single- and multiple-dose, metformin-cimetidine
drug interaction studies with a 60% increase in peak metformin plasma, and whole blood
concentrations and a 40% increase in plasma and whole blood metformin AUC. There was no
change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine
pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful
patient monitoring and dose adjustment of Actosmet and/or the interfering drug is recommended
in patients who are taking cationic medications that are excreted via the proximal renal tubular
A number of medicinal products are known to interact with the glucose metabolism.
The following substances may reduce the patient's insulin requirement: Oral hypoglycemic agents
(OHA), monoamine oxidase inhibitors (MAOIs), nonselective ß-blocking agents, angiotensin-
converting enzyme (ACE) inhibitors, salicylates, alcohol, anabolic steroids and sulfonamides.
The following substances may increase the patient's insulin requirement: Oral contraceptives,
thiazides, glucocorticoids, thyroid hormones, ß-sympathomimetics and danazol.
Beta-blocking agents may mask the symptoms of hypoglycemia and delay recovery from it.
Octreotide/lanreotide may both decrease and increase insulin requirement.
Alcohol may intensify and prolong the hypoglycemic effect of insulin.
Combination of Thiazolidinediones with Insulin: Cases of congestive heart failure (CHF) have been
reported when thiazolidinediones were used in combination with insulin, especially in patients with
risk factors for development of CHF. This should be kept in mind if treatment with the combination
of thiazolidinediones and insulin medicinal products is considered. If this combination is used,
patients should be observed for signs and symptoms of CHF, weight gain and edema.
Thiazolidinediones should be discontinued if any symptom of deterioration in cardiac function
occurs.
The safety and effectiveness of the use of sodium hyaluronate concomitantly with other intra-
articular injection has not yet been established.
As sodium hyaluronate is precipitated by quaternary amine bactericides or disinfectants eg,
benzalkonium chloride and chlorhexidine, etc, adequate attention should be given.
Caution For Usage During Injection: When sodium hyaluronate is administered into the cavity of the
knee joint, it should be performed according to strict aseptic procedure. In case improvement of
symptoms is not recognized after treatment, administration should be limited to 5 times before
discontinuing. When accumulation of articular fluid occurs, it should be drained out of syringe if the
condition necessitates.
Others: Sodium hyaluronate should not be administered into blood vessels, it should not be applied
for ophthalmological treatment. Because the drug is viscous, the use of 22-23 G syringe is desired.
Since it is kept in a cool place, restore to room temperature before administering. It is intended for 1
application, therefore it should be used as soon as possible after opening. Discard after using.
No clinically relevant interactions with Aerius tablets were observed in clinical trials in which
erythromycin or ketoconazole were co-administered (see Pharmacokinetics: Drug Interactions
under Actions).
There was no effect of food or grapefruit juice on the disposition of desloratadine.
Aerius concomitantly taken with alcohol did not potentiate the performance impairing effects of
alcohol.
In clinical pharmacology studies in healthy volunteers, there were no clinically relevant changes in
the safety profile of desloratadine when co-administered with erythromycin, ketoconazole,
azithromycin, fluoxetine and cimetidine as assessed by electrocardiographic parameters (including
the corrected QT interval), clinical laboratory test, vital signs and adverse events. Concurrent
administration with sympathomimetic medicines may result in critical hypertension reactions.
Dihydroergotamine, ergotamine, methylergotamine: Risk of vasoconstriction and increase in blood
pressure.
MAOIs.
Oral anticoagulants eg warfarin, glycoprotein IIb/IIIa inhibitors, ASA, heparin, thrombolytics, NSAIDs.
Phenytoin, tolbutamide, diuretics, ß-blockers, ACE inhibitors, Ca antagonists, cholesterol lowering
agents, coronary vasodilators, antidiabetic agents (including insulin), antiepileptic agents, hormone
replacement therapy.
Antacid containing Al or Mg(OH)2. Concomitant intake w/ NSAIDs can lead to convulsion. May
increase theophylline plasma levels. Effect of warfarin is intensified.
Antidiabetic drugs.
Acetosal, other drugs which contain paracetamol & ibuprofen, warfarin anticoagulants, alcohol.
ACE inhibitors.
May precipitate a hypertensive crisis if used w/ MAOI.
Pemetrexed is mainly eliminated unchanged renally by tubular secretion and to a lesser extent by
glomerular filtration. Concomitant administration of nephrotoxic drugs (eg, aminoglycoside, loop
diuretics, platinum compounds, cyclosporin) could potentially result in delayed clearance of
pemetrexed. This combination should be used with caution. If necessary, creatinine clearance
should be closely monitored.
Concomitant administration of substances that are also tubularly secreted (eg, probenecid,
penicillin) could potentially result in delayed clearance of pemetrexed. Caution should be made
when these drugs are combined with pemetrexed. If necessary, creatinine clearance should be
closely monitored.
In patients with normal renal function (CrCl =80 mL/min), high doses of nonsteroidal anti-
inflammatory drugs (NSAIDs eg, ibuprofen >1,600 mg/day) and aspirin at higher dosage (=1.3 g
daily) may decrease pemetrexed elimination and consequently, increase the occurrence of
pemetrexed adverse events. Therefore, caution should be made when administering higher doses
of NSAIDs or aspirin at higher dosage, concurrently with pemetrexed to patients with normal
function (CrCl =80 mL/min).
In patients with mild to moderate renal insufficiency (CrCl 45-79 mL/min), the concomitant
administration of pemetrexed with NSAIDs (eg, ibuprofen) or aspirin at higher dosage should be
avoided for 2 days before, on the day of and 2 days following pemetrexed administration (see
Precautions).
In the absence of data regarding potential interaction with NSAIDs having longer t1/2 as piroxicam
or rofecoxib, the concomitant administration with pemetrexed should be avoided for at least 5 days
prior to, on the day and at least 2 days following pemetrexed administration (see Precautions).
Pemetrexed undergoes limited hepatic metabolism. Results from in vitro studies with human liver
microsomes indicated that pemetrexed would not be predicted to cause clinically significant
inhibition of the metabolic clearance of drugs metabolised by CYP3A, CYP2D6, CYP2C9 and CYP1A2.
Interactions Common to All Cytotoxics: Due to the increased thrombotic risk in patients with cancer,
the use of anticoagulation treatment is frequent. The high intraindividual variability of the
coagulation status during diseases and the possibility of interaction between oral anticoagulants
and anticancer chemotherapy require increased frequency of international normalised ratio (INR)
monitoring, if it is decided to treat the patient with oral anticoagulants.
Concomitant Use Contraindicated: Yellow Fever Vaccine: Risk of fatal generalised vaccinale disease
(see Contraindications).
Concomitant Use Not Recommended: Live Attenuated Vaccines (Except Yellow Fever, for which
Concomitant Use is Contraindicated): Risk of systemic, possibly fatal, disease. The risk is increased in
subjects who are already immunosuppressed by their underlying disease. Use an inactivated
vaccine where it exists (poliomyelitis) (see Precautions).
Incompatibilities: Pemetrexed is physically incompatible with diluents containing calcium, including
lactated Ringer's Injection and Ringer's Injection. In the absence of compatibility studies, Alimta
May potentiate other CNS depressants. Actions prolonged by MAOI.
Hormone replacement therapy, Ca supplements, antacids, NSAIDs, aspirin.
Effects enhanced by CNS depressants, alcohol, barbiturates. Cimetidine may delay clearance.
Anticholinergics, succinylcholine.
Effects potentiated when used w/ insulin & other antidiabetics, ACE inhibitors, allopurinol, anabolic
steroids & male sex hormones, chloramphenicol, coumarin derivatives, cyclophosphamide,
disopyramide, fenfluramine, fenyramidol, fibrates, fluoxetine, guanethidine, ifosfamide, MAOIs,
miconazole, para-aminosalicylic acid, pentoxifylline (high-dose parenteral), phenylbutazone,
azapropazone, oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, sulfonamides,
tetracyclines, tritoqualine, trofosfamide. Effects weakened when used w/ acetazolamide,
barbiturates, corticosteroids, diazoxide, diuretics, epinephrine & other sympathomimetics,
glucagon, laxatives (after protracted use), nicotinic acid (high dose), oestrogens & progestogens,
phenothiazines, phenytoin, rifampicin, thyroid hormones. ß-blockers decrease glucose tolerance.
Patients who take or discontinue taking certain other medicines while undergoing treatment with
Amaryl may experience changes in blood sugar control.
Based on experience with Amaryl and on what is known of other sulfonylureas, the following
interactions must be considered: Potentiation of the blood sugar-lowering effect and thus, in some
instances, hypoglycaemia may occur when one of the following medicines is taken eg, insulin and
other oral antidiabetics, ACE inhibitors, allopurinol, anabolic steroids and male sex hormones,
chloramphenicol, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine,
fenyramidol, fibrates, fluoxetine, guanethidine, ifosfamide, MAO inhibitors, miconazole, fluconazole,
para-aminosalicylic acid, pentoxifylline (high-dose parenteral), phenylbutazone, azapropazone,
oxyphenbutazone, probenecid, quinolones, salicylates, sulfinpyrazone, clarithromycin,
sulfonamides, tetracyclines, tritoqualine and trofosfamide.
Weakening of the blood sugar-lowering effect and thus, raised blood sugar levels may occur when
one of the following medicines is taken eg, acetazolamide, barbiturates, corticosteroids, diazoxide,
diuretics, epinephrine (adrenaline) and other sympathomimetic agents, glucagon, laxatives (after
protracted dose), nicotinic acid (in high doses), oestrogens and progestogens, phenothiazines,
phenytoin, rifampicin and thyroid hormones.
H2-Receptor antagonists, clonidine and reserpine may lead to either potentiation or weakening of
the blood sugar-lowering effect.
Beta-blockers decrease glucose tolerance. In patients with diabetes mellitus, this may lead to
deterioration of metabolic control. In addition, ß-blockers may increase the tendency to
hypoglycaemia (due to impaired counter-regulation).
Under the influence of sympatholytic drugs eg, ß-blockers, clonidine, guanethidine and reserpine,
the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.
Both acute and chronic alcohol intake may potentiate or weaken the blood sugar-lowering action of
Amaryl unpredictably.
The effect of coumarin derivatives may be potentiated or weakened.
Glimepiride: When other drugs are concomitantly administered to or withdrawn from a patient
receiving this drug, both undesired increases and decreases in the hypoglycemic action of
glimepiride can occur. Based on experience with this drug and with other sulfonylureas, the
following interactions must be considered:
Glimepiride is metabolized by cytochrome P-450 2C9 (CYP2C9). Its metabolism is known to be
influenced by concomitant administration of CYP2C9 inducers (eg, rifampicin) or inhibitors (eg,
fluconazole).
Drugs potentiating the blood glucose-lowering effect: Insulin and oral antidiabetic products, ACE
inhibitors, allopurinol, anabolic steroids, male sex hormones, chloramphenicol, coumarin
anticoagulants, cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluoxetine,
guanethidine, ifosfamide, MAO inhibitors, miconazole, fluconazole, para-aminosalicylic acid,
pentoxifylline (high-dose parenteral), phenylbutazone, probenecid, quinolone antibiotics,
salicylates, sulfinpyrazone, sulfonamide, tetracyclines, tritoqualine, trofosfamide, azapropazone,
oxyphenbutazone.
Drugs weakening the blood glucose-lowering effect: Acetazolamide, barbiturates, corticosteroids,
diazoxide, diuretics, epinephrine (adrenaline) or sympathomimetics, glucagons, laxatives (long-term
use), nicotinic acid (high dose), estrogens, progestogens, phenothiazines, phenytoin, rifampicin,
thyroid hormones.
Drugs either potentiating or weakening the blood glucose-lowering effect: H2-antagonists,
clonidine, reserpine.
Beta-blockers reduce glucose tolerance. Reduction of glucose tolerance may change metabolic
control. Beta-blockers may increase the risk of hypoglycemia (due to failure of counter-regulation).
Drugs reducing or blocking the signs of adrenergic counter-regulation to hypoglycemia:
Sympatholytic drugs (eg, ß-blockers), clonidine, guanethidine, reserpine.
Both acute and chronic alcohol intake may potentiate or weaken the blood glucose-lowering action
of this drug in an unpredictable fashion.
This drug may either potentiate or weaken the effects of coumarin derivatives.
Metformin: Lactic acidosis may occur by concomitant administration of the following drugs. When
these drugs are administered concomitantly, patients should be closely monitored: Iodinated
contrast materials, antibiotics having strong nephrotoxicity (gentamicin, etc).
The hypoglycemic action of co-administration with the following drugs may be potentiated or
weakened. When these drugs are administered, the blood glucose level and patient should be
observed closely.
Drugs Potentiating the Effect: Insulin, sulfonamides and sulfonylureas products, anabolic steroids,
guanethidine, salicylates (aspirin, etc), ß-blockers (propranolol, etc), MAO inhibitors.
Drugs Weakening the Effect: Epinephrine, corticosteroids, thyroid hormones, estrogens, diuretics,
pyrazinamide, isoniazid, nicotinic acid, phenothiazines.
Glyburide: In a single-dose interaction study in type 2 diabetes subjects, co-administration of
Tetracyclines, probenecid, OC, allopurinol.
Amlodipine has been safely administered with thiazide diuretics, a-blockers, ACE inhibitors, long-
acting nitrates, sublingual nitroglycerin, nonsteroidal anti-inflammatory (NSAIDs) drugs, antibiotics
and oral hypoglycemic drugs.
Studies have indicated that the co-administration of amlodipine with digoxin did not change serum
digoxin levels or digoxin renal clearance in normal volunteers, and that co-administration of
cimetidine did not alter the pharmacokinetics of amlodipine.
In vitro data from studies with human-plasma indicates that amlodipine has no effect on protein-
binding of the drug tested (digoxin, phenytoin, warfarin or indomethacin).
In healthy male volunteers, the co-administration of amlodipine does not significantly alter the
effect of warfarin on prothrombin response time.
Nonselective MAOIs may cause HTN. Drugs which will form insoluble comp w/ Ca eg tetracycline.
Antacids, other Ca-containing drugs.
Gentamicin, tobramycin, neomycin, streptomycin, cephaloridine, polymixin B, colistin, ethacrynic
acid, furosemide, potent diuretic agents (ethacrynate, furosemide, mannitol).
Ca prep.
Probenecid prolongs blood level of amoxicillin. Allopurinol increases incidence of skin rashes.
Chlorpromazine, cimetidine, alcohol, other CNS depressants.
Selective/non-selective MAOIs, alcohol, carbamazepine & other enzyme inducers, opioid agonist-
antagonist eg buprenorphine, nalbuphine, pentazocine; SSRIs, triptans, other opioid derivatives,
benzodiazepines, barbiturates, CNS depressants, warfarin-like compounds, CYP3A4 inhibitors eg,
ketoconazole & erythromycin, drugs reducing seizure threshold.
Increased & prolonged amoxicillin blood levels w/ probenecid. Increased skin allergic reaction w/
allopurinol.
Enhanced central sedative effect of neuroleptics, tranquilizers, antidepressants, sleep-inducing
drugs, analgesics, anesth. Potentiation w/ alcohol, erythromycin, ketoconazole, itraconazole,
diltiazem, verapamil, cimetidine, hepatic enzyme inhibitors.
Antihistamines may potentiate other CNS depressants. Actions prolonged by MAOI. Prolonged use
of paracetamol may potentiate oral anticoagulant.
Increase plasma conc of lithium & digoxin. Diuretics or antihypertensive agents (eg, ß-blocker, ACE
inhibitors). Increased frequency of GI undesirable effects w/ other systemic NSAIDs or
corticosteroids. Increase the risk of bleeding w/ anticoagulants & antiplatelet agents. Increase risk
of GI bleeding w/ SSRIs. Increased toxicity of methotrexate. May increase nephrotoxicity of
ciclosporin. Antidiabetics, quinolone antibacterials, warfarin.
A number of substances affect glucose metabolism and may require dose adjustment of insulin
glulisine and particularly, close monitoring.
Substances that may enhance the blood glucose-lowering effect and increase susceptibility to
hypoglycemia include oral antidiabetic agents, angiotensin-converting enzyme (ACE) inhibitors,
disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors (MAOIs), pentoxifylline,
propoxyphene, salicylates and sulfonamide antibiotics.
Substances that may reduce the blood glucose-lowering effect include corticosteroids, danazol,
diazoxide, diuretics, glucagon, isoniazid, phenothiazine derivatives, somatropin, sympathomimetic
agents (eg, epinephrine, adrenaline, salbutamol, terbutaline), thyroid hormones, estrogens,
progestins (eg, oral contraceptives), protease inhibitors and atypical antipsychotic medication (eg,
olanzapine and clozapine).
Beta-blockers, clonidine, lithium salts or alcohol may potentiate or weaken the blood glucose-
lowering activity of insulin. Pentamidine may cause hypoglycemia, which may sometimes be
followed by hyperglycemia. In addittion, under the influence of sympatholytic medicinal products
eg, ß-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation
may be reduced or absent.
Warfarin: In subjects stabilized on chronic warfarin therapy, the administration of Arcoxia 120 mg
daily was associated with an approximate 13% increase in International Normalized Ratio (INR)
prothrombin time. Standard monitoring of INR values should be conducted when therapy with
Arcoxia is initiated or changed, particularly in the first few days, in patients receiving warfarin or
similar agents.
Rifampin: Co-administration of Arcoxia with rifampin, a potent inducer of hepatic metabolism,
produced a 65% decrease in etoricoxib plasma area under the curve (AUC). This interaction should
be considered when Arcoxia is co-administered with rifampin.
Methotrexate: Two studies investigated the effects of Arcoxia 60, 90 or 120 mg administered once
daily for 7 days in patients receiving once-weekly methotrexate doses of 7.5-20 mg for rheumatoid
arthritis. Arcoxia at 60 mg and 90 mg had no effect on methotrexate plasma concentrations (as
measured by AUC) or renal clearance. In one study, Arcoxia 120 mg had no effect on methotrexate
plasma concentrations (as measured by AUC) or renal clearance. In the other study, Arcoxia 120 mg
increased methotrexate plasma concentrations by 28% (as measured by AUC) and reduced renal
clearance of methotrexate by 13%. Monitoring for methotrexate-related toxicity should be
considered when Arcoxia at doses >90 mg daily and methotrexate are administered concomitantly.
Diuretics, Angiotension Converting Enzyme (ACE) Inhibitors and Angiotensin II Antagonists (AIIAs):
Reports suggest that NSAIDs including selective COX-2 inhibitors may diminish the antihypertensive
effect of diuretics, ACE inhibitors and AIIAs. This interaction should be given consideration in
patients taking Arcoxia concomitantly with these products.
Lithium: Reports suggest that nonselective NSAIDs and selective COX-2 inhibitors may increase
plasma lithium levels. This interaction should be given consideration in patients taking Arcoxia
concomitantly with lithium.
Aspirin: Arcoxia can be used concomitantly with low-dose aspirin at doses for cardiovascular
prophylaxis. However, concomitant administration of low-dose aspirin with Arcoxia results in an
increased rate of GI ulceration or other complications compared to use of Arcoxia alone. At steady-
state, etoricoxib 120 mg once daily had no effect on the antiplatelet activity of low-dose aspirin (81
mg once daily). (See Precautions).
Oral Contraceptives: Arcoxia 60 mg given concomitantly with an oral contraceptive containing 35
mcg ethinyl estradiol (EE) and 0.5-1 mg norethindrone for 21 days increased the steady state AUC0-
24hr of EE by 37%. Arcoxia 120 mg given with the same oral contraceptive concomitantly or
separated by 12 hrs, increased the steady-state AUC0-24hr of EE by 50-60%. This increase in EE
concentration should be considered when selecting an oral contraceptive for use with etoricoxib. An
increase in EE exposure can increase the incidence of adverse events associated with oral
contraceptives (eg, venous thromboembolic events in women at risk).
Hormone Replacement Therapy: Administration of Arcoxia 120 mg with hormone replacement
therapy consisting of conjugated estrogens (0.625 mg Premarin) for 28 days, increased the mean
steady state AUC0-24hr of unconjugated estrone (41%), equilin (76%) and 17-ß-estradiol (22%). The
Cyclopropane & halothane, MAOIs, tryptiline- or imipramine-type antidepressants.
Antipyrine and cimetidine clinical interaction studies indicate that the co-administration of Arimidex
with other drugs is unlikely to result in clinically significant drug interactions mediated by
cytochrome P-450.
A review of the clinical trial safety database did not reveal evidence of clinically significant
interaction in patients treated with Arimidex who also received other commonly prescribed drugs.
Tamoxifen and/or other therapies containing oestrogen should not be co-administered with
Arimidex, as they may diminish its pharmacological action (see Contraindications).
Incompatibilities: Not applicable.
May negate the pharmacological action w/ oestrogen-containing medicines. May reduce efficacy w/
rifampicin, anticonvulsants (eg, phenytoin & carbamazepine) & St. John's wort.
Warfarin, aspirin, heparin, thrombolytics or NSAIDs.
Digoxin, diuretics, lithium, phenytoin, ibuprofen-containing drugs, oral anticoagulants (eg, warfarin).
Aspirin.
Concomitant use w/ coumarin anticoagulant may increase risk of bleeding. Acetosal may reduce
ibuprofen conc in blood & reduce anti-inflammatory effect.
Oral anticoagulants.
Increased risk of myopathy w/ cyclosporine, fibric acid derivatives, erythromycin, azole antifungals
or niacin. Decreased plasma conc w/ oral antacid susp. Increased plasma conc w/ erythromycin,
clarithromycin, protease inhibitors. Digoxin, OCs.
The risk of myopathy during treatment with drugs in this class in increased with concurrent
administration of cyclosporine, fibric acid derivatives, erythromycin, azole antifungals or niacin (see
Precautions).
Antacids: Co-administration of atorvastatin with an oral antacid suspension containing magnesium
and alumunium hydroxides, decreased atorvastatin plasma concentrations approximately 35%;
however, LDL-C reduction was not altered.
Antypirine: Because atorvastatin does not affect the pharmacokinetics of antipyrine, interactions
with other drugs metabolized via the same cytochrome isozyme are not expected.
Colestipol: Plasma concentrations of atorvastatin were lower (approximately 25%) when colestipol
was administered with atorvastatin. However, lipid effects were greater when atorvastatin and
colestipol were co-administered than when either drug was given alone.
Digoxin: When multiple doses of digoxin and atorvastatin 10 mg were co-administered, steady state
plasma digoxin concentrations were unaffected. However, digoxin concentrations increased
approximately 20% following administration of digoxin with atorvastatin 80 mg daily. Patients taking
digoxin should be monitored appropriately.
Erythromycin/Clarithromycin: Co-administration of atorvastatin and erythromycin (500 mg 4 times
daily) or clarithromycin (500 mg twice daily) known inhibitors of cytochrome P450 3A4, was
associated with higher plasma concentrations of atorvastatin (see Precautions).
Azithromycin: Co-administration of atorvastatin (10 mg once daily) and azithromycin (500 mg once
daily) did not alter the plasma concentrations of atorvastatin.
Terfenadine: Co-administration of atorvastatin and terfenadine did not produce a clinically
significant effect on the pharmacokinetics of terfenadine.
Oral Contraceptives: Co-administration with an oral contraceptive containing norethindrone and
ethinyl estradiol increased area under the curve (AUC) values for norethindrone and ethinyl
estradiol by approximately 30% and 20%. These increases should be considered when selecting an
oral contraceptive for a woman taking atorvastatin.
Warfarin: An atorvastatin interaction studies with warfarin was conducted and no clinically
significant interactions were seen.
Cimetidine: An atorvastatin interaction study with cimetidine was conducted and no clinically
significant interactions were seen.
Amlodipine: Atorvastatin pharmacokinetics were not altered by the co-administration of
atorvastatin 80 mg and amlodipine 10 mg at steady state.
Protease Inhibitors: Co-administration of atorvastatin and protease inhibitors, known inhibitors of
cytochrome P450 3A4, was associated with increased plasma concentrations of atorvastatin.
Other Concomitant Therapy: In clinical studies, atorvastatin was used concomitantly with
antihypertensive agents and estrogen replacement therapy without evidence of clinically significant
adverse interactions. Interaction studies with specific agents have not been conducted.
Endocrine Function: HMG-CoA reductase inhibitors interfere with cholesterol synthesis and
Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular
secretion of amoxicillin. Concomitant use with Augmentin may result in increased and prolonged
blood levels of amoxicillin but not of clavulanic acid.
Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of
allergic skin reactions. There are no data on the concomitant use of amoxicillin-clavulanate and
allopurinol.
In common with other broad-spectrum antibiotics, amoxicillin-clavulanate may reduce the efficacy
of oral contraceptives and patients should be warned accordingly.
Incompatibilities: None known.
Fluticasone furoate is rapidly cleared by extensive first-pass metabolism mediated by the
cytochrome P-450 3A4. Based on data with another glucocorticoid (fluticasone propionate) that is
metabolized by CYP3A4, co-administration with ritonavir is not recommended because of the risk of
increased systemic exposure of fluticasone furoate. Caution is recommended when co-
administering fluticasone furoate with potent CYP3A4 inhibitors as an increase in systemic exposure
cannot be ruled out. In a drug interaction study of fluticasone furoate with the potent CYP3A4
inhibitor ketoconazole, there were more subjects with measurable fluticasone furoate plasma
concentrations in the ketoconazole group (6 of the 20 subjects) compared to placebo (1 of the 20
subjects). This small increase in exposure did not result in a statistically significant difference in 24-
hr serum cortisol levels between the 2 groups. The enzyme induction and inhibition data suggest
that there is no theoretical basis for anticipating metabolic interactions between fluticasone furoate
and the cytochrome P-450-mediated metabolism of other compounds at clinically relevant
intranasal doses. Therefore, no clinical studies have been conducted to investigate interactions of
fluticasone furoate on other drugs (see Pharmacokinetics under Actions and Precautions).
Incompatibilities: None.
Alcohol, theophylline & other CNS depressants.
For information on the decreased serum PSA levels during treatment with dutasteride and guidance
concerning prostate cancer detection see Precautions.
Effects of Other Drugs on the Pharmacokinetics of Dutasteride: Use Together with CYP3A4 and/or P-
Glycoprotein-Inhibitors: Dutasteride is mainly eliminated via metabolism. In vitro studies indicate
that this metabolism is catalysed by CYP3A4 and CYP3A5. No formal interaction studies have been
performed with potent CYP3A4 inhibitors. However, in a population pharmacokinetic study,
dutasteride serum concentration were on average 1.6-1.8 times greater, respectively, in a small
number of patients treated concurrently with verapamil or diltiazem (moderate inhibitors of
CYP3A4 and inhibitors of P-glycoprotein) than in other patients.
Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4
(eg, ritonavir, indinavir, nefazodone, itraconazole, ketoconazole administered orally) may increase
serum concentrations of dutasteride. Further inhibition of 5a-reductase at increased dutasteride
exposure, is not likely. However, a reduction of the dutasteride dosing frequency can be considered
if side effects are noted. It should be noted that in the case of enzyme inhibition, the long t½ may
be further prolonged and it can take >6 months of concurrent therapy before a new steady-state is
reached.
Administration of cholestyramine 12 g 1 hr before a 5 mg single-dose of dutasteride did not affect
the pharmacokinetics of dutasteride.
Effects of Dutasteride on the Pharmacokinetics of Other Drugs: Dutasteride has no effect on the
pharmacokinetics of warfarin or digoxin. This indicates that dutasteride does not inhibit/induce
CYP2C9 or the transporter P-glycoprotein. In vitro interaction studies indicate that dutasteride does
not inhibit the enzyme CYP1A2, CYP2D6, CYP2C9, CYP2C19 or CYP3A4.
In a small study (N=24) of 2 weeks duration in healthy men, dutasteride (0.5 mg daily) had no effect
on the pharmacokinetics of tamsulosin or terazosin. There was also no indication of a
pharmacodynamic interaction in this study.
Al- & Mg-containing antacids, warfarin, ergot derivatives, theophylline. Disturb cyclosporin
metabolism. Increase digoxin conc.
Ethambutol reduces the efficacy of uricosuric agents, esp in the presence of INH & pyridoxine. INH
enhances the effects of phenytoin & inhibits metabolism of primidone.
May reduce efficacy of uricosurics, esp in the presence of INH & pyridoxine. Al-containing antacids.
Al- or Mg-containing antacids may reduce absorption. May increase plasma theophylline levels.
Probenecid, clindamycin, metronidazole.
None reported.
Alcohol, false +ve reaction in the urine may occur w/ Benedict's or Fehling's soln.
Immunosuppressants.
Other ß-adrenergics, anticholinergics and xanthine derivatives (eg, theophylline) may enhance the
bronchodilatory effect of Berodual. The concurrent administration of other ß-mimetics, systemically
available anticholinergics and xanthine derivatives (eg, theophylline) may increase the side effects.
A potentially serious reduction in bronchodilatation may occur during concurrent administration of
ß-blockers.
Beta-agonist-induced hypokalemia may be increased by concomitant treatment with xanthine
derivatives, corticosteroids and diuretics. This should be taken into account particularly in patients
with severe airway obstruction.
Hypokalemia may result in an increased susceptibility to arrhythmias in patients receiving digoxin.
Additionally, hypoxia may aggravate the effects of hypokalemia on cardiac rhythm. It is
recommended that serum potassium levels are monitored in such situations.
Beta-adrenergic agonists should be administered with caution to patients being treated with
monoamine oxidase inhibitors or tricyclic antidepressants, since the action of ß-adrenergic agonists
may be enhanced.
Inhalation of halogenated hydrocarbon anesthetics eg, halothane, trichloroethylene and enflurane
may increase the susceptibility on the cardiovascular effects of ß-agonists.
Beta-adrenergics, anticholinergics and xanthine derivatives (eg, theophylline) may enhance the
effect of Berotec. The concurrent administration of other ß-mimetics, systemically available
anticholinergics and xanthine derivatives (eg, theophylline) may increase the side effects.
A potentially serious reduction in bronchodilation may occur during concurrent administration of ß-
blockers.
Beta-adrenergic agonists should be administered with caution to patients being treated with
monoamine oxidase inhibitors or tricyclic antidepressants, since the action of ß-adrenergic agonists
may be enhanced.
Inhalation of halogenated hydrocarbon anaesthetics eg, halothane, trichloroethylene and enflurane
may increase the susceptibility to the cardiovascular effects of ß-agonists.
Reduced absorption w/ Al-/Mg- containing antacids. May increase plasma conc of theophylline.
Increased serum creatinine level w/ cyclosporine; bleeding time w/ oral anticoagulant; may
accelerate absorption w/ metoclopramide. Probenecid.
Penicillins, amphotericin, cephalosporins, erythromycin, heparin, Na bicarbonate.
Theophylline, antacids.
Alcohol.
No in vivo interaction studies have been performed. Based on in vitro data, no in vivo inhibition on
cytochrome P450 enzymes is expected.
Anticoagulants.
Dicumarol, phenytoin, tolbutamide, phenobarb.
Ca antagonist, clonidine, MAOIs (except MAO-B inhibitors), class I & III antiarrhythmics,
parasympathomimetics, other ß-blockers (including eye drops); insulin & oral antidiabetics, anesth
agents, digitalis glycosides, prostaglandin synthetase inhibitors, ergotamine derivatives,
sympathomimetics, TCA, barbiturates, phenothiazines, other antihypertensives, rifampicin.
Anesth drugs, nitroglycerine, ergot alkaloid vasoconstrictors.
Saquinavir, ritonavir, ß-blockers, fentanyl, cimetidine, digoxin, phenytoin, rifampicin, dantrolene Na,
tandospirone citrate, nitroglycerin, pancuronium Br, vecuronium Br.
No drug interactions of clinical significance have been identified.
Compounds which have been investigated in clinical pharmacokinetic studies include
hydrochlorothiazide, warfarin, digoxin, oral contraceptives (i.e. ethinylestradiol/levonorgestrel),
glibenclamide, nifedipine and enalapril.
Candesartan is eliminated only to a minor extent by hepatic metabolism (CYP2C9). Available
interaction studies indicate no effect on CYP2C9 and CYP3A4 but the effect on other cytochrome
P450 isoenzymes is presently unknown.
The antihypertensive effect of Blopress may be enhanced by other antihypertensives.
Based on experiences with the use of other drugs that affect the renin-angiotensin-aldosterone
system, concomitant use of potassium-sparing diuretics, potassium supplements, salts substitutes
containing potassium, or other drugs that may increase potassium levels (e.g. heparin) may lead to
increase in serum potassium.
Reversible increase in serum lithium concentrations and toxicity have been reported during
concomitant administration of lithium with ACE inhibitors. A similar effect may occur with
angiotensin II receptor antagonists and careful monitoring of serum lithium levels is recommended
during concomitant use.
As with other antihypertensive agents, the antihypertensive effect of candesartan may be
attenuated by non-steroidal anti-inflammatory drugs such as indomethacin.
The bioavailability of candesartan is not affected by food.
Candesartan Cilexetil: No significant drug interactions have been reported in studies of candesartan
cilexetil given with other drugs eg, glyburide, nifedipine, digoxin, warfarin, hydrochlorothiazide and
oral contraceptives in healthy volunteers. Because candesartan is not significantly metabolized by
the cytochrome P-450 system, and at therapeutic concentrations has no effects on P-450 enzymes,
interactions with drugs that inhibit, or rarely metabolized by those enzymes would not be expected.
Hydrochlorothiazide: When administered concurrently, the following drugs may interact with
thiazide diuretics: Alcohol, barbiturates or narcotics. Potentiation of orthostatic hypotension may
occur.
Antidiabetic Drugs (Oral Agent and Insulin): Dosage adjustment of the antidiabetic drug may be
required.
Other Antihypertensive Drugs: Additive effect or potentiation.
Cholestyramine and Colestipol Resins: Absorption of hydrochlorothiazide is impaired in the
presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind
the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and
43%, respectively.
Corticosteroids: ACTH-intensified electrolyte depletion, particularly hypokalemia.
Pressor Amines (eg, Norepinephrine): Possible decreased response to pressor amines but not
sufficient to preclude their use.
Nondepolarizing Skeletal Muscle Relaxants (eg, Tubocurarine): Possible increased responsiveness to
the muscle relaxant.
Lithium: Generally should not be given with diuretic agents because the renal clearance of lithium is
reduced and a high risk of lithium toxicity is added. Refer to the package insert for lithium
preparation before use of such preparations with Blopress Plus.
Nonsteroidal Anti-Inflammatory Drugs: In some patients, the administration of a nonsteroidal anti-
inflammatory agent can reduce the diuretic, natriuretic and antihypertensive effects of loop,
potassium-sparing and thiazide diuretics.
Therefore, when Blopress Plus and nonsteroidal anti-inflammatory agents are used concomitantly,
the patient should be observed closely to determine if the desired effect of diuretic is obtained.
Rifampicin may reduce AUC or Cmax. Cimetidine & grapefruit juice may increase AUC. Quinidine,
fluoxetine, paroxetine & propafenone may increase blood levels of R(+) enantiomer. Digoxin plasma
conc increased when administered concomitantly. Clonidine may potentiate BP & heart rate-
lowering effects.
Ranitidine, aminoglycosides.
Mg-containing prep, digitalis prep, Ca & vit D derivatives, barbiturates & other anticonvulsants.
Neuromuscular transmission may be potentiated by aminoglycosides, curare-like nondepolarizing
blockers, lincosamides, polymyxins, quinidine, Mg sulfate, anticholinesterases, succinylcholine
chloride.
Compd that induce, inhibit or are metabolized by CYP450 3A4 eg, cyclosporine, terfenadine,
ketoconazole, erythromycin & troleandomycin. Increased clearance w/ doxorubicin. Carboplatin.
ß-receptor blocking agents (including eye drops) especially those which are nonselective may partly
or totally inhibit the effect of ß-receptor stimulants.
Hypokalemia may result from ß2-agonist therapy and may be potentiated by concomitant
treatment with xanthine derivatives, steroids and diuretics (see Precautions).
Effects of Other Drugs: Ticagrelor is predominantly metabolized by CYP3A4 and to a lesser extent by
CYP3A5. Ticagrelor is also a p-glycoprotein (P-gp) substrate.
CYP3A Inhibitors: Avoid use of strong inhibitors of CYP3A (eg, ketoconazole, itraconazole,
voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and
telithromycin). (See Pharmacology under Actions, Warnings and Precautions.)
CYP3A Inducers: Avoid use with potent inducers of CYP3A (eg, rifampin, dexamethasone, phenytoin,
carbamazepine and phenobarbital). (See Pharmacology under Actions, Warnings and Precautions.)
Aspirin: Use of BRILINTA with aspirin maintenance doses >100 mg reduced the effectiveness of
Brilinta (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions, Warnings and
Precautions).
Effect of Brilinta on Other Drugs: Ticagrelor is an inhibitor of CYP3A4/5 and the P-gp transporter.
Simvastatin and Lovastatin: BRILINTA will result in higher serum concentrations of simvastatin and
lovastatin because these drugs are metabolized by CYP3A4. Avoid simvastatin and lovastatin doses
greater than 40 mg (see Pharmacology under Actions).
Digoxin: Because of inhibition of the P-gp transporter, monitor digoxin levels with initiation of or any
change in BRILINTA therapy (see Pharmacology under Actions).
Other Concomitant Therapy: BRILINTA can be administered with unfractionated or low-molecular-
weight heparin, GPIIb/IIIa inhibitors, proton-pump inhibitors, ß-blockers, angiotensin converting
enzyme inhibitors and angiotensin receptor blockers.
MAOI may prolong & enhance antihistamine effects which can lead to severe hypotension. W/
alcohol, TCAs, barbiturate or other antidepressants may enhance sedative effect of
dexchlorpheniramine maleate.
Serum K level may be increased in concomitant use of candesartan cilexetil w/ K-sparing diuretics, K
supplements, K-containing salt substitutes. W/ ACE inhibitors may increase serum litium level &
toxicity. Antihypertensive effect may be reduced by NSAIDs eg, indomethacin.
Chloramphenicol, dicoumarol, phenytoin, tolbutamide, phenobarbital.
Aminoglycosides or loop diuretics may cause nephrotoxicity; probenecid increases drug plasma
conc of cefpirome; drugs which may cause fecal stasis.
Nitroprusside, ß-blocker.
Warfarin.
In vitro studies have shown that R-bicalutamide is an inhibitor of CYP3A4, with lesser inhibitory
effects on CYP2C9, 2C19 and 2D6 activity.
Although clinical studies using antipyrine as a marker of cytochrome P-450 (CYP) activity showed no
evidence of a drug interaction potential with Casodex, mean midazolam exposure (AUC) was
increased by up to 80% after co-administration of Casodex for 28 days. For drugs with a narrow
therapeutic index, such an increase could be of relevance. As such, concomitant use of terfenadine,
astemizole and cisapride is contraindicated (see Contraindications) and caution should be exercised
with the co-administration of Casodex with compounds eg, ciclosporin and calcium-channel
blockers. Dosage reduction may be required for these drugs particularly if there is evidence of
enhanced or adverse drug effect. For ciclosporin, it is recommended that plasma concentrations
and clinical condition be closely monitored following initiation or cessation of Casodex therapy.
Caution should be exercised when prescribing Casodex with other drugs which may inhibit drug
oxidation eg, cimetidine and ketoconazole. In theory, this could result in increased plasma
concentrations of Casodex which theoretically could lead to an increase in side effects.
In vitro studies have shown that Casodex can displace the coumarin anticoagulant, warfarin, from
its protein-binding sites. It is therefore, recommended that if Casodex is started in patients who are
already receiving coumarin anticoagulants, prothrombin time should be closely monitored.
50 mg: There is no evidence of any pharmacodynamic or pharmacokinetic interactions between
Casodex and LHRH analogues.
The following interactions include those observed with Cataflam/Cataflam D and/or other
pharmaceutical forms of diclofenac.
Lithium, Digoxin: Cataflam/Cataflam D may raise plasma concentrations of lithium or digoxin.
Monitoring of serum lithium or digoxin level is recommended.
Diuretics and Antihypertensive Agents: Like other NSAIDs, concomitant use of diclofenac with
diuretics or antihypertensive agents (eg, ß-blockers, ACE inhibitors) may cause a decrease in their
antihypertensive effect. Therefore, the combination should be administered with caution and
patients, especially the elderly, should have their blood pressure periodically monitored. Patients
should be adequately hydrated and consideration should be given to monitoring of renal function
after initiation of concomitant therapy and periodically thereafter, particularly for diuretics and ACE
inhibitors due to the increased risk of nephrotoxicity.
Concomitant treatment with potassium-sparing drugs may be associated with increased serum
potassium levels, which should therefore be monitored frequently (see Precautions).
Other NSAIDs and Corticosteroids: Concomitant administration of diclofenac and other systemic
NSAIDs may increase the frequency of side effects (See Warnings and Precaution).
Anticoagulants and Antiplatelet Agents: Caution is recommended since concomitant administration
could increase the risk of bleeding (see Warnings and Precautions). Although clinical investigations
do not appear to indicate that Cataflam/Cataflam D affects the action of anticoagulants, there are
isolated reports of an increased risk of haemorrhage in patients receiving Cataflam/Cataflam D and
anticoagulants concomitantly. Close monitoring of such patients is therefore recommended.
Selective Serotonin Re-Uptake Inhibitors (SSRIs): Concomitant administration of systemic NSAIDs,
including diclofenac, and SSRIs may increase the risk of GI bleeding (see Warnings and Precautions).
Antidiabetics: Clinical studies have shown that Cataflam/Cataflam D can be given together with oral
antidiabetic agents without influencing their clinical effect. However, isolated cases have been
reported of both hypoglycaemic and hyperglycaemic effects necessitating changes in the dosage of
hypoglycaemic agents during treatment with diclofenac. For this reason, monitoring of the blood
glucose level is recommended as a precautionary measure during concomitant therapy.
Methotrexate: Caution is recommended when NSAIDs, including diclofenac, are administered <24
hrs before or after treatment with methotrexate since blood concentrations of methotrexate may
rise and the toxicity of methotrexate increased.
Ciclosporin: Diclofenac, like other NSAIDs, may increase the nephrotoxicity of ciclosporin due to the
effect on renal prostaglandins. Therefore, Cataflam/Cataflam D should be given at doses lower than
those that would be used in patients not receiving ciclosporin.
Quinolone Antibacterials: There have been isolated reports of convulsions which may have been
due to concomitant use of quinolones and NSAIDs.
Warfarin: The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both
drugs together have a risk of serious GI bleeding higher than users of either drug alone.
The reduction in blood pressure induced by clonidine can be further potentiated by concurrent
administration of other hypotensive agents. This can be of therapeutic use in the case of other
antihypertensive agents eg, diuretics, vasodilators, ß-receptor blockers, calcium antagonists and ACE
inhibitors, but not a1-blocking agents.
Substances which raise blood pressure or induce a Na+- and water-retaining effect eg, nonsteroidal
anti-inflammatory agents, can reduce the therapeutic effect of clonidine.
Substances with a2-receptor-blocking properties eg, phentolamine or tolazoline may abolish the a2-
receptor-mediated effects of clonidine in a dose-dependent manner.
Concomitant administration of substances with a negative chronotropic or dromotropic effect eg, ß-
receptor blockers or digitalis glycosides, can cause or potentiate bradycardic rhythm disturbances.
It cannot be ruled out that concomitant administration of a ß-receptor blocker will cause or
potentiate peripheral vascular disorders.
The antihypertensive effect of clonidine may be reduced or abolished and orthostatic regulation
disturbances may be provoked or aggravated by concomitant administration of tricyclic
antidepressants or neuroleptics with a-receptor-blocking properties.
Based on observations in patients in a state of alcoholic delirium, it has been suggested that high IV
doses of clonidine may increase the arrhythmogenic potential (QT-prolongation, ventricular
fibrillation) of high IV doses of haloperidol. Causal relationship and relevance for antihypertensive
treatment have not been established.
The effects of centrally-depressant drugs or alcohol can be potentiated by clonidine.
Alcohol, may cause false positive in urine glucose test by Benedict's or Fehling's soln.
Bacteriostatic antibiotics may reduce cephalosporin effectiveness. Probenecid may increase &
prolong cephalosporin plasma levels & toxicity.
Potent diuretics, nephrotoxics & nephrotic antibiotics; probenecid.
Category C: Either studies in animals have revealed adverse effects on Abbotic: Store at 25°-30°C.
the foetus (teratogenic or embryocidal or other) and there are no Abbotic Granule: Store at cool
controlled studies in women or studies in women and animals are not temperature. The reconstituted
available. Drugs should be given only if the potential benefit justifies suspension can be used for up to 7 days
the potential risk to the foetus. when stored at cool temperature.
Abbotic XL: Store at room temperature
below 25°C. Protect from light.
Category C: Either studies in animals have revealed adverse effects on Store at 25°C (77°F); excursions
the foetus (teratogenic or embryocidal or other) and there are no permitted to 15°-30°C (59°-86°F).
controlled studies in women or studies in women and animals are not
available. Drugs should be given only if the potential benefit justifies
the potential risk to the foetus.
Category B: Either animal-reproduction studies have not demonstrated Do not store above 30°C.
a foetal risk but there are no controlled studies in pregnant women or
animal-reproduction studies have shown an adverse effect (other than
a decrease in fertility) that was not confirmed in controlled studies in
women in the 1st trimester (and there is no evidence of a risk in later
trimesters).
Category D: There is positive evidence of human foetal risk, but the
benefits from use in pregnant women may be acceptable despite the
risk (e.g., if the drug is needed in a life-threatening situation or for a
serious disease for which safer drugs cannot be used or are
ineffective).
Category C: Either studies in animals have revealed adverse effects on Store below 25°C. Protect from moisture
the foetus (teratogenic or embryocidal or other) and there are no and humidity.
controlled studies in women or studies in women and animals are not
available. Drugs should be given only if the potential benefit justifies
the potential risk to the foetus.
Category B: Either animal-reproduction studies have not demonstrated Store Actrapid HM/Penfill which are not
a foetal risk but there are no controlled studies in pregnant women or in use in a refrigerator (2°-8°C) in the
animal-reproduction studies have shown an adverse effect (other than original package, not in or near the
a decrease in fertility) that was not confirmed in controlled studies in cooling compartment. Do not freeze.
women in the 1st trimester (and there is no evidence of a risk in later Keep the vial or cartridge in the outer
trimesters). carton and the pen cap in order to
protect from light. Protect from
excessive heat and sunlight.
Actrapid HM/Penfill in use should not
be kept in a refrigerator. It may be kept
at room temperature (Penfill: Below
30°C; Vial: Below 30°C) for up to 6
weeks after first opening.
Shelf-Life: 30 months.
Parenteral
Category C: Either studies in animals have revealed adverse effects on
the foetus (teratogenic or embryocidal or other) and there are no
controlled studies in women or studies in women and animals are not
available. Drugs should be given only if the potential benefit justifies
the potential risk to the foetus.
See table.
Each liter of Aminovel 600 contains amino
acids (L-form) 50 g, D-sorbitol 100 g, ascorbic
acid 400 mg, inositol 500 mg, nicotinamide 60
mg, pyridoxine HCl 40 mg, riboflavin sodium
phosphate 2.5 mg and the following
electrolytes: Sodium 35 mEq, potassium 25
mEq, magnesium 5 mEq, acetate 35 mEq,
maleate 22 mEq, chloride 38 mEq.
Each 50 g of amino acids contains the
following: L-isoleucine 3.2 g, L-leucine 2.4 g, L-
lysine (calculated as base) 2 g, L-methionine 3
g, L-phenylalanine 4 g, L-threonine 2 g, L-
tryptophan 1 g, L-valine 3.2 g, L-arginine
(calculated as base) 6.2 g, L-histidine
(calculated as base) 1 g, L-alanine 6 g, glycine
14 g, L-proline 2 g.
Aminovel 600 is a sterile aqueous solution
supplying approximately 600 cal/L. Each lot is
examined by exothermic substance test,
sterility test and toxicity test, and is
manufactured under severe standards.
With these procedures, a report from the laboratory of "susceptible" indicates that the infecting organism is likely to respond to therapy. A report of "resistant"
indicates that the infective organism is not likely to respond to therapy. A report of "intermediate susceptibility" suggests that the therapeutic effect of the drug may
be equivocal or that the organism would be susceptible if higher doses were used. (Intermediate susceptibility is also referred to as moderately susceptible.) This
category provides a better zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretations.
However, standardized diffusion methods for routine in vitro susceptibility testing, using the 15-mcg clarithromycin disc, do not measure the additive antimicrobial
activity of the 14-OH metabolite and thus may underestimate the drug's potential activity against Haemophilus influenzae isolates falling into the "intermediate"
category which often respond to treatment.
Standardized procedures require the use of laboratory control organisms. The 15-mcg clarithromycin disc should be given the following zone diameter: S. aureus ATCC
25923: 23-30 mm.
Pharmacology: Pharmacodynamics: Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors (Ki values of 0.34, 0.8, 1.7 and
3.4 nM, respectively), moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, a1-adrenergic and histamine H1 receptors (Ki values of 44, 15, 39, 57 and 61
nM, respectively), and moderate affinity for the serotonin re-uptake site (Ki=98 nM). Aripiprazole has no appreciable affinity for cholinergic-muscarinic receptors (IC50
>1000 nM). Aripiprazole functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptor.
The mechanism of action of aripiprazole, as with other drugs having efficacy in schizophrenia and bipolar disorder is unknown. However, it has been proposed that the
efficacy of aripiprazole is mediated through a combination of partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Actions at
receptors other than D2, 5-HT1A and 5-HT2A may explain some of the other clinical effects of aripiprazole eg, the orthostatic hypotension observed with aripiprazole
may be explained by its antagonist activity at adrenergic a1-receptors.
Pharmacokinetics: Abilify activity is presumably primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole,
which has been shown to have affinities for D2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma. The mean elimination
half-lives are about 75 and 94 hrs for aripiprazole and dehydro-aripiprazole, respectively. Steady-state concentrations are attained within 14 days of dosing for both
active moieties. Aripiprazole accumulation is predictable from single-dose pharmacokinetics. At steady state, the pharmacokinetics of aripiprazole is dose-
proportional. Elimination of aripiprazole is mainly through hepatic metabolism involving two P-450 isozymes, CYP2D6 and CYP3A4.
Absorption: Aripiprazole is well absorbed after administration of the tablet, with peak plasma concentrations occurring within 3-5 hrs; the absolute oral bioavailability
of the tablet formulation is 87%. Abilify can be administered with or without food. Administration of a 15-mg tablet with a standard high-fat meal did not significantly
affect the Cmax or AUC of aripiprazole or its active metabolite, dehydro-aripiprazole, but delayed Tmax by 3 hrs for aripiprazole and 12 hrs for dehydro-aripiprazole.
Distribution: The steady-state volume of distribution of aripiprazole following IV administration is high (404 L or 4.9 L/kg), indicating extensive extravascular
distribution. At therapeutic concentrations, aripiprazole and its major metabolite are >99% bound to serum proteins, primarily to albumin. In healthy human
volunteers administered with aripiprazole 0.5-30 mg/day for 14 days, there was dose-dependent D2-receptor occupancy indicating brain penetration of aripiprazole in
humans.
Metabolism and Elimination: Aripiprazole is metabolized primarily by 3 biotransformation pathways: Dehydrogenation, hydroxylation and N-dealkylation. Based on in
vitro studies, CYP3A4 and CYP2D6 enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP3A4.
Aripiprazole is the predominant drug moiety in the systemic circulation. At steady state, dehydro-aripiprazole, the active metabolite, represents about 40% of
aripiprazole AUC in plasma.
Approximately 8% of Caucasians lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PM), whereas the rest are extensive
metabolizers (EM). PMs have about an 80% increase in aripiprazole exposure and about a 30% decrease in exposure to the active metabolite compared to EMs,
resulting in about a 60% higher exposure to the total active moieties from a given dose of aripiprazole compared to EMs. Co-administration of Abilify with known
inhibitors of CYP2D6 eg, quinidine in EMs, results in a 112% increase in aripiprazole plasma exposure, and dosing adjustment is needed (see Interactions). The mean
elimination half-lives are about 75 and 146 hrs for aripiprazole in EMs and PMs, respectively. Aripiprazole does not inhibit or induce the CYP2D6 pathway.
Following a single oral dose of [14C]-labeled aripiprazole, approximately 25% and 55% of the administered radioactivity was recovered in the urine and feces,
respectively. Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces.
Special Populations: In general, no dosage adjustment for Abilify is required on the basis of a patient's age, gender, race, smoking status, hepatic function, or renal
function (see Dosage & Administration). The pharmacokinetics of aripiprazole in special populations are described as follows.
Hepatic Impairment (HI): In a single-dose study (aripiprazole 15 mg) in subjects with varying degrees of liver cirrhosis (Child-Pugh Classes A, B and C), the AUC of
aripiprazole, compared to healthy subjects, increased 31% in mild HI, increased 8% in moderate HI, and decreased 20% in severe HI. None of these differences would
require dose adjustment.
Renal Impairment: In patients with severe renal impairment (creatinine clearance <30 mL/min), Cmax of aripiprazole (given in a single dose of 15 mg) and dehydro-
aripiprazole increased by 36% and 53%, respectively, but AUC was 15% lower for aripiprazole and 7% higher for dehydro-aripiprazole. Renal excretion of both
Pharmacology: Mechanism of Action: Actosmet combines 2 antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in
patients with the type 2 diabetes: Pioglitazone hydrochloride, a member of the thiazolidinedione class, and metformin hydrochloride, a member of the biguanide
class. Thiazolidinediones are insulin-sensitizing agents that act primarily by enhancing peripheral glucose utilization, whereas biguanides act primarily by decreasing
endogenous hepatic glucose production.
Pioglitazone Hydrochloride: Pioglitazone depends on the presence of insulin for its metabolism of action. Piolitazone decreases insulin resistance in the periphery and
in the liver resulting in increased insulin-dependent glucose disposal, and decreased hepatic glucose output. Unlike sulfonylureas, piogltiazone is not an insulin
secretagogue. Pioglitazone is a potent and highly selective agonist for peroxisome proliferator-activated receptor-? (PPAR?). PPAR receptors are found in tissues
important for insulin action eg, adipose tissue, skeletal muscle and liver. Activation of PPAR? nuclear receptors modulates the transcription of a number of insulin
responsive genes involved in the control of glucose and lipid metabolism.
In animal models of diabetes, pioglitazone reduces the hyperglycemia, hyperinsulinemia and hypertriglyceridemia characteristic of insulin-resistant states eg, type 2
diabetes. The metabolic changes produced by pioglitazone result in increased responsiveness of insulin-dependent tissues and are observed in numerous animal
models of insulin resistance.
Since pioglitazone enhances the effects of circulating insulin (by decreasing insulin resistance), it does not lower blood glucose in animal models that lack endogeous
insulin.
Metformin Hydrochloride: Metformin hydrochloride improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose.
Metformin decreased hepatic glucose production, decreased intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake
and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects (except in special
circumstances, see General: Metformin Hydrochloride under Precautions) and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains
unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.
Pharmacodynamics: Clinical Effects: Pioglitazone Hydrochloride: Clinical studies demonstrate that pioglitazone improves insulin sensitivity in insulin-resistant patients.
Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, improves hepatic sensitivity to insulin, and improves
dysfunctional glucose homeostasis. In patients with type 2 diabetes, the decreased insulin resistance produced by pioglitazone results in lower plasma glucose
concentrations, lower plasma insulin levels, and lower HbA1c values. Based on results from an open-label extension study, the glucose-lowering effects of pioglitazone
appear to persist for at least 1 year. In controlled clinical studies, pioglitazone in combination with metformin had an additive effect on glycemic control.
Patients with lipid abnormalities were included in placebo-controlled monotherapy clinical studies with pioglitazone. Overall, patients treated with pioglitazone had
mean decreases in triglycerides, mean increases in HDL-cholesterol, and no consistent mean changes in LDL-cholesterol and total cholesterol compared to the placebo
group. A similar pattern of results was seen in 16- and 24-week combination therapy studies of pioglitazone with metformin.
Pharmacokinetics: Absorption and Bioavailability: In bioequivalence studies of Actosmet 15 mg/850 mg, the area under the curve (AUC) and maximum concentration
(Cmax) of both the pioglitazone and the metformin component following a single dose of the combination tablet were bioequivalent to Actos 15 mg concomitantly
administered with metformin hydrochloride 850-mg tablet under fasted conditions in healthy subjects (see Table 1).
Administration of Actosmet 15 mg/850 mg with food resulted in no change in overall exposure of pioglitazone. With metformin there was no change in AUC, however
mean peak serum concentration of metformin was decreased by 28% when administered with food. A delayed time to peak serum concentration was observed for
both components (1.9 hrs for pioglitazone and 0.8 hrs for metformin) under fed conditions. These changes are not likely to be clinically significant.
Pioglitazone Hydrochloride: Following oral administration, in the fasting state, pioglitazone is 1st measurable in serum within 30 min, with peak concentrations
observed within 2 hrs. Food slightly delays the time to peak serum concentration to 3-4 hrs, but does not alter the extent of absorption.
Metformin Hydrochloride: The absolute bioavailabifity of a metformin 500-mg tablet given under fasting conditions is approximately 50 or 60%. Studies using single
oral doses of metformin tablets of 500 mg to 1500 mg and 850 mg to 2550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due
Pharmacotherapeutic Group: Insulins and analogues, fast-acting, insulin (human). ATC Code: A10AB01.
Pharmacology: Pharmacodynamics: The blood glucose-lowering effect of insulin occurs when the molecules facilitate the uptake of glucose by binding to insulin
receptors on muscle and fat cells, thus simultaneously inhibiting the output of glucose from the liver.
Actrapid HM/Penfill is a fast-acting insulin with an onset of action within ½ hr, reaching a maximum effect within 1.5-3.5 hrs and the duration of action is
approximately 7-8 hrs.
Pharmacokinetics: Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by
its absorption characteristics. This process is influenced by several factors (eg, insulin dosage, injection route and site, thickness of SC fat, type of diabetes). The
pharmacokinetics of insulin are therefore affected by significant intra- and inter-individual variation.
Absorption: The maximum plasma concentration of insulin is reached within 1.5-2.5 hrs after SC administration.
Distribution: No profound binding to plasma proteins, except circulating insulin antibodies (if present) has been observed.
Metabolism: Human insulin is reported to be degraded by insulin protease or insulin-degrading enzymes and possibly protein disulfide isomerase. A number of
cleavage (hydrolysis) sites on the human insulin molecule have been proposed; none of the metabolites formed following the cleavage are active.
Elimination: The terminal half-life (t½) is determined by the rate of absorption from the SC tissue. The t½ is therefore a measure of the absorption rather than of the
elimination per se of insulin from plasma (insulin in the blood stream has a t½ of a few minutes). Trials have indicated a t½ of about 2-5 hrs.
The pharmacokinetic profile of Actrapid HM/Penfill has been studied in a small number (n=18) of diabetic children (6-12 years) and adolescents (13-17 years). The
data are limited but suggest that the pharmacokinetic profile in children and adolescents may be similar to that in adults. However, there were differences between
age groups in Cmax stressing the importance of individual dose titration.
Toxicology: Preclinical Safety Data: Preclinical data reveal no specific hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity,
genotoxicity, carcinogenic potential, toxicity to reproduction.
Microbiology: Antibacterial Spectrum: In vitro antibacterial activity of nadifloxacin showed a potent and broad spectrum against aerobic gram-positive, gram-negative
and anaerobic bacteria, including Propionibacterium acnes and Staphylococcus epidermidis. Acuatim activity is bactericidal. Nadifloxacin showed potent antibacterial
activity against methicillin-resistant Staphylococcus aureus (MRSA) that was similar to the potency against methicillin-sensitive Staphylococcus aureus (MSSA).
Acuatim was also active against new quinolone-resistant MRSA. Nadifloxacin was not cross-resistant with other new quinolones.
In vivo Antibacterial Activity: The in vivo therapeutic effect of Acuatim cream was superior to the cream base alone in experimental models of infections in mice which
were subcutaneously infected with P. acnes and S. epidermidis.
Antibacterial Effects: Results of follicular analysis obtained in clinical studies using acne patients indicated that Acuatim cream significantly decreased the counts of P.
acnes and other microorganisms in the follicles, as compared to the control (cream base) treatment. Microbacterial tests were negative for Staphylococcus aureus,
CNS, P. acnes and other microorganisms in 86.4% of the patients with folliculitis or sycosis vulgaris after the application of Acuatim cream. The minimum inhibitory
concentrations (MIC) of nadifloxacin against 394 clinical isolates of P. acnes, 76 of Staphylococcus epidermidis, 45 of CNS and 24 of Staphylococcus aureus were not
higher than 0.78, 0.39, 0.05 and 0.39 mcg/mL, respectively, evidencing its potent antibacterial activity. In addition, no resistance to nadifloxacin developed.
Mechanism of Action: Nadifloxacin showed an inhibitory effect on bacterial DNA gyrase activity (involved in DNA synthesis and replication) ie, converting relaxed DNA
to supercoiled DNA.
Development of Resistance: The development of resistance after serial passage of nadifloxacin was rare as compared with that of other new quinolone antibacterial
agents. The frequency of spontaneous mutants resistant to nadifloxacin was <10-8.
Pharmacokinetics: Following a single topical application of nadifloxacin 1% cream at 10 g to normal human back skin, the highest plasma concentration was
determined to be 1.7 ng/mL with an elimination half-life of 19.4 hrs. Approximately 0.09% of the administered dose was excreted in the urine over 48 hrs post-dosing.
The plasma concentration reached a steady state on day 5 of the repeated administration study when nadifloxacin 1% cream was administered at 5 g twice daily to
normal healthy individuals for a period of 7 days. The plasma concentration reached a peak of 4.1 ng/mL at 8 hrs post-final dosing with an elimination half-life of 23.2
hrs. The urinary excretion rate reached 0.16% on day 7.
Clinical Studies: Clinical Efficacy: Nadifloxacin was studied in a total of 519 acne patients using both the open and double-blind test methods. Acuatim was applied to
the face twice (morning and evening) daily after washing for 4 weeks. Efficacy (effective or markedly effective) was obtained in 67.1% (348/519) of the subjects. A
double-blind study in acne patients with multiple inflamed lesions demonstrated that 81.3% (39/48) of the treated patients showed a decreased in the lesion count
and improvement of inflammation.
Pharmacology: Sodium hyaluronate has a covering and protective action to the cartilage surface of the joint, a suppressive action to the degenerative change in the
cartilage tissue and an ameliorative action to the mobility range in articular contracture. It relieves pain in general arthrosis deformans, improves mobility range of the
joints and normalizes synovial fluid.
Action to the Cartilage of the Joint: Sodium hyaluronate was recognized to have entered into the surface layer of the cartilage by administration into the cavity of the
knee joint of a normal rabbit. Moreover, in the cartilage of man with arthrosis deformans in the knee (in vitro), distribution of sodium hyaluronate extends widely from
the surface layer into the entire layer of the cartilage with the progress of time. This distribution within the cartilage was in agreement with the parts deprived of
proteoglycan. Separation of proteoglycan in the cells of articular cartilage of a cow is suppressed by sodium hyaluronate. Administration of sodium hyaluronate in the
joint cavity of the knee using a rabbit as the model of arthrosis deformans of the knee and the model of fixed articular contracture of the knee, proved to have
suppressed degeneration of cartilage.
Improvement of Mobility Range of the Joints: In the model of fixed articular contracture using the rabbit, mobility range of the joint was improved by administration of
sodium hyaluronate into articular cavity.
Toxicology: Nonclinical Tests: Acute Toxicity: LD50 value obtained when single administration was given intra-abdominally in male and female rats were 2014 and 1761
mg/kg, respectively.
Subacute Toxicity: When repeated intra-abdominal administrations were given in rats during 28 days at a dose level of 30, 60, 120 and 240 mg/kg, the indifferent dose
recognized was 30 mg/kg. Doses of >60 mg/kg caused a decrease of red blood cells (RBC) and total protein, which was recognized to be dose-dependent. This was
considered to have relation with the change of blood picture by the use of sodium hyaluronate, however a tendency of recovery was shown after discontinuation of
the drug.
Antigenicity: Sodium hyaluronate was allowed to exhibit its action by IM and intra-articular administration in guinea pigs, and the tests for mobile anaphylaxis, corneal
and PCA reactions was carried out. The result showed that there was no antigenicity observed in any of the tests.
Mutagenicity: In the Ames test using bacteria, occurrence of mutagenicity was not recognized.
Local Irritability: Sodium hyaluronate 0.1 mL was dropped into the rabbit eyes and it showed no influence on the cornea, iris and conjunctiva. Irritation to the mucous
membrane of the eyes was also negative.
Pharmacotherapeutic Group: Antihistamine-H1 antagonist. ATC Code: R06AX27.
Pharmacology: Mechanism of Action: Desloratadine is a non-sedating, long-acting tricyclic histamine antagonist with selective peripheral H1-receptor histamine
antagonist activity. Receptor-binding data indicate that at a concentration of 2-3 ng/mL (7 nM), desloratadine shows significant interaction with the human histamine
H1-receptor. Desloratadine inhibited histamine release from human mast cells in vitro.
Results of a radiolabeled tissue distribution study in rats and a radioligand H1-receptor-binding study in guinea pigs showed that desloratadine did not readily cross
the blood-brain barrier.
After oral administration, desloratadine selectively blocks peripheral histamine H1-receptors because the substance is excluded from entry to the central nervous
system. Desloratadine does not readily penetrate the central nervous system. At the recommended dose of 5 mg daily for adults and adolescents, there was no excess
incidence of somnolence as compared to placebo. Aerius tablets given at a single daily dose of 7.5 mg to adults and adolescents did not affect psychomotor
performance in clinical trials. In a single-dose study performed in adults, desloratadine 5 mg did not affect standard measures of flight performance including
exacerbation of subjective sleepiness or tasks related to flying.
Desloratadine has demonstrated antiallergic properties from in vitro studies. These include inhibiting the release of proinflammatory cytokines eg, IL-4, IL-6, IL-8 and
IL-13 from human mast cells/basophils, as well as inhibition of the expression of the adhesion molecule-P selection on endothelial cells. The clinical relevance of these
observations remains to be confirmed.
Efficacy of Aerius syrup has not been investigated in separate pediatric trials. Safety of Aerius syrup was demonstrated in 3 pediatric trials. Children 1-11 years who
were candidates for antihistamine therapy received a daily dose of 1.25 mg (1-5 years) and 2.5 mg (6-11 years). Treatment was well tolerated as documented by
clinical laboratory tests, vital signs and ECG internal data including QTc. When given at the recommended doses, the plasma concentration of desloratadine was
comparable in the pediatric and adult populations. Thus, since the course of seasonal allergic rhinitis/chronic idiopathic urticaria and the profile of desloratadine are
similar in adults and pediatric patients, desloratadine efficacy data in adults can be extrapolated to the pediatric population.
In a multiple dose clinical trial in adults and adolescents in which up to 20 mg of desloratadine was administered daily for 14 days, no statistically or clinically relevant
cardiovascular effect was observed in a clinical pharmacology trial in adults and adolescents, in which desloratadine was administered to adults at a dose of 45 mg
daily (9 times the clinical dose) for 10 days, no prolongation of QTc interval was seen.
Pharmacodynamics: Wheal and Flare: Human histamine skin wheal studies following single and repeated 5-mg doses of desloratadine have shown that the drug
exhibits an antihistaminic effect by 1 hr; this activity may persist for as long as 24 hrs. There was no evidence of histamine-induced skin wheal tachyphylaxis within the
desloratadine 5-mg group over the 28-day treatment period.
The clinical relevance of histamine wheal skin testing is unknown.
Effects on QTc: Single-dose administration of desloratadine did not alter the corrected QT interval (QTc) in rats (up to 12 mg/kg, oral), or guinea pigs (25 mg/kg, IV).
Repeated oral administration at doses up to 24 mg/kg for durations up to 3 months in monkeys did not alter the QTc at an estimated desloratadine exposure (AUC)
that was approximately 955 times the mean AUC in humans at the recommended daily oral dose. (See Overdosage for information on human QTc experience.)
Clinical Trials: Seasonal Allergic Rhinitis: The clinical efficacy and safety of Aerius tablets were evaluated in >2300 patients 12-75 years with seasonal allergic rhinitis. A
total of 1838 patients received Aerius 2.5-20 mg/day in 4 double-blind, randomized, placebo-controlled clinical trials of 2- to 4-week duration conducted in the United
States. The results of these studies demonstrated the efficacy and safety of Aerius 5 mg in the treatment of adult and adolescent patients with seasonal allergic
rhinitis. In a dose ranging trial, Aerius 2.5-20 mg/day was studied. Doses of 5, 7.5, 10 and 20 mg/day were superior to placebo; and no additional benefit was seen at
doses >5 mg. In the same study, an increase in the incidence of somnolence was observed at doses of 10 and 20 mg/day (5.2% and 7.6%, respectively), compared to
placebo (2.3%).
In two 4-week studies of 924 patients (15-75 years) with seasonal allergic rhinitis and concomitant asthma, Aerius tablets 5 mg once daily improved rhinitis symptoms,
with no decrease in pulmonary function. This supports the safety of administering Aerius tablets to adult patients with seasonal allergic rhinitis with mild to moderate
asthma.
Pharmacotherapeutic Group: Folic acid analogues. ATC Code: L01BA04.
Pharmacology: Pharmacodynamics: Pemetrexed is a multi-targeted anticancer antifolate agent that exerts its action by disrupting crucial folate-dependent metabolic
processes essential for cell replication.
In vitro studies have shown that pemetrexed behaves as a multi-targeted antifolate by inhibiting thymidylate synthase (TS), dihydrofolate reductase (DHFR) and
glycinamide ribonucleotide formyltransferase (GARFT), which are key folate-dependent enzymes for the de novo biosynthesis of thymidine and purine nucleotides.
Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is rapidly
and efficiently converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are even more
potent inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumour cells and, to a lesser extent, in normal
tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
Clinical Efficacy: Mesothelioma: EMPHACIS, a multicentre, randomised, single-blind phase 3 study of Alimta plus cisplatin versus cisplatin in chemo-naive patients with
malignant pleural mesothelioma, has shown that patients treated with Alimta and cisplatin had a clinically meaningful 2.8-month median survival advantage over
patients receiving cisplatin alone. During the study, low-dose folic acid and vitamin B12 supplementation was introduced to patient therapy to reduce toxicity. The
primary analysis of this study was performed on the population of all patients randomly assigned to a treatment arm who received the study drug (randomised and
treated). A subgroup analysis was performed on patients who received folic acid and vitamin B12 supplementation during the entire course of study therapy (fully
supplemented). The results of these analyses of efficacy are summarised in Table 1. (See Table 1.)
A statistically significant improvement of the clinically relevant symptoms (pain and dyspnoea) associated with malignant pleural mesothelioma in the Alimta/cisplatin
arm (212 patients) versus the cisplatin arm alone (218 patients) was demonstrated using the lung cancer symptom scale. Statistically significant differences in
pulmonary function tests were also observed. The separation between the treatment arms was achieved by improvement in lung function in the Alimta/cisplatin arm
and deterioration of lung function over time in the control arm.
There are limited data in patients with malignant pleural mesothelioma treated with Alimta alone. Alimta at a dose of 500 mg/m2 was studied as a single-agent in 64
chemo-naive patients with malignant pleural mesothelioma. The overall response rate was 14.1%.
Non-Small Cell Lung Cancer (NSCLC) 2nd-Line Treatment: A multicentre, randomised, open-label phase 3 study of Alimta versus docetaxel in patients with locally
advanced or metastatic NSCLC after prior chemotherapy has shown median survival times of 8.3 months for patients treated with Alimta [intent to treat population
(ITT) n=283] and 7.9 months for patients treated with docetaxel (ITT n=288). An analysis of the impact of NSCLC histology on the treatment effect on overall survival
was in favour of Alimta versus docetaxel for other than predominantly squamous histologies (n=399, 9.3 versus 8 months, adjusted HR=0.78; 95% CI=0.61-1, p=0.047)
and was in favour of docetaxel for squamous cell carcinoma histology (n=172, 6.2 versus 7.4 months, adjusted hazard ratio (HR)=1.56; 95% CI=1.08-2.26, p=0.018).
There were no clinically relevant differences observed for the safety profile of Alimta within the histology subgroups.
Limited clinical data from a separate randomized, phase 3, controlled trial, suggest that efficacy data (overall survival, progression-free survival) for pemetrexed are
similar between patients previously pre-treated with docetaxel (n=41) and patients who did not receive previous docetaxel treatment (n=540). (See Table 2.)
Non-Small Cell Lung Cancer, 1st-Line Treatment: A multicentre, randomised, open-label, phase 3 study of Alimta plus cisplatin versus gemcitabine plus cisplatin in
chemonaive patients with locally advanced or metastatic (stage IIIb or IV) NSCLC showed that Alimta plus cisplatin (ITT population n=862) met its primary endpoint
and showed similar clinical efficacy as gemcitabine plus cisplatin (ITT n=863) in overall survival (adjusted HR 0.94; 95% CI=0.84-1.05). All patients included in this study
had an eastern cooperative oncology group (ECOG) performance status 0 or 1.
The primary efficacy analysis was based on the ITT population. Sensitivity analyses of main efficacy endpoints were also assessed on the protocol qualified (PQ)
population. The efficacy analyses using PQ population are consistent with the analyses for the ITT population and support the non-inferiority of AC versus GC.
Progression free survival (PFS) and overall response rate were similar between treatment arms: Median PFS was 4.8 months for Alimta plus cisplatin versus 5.1 months
Alinamin/Alinamin-F enhances the metabolism activity in the whole body.
Vitamins B1 (thiamine) and B2 (riboflavin) are essential substances for nerve function and carbohydrate metabolism.
Vitamins B1 and B2 supplements are needed in the following conditions: Increase in requirement eg, during pregnancy and lactation period, when the body needs
more energy; impairment of absorption eg, in diarrhoea and other digestive disturbances. Alinamin/Alinamin-F tablet contains vitamin B1 in TTFD (thiamine
tetrahydrofurfuryl disulfide HCl). TTFD cannot be damaged by enzyme aneurinase, an enzyme produced by several bacteria in the intestine, which damages vitamin B.
Pharmacokinetics: Absorption of TTFD in the gastrointestinal tract is optimal.
Pharmacology: Glimepiride is a sulfonylurea antidiabetic agent which decreases blood glucose concentrations. The primary mechanism of action of glimepiride
appears to be dependent on stimulating the release of insulin from functioning pancreatic ß cells. Glimepiride acts in concert with glucose by improving the sensitivity
of ß cells to physiological glucose stimulus, resulting in insulin secretion in the rhythim of meals. In addition, extrapancreatic effects (eg, reduction of basal hepatic
glucose production and increased peripheral tissue sensitivity to insulin and glucose uptake) may also play a limited role in the activity of glimepiride.
In nonfasting diabetic patients, the hypoglycaemic action of a single dose of glimepiride persist for 24 hrs.
Evidence from in vitro and animal studies suggests that there is lower glucagon secretion with glimepiride than glibenclamide and this may give rise to a prolonged
reduction of blood glucose levels without increased plasma insulin levels. The clinical significance of these findings is yet to be clarified. A long-term, randomized,
placebo-controlled clinical trial demonstrated that Amaryl therapy improves postprandial insulin/C-peptide responses and overall glycaemic control without producing
clinically meaningful increases in fasting insulin/C-peptide levels.
The efficacy of Amaryl is not affected by age, gender or weight. Amaryl therapy is effective in controlling blood glucose without deleterious changes in the plasma
lipoprotein profile in patients. The physiological response to acute exercise (ie, reduction of insulin secretion) is still present during glimepiride therapy.
Pharmacology: Glimepiride is a blood sugar-lowering agent belonging to the sulfonylurea group. The decrease in blood sugar is achieved principally by means of the
stimulation of insulin release from pancreatic ß-cells. This effect is predominantly based on improved responsiveness of these cells to the physiological glucose
stimulus. Glimepiride augments the normal action of insulin on peripheral glucose uptake. Moreover, it mimics such action as well as the glucose output of the liver.
Good metabolic control over 24 hrs can be achieved with a single dose of Amaryl M.
In patients with insufficient response to the maximum dose, combined use with an additional oral antidiabetic containing metformin or with insulin improves
metabolic control.
Metformin is a blood sugar-lowering agent belonging to the biguanide group. The decrease in blood sugar is achieved principally by not increasing insulin secretion.
Moreover, metformin is not metabolized in the liver; excretion is through urine and feces.
Pharmacology: Pharmacodynamics: Amlodipine is a calcium ion-influx inhibitor (slow channel blocker or calcium-ion antagonist) and inhibits the transmembrane
influx of calcium ions into cardiac and vascular smooth muscles.
The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle. The precise mechanism by which
amlodipine relieves angina has not been fully determined but amlodipine reduces the total ischemic burden by the following 2 actions: Amlodipine dilates peripheral
arterioles and thus, reduces the total peripheral resistance (afterload) against which the heart works. Since the heart rate remains stable, this unloading of the heart
reduces myocardial energy consumption and oxygen requirements.
The mechanism of action of amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischemic regions.
This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (prinzmetal's or variant angina).
In patients with hypertension, once a day dosing provides clinically significant reductions of blood pressure in both the supine and standing positions throughout the
24-hr interval. Due to the slow onset of action, acute hypotension is not a feature of amlodipine administration.
In patients with angina, once a day administration of amlodipine increases total exercise time, time to angina onset and time to 1 mm ST segment depression and
decreases both angina attack frequency and nitroglycerine tablet consumption.
In vitro studies have shown that approximately 97.5% of circulating amlodipine is bound to plasma proteins. Amlodipine has not been associated with any adverse
metabolic effect or change in plasma lipids and is suitable for use in patients with asthma, diabetes and gout.
Pharmacokinetic studies with cyclosporin have demonstrated that amlodipine does not significantly alter the pharmacokinetics of cyclosporin.
Hemodynamic studies and exercise-based controlled clinical trial in NYHA Class II-IV heart failure patients have shown that amlodipine did not lead to clinical
deterioration as measured by exercise tolerance, left ventricular ejection fraction (LVEF) and clinical symptomatology.
A placebo-controlled study (PRAISE) designed to evaluate patients with NYHA Class II-IV heart failure receiving digoxin, diuretics and angiotensin-converting enzyme
(ACE) inhibitors has shown that amlodipine did not lead to an increase risk of mortality or combined mortality and morbidity in patients with heart failure. In the same
study, in a group of patients without clinical signs or symptoms suggestive of underlying ischemic disease, a clinically and statistically significant reductions in mortality
and combined mortality and morbidity was observed with amlodipine.
Pharmacokinetics: Absorption: After oral administration of therapeutic doses, amlodipine is well absorbed with peak blood levels between 6-12 hrs post-dose.
Absolute bioavailability has been estimated to be between 64% and 80%. The volume of distribution is approximately 21 L/kg. Absorption of amlodipine is unaffected
by consumption of food.
Biotransformation/Elimination: The terminal plasma elimination half-life is about 35-50 hrs and is consistent with once-daily dosing. Steady-state plasma levels are
reached after 7-8 days of consecutive dosing. Amlodipine is extensively metabolized by the liver to inactive metabolites with 10% of the parent compound and 60% of
metabolites excreted in the urine.
Pharmacology: Aminoleban Infusion normalized the pattern of free amino acids in the plasma and brain, improved serotonin metabolism in the brain and corrected a
sleep-wakefulness pattern in a rat model of chronic hepatic insufficiency which underwent a portacaval shunt operation.
When infused to portacaval-shunted rats loaded with ammonia, Aminoleban Infusion improved EEG pattern, and corrected amine metabolism in the brain as
evidenced by correction of the free amino acid pattern in the plasma and brain, and by suppression of an increase of the false neurotransmitter octopamine.
Aminovel 600 is a well-balanced mixture of L-amino acids optimally proportioned for maximum protein synthesis.
Sorbitol, vitamins and electrolytes supplement nutritional needs for the body.
Aminovel 600 supplies the following essential components for parenteral nutrition:
L-Forms of amino acids which can only be utilized in the body for the synthesis of its various protein constituents. It is known that the body does not normally
preserve nitrogen balance with D-isomers of amino acids.
Eight Essential Amino Acids: Isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine are indispensable for protein synthesis.
Semi-Essential Amino Acids: Histidine utilizes optimally amino acid mixtures and is essential for infants and in uraemia; arginine utilizes optimally amino acid mixtures
and is essential for detoxification.
L-Alanine and L-proline are necessary for optimal utilization of amino acid mixtures.
Glycine is a source for nonspecific nitrogen.
Sorbitol to supply sufficient non-nitrogen calories to meet metabolic energy requirements.
Vitamins to prevent deficiencies and to promote the biosynthesis of protein.
Minerals to maintain electrolyte balance and to promote protein synthesis.
Water to meet the body's requirements.
Aminovel 600 provides all these substances optimally and in exactly balanced proportions necessary to ensure maximum protein synthesis without depletion of the
body's own reserves.
Amiparen is a new formula of total amino acid solution intended for use in hyperalimentation and general parenteral nutrition.
Amiparen contains relatively larger amounts of branched-chain amino acids (leucine, isoleucine and valine), which suppress protein breakdown and promote protein
synthesis in muscle tissue, and smaller amounts of aromatic and acidic amino acids. A series of preclinical and clinical studies have demonstrated that Amiparen was
effective in sparing protein under various types of insults and malnutritional state.
Amiparen is also formulated to contain no chloride ions and minimum sodium ions to facilitate easy supplementation of electrolytes.
Pharmacology: The value of Amiparen as a source of amino acids in nutritional support was assessed in hyperalimentation therapy using normal rats and insulted rats.
Amiparen promptly improved and maintained nitrogen balance, and exhibited a pronounced nitrogen-sparing effect in these models.
The solution promoted synthesis of plasma total protein and albumin.
The urinary 3-methylhistidine/creatinine ratio, an indicator of protein catabolism in the muscle under insult, was low after infusion treatment, indicating a very potent
inhibitory effect of the solution on muscle protein breakdown.
Plasma concentrations of free amino acids, including branched-chain amino acids, showed minor fluctuation during infusion treatment. Amino acid metabolism was
judged to be steady during Amiparen therapy.
Clinical Studies: Clinical studies of Amiparen were conducted in a total of 546 patients undergoing central or peripheral venous nutritional management.
These studies provided evidence of the high clinical value of Amiparen as a source of amino acids in terms of major protein metabolism-related indices, including
nitrogen balance, serum total protein and albumin levels, rapid protein turnover, and urinary 3-methylhistidine/creatinine ratio.
Adverse Reactions and Abnormal Laboratory Values: In 546 treated patients, 17 cases of side effects were reported. Complaints included vascular pain (0.4%), nausea
and vomiting (0.4%). Abnormal laboratory tests showed an increase in SGOT and/or SGPT (0.7%), an increase in BUN (0.5%) and an increase in total bilirubin (0.4%).
Pharmacokinetics: 14C-amino acids formulated in Amiparen were readily taken up into plasma protein fractions after IV infusion in normal rats at 3, 7 and 57 weeks of
age. The radioactivity was distributed in higher concentrations to protein fractions of the spleen, liver and kidneys, as well as the muscles.
Respiratory excretion accounted for 37.1-44.2% over 72 hrs post-infusion.
As other major routes of elimination, 3.9-5.2% and 1.2-3.1% of the radioactivity were recovered from the urine and feces, respectively.
Amino acid fractions in the urine contained only 1.1-1.5% of the amino acids given. The overall retention of amino acids in the body amounted to >98.5% of the dose.
Toxicology: Acute Toxicity: LD50 values (IV, infusion rate: 4 mL/min): 107 mL/kg male rabbits, 120 mL/kg female rabbits.
Long-Term Toxicity Studies (Rabbits, IV, 13 and 26 Weeks): An antigenicity study and a local irritation study did not reveal any Amiparen-related specific toxic
symptoms.
Pharmacotherapeutic Group: Insulin and analogues, fast-acting. ATC Code: A10AB06.
Pharmacology: Pharmacodynamics: Insulin glulisine is a recombinant human insulin analogue that is equipotent to regular human insulin. Insulin glulisine has more
rapid onset of action and a shorter duration of action than regular human insulin. The primary activity of insulins and insulin analogues, including human insulin
glulisine, is regulation of glucose metabolism. Insulins lower blood glucose levels by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by
inhibiting hepatic glucose production. Insulin inhibits lypolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis.
Studies in healthy volunteers and patients with diabetes demonstrated that insulin glulisine is more rapid in onset of action and of shorter duration of action than
regular human insulin when given subcutaneously. When insulin glulisine is injected subcutaneously, the glucose-lowering activity will begin within 10-20 min. The
glucose-lowering activities of insulin glulisine and regular human insulin are equipotent when administered by IV route. One unit of insulin glulisine has the same
glucose-lowering activity as one unit of regular human insulin.
A phase I study in patients with type 1 diabetes mellitus assessed the glucose-lowering profiles of insulin glulisine and regular human insulin administered
subcutaneously at a dose of 0.15 u/kg at different times in relation to a 15-min standard meal. Data indicated that insulin glulisine administered 2 min before the meal
gives similar postprandial glycemic control compared to regular insulin given 30 min before the meal. When given 2 min prior to meal, insulin glulisine provided better
postprandial control than regular human insulin given 2 min before the meal. Insulin glulisine administered 15 min after starting the meal gives similar glycemic
control as regular human insulin given 2 min before the meal.
Obesity: A phase I study carried out with insulin glulisine, lispro and regular human insulin in an obese population has demonstrated that insulin glulisine maintains its
rapid-acting properties.
In this study, the time to 20% of total AUC and the AUC (0-2 hrs) representing the early glucose-lowering activity were 144 min and 427 mg/kg for insulin glulisine, 121
min and 354 mg/kg for lispro, 150 min and 197 mg/kg for regular human insulin.
Clinical Studies: Type 1 Diabetes Mellitus: In a 26-week, phase III clinical study comparing insulin glulisine with insulin lispro both injected subcutaneously shortly (0-15
min) before a meal in patients with type 1 diabetes mellitus using insulin glargine as basal insulin, insulin glulisine was comparable to insulin lispro for glycemic control
as reflected by changes in glycated hemoglobin (expressed as HbA1c equivalent) from baseline to endpoint. Comparable self-monitored blood glucose values were
observed. No increase in the basal insulin dose was needed with insulin glulisine, in contrast to insulin lispro.
A 12-week, phase III clinical study performed in patients with type 1 diabetes mellitus receiving insulin glargine as basal therapy indicate that the immediate postmeal
administration of insulin glulisine provides efficacy that was comparable to immediate premeal insulin glulisine (0-15 min) or regular insulin (30-45 min).
In the per-protocol population, there was a significantly larger observed reduction in GHb in the premeal glulisine group compared with the regular insulin group.
Type 2 Diabetes Mellitus: A 26-week, phase III clinical study followed by a 26-week extension safety study was conducted to compare insulin glulisine (0-15 min before
a meal) with regular human insulin (30-45 min before a meal) injected subcutaneously in patients with type 2 diabetes mellitus also using NPH insulin as basal insulin.
The average body mass index (BMI) of patients was 34.55 kg/m2.
Insulin glulisine was shown to be comparable to regular human insulin with regard to glycated hemoglobin (expressed as HbA1c equivalent) changes from baseline to
the 6-month endpoint (-0.46% for insulin glulisine and -0.3% for regular human insulin, p=0.0029) and from baseline to the 12-month endpoint (-0.23% for insulin
glulisine and -0.13% for regular human insulin, difference is not significant). In this study, the majority of patients (79%) mixed their short-acting insulin with NPH
insulin immediately prior to injection and 58% of subjects used oral hypoglycemic agents at randomization and were instructed to continue to use them at the same
dose.
Race and Gender: In controlled clinical trials in adults, insulin glulisine did not show differences in safety and efficacy in subgroup analyses based on race and gender.
Pharmacokinetics: In insulin glulisine, the replacement of the human insulin amino acid, asparagine, in position B3 by lysine and the lysine in position B29 by glutamic
acid favors more rapid absorption.
Absorption and Bioavailability: Pharmacokinetic profiles in healthy volunteers and diabetes patients (type 1 or 2) demonstrated that absorption of insulin glulisine was
about twice as fast with peak concentration approximately twice as high as compared to regular human insulin.
Pharmacotherapeutic Group: Angiotensin II receptor antagonist. ATC Code: C09CA04.
Pharmacology: Irbesartan is a potent, orally active, selective angiotensin II receptor (type AT1) antagonist.
Mechanism of Action: It is expected to block all actions of angiotensin II mediated by the AT1 receptor, regardless of the source or route of synthesis of angiotensin II.
The selective antagonism of the angiotensin II (AT1) receptors results in increases in plasma renin levels and angiotensin II levels, and a decrease in plasma aldosterone
concentration. Serum potassium levels are not significantly affected by irbesartan alone at the recommended doses. Irbesartan does not inhibit [angiotensin-
converting enzyme (ACE) (kininase II)], an enzyme which generates angiotensin II and also degrades bradykinin into inactive metabolites. Irbesartan does not require
metabolic activation for its activity.
Clinical Efficacy: Hypertension: Irbesartan lowers blood pressure with minimal change in heart rate. The decrease in blood pressure is dose-related for once-a-day
doses with a tendency towards plateau at doses >300 mg. Doses of 150-300 mg once daily lower supine or seated blood pressures at trough (ie, 24 hrs after dosing) by
an average of 8-13/5-8 mmHg (systolic/diastolic) greater than those associated with placebo.
Peak reduction of blood pressure is achieved within 3-6 hrs after administration and the blood pressure-lowering effect is maintained for at least 24 hrs. At 24 hrs, the
reduction of blood pressure was 60-70% of the corresponding peak diastolic and systolic responses at the recommended doses. Once-daily dosing with 150 mg
produced trough and mean 24-hr responses similar to twice-daily dosing on the same total dose.
The blood pressure-lowering effect of Aprovel is evident within 1-2 weeks, with the maximal effect occurring by 4-6 weeks after start of therapy. The antihypertensive
effects are maintained during long-term therapy. After withdrawal of therapy, blood pressure gradually returns toward baseline. Rebound hypertension has not been
observed.
The blood pressure-lowering effects of irbesartan and thiazide-type diuretics are additive. In patients not adequately controlled by irbesartan alone, the addition of a
low dose of hydrochlorothiazide (12.5 mg) to irbesartan once daily results in a further placebo-adjusted blood pressure reduction at trough of 7-10/3-6 mmHg
(systolic/diastolic).
The efficacy of Aprovel is not influenced by age or gender. As is the case with other drugs that affect the renin-angiotensin system, Black hypertensive patients have
notably less response to irbesartan monotherapy. When irbesartan is administered concomitantly with a low dose of hydrochlorothiazide (eg, 12.5 mg daily), the
antihypertensive response in Black patients approaches that of White patients.
There is no clinically important effect on serum uric acid or urinary uric acid secretion.
Hypertension and Type 2 Diabetes with Renal Disease: The "Irbesartan Diabetic Neuropathy Trial (IDNT)" shows that irbesartan decreases the progression of renal
disease in patients with chronic renal insufficiency and overt proteinuria. IDNT was a double-blind, controlled, morbidity and mortality trial comparing Aprovel,
amlodipine and placebo. In 1715 hypertensive patients with type 2 diabetes, proteinuria =900 mg/day and serum creatinine ranging from 1-3 mg/dL, the long-term
effects (mean 2.6 years) of Aprovel on the progression of renal disease and all-cause mortality were examined. Patients were titrated from 75 mg to a maintenance
dose of Aprovel 300 mg, from amlodipine 2.5 mg to 10 mg, or placebo as tolerated.
Patients in all treatment groups typically received between 2 and 4 antihypertensive agents (eg, diuretics, ß-blockers, a-blockers) to reach a predefined blood pressure
goal of =135/85 mmHg or a 10 mmHg reduction in systolic pressure if baseline was >160 mmHg. Sixty percent (60%) of patients in the placebo groups reached this
target blood pressure whereas this figure was 76% and 78% in the irbesartan and amlodipine groups respectively. Irbesartan significantly reduced and relative risk in
the primary combined endpoint of doubling serum creatinine, end-stage renal disease (ESRD) or all-cause mortality. Approximately 33% of patients in the irbesartan
group reached the primary renal composite endpoint compared to 39% and 41% in the placebo and amlodipine groups [20% relative risk versus placebo (p=0.024) and
23% relative risk reduction compared to amlodipine (p=0.006)]. When the individual components of the primary endpoint were analysed, no effect in all cause
mortality was observed, while a positive trend in the reduction in ESRD and a significant reduction in doubling of serum creatinine were observed.
Subgroups consisting of gender, race, age, duration of diabetes, baseline blood pressure, serum creatinine and albumin excretion rate were assessed for treatment
effect. In the female and Black subgroups which represented 32% and 26% of the overall study population respectively, a renal benefit was not evident, although the
confidence intervals do not exclude it. As for the secondary endpoint of fatal and nonfatal cardiovascular events, there was no difference among the 3 groups in the
Pharmacology: Amoxicillin-clavulanate (ß-lactam antibacterial penicillin co-formulated with a ß-lactamase inhibitor) is an antibiotic agent with a notably broad
spectrum of activity against the commonly occurring bacterial pathogens in general practice and hospital. The ß-lactamase inhibitory action of clavulanate extends the
spectrum of amoxicillin to embrace a wider range of organisms, including many resistant to other ß-lactam antibiotics.
Pharmacodynamics: Mechanism of Action: Amoxicillin is a semisynthetic antibiotic with a broad spectrum of antibacterial activity against many gram-positive and
gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by ß-lactamases and therefore the spectrum of activity of amoxicillin alone does
not include organisms which produce these enzymes.
Clavulanic acid is a ß-lactam, structurally related to penicillins, which possesses the ability to inactivate a wide range of ß-lactamase enzymes commonly found in
microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated ß-lactamases frequently
responsible for transferred drug resistance. It is generally less effective against chromosomally-mediated type 1 ß-lactamases.
The presence of clavulanic acid in amoxicillin-clavulanate formulations protects amoxicillin from degradation by ß-lactamase enzymes and effectively extends the
antibacterial spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other penicillins and cephalosporins. Thus, amoxicillin-clavulanate
possesses the distinctive properties of a broad-spectrum antibiotic and a ß-lactamase inhibitor.
Microbiology: Amoxicillin-clavulanate is bactericidal to a wide range of organisms including:
Gram-Positive: Aerobes: Bacillus anthracis*, Corynebacterium spp, Enterococcus faecalis*, Enterococcus faecium*, Listeria monocytogenes, Staphylococcus aureus*,
coagulase-negative staphylococci* (Staphylococcus epidermidis*), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus spp,
Streptococcus viridans*.
Gram-Positive: Anaerobes: Clostridium spp, Peptococcus spp, Peptostreptococcus spp.
Gram-Negative: Aerobes: Bordetella pertussis, Brucella spp, Escherichia coli*, Gardnerella vaginalis, Haemophilus influenzae*, Helicobacter pylori, Klebsiella spp*,
Legionella spp, Moraxella catarrhalis* (Branhamella catarrhalis), Neisseria gonorrhoeae*, Neisseria meningitidis*, Pasteurella multocida, Proteus mirabilis*, Proteus
vulgaris*, Salmonella spp*, Shigella spp*, Vibrio cholerae, Yersinia enterolitica*.
Gram-Negative Anaerobes: Bacteroides spp* (including Bacteroides fragilis), Fusobacterium spp*.
Note: *Some members of these species produce ß-lactamase, rendering them insensitive to amoxicillin alone.
Pharmacokinetics: Absorption: The 2 components of amoxicillin-clavulanate, amoxicillin and clavulanic acid are fully dissociated in aqueous solution at physiological
pH. Both components are rapidly and well absorbed by the oral route of administration. Absorption of amoxicillin-clavulanate is optimized when taken at the start of
the meal. Amoxicillin serum concentrations achieved with amoxicillin-clavulanate are similar to those produced by the oral administration of equivalent doses of
amoxicillin alone.
Distribution: Following IV administration, therapeutic concentrations of both amoxicillin and clavulanic acid may be detected in the tissues and interstitial fluid.
Therapeutic concentrations of both drugs have been found in gallbladder, abdominal tissues, skin, fat and muscle tissues; fluids found to have therapeutic levels
include synovial and peritoneal fluids, bile and pus.
Neither amoxicillin nor clavulanic acid is highly protein bound, studies show that about 25% for clavulanic acid and 18% for amoxicillin of total plasma drug content is
bound to protein. From animal studies, there is no evidence to suggest that either component accumulates in any organ.
Amoxicillin, like most penicillins, can be detected in breast milk. Trace quantities of clavulanate can also be detected in breast milk. With the exception of the risk of
sensitization associated with this excretion, there are no known detrimental effects for the breastfed infant.
Reproduction studies in animals have shown that both amoxicillin and clavulanic acid penetrate the placental barrier. However, no evidence of impaired fertility or
harm to the fetus was detected.
Metabolism: Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to 10-25% of the initial dose. Clavulanic acid is extensively
metabolized in man to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and eliminated in urine and feces as
carbon dioxide in expired air.
Pharmacology: Mechanism of Action: Fluticasone furoate is a synthetic trifluorinated corticosteroid that possesses a very high affinity for the glucocorticoid receptor
and has a potent anti-inflammatory action.
Pharmacokinetics: Absorption: Fluticasone furoate undergoes extensive first-pass metabolism and incomplete absorption in the liver and gut resulting in negligible
systemic exposure. The intranasal dosing of 110 mcg once daily does not typically result in measurable plasma concentrations (<10 pg/mL). The absolute
bioavailability for fluticasone furoate administered as 880 mcg 3 times daily (2640 mcg total daily dose) is 0.5%.
Distribution: The plasma protein-binding of fluticasone furoate is >99%. Fluticasone furoate is widely distributed with volume of distribution at steady state of, on
average, 608 L.
Metabolism: Fluticasone furoate is rapidly cleared (total plasma clearance of 58.7 L/hr) from systemic circulation principally by hepatic metabolism to an inactive 17ß-
carboxylic metabolite (GW694301X) by the cytochrome P-450 enzyme CYP3A4. The principal route of metabolism was hydrolysis of the S-fluoromethyl carbothioate
function to form 17ß-carboxylic acid metabolite. In vivo studies have revealed no evidence of cleavage of the furoate moiety to form fluticasone.
Elimination: Elimination was primarily via the fecal route following oral and IV administration indicative of excretion of fluticasone furoate and its metabolites via the
bile. Following IV administration, the elimination phase half-life averaged 15.1 hrs. Urinary excretion accounted for approximately 1% and 2% of the orally and IV
administered dose, respectively.
Special Patient Populations: Elderly: Only a small number of elderly subjects (n=23/872; 2.6%) provided pharmacokinetic data. There was no evidence for a higher
incidence of subjects with quantifiable fluticasone furoate concentrations in the elderly, when compared to younger subjects.
Children: Fluticasone furoate is typically not quantifiable (<10 pg/mL) following intranasal dosing of 110 mcg once daily. Quantifiable levels were observed in <16% of
pediatric patients following intranasal dosing of 110 mcg once daily and only <7% of pediatric patients following 55 mcg once daily. There was no evidence for a higher
incidence of quantifiable levels of fluticasone furoate in younger children (<6 years).
Renal Impairment: Fluticasone furoate is not detectable in urine from healthy volunteers after intranasal dosing. Less than 1% of dose-related material is excreted in
urine and therefore renal impairment would not be expected to affect the pharmacokinetics of fluticasone furoate.
Hepatic Impairment: A study of a single 400-mcg dose of orally inhaled fluticasone furoate in patients with moderate hepatic impairment resulted in increased Cmax
(42%) and AUC(0-8) (172%) and a modest (on average 23%) decrease in cortisol levels in patients compared to healthy subjects. From this study, the average predicted
exposure for intranasal fluticasone furoate 110 mcg in patients with moderate hepatic impairment would not be expected to result in suppression of cortisol.
Therefore, moderate hepatic impairment is not predicted to result in a clinically relevant effect for the normal adult dose. There are no data in patients with severe
hepatic impairment. The exposure of fluticasone furoate is likely to be further increased in such patients.
Others: Fluticasone furoate is typically not quantifiable (<10 pg/mL) following intranasal dosing of 110 mcg once daily. Quantifiable levels were only observed in <31%
of patients =12 years and in <16% of pediatric patients following intranasal dosing of 110 mcg once daily. There was no evidence for gender, age (including pediatrics)
or race to be related to those subjects with quantifiable levels, when compared to those without.
Clinical Studies: Adult and Adolescent Seasonal Allergic Rhinitis: Avamys nasal spray 110 mcg once daily resulted in a significant improvement in daily reflective (how
patient felt over the preceding 12 hrs) and instantaneous (how patient felt at the time of assessment) pre-dose total nasal symptom scores (rTNSS and iTNSS,
comprising rhinorrhea, nasal congestion, sneezing and nasal itching) and daily reflective and instantaneous total ocular symptom scores (rTOSS, comprising
itching/burning, tearing/watering and redness of the eyes) versus placebo (see table). The improvement in nasal and ocular symptoms was maintained over the full 24
hrs after once-daily administration. (See table.)
The distribution of the patients' perception of overall response to therapy (using a 7-point scale ranging from significantly improved to significantly worse) favoured
Avamys nasal spray 110 mcg over placebo, with a statistically significant treatment difference. Onset of action was experienced as early as 8 hrs after initial
administration in 2 studies. Significant improvement in symptoms was observed in the first 24 hrs in all 4 studies and continued to improve over several days. The
patients' quality of life (as assessed by the Rhinoconjunctivitis Quality of Life Questionnaire - RQLQ), was significantly improved from baseline with Avamys nasal spray
Pharmacology: Pharmacodynamics: Dutasteride is a dual inhibitor of 5a-reductase. It inhibits both type 1 and type 2, 5a-reductase isoenzymes, which are responsible
for the conversion of testosterone to 5a-dihydrotestosterone (DHT). DHT is the androgen primarily responsible for hyperplasia of glandular prostatic tissue.
Effects on DHT/Testosterone: The maximum effect of daily doses of Avodart on the reduction of DHT is dose-dependent and is observed within 1-2 weeks. After 1
week and 2 weeks of daily dosing of Avodart 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively.
In benign prostatic hyperplasia (BPH) patients treated with 0.5 mg of dutasteride daily, the median decrease in DHT was 94% at 1 year and 93% at 2 years and the
median increase in serum testosterone was 19% at both 1 and 2 years. This is an expected consequence of 5a-reductase inhibition and did not result in any known
adverse events.
Clinical Studies: Avodart Monotherapy: Dutasteride 0.5 mg/day or placebo was evaluated in 4325 male subjects with enlarged prostates (>30 cc) in 3 primary efficacy
2-year multicenter, placebo-controlled, double-blind studies.
In men with BPH, Avodart treats and prevents disease progression by reducing the risk of both acute urinary retention (AUR) and the need for surgical intervention (SI)
and by providing statistically significant improvement of lower urinary tract symptoms (LUTS), maximum urinary flow rate (Qmax) and prostate volume relative to
placebo. These improvements in LUTS, Qmax and prostate volume were seen in the course of 24 months, and LUTS and Qmax continued to improve for a further 2
years in open-label extension studies. In addition, reductions in prostate volume were sustained for a further 2 years in open-label extension studies.
Avodart and Tamsulosin Combination Therapy: Avodart 0.5 mg/day, tamsulosin 0.4 mg/day or the combination of Avodart 0.5 mg plus tamsulosin 0.4 mg was
evaluated in 4844 male subjects with enlarged prostates =30 cc) in a multicenter, double blind, parallel group study over 2 years. The primary efficacy endpoint at 2
years of treatment was the level of improvement from baseline in the international prostate symptom score (IPSS).
After 2 years of treatment, combination therapy showed a statistically significant adjusted mean improvement in symptom scores from baseline of -6.2 units. The
adjusted mean improvements in symptom scores observed with the individual therapies were -4.9 units for Avodart and -4.3 units for tamsulosin. The adjusted mean
improvement in flow rate from baseline was 2.4 mL/sec for the combination, 1.9 mL/sec for Avodart and 0.9 mL/sec for tamsulosin. The adjusted mean improvement
in BPH Impact Index (BII) from baseline was -2.1 units for the combination, -1.7 for Avodart and -1.5 for tamsulosin.
The reduction in total prostate volume and transition zone volume after 2 years of treatment was statistically significant for combination therapy compared to
tamsulosin monotherapy alone.
The primary efficacy endpoint at 4 years of treatment was time to first event of AUR or BPH-related surgery. After 4 years of treatment, combination therapy
statistically significantly reduced the risk of AUR or BPH-related surgery (65.8% reduction in risk p<0.001 [95% CI 54.7% to 74.1%]) compared to tamsulosin
monotherapy. The incidence of AUR or BPH-related surgery by Year 4 was 4.2% for combination therapy and 11.9% for tamsulosin (p<0.001). Compared to Avodart
monotherapy, combination therapy reduced the risk of AUR or BPH-related surgery by 19.6%; the difference between treatment groups was not significant (p=0.18
[95% CI -10.9% to 41.7%]). The incidence of AUR or BPH-related surgery by Year 4 was 4.2% for combination therapy and 5.2% for Avodart.
Clinical progression was defined as a composite of worsening symptoms, (IPSS), and BPH-related events of AUR, incontinence, UTI, and renal insufficiency.
Combination therapy was associated with a statistically significantly lower rate of clinical progression compared with tamsulosin (p<0.001, 44.1% risk reduction [95 %
CI: 33.6% to 53.0%]) after 4 years. The rates of clinical progression for combination therapy, tamsulosin, and Avodart were: 12.6%, 21.5%, and 17.8%, respectively.
The statistically significant adjusted mean improvement in symptom scores (IPSS) from baseline was maintained from year 2 to year 4. At 4 years, the adjusted mean
improvements in symptom scores observed were -6.3 units for combination therapy, -5.3 units for Avodart monotherapy and -3.8 units for tamsulosin monotherapy.
After 4 years of treatment, the adjusted mean improvement in flow rate (Qmax) from baseline was 2.4 mL/sec for combination therapy, 2 mL/sec for Avodart
monotherapy and 0.7 mL/sec for tamsulosin monotherapy. Compared with tamsulosin, the adjusted mean improvement from baseline in Qmax was statistically
significantly greater with combination therapy at each 6-month assessment from Month 6 to Month 48 (p<0.001). Compared with Avodart, the adjusted mean
improvement from baseline in Qmax was not statistically significantly different than with combination therapy (p=0.05 at Month 48).
Combination therapy was significantly superior (p<0.001) to tamsulosin monotherapy and to Avodart monotherapy for the improvement in health outcome
parameters BII and BPH-related Health Status (BHS) at 4 years. The adjusted mean improvement in BII from baseline was -2.2 units for the combination, -1.8 for
Pharmacology: Mode of Action: Endometriosis and Menorrhagia: In woman of reproductive age, Azol suppresses the pituitary ovarian axis. This suppression is
probably a combination of depressed hypothalamic-pituitary response to lowered estrogen production, the alteration of sex steroid metabolism and the interaction of
Azol with sex hormone receptors.
The only other demonstrable hormonal effect is weak androgenic activity and associated anabolic activity. No significant estrogenic or progestational activity
attributable to Azol has been found.
Azol depressed the output of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
In the treatment of endometriosis, Azol alters the normal and ectopic endometrial tissue so that it becomes inactive and atrophic. Complete resolution of endometrial
lesions occurs in the majority of cases.
Change in vaginal cytology and cervical mucus reflect the suppressive effect of Azol on the pituitary-ovarian axis.
The mechanism of action of Azol in the suppression of menstrual blood loss is not clear. However, Azol inhibits ovulation and plasma levels of oestradiol-17b fall.
Whether endometrial proliferation is inhibited by reduced oestradiol levels or by a direct effect of Azol on endometrial oestrogen receptors is not known.
Generally, the pituitary suppressive action of Azol is reversible. When Azol treatment is discontinued, ovulation usually resumes within a few weeks as demonstrated
by the major surge of luteinizing hormone (LH) and minor follicle stimulating hormone (FSH) surge that accompany ovulation.
Fibrocystic Breast Disease: Azol suppresses the ovulatory luteinizing surge, interferes with gonadal steroidogenesis (directly and indirectly) and dampens the
gonadotrophin response to luteinizing hormone.
Clinical Experience: Endometriosis and Menorrhagia: Clinically, the action of Azol has been demonstrated by human pharmacological studies and clinical trials. At a
sufficiently high daily dose, Azol therapy results in inhibition of ovulation, suppression of menses, regressive changes of the vaginal mucosa and marked atrophy of the
endometrium.
Vaginal spotting or bleeding may occur in some patients during therapy with Azol; in cases where it has been examined, this bleeding was associated with an atrophic
endometrium.
Azol therapy has been successful in the treatment of endometriosis, relief of the common presenting symptoms of dysmenorrhoea, pelvic pain and dyspareunia,
resolution of ectopic endometrial implants and induration of the cul-de-sac has been obtained. Significant reversal of infertility associated with endometriosis has
followed a course of Azol therapy.
Clinical studies have demonstrated the efficacy of Azol in the short-term management of menorrhagia. The reduction in blood loss continued for up to 3 months after
stopping treatment. Other benefits have been relief of dysmenorrhoea, failure to influence menstrual cycle length, reduction in the number of days bleeding and a
steady improvement in haemoglobin values despite the absence of iron therapy.
Fibrocystic Breast Disease: Both placebo-controlled and open studies with Azol in treating severe fibrocystic breast disease or mastalgia associated with severe breast
disease have shown Azol to produce partial to complete disappearance of nodularity and complete relief of pain and tenderness. Limited studies suggest Azol to be
effective in reducing breast cyst formation. Changes in the menstrual pattern may occur.
Pharmacology: Pharmacodynamics: Mupirocin is a novel antibiotic produced through fermentation by Pseudomonas fluorescens. Mupirocin inhibits isoleucyl transfer-
RNA synthetase, thereby arresting bacterial protein synthesis. Due to this particular mode of action and its unique chemical structure, mupirocin does not show any
cross-resistance with other clinically available antibiotics. Mupirocin shows little risk of selection of bacterial resistance if used as prescribed. Mupirocin has
bacteriostatic properties at minimum inhibitory concentrations and bactericidal properties at the higher concentrations reached when applied locally.
Pharmacokinetics: Systemic absorption of mupirocin through intact human skin is low although it may occur through broken/diseased skin. However, clinical trials
have shown that when given systemically, it is metabolised to the microbiologically inactive metabolite monic acid and rapidly excreted. Mupirocin is rapidly
eliminated from the body by metabolism to its inactive metabolite monic acid, which is rapidly excreted by the kidney.
Toxicology: Preclinical Safety Data: No further information of relevance.
Microbiology: Mupirocin is a topical antibacterial agent showing in vivo activity against Staphylococcus aureus (including methicillin-resistant strains), S. epidermidis
and ß-hemolytic Streptococcus species.
The in vitro spectrum of activity includes the following bacteria: Aerobic Gram-Positive: Staphylococcus aureus (including ß-lactamase-producing and methicillin-
resistant strains); Staphylococcus epidermidis (including ß-lactamase-producing and methicillin-resistant strains); other coagulase-negative Staphylococci (including
methicillin-resistant strains); Streptococcus species.
Aerobic Gram-Negative: Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis and Pasteurella multocida.
Microbiology: Mechanism of Action: Entecavir, a guanosine nucleoside analogue with activity against HBV polymerase, is efficiently phosphorylated to the active
triphosphate form, which has an intracellular half-life of 15 hrs. By competing with the natural substrate deoxyguanosine triphosphate, entecavir triphosphate
functionally inhibits all three activities of the HBV polymerase [reverse transcriptase (RT)]: 1) Base priming. 2) Reverse transcription of the negative strand from the
pregenomic messenger RNA. 3) Synthesis of the positive strand of HBV DNA. Entecavir triphosphate is a weak inhibitor of cellular DNA polymerases a, ß and d and
mitochondrial DNA polymerase ? with Ki values ranging from 18 to >160 mcM.
Antiviral Activity: Entecavir inhibited HBV DNA synthesis [50% reduction, maximum effective concentration (EC50)] at a concentration of 0.004 mcM in human HepG2
cells transfected with wild-type HBV. The median EC50 value for entecavir against lamivudine-resistant HBV (rtL180M, rtM204V) was 0.026 mcM (range 0.01-0.059
mcM).
The co-administration of human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitors (NRTIs) with Baraclude is unlikely to reduce the antiviral
efficacy of Baraclude against HBV or of any of these agents against HIV. In HBV combination assays in cell culture, abacavir, didanosine, lamivudine, stavudine,
tenofovir or zidovudine were not antagonistic to the anti-HBV activity of entecavir over a wide range of concentrations. In HIV antiviral assays, entecavir was not
antagonistic to the cell culture anti-HIV activity of these 6 NRTIs at >4 times the peak plasma drug concentration (Cmax) of entecavir.
Antiviral Activity Against Human Immunodeficiency Virus (HIV): A comprehensive analysis of the inhibitory activity of entecavir against a panel of laboratory and
clinical human immunodeficiency virus type 1 (HIV-1) isolates using a variety of cells and assay conditions yielded EC50 values ranging from 0.026 to >10 mcM; lower
EC50 values were observed when decreased levels of virus were used in the assay. In cell culture, entecavir selected for an M184l substitution in HIV reverse
transcriptase at micromolar concentrations, confirming inhibitory pressure at high entecavir concentrations. HIV variants containing the M184V substitution showed
loss of susceptibility to entecavir.
Resistance: In Cell Culture: In cell-based assays, 8- to 30-fold reductions in entecavir phenotypic susceptibility were observed for lamivudine-resistant strains. Further
reductions (>70-fold) in entecavir phenotypic susceptibility required the presence of amino acid substitutions rtM204I/V and/or rtL180M along with additional
substitutions at residues rtT184, rtS202 or rtM250, or a combination of these substitutions with or without an rtI169 substitution in the HBV polymerase.
Clinical Studies: All patients in clinical trials initially treated with entecavir 0.5 mg (nucleoside-naive, studies AI463022, AI463027 and rollover study AI463901) or 1 mg
(lamivudine-refractory, studies AI463026, AI463014, AI463015 and rollover study AI463901) and with an on-therapy PCR HBV DNA measurement at or after week-24
were monitored for resistance.
Nucleoside-Naive Subjects: Genotypic evidence of entecavir resistance-associated (ETVr) substitutions at rtT184, rtS202 and/or rtM250 were identified in <1% of
patients treated with entecavir for up to 144 weeks in nucleoside-naive studies (Table 1). These substitutions were observed only in the presence of lamivudine
resistance-associated (LVDr) substitutions (rtM204V and rtL180M) (see Table 1).
Lamivudine-Refractory Subjects: ETVr substitutions were observed at baseline in isolates from 10/187 (5%) lamivudine-refractory patients treated with entecavir and
monitored for resistance, indicating that prior lamivudine treatment can select these resistance substitutions and that they can exist at a low frequency before
entecavir treatment. Through week 144, 3 of the 10 patients experienced virologic rebound (=1 log10 increase above nadir). Emerging entecavir resistance in
lamivudine-refractory studies through week 144 is summarized in Table 2. (See Table 2.)
Cross-Resistance: Cross-resistance has been observed among HBV nucleoside analogues. In cell-based assays, entecavir had 8- to 30-fold less inhibition of HBV DNA
synthesis for HBV containing lamivudine and telbivudine resistance substitutions rtM204I/V ± rtL180M than for wild-type HBV. Substitutions rtM204I/V ± rtL180M,
rtL80I/V or rtV173L, which are associated with lamivudine and telbivudine resistance, also confer decreased phenotypic susceptibility to entecavir. Recombinant HBV
genomes encoding adefovir resistance-associated substitutions at either rtN236T or rtA181V had 0.3- and 1.1-fold shifts in susceptibility to entecavir in cell culture,
respectively. The efficacy of entecavir against HBV harboring adefovir resistance-associated substitutions has not been established in clinical trials. HBV isolates from
lamivudine-refractory subjects failing entecavir therapy were susceptible in cell culture to adefovir but remained to lamivudine.
Trials with treatment duration of up to 3 months involving adult asthmatics and chronic obstructive pulmonary disease (COPD) patients, and asthmatic children, in
which the hydrofluroalkane (HFA) formulation and the chlorofluorocarbon (CFC) formulation have been compared, have shown the 2 formulations to be
therapeutically equivalent.
Berodual contains 2 active bronchodilating ingredients: Ipratropium bromide, exhibiting an anticholinergic effect and fenoterol HBr, a ß-adrenergic agent.
Ipratropium bromide: Quaternary ammonium compound with anticholinergic (parasympatholytic) properties. In preclinical studies, it inhibits vagally mediated reflexes
by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve. Anticholinergics prevent the increase in intracellular concentration of
Ca++ caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle, Ca++ release is mediated by the 2nd messenger system
consisting of IP3 (inositol triphosphate) and DAG (diacylglycerol).
The bronchodilatation following inhalation of ipatropium bromide is primarily a local, site-specific effect, not a systemic one.
Preclinical and clinical evidence suggest no deleterious effect of ipratropium bromide on airway mucous secretion, mucociliary clearance or gas exchange.
Fenoterol hydrobromide: Direct-acting sympathomimetic agent, selectively stimulating ß2-receptors in the therapeutic dose range. The stimulation of ß1-receptors
comes into effect at a higher dose range (eg, as administered in tocolysis). Occupation of ß2-receptors activates adenyl cyclase via a stimulatory GS-protein. The
increase in cyclic AMP activates protein kinase A which then phosphorylates target proteins in smooth muscle cells. This in turn leads to the phosphorylation of myosin
light chain kinase, inhibition of phosphoinositide hydrolysis, and the opening of large-conductance calcium-activated potassium channels.
Fenoterol hydrobromide relaxes bronchial and vascular smooth muscle and protects against bronchoconstricting stimuli eg, histamine, methacholine, cold air and
allergen (early response). After acute administration, the release of bronchoconstricting and pro-inflammatory mediators from mast cells is inhibited. Further, an
increase in mucociliary clearance has been demonstrated after administration of doses of fenoterol (0.6 mg).
Higher plasma concentrations, which are more frequently achieved with oral, or even more so, with IV administration, inhibit uterine motility. Also, at higher doses,
metabolic effects are observed: Lipolysis, glycogenolysis, hyperglycemia and hypokalemia, the latter caused by increased K+-uptake primarily into skeletal muscle.
Beta-adrenergic effects on the heart eg, increased heart rate and contractility are caused by the vascular effects of fenoterol, cardiac ß2-receptor stimulation, and at
supratherapeutic doses, by ß1-receptor stimulation. As with other ß-adrenergic agents, QT prolongations have been reported. For fenoterol MDIs, these were discrete
and observed at doses higher than recommended. However, systemic exposure after administration with nebulisers (UDVs, solution for inhalation) might be higher
than with recommended metered dose inhalers (MDI) doses. The clinical significance has not been established. Tremor is a more frequently observed effect of ß-
agonists. Unlike the effects on the bronchial smooth muscle, the systemic effects of ß-agonists are subject to the development of tolerance.
Concurrent use of these 2 active ingredients dilates the bronchi by affecting different pharmacological sites of action. The 2 active substances, thus, complement each
other in their spasmolytic action on the bronchial muscles and allow a broad therapeutic use in the field of bronchopulmonary disorders associated with constriction
of the respiratory tract. The complementary action is such that only a very low proportion of the ß-adrenergic component is needed to obtain the desired effect,
facilitating individual dosage suited to each patient with a minimum of adverse reactions.
In patients with asthma and with chronic obstructive pulmonary disease (COPD), better efficacy compared to its components ipatropium or fenoterol was
demonstrated. Two studies (1 with asthma patients, 1 with COPD patients) have shown that Berodual is as efficacious as double the dose of fenoterol administered
without ipratropium but was better tolerated in cumulative dose response studies.
In acute bronchoconstriction, Berodual is effective shortly after administration and is, therefore, also suitable for treating acute attacks of asthma.
Pharmacology: Berotec is an effective bronchodilator for use in acute asthma and in other conditions with reversible airway narrowing eg, chronic obstructive
bronchitis with or without pulmonary emphysema. After oral administration, Berotec acts within a few mins with a duration of action up to 8 hrs.
Following inhalation of fenoterol hydrobromide in obstructive lung diseases, bronchodilatation occurs within a few minutes. The bronchodilator effect lasts 3-5 hrs.
Trials with a treatment duration of up to 3 months involving adult asthmatics and chronic obstructive pulmonary disease (COPD) patients and asthmatic children, in
which the HFA formulation and the CFC formulation have been compared have shown the 2 formulations to be therapeutically equivalent.
Fenoterol HBr is a direct-acting sympathomimetic agent, selectively stimulating ß2-receptors in the therapeutic dose range. The stimulation of ß1-receptors comes into
effect at a higher dose range (eg, as administered in tocolysis). Occupation of ß2-receptors activates adenyl cyclase via a stimulatory Gs-protein. The increase in cyclic
AMP activates protein kinase A which then phosphorylates target proteins in smooth muscle cells. This in turn leads to the phosphorylation of myosin light chain
kinase, inhibition of phosphoinositide hydrolysis and the opening of large-conductance calcium-activated potassium channels. There is some evidence that the "maxi-
K channel" can be directly activated via the Gs-protein.
Fenoterol relaxes bronchial and vascular smooth muscle and protects against bronchoconstricting stimuli eg, histamine, methacholine, cold air and allergen (early
response).
After acute administration, the release of bronchoconstricting and pro-inflammatory mediators from mast cells is inhibited. Furthermore, an increase in mucociliary
clearance has been demonstrated after administration of doses of fenoterol (0.6 mg).
Higher plasma concentrations, which are more frequently achieved with oral, or even more so with IV administration, inhibit uterine motility. Also at higher doses,
metabolic effects are observed: Lipolysis, glycogenolysis, hyperglycaemia and hypokalaemia, the latter caused by increased K+-uptake primarily into skeletal muscle.
Beta-adrenergic effects on the heart eg, increase in heart rate and contractility, are caused by the vascular effects of fenoterol, cardiac ß2-receptor stimulation and at
supratherapeutic doses, by ß1-receptor stimulation. As with other ß-adrenergic agents, QTc prolongation has been reported. For fenoterol MDIs, these events were
discrete and observed at doses higher than recommended. However, systemic exposure after adminstration with nebulisers (UDVs, solution for inhalation) might be
higher than with recommended MDI doses (see Dosage & Administration). The clinical significance has not been established. Tremor is a more frequently observed
effect of ß-agonists. Unlike the effects on the bronchial smooth muscle, the systemic effects on skeletal muscle of ß-agonists are subject to the development of
tolerance.
In clinical studies, fenoterol was shown to be highly efficacious in manifest bronchospasm. It prevents bronchoconstriction following exposure to various stimuli eg,
exercise cold air and the early response following allergen exposure.
Pharmacotherapeutic Group: Anti-vertigo preparations. ATC Code: N07CA01.
Pharmacology: Pharmacodynamics: The mechanism of action of betahistine is partly known.
In biochemical studies, betahistine was found to have weak H1 receptor agonistic and potent H3 antagonistic properties in the CNS and autonomic nervous system.
Pharmacological testing in animals has shown that the blood circulation in the striae vascularis of the inner ear improves, probably by means of a relaxation of the
precapillary sphincters of the microcirculation of the inner ear.
Betahistine was also found to have a dose dependent inhibiting effect on spike generation of neurons in lateral and medial vestibular nuclei.
Betahistine accelerates the vestibular recovery after unilateral neurectomy, by promoting and facilitating central vestibular compensation; this effect, which is
characterized by an up-regulation of histamine turnover and release, is mediated through the H3 receptor antagonism.
Taken together, these properties contribute to the beneficial therapeutic effects of betahistine in Meniere's disease and vestibular vertigo.
Betahistine increases histamine turnover and release by blocking presynaptic H3-receptors and inducing H3-receptor down regulation. This effect on the histaminergic
system provides explanation for the efficacy of betahistine in the treatment of vertigo and vestibular diseases.
Pharmacokinetics: Orally administered betahistine is readily and almost completely absorbed from all parts of the gastrointestinal tract. After absorption, the drug is
rapidly and almost completely metabolized into 2-PAA (which has no pharmacological activity). Plasma levels of betahistine are very low (i.e., below the detection limit
of 100 pg/ml). All pharmacokinetic analyses are therefore based on 2-PAA measurements in plasma and urine.
The plasma concentration of 2-PAA reaches its maximum 1 hour after intake. The half-life of approximately 3.5 hours. 2-PAA is readily excreted in the urine. In the dose
range between 8 and 48 mg, about 85% of the original dose is recovered in the urine. Renal or fecal excretion of betahistine itself is of minor importance. Recovery
rates are constant over the oral dose range of 8-48 mg indicating that the pharmacokinetics of betahistine are linear, and suggesting that the involved metabolic
pathway is not saturated. Under fed conditions, Cmax is lower compared to fasted conditions. However, total absorption of betahistine is similar under both
conditions, indicating that food intake only slows down the absorption of betahistine.
Toxicology: Preclinical Safety Data: Oral dosing up to and above 250 mg/kg in dogs and in rats, respectively, of betahistine dihydrochloride administered during 3
months did not result in adverse effects. Side effects in the nervous system were seen in dogs and baboons after intravenous doses at and above 120 mg/kg. Emesis
was observed at 300 mg/kg and 120 mg/kg following oral and IV dosing, respectively, in dogs and sporadically in baboons.
Betahistine has not shown any mutagenic effect.
Pharmacotherapeutic Group: ACE inhibitor, plain. ATC Code: C09AA04.
Pharmacology: Pharmacodynamics: Perindopril is an inhibitor of the enzyme that converts angiotensin I into angiotensin II [angiotensin-converting enzyme (ACE)]. The
converting enzyme, or kinase, is an exopeptidase that allows conversion of angiotensin I into the vasoconstrictor angiotensin II as well as causing the degradation of
the vasodilator bradykinin into an inactive heptapeptide. Inhibition of ACE results in a reduction of angiotensin II in the plasma, which leads to increased plasma renin
activity (by inhibition of the negative feedback of renin release) and reduced secretion of aldosterone. Since ACE inactivates bradykinin, inhibition of ACE also results in
an increased activity of circulating and local kallikrein-kinin systems (and thus also activation of the prostaglandin system). It is possible that this mechanism
contributes to the blood pressure-lowering action of ACE inhibitors and is partially responsible for certain of their side effects (eg, cough).
Perindopril acts through its active metabolite, perindoprilat. The other metabolites show no inhibition of ACE activity in vitro.
Hypertension: Perindopril is active in all grades of hypertension: Mild, moderate, severe; a reduction in systolic and diastolic blood pressures in both supine and
standing positions is observed.
Perindopril reduces peripheral vascular resistance, leading to blood pressure reduction. As a consequence, peripheral blood flow increases, with no effect on heart
rate. Renal blood flow increases as a rule, while the glomerular filtration rate (GFR) is usually unchanged. The antihypertensive activity is maximal between 4 and 6 hrs
after a single dose and is sustained for at least 24 hrs: Trough effects are about 87-100% of peak effects.
The decrease in blood pressure occurs rapidly. In responding patients, normalisation is achieved within a month and persists without the occurrence of tachyphylaxis.
Discontinuation of treatment does not lead to a rebound effect.
Perindopril reduces left ventricular hypertrophy.
In man, perindopril has been confirmed to demonstrate vasodilatory properties. It improves large artery elasticity and decreases the media:lumen ratio of small
arteries.
An adjunctive therapy with a thiazide-diuretic produces an additive-type of synergy. The combination of an ACE inhibitor and a thiazide also decreases the risk of
hypokalaemia induced by the diuretic treatment.
Heart Failure: Perindopril reduces cardiac work by a decrease in pre- and afterload. Studies in patients with heart failure have demonstrated decreased left and right
ventricular filling pressures, reduced total peripheral vascular resistance, increased cardiac output and improved cardiac index.
In comparative studies, the 1st administration of perindopril arginine 2.5 mg to patients with mild to moderate heart failure was not associated with any significant
reduction of blood pressure as compared to placebo.
Patients with Stable Coronary Artery Disease: The EUROPA trial was a multicentre, international, randomised, double-blind, placebo-controlled clinical trial lasting 4
years.
Twelve thousand two hundred and eighteen (12,218) patients >18 years were randomised to perindopril tert-butylamine 8 mg (equivalent to perindopril arginine 10
mg) (n=6110) or placebo (n=6108).
The trial population had evidence of coronary artery disease with no evidence of clinical signs of heart failure. Overall, 90% of the patients had a previous myocardial
infarction and/or a previous coronary revascularisation. Most of the patients received the study medication on top of conventional therapy including platelet
inhibitors, lipid-lowering agents and ß-blockers.
The main efficacy criterion was the composite of cardiovascular mortality, nonfatal myocardial infarction and/or cardiac arrest with successful resuscitation. The
treatment with perindopril tert-butylamine 8 mg (equivalent to perindopril arginine 10 mg) once daily resulted in a significant absolute reduction in the primary
endpoint of 1.9% [relative risk reduction (RRR) of 20%, 95% CI (9.4; 28.6); p<0.001].
In patients with a history of myocardial infarction and/or revascularisation, an absolute reduction of 2.2% corresponding to a RRR of 22.4% [95% CI (12.0; 31.6);
p<0.001] in the primary endpoint was observed by comparison to placebo.
Pharmacokinetics: After oral administration, the absorption of perindopril is rapid and the peak concentration is achieved within 1 hr. The plasma half-life of
perindopril is equal to 1 hr.
Pharmacotherapeutic Group: Perindopril and diuretics. ATC Code: C09BA04.
Pharmacology: Mechanism of Action: Bioprexum Plus produces an additive synergy of the antihypertensive effects of the two components.
Pharmacodynamics: Bioprexum Plus is a combination of perindopril arginine salt, an ACE inhibitor and indapamide, a chlorosulphamoyl diuretic. Its pharmacological
properties are derived from those of each of the components taken separately, in addition to those due to the additive synergistic action of the 2 products when
combined.
Perindopril: Perindopril is an angiotensin-converting enzyme (ACE) inhibitor which converts angiotensin I to angiotensin II, a vasoconstricting substance; in addition,
the enzyme stimulates the secretion of aldosterone by the adrenal cortex and the degradation of bradykinin, a vasodilatory substance, into inactive heptapeptides.
This results in a reduction in aldosterone secretion; an increase in plasma renin activity, since aldosterone no longer exercises negative feedback; and a reduction in
total peripheral resistance with a preferential action on the vascular bed in muscle and the kidney, with no accompanying salt and water retention or reflex
tachycardia, with chronic treatment.
The antihypertensive action of perindopril also occurs in patients with low or normal renin concentrations.
Perindopril acts through its active metabolite, perindoprilat. The other metabolites are inactive.
Perindopril reduces the work of the heart by a vasodilatory effect on veins, probably caused by changes in the metabolism of prostaglandins, therefore having a
reduction in preload; by reduction of the total peripheral resistance, therefore having a reduction in afterload.
Studies carried out on patients with cardiac insufficiency have shown a reduction in left and right ventricular filling pressures and total peripheral vascular resistance,
an increase in cardiac output and regional blood flow in muscle and an improvement in the cardiac index. Exercise test results also showed improvement.
Indapamide: Indapamide is a sulphonamide derivative with an indole ring, pharmacologically related to the thiazide group of diuretics. Indapamide inhibits the
reabsorption of sodium in the cortical dilution segment. It increases the urinary excretion of sodium and chlorides and to a lesser extent, the excretion of potassium
and magnesium, thereby increasing urine output and having an antihypertensive action.
Characteristics of Antihypertensive Action: Bioprexum Plus: In hypertensive patients regardless of age, Bioprexum Plus exerts a dose-dependent antihypertensive
effect on diastolic and systolic arterial pressure whilst supine or standing. This antihypertensive effect lasts for 24 hrs. The reduction in blood pressure is obtained in <1
month without tachyphylaxis; stopping treatment has no rebound effect. During clinical trials, the concomitant administration of perindopril and indapamide
produced antihypertensive effects of a synergistic nature in relation to each of the products administered alone.
PICXEL, a multicenter, randomised, double-blind active controlled study has assessed on echocardiography the effect of perindopril/indapamide combination on left
ventricular hypertrophy (LVH) versus enalapril monotherapy.
In PICXEL, hypertensive patients with LVH, defined as left ventricular mass index (LVMI) >120 g/m2 in male and >100 g/m2 in female) were randomised either to
perindopril tert-butylamine 2 mg (equivalent to perindopril arginine 2.5 mg)/indapamide 0.625 mg or to enalapril 10 mg once a day for a 1-year treatment. The dose
was adapted according to blood pressure control, up to perindopril tert-butylamine 8 mg (equivalent to perindopril arginine 10 mg) and indapamide 2.5 mg or
enalapril 40 mg once a day. Only 34% of the subjects remained treated with perindopril tert-butylamine 2 mg (equivalent to perindopril arginine 2.5 mg)/indapamide
0.625 mg (versus 20% with enalapril 10 mg).
At the end of treatment, LVMI had decreased significantly more in the perindopril/indapamide group (-10.1 g/m2) than in the enalapril group (-1.1 g/m2) in all the
randomised patients population. The between group difference in LVMI change was -8.3 [95% CI (-11.5, -5), p<0.0001].
A better effect on LVMI was reached with higher perindopril/indapamide doses than those licensed for Bioprexum Plus.
Regarding blood pressure, the estimated mean between group differences in the randomised population were -5.8 mm Hg [95% CI (-7.9, -3.7), p<0.0001] for systolic
blood pressure and -2.3 mm Hg [95% CI (-3.6, -0.9), p=0.0004] for diastolic blood pressure respectively, in favor of the perindopril/indapamide group.
Perindopril: Perindopril is active in all grades of hypertension, from mild to moderate or severe. A reduction in systolic and diastolic arterial pressure is observed in the
lying and standing position.
The antihypertensive activity after a single dose is maximal between 4 and 6 hrs and is maintained over 24 hrs.
Pharmacology: Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldosterone system and plays a significant role in the pathophysiology of
hypertension, heart failure and other cardiovascular disorders. It is also has an important role in the pathogenesis of end organ hypertrophy and damage.
The major physiological effects of angiotensin II, such as vasoconstriction, aldosterone stimulation, regulation of salt and water homeostasis and stimulation of cell
growth, are mediated via the type I (AT1) receptor.
Blopress is a prodrug suitable for oral use. It is rapidly converted to the active drug, candesartan, by ester hydrolysis during absorption from the gastrointestinal tract.
Blopress is an angiotensin II receptor antagonist, selective for AT1 receptor, with tight binding to and slow dissociation from the receptor. It has no agonist activity.
Candesartan does not inhibit ACE, which convert angiotensin I to angiotensin II and degrades bradykinin. There is no effect on ACE and no potentiation of bradykinin
or substance P. In controlled clinical trials comparing Blopress with ACE-inhibitor, the incidence of cough was lower in patients receiving Blopress. Candesartan does
not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Hypertension: In hypertension, Blopress causes a dose-dependent, long lasting reduction in arterial blood pressure. The antihypertensive action is due to decreased
systemic peripheral resistance, while heart rate, stroke volume and cardiac output are not affected. There is no indication of serious exaggerate first-dose hypotension
or rebound effect after cessation of treatment.
Blopress is effective in all grades of hypertension.
After administration of a single dose. Onset of antihypertensive effect generally occurs within 2 hours. With continuous treatment, the maximum reduction in blood
pressure with any dose generally attained within 4 weeks and is sustained during long-term treatment. It provides effective and smooth blood pressure reduction over
the 24-hr with little difference between maximum and trough effects during the dosing interval.
When Blopress is used together with hydrochlorothiazide, the reduction in blood pressure is additive. Blopress is similarly effective in patients irrespective of age and
gender.
Blopress increases renal blood flow and either has no effect on, or increases glomerular filtration rate while renal vascular resistance and filtration fraction are
reduced. Blopress has no adverse effect on blood glucose or lipid profile.
Heart Failure: Treatment with candesartan cilexetil reduces mortality, reduces hospitalization due to heart failure and improves symptoms in patients with left
ventricular systolic dysfunction as shown in the Candesartan in Heart Failure - Assessment of Reduction in Mortality and Morbidity (CHARM) programme.
This multinational, placebo controlled, double-blind study programme in chronic heart failure (CHF) patients with NYHA functional class II to IV consisted of three
separate studies: CHARM-Alternative (n=2,028) in patients with LVEF =40% not treated with an ACE inhibitor because of intolerance (mainly due to cough, 72%),
CHARM-Added (n=2,548) in patients with LVEF =40% and treated with an ACE inhibitor, and CHARM-Preserved (n=3,023) in patients with LVEF >40%. Patients on
optimal CHF therapy at baseline were randomised to placebo or candesartan cilexetil (titrated from 4 mg or 8 mg once daily to 32 mg once daily or the highest
tolerated dose, mean dose 24 mg) and followed for a median of 37.7 months. After 6 months of treatment, 63% of the patients still taking candesartan cilexetil (89%)
were at the target dose of 32 mg.
In CHARM-Alternative, the composite endpoint of cardiovascular mortality or first CHF hospitalisation was significantly reduced with candesartan in comparison with
placebo [hazard ratio (HR) 0.77, 95% CI 0.67-0.89, p <0.001]. This corresponds to a relative risk reduction of 23%. Fourteen patients needed to be treated for the
duration of the study to prevent one patient from dying of a cardiovascular event or being hospitalised for treatment of heart failure. The composite endpoint of all-
cause mortality or first CHF hospitalisation was also significantly reduced with candesartan (HR 0.80, 95% CI 0.70-0.92, p=0.001). Both the mortality and morbidity
(CHF hospitalisation) components of these composite endpoints contributed to the favourable effects of candesartan. Treatment with candesartan cilexetil resulted in
improved NYHA functional class (p=0.008).
In CHARM-Added, the composite endpoint of cardiovascular mortality or first CHF hospitalisation was significantly reduced with candesartan in comparison with
placebo (HR 0.85, 95% CI 0.75-0.96, p=0.011). This corresponds to a relative risk reduction of 15%. Twenty-three patients needed to be treated for the duration of the
study to prevent one patient from dying of a cardiovascular event or being hospitalised for treatment of heart failure. The composite endpoint of all-cause mortality or
first CHF hospitalisation
Pharmacology: Blopress was
Plusalso significantly
contains reduced
candesartan with candesartan
cilexetil, (HRII 0.87,
an angiotensin 95% CIand
antagonist 0.78-0.98, p=0.021). Both
hydrochlorothiazide, the mortality and morbidity components of these
a diuretic.
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of
the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal
reabsorption of sodium. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II
to the AT1 receptor in many tissues such as vascular smooth muscle and the adrenal gland. Its action is therefore, independent of the pathways for angiotensin II
synthesis.
There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Candesartan has much greater affinity
(>10,000-fold) for the AT1 receptor than for the AT2 receptor.
Blockade of the renin-angiotensin system with ACE inhibitor, which inhibits the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of
hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalysed by ACE. Because candesartan does not inhibit ACE (kininase II), it does
not affect the response of bradykinin. Whether this difference has clinical relevancies not yet known. Candesartan does not bind to or block other hormone receptors,
or ion channels known to be important in cardiovascular regulation.
Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity
and angiotensin II circulating levels do not overcome the effect of candesartan on blood pressure.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanism's electrolyte reabsorption, directly increasing excretion of sodium and chloride
in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity,
increases in aldosterone secretion, increases in urinary potassium loss and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II,
therefore co-administration of an angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.
The mechanism of the antihypertensive effects of thiazides is unknown.
Antihemorrhoidal.
It alleviates inflammation, itching, edema, pain and allergic symptoms, and promotes healing.
Borraginol-N has prompt antiphlogistic, analgesic, antiseptic, antipruritic and hemostatic actions on hemorrhoids, hemorrhoidal bleeding, wounds and burns, and
accelerates the formation of granulation and epithelium of ulcerated wounds.
Antihemorrhoidal.
Borraginol-S is a therapeutic agent for hemorrhoids. It alleviates inflammation, itching, edema, pain and allergic symptoms, and promotes healing.
Borraginol-S has prompt antiphlogistic, analgesic, antiseptic, antipruritic and hemostatic actions on hemorrhoids, hemorrhoidal bleeding, wounds and burns, and help
the formation of granulation and epithelium of ulcerated wounds.
Pharmacotherapeutic Group: Selective ß2-agonist, terbutaline. ATC Code: R03C C03.
Pharmacology: Pharmacodynamics: Terbutaline is a sympathomimetic bronchodilator with a degree of selective ß2-stimulant activity on the respiratory system.
Terbutaline is an adrenergic agonist which predominantly stimulates ß2-receptors, thus, producing relaxation of bronchial smooth muscle, inhibition of the release of
endogenous spasmogens, inhibition of edema caused by endogenous mediators and increased mucociliary clearance.
Injection: After SC injection of terbutaline the duration of onset regarding the bronchodilating effect is <5 minutes. Maximum effect is reached within 30 minutes.
Respules: Inhaled terbutaline acts within a few min and has a duration for up to 6 hours. Bricasma respules is to be used in nebulizers with or without assisted
breathing in acute or subacute disorders where conventional inhalers prove unsatisfactory, and in maintenance therapy in severe broncho-obstructive condition.
Bricasma respules is ready for use without dilution. Bricasma respules is isotonic and contains no preservatives.
Turbuhaler: Inhaled terbutaline acts within a few min and has a duration for up to 6 hours.
About 10% of the dose is deposited in the lungs. Terbutaline is metabolized mainly by conjugation with the sulphuric acid and excreted as the sulphate conjugate. No
active metabolites are formed. BRICASMA TURBUHALER contains pure terbutaline sulphate and is free from propellants lubricants, preservatives, carrier substances or
other additives.
BRICASMA TURBUHALER is breath actuated and hence, there is no need to coordinate the release of the dose and the inhalation as with a pressurized inhaler. When
inhaling, the substance follows the inspired air into the airways.
Pharmacokinetics: Terbutaline is metabolized mainly by conjugation with the sulphuric acid and excreted as the sulphate conjugate. No active metabolites are formed.
Injection: The plasma half-life is about 16 hours. After IV and SC administration of terbutaline 90% is excreted renally during 48-96 hours. Of this, about 60% consists
of unmetabolized terbutaline.
Turbuhaler: About 20-30% of the metered dose is deposited in the lungs at a normal inhalation flow rate.
Toxicology: Preclinical Safety Data: Ampoule: The major toxic effect of terbutaline, observed in toxicological studies, is focal myocardial necrosis. This type of
cardiotoxicity is a well-known class effect and the effect of terbutaline is similar to or less pronounced than that of other ß-receptor agonists. Terbutaline has been
used extensively over many years for the relief of bronchospasm without identifying any areas of concern.
Pharmacology: Mechanism of Action: Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and
platelet activation. Ticagrelor and its active metabolite are approximately equipotent.
Pharmacodynamics: The inhibition of platelet aggregation (IPA) by ticagrelor and clopidogrel was compared in a 6 week study examining both acute and chronic
platelet inhibition effects in response to adenosine diphosphate (ADP) 20 micromolar as the platelet aggregation agonist.
The onset of IPA was evaluated on day 1 of the study following loading doses of ticagrelor 180 mg or clopidogrel 600 mg. As shown in Figure 1, IPA was higher in the
ticagrelor group at all time points. The maximum IPA effect of ticagrelor was reached at around 2 hrs and was maintained for at least 8 hrs.
The offset of IPA was examined after 6 weeks on ticagrelor 90 mg twice daily or clopidogrel 75 mg daily, again in response to ADP 20 micromolar.
As shown in Figure 2, mean maximum IPA following the last dose of ticagrelor was 88% and 62% for clopidogrel. The insert in figure 2 shows that after 24 hrs, IPA in
the ticagrelor group (58%) was similar to IPA in clopidogrel group (52%), indicating that patients who miss a dose of ticagrelor would still maintain IPA similar to the
trough IPA of patients treated with clopidogrel. After 5 days, IPA in the ticagrelor group was similar to IPA in the placebo group. It is not known how either bleeding risk
or thrombotic risk track with IPA, for either ticagrelor or clopidogrel. (See Figures 1 and 2.)
Transitioning from clopidogrel to BRILINTA resulted in an absolute IPA increase of 26.4% and from BRILINTA to clopidogrel resulted in an absolute IPA decrease of
24.5%. Patients can be transitioned from clopidogrel to BRILINTA without interruption of antiplatelet effect (see Dosage & Administration).
Clinical Studies: The clinical evidence for the effectiveness of BRILINTA is derived from PLATO, a randomized double-blind study comparing BRILINTA (N=9,333) to
clopidogrel (N=9,291), both given in combination with aspirin and other standard therapy, in patients with acute coronary syndromes (ACS). Patients were treated for
at least 6 months and for up to 12 months. Study endpoints were obtained until the study was complete, even if drug was discontinued.
Patients who presented within 24 hours of onset of the most recent episode of chest pain or symptoms were randomized to receive BRILINTA or clopidogrel. Patients
who had already been treated with clopidogrel could be enrolled and randomized to either study treatment. Patients could be included whether there was intent to
manage the ACS medically or invasively, but patient randomization was not stratified by this intent. Subjects in the clopidogrel arm were treated with an initial loading
dose of clopidogrel 300 mg, if previous clopidogrel therapy had not been given prior to randomization. Patients undergoing PCI could receive an additional clopidogrel
300 mg at investigator discretion. All subjects randomized to BRILINTA received a loading dose of 180 mg followed by a maintenance dose of 90 mg twice daily.
Concomitant aspirin was recommended at a loading dose of 160-500 mg. A daily maintenance dose of aspirin 75-100 mg was recommended, but higher maintenance
doses of aspirin were allowed according to local judgment.
Because of ticagrelor's metabolism by CYP3A enzymes, the protocol recommended limiting the maximum dosage of simvastatin and lovastatin to 40 mg in both study
arms. Because of an increased bleeding risk, the study excluded patients with previous intracranial hemorrhage, a gastrointestinal bleed within the past 6 months, or
other factors that predispose to bleeding.
PLATO patients were predominantly male (72%) and Caucasian (92%). About 43% of patients were >65 years and 15% were >75 years.
The study's primary endpoint was the composite of 1st occurrence of cardiovascular death, nonfatal MI (excluding silent MI), or non-fatal stroke. The components
were assessed as secondary endpoints.
Median exposure to study drug was 277 days. About half of the patients received pre-study clopidogrel and about 99% of the patients received aspirin at some time
during PLATO. About 35% of patients were receiving a statin at baseline and 93% received a statin sometime during PLATO.
Table 1 shows the study results for the primary composite endpoint and the contribution of each component to the primary endpoint. Separate secondary endpoint
analyses are shown for the overall occurrence of CV death, MI, and stroke and overall mortality. (See Table 1.)
The difference between treatments on the composite resulted from effects on CV death and MI; each was statistically significant when considered as a secondary
endpoint and there was no beneficial effect on strokes. For all-cause mortality the benefit was also statistically significant (p=0.0003) with a hazard ratio of 0.78.
Pharmacology: Amlodipine/Atorvastatin Pharmacodynamics: Caduet combines 2 mechanisms of action: The dihydropyridine calcium antagonist (calcium ion
antagonist or slow-channel blocker) action of amlodipine and the HMG-CoA reductase inhibition of atorvastatin. The amlodipine component of
amlodipine/atorvastatin inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The atorvastatin component of
amlodipine/atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to
mevalonate, a precursor of sterols including cholesterol.
Clinical Studies of Combined Amlodipine and Atorvastatin in Patients with Hypertension and Dyslipidemia: In a double-blind, placebo-controlled study of 1660 patients
with co-morbid hypertension and dyslipidemia, once daily treatment with 8 dose combinations of amlodipine and atorvastatin (5/10, 10/10, 5/20, 10/20, 5/40, 10/40,
5/80, or 10/80 mg) was compared versus amlodipine alone (5 or 10 mg), atorvastatin alone (10, 20, 40 or 80 mg), and placebo. In addition to concomitant
hypertension and dyslipidemia, 15% of the patients had diabetes mellitus, 22% were smokers and 14% had a positive family history of cardiovascular disease. At 8
weeks, all 8 combination-treatment groups demonstrated statistically significant dose-related reductions in systolic blood pressure (SBP), diastolic blood pressure
(DBP) and LDL-C compared to placebo, with no overall modification of effect of either component on SBP, DBP and LDL-C (see Table 1).
In an open-label trial, 1220 patients with co-morbid hypertension and dyslipidemia received elective dose-titration with amlodipine/atorvastatin over a 14-week
period. Patients were required to have uncontrolled blood pressure to enter the trial (whether or not they were using antihypertensive medications at enrollment;
patients were allowed to continue on previous antihypertensives, other than calcium-channel blockers, during the 14-week dose-titration period) but could enter with
either controlled or uncontrolled LDL-C. As a result, no patient entered the trial with both blood pressure and LDL-C controlled, and neither was controlled in 62% of
patients. Treatment with amlodipine/atorvastatin reduced mean blood pressure by -17.1 mmHg systolic and -9.6 mmHg diastolic, and reduced mean LDL-C by -32.7%,
resulting in control of both blood pressure and LDL-C for 58% of these patients (controlled blood pressure and LDL-C were defined, respectively, as <140/90 mmHg and
<160 mg/dL for patients with co-morbid hypertension and dyslipidemia only; <140/90 mmHg and <130 mg/dL for patients with co-morbid hypertension and
dyslipidemia plus 1 additional cardiovascular risk factor, excluding known coronary heart disease (CHD) or diabetes mellitus; and <130/85 mmHg and <100 mg/dL for
patients with co-morbid hypertension and dyslipidemia plus known CHD, diabetes mellitus, or other atherosclerotic disease). Only 13% of the patients in this trial used
amlodipine/atorvastatin as initial therapy for co-morbid hypertension and dyslipidemia, whereas the amlodipine component of amlodipine/atorvastatin comprised
add-on therapy for hypertension in 56% of patients, including patients for whom the atorvastatin component of amlodipine/atorvastatin comprised initial therapy for
dyslipidemia (20%), a substitution for atorvastatin taken previously (18%), or a switch from another statin (18%). When evaluated according to use of antihypertensive
and lipid-lowering medications at enrollment, results showed that both blood pressure and LDL-C were brought under control for 65% of patients who used
amlodipine/atorvastatin as initial therapy for co-morbid hypertension and dyslipidemia and for 55-64% of patients for whom the amlodipine component of
amlodipine/atorvastatin constituted add-on therapy for hypertension (55% for such patients who had previously used lipid-lowering medications other than
atorvastatin, 58% for such patients who had previously used atorvastatin, and 64% for such patients who had not previously used lipid-lowering medications).
Amlodipine Pharmacodynamics: Amlodipine is a calcium-ion influx inhibitor (slow channel blocker or calcium-ion antagonist) and inhibits the transmembrane influx of
calcium ions into cardiac and vascular smooth muscle.
The mechanism of the antihypertensive action of amlodipine is due to a direct relaxant effect on vascular smooth muscle. The precise mechanism by which
amlodipine relieves angina has not been fully determined but amlodipine reduces total ischemic burden by the following 2 actions.
Amlodipine dilates peripheral arterioles and thus, reduces the total peripheral resistance (afterload) against which the heart works. Since the heart rate remains
stable, this unloading of the heart reduces myocardial energy consumption and oxygen requirements.
The mechanism of action of amlodipine also probably involves dilatation of the main coronary arteries and coronary arterioles, both in normal and ischemic regions.
This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (Prinzmetal's or variant angina) and blunts smoking-induced coronary
vasoconstriction.
In patients with hypertension, once-daily dosing provides clinically significant reductions of blood pressure in both the supine and standing positions throughout the
Calcium is an essential mineral necessary for the maintenance of electrolyte equilibrium in the body and for the proper functioning of numerous regulatory
mechanisms. Calcium deficiency is associated with neuromuscular disorders and bone demineralization.
CalSource/CalSource Forte: Contains readily soluble and ionizable calcium salts. About 30% of ionized calcium is absorbed from the gastrointestinal tract. It is used for
the prevention and therapy of acute and chronic calcium deficiency states, and for treatment of various forms of disturbed bone metabolism in both children and
adults.
CalSource Plus Vitamin C: Ascorbic acid (vitamin C) plays an important role in biological oxidation and reduction processes, and in cellular respiration. It is also
essential for collagen formation and tissue repair.
Calcium and ascorbic acid deficiency can be the result of inadequate nutrition or may occur in various conditions associated with increased demands (see Indications).
CalSource Plus Vitamin C provides vitamin C and ionizable calcium in sufficient amounts for covering the daily needs at time of increased requirements.
Pharmacotherapeutic Group: Cytostatic topoisomerase I inhibitor.
Pharmacology: Pharmacodynamics: The intensity of the major toxicities encountered with Campto (eg, leukoneutropenia and diarrhea) are related to the exposure
(AUC) to parent drug and metabolite SN-38.
Significant correlations were observed between hematological toxicity (decrease in white cells and neutrophils at nadir) or intensity of diarrhea and both irinotecan
HCl and metabolite SN-38 AUC values in monotherapy.
Experimental Data: Irinotecan is a semisynthetic derivative of camptothecin. It is an antineoplastic agent which acts as a specific inhibitor of DNA topoisomerase I. It is
metabolized by carboxylesterase in most tissues to SN-38, which was found to be more active than irinotecan in purified topoisomerase I and more cytotoxic than
irinotecan against several murine and human tumor cell lines. The inhibition of DNA topoisomerase I by irinotecan or SN-38 induces single-strand DNA lesions which
blocks the DNA replication fork and are responsible for the cytotoxicity. This cytotoxic activity was found to be time-dependent and was specific to the S-phase.
Therapeutic Class: Irinotecan HCl is an antineoplastic agent of the topoisomerase I inhibitor class, clinically investigated as CPT-11. Irinotecan is a semisynthetic
derivative of camptothecin, an alkaloid extract from plants eg, Camptotheca acuminata or is chemically synthesized.
Mechanism of Action: Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks.
Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact
with the ternary complex formed by topoisomerase I, DNA and either irinotecan or SN-38.
Irinotecan serves as a water-soluble precursor of the lipophilic metabolite SN-38. SN-38 is formed from irinotecan by carboxylesterase-mediated cleavage of the
carbamate bond between the camptothecin moiety and the dipiperidino side chain. SN-38 is approximately 1000 times as potent as irinotecan as an inhibitor of
topoisomerase I purified from human and rodent tumor cell lines. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to
2000-fold. However, the plasma area under the concentration versus time curve (AUC) values for SN-38 are 2-8% of irinotecan and SN-38 is 95% bound to plasma
proteins compared to approximately 50% bound to plasma proteins for irinotecan. The precise contribution of SN-38 to the activity of irinotecan is thus unknown.
Both irinotecan and SN-38 exist in an active lactone form and an inactive hydroxy acid anion form. A pH-dependent equilibrium exists between the 2 forms such that
an acid pH promotes the formation of the lactone, while a more basic pH favors the hydroxy acid anion form.
Pharmacokinetics: Absorption and Distribution: After IV infusion in humans, irinotecan plasma concentrations decline in a multiexponential manner, with a mean
terminal elimination half-life of about 6 hrs. The mean terminal elimination half-life of the active metabolite SN-38 is about 10 hrs. The half-lives of the lactone (active)
forms of irinotecan and SN-38 are similar to those of total irinotecan and SN-38, as the lactone and hydroxy acid forms are in equilibrium.
Over the dose range of 50-350 mg/m2, the AUC of irinotecan increases linearly with dose; the AUC of SN-38 increases less than proportionally with dose. Maximum
concentrations of the active metabolite SN-38 are generally seen within 1 hr following the end of a 90-min infusion of irinotecan.
Irinotecan exhibits moderate plasma protein-binding (30-68% bound). SN-38 is highly bound to human plasma proteins (approximately 95% bound). The plasma
protein to which irinotecan and SN-38 predominantly binds is albumin.
Metabolism and Excretion: The metabolic conversion of irinotecan to the active metabolite SN-38 is mediated by carboxylesterase enzymes and primarily occurs in the
liver. SN-38 subsequently undergoes conjugation predominantly by the enzyme UDP-glucuronosyl transferase 1A1 (UGT1A1) to form a glucuronide metabolite.
UGT1A1 acitivity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity eg, the UGT1A1*28 polymorphism (see Precautions). SN-
38 glucuronide had 1/50-1/100 the activity of SN-38 in cytotoxicity assays using 2 cell lines in vitro. The disposition of irinotecan has not been fully elucidated in
humans. The urinary excretion of irinotecan is 11-20%; SN-38, <1%; and SN-38 glucuronide, 3%. The cumulative biliary and urinary excretion of irinotecan and its
metabolites (SN-38 and SN-38 glucuronide) over a period of 48 hrs following administration of irinotecan in 2 patients ranged from approximately 25% (100 mg/m2) to
50% (300 mg/m2).
Special Populations: Geriatric: The pharmacokinetics of irinotecan administered using the weekly schedule was evaluated in a study of 183 patients that was
prospectively designed to investigate the effect of age on irinotecan toxicity. Results from this trial indicate that there are no differences in the pharmacokinetics of
irinotecan, SN-38 and SN-38 glucuronide in patients <65 years compared with patients =65 years. In a study of 162 patients that was not prospectively designed to
Pharmacology: Ramiprilat, the active metabolite of ramipril, is a potent and long-acting angiotensin-converting enzyme (ACE) inhibitor.
Administration of Cardace results in vasodilatation especially in hypertensive patients, and in the reduction of blood pressure. The blood pressure-lowering effect of a
single dose occurs within 1-2 hrs after intake, reaching its peak within 3-6 hrs and usually lasts for 24 hrs.
Cardace is also effective in the treatment of congestive heart failure. Further, in patients demonstrating clinical signs of congestive heart failure after an acute
myocardial infarction. Cardace has been shown to decrease the mortality risk including the risks of sudden death, progression to severe/resistant heart failure and
failure-related hospitalization.
Cardace, when administered on a preventive basis, significantly reduces the incidence of myocardial infarction, stroke or cardiovascular deaths in patients with an
increased cardiovascular risk attributable to vascular diseases (eg, manifest coronary heart disease or a history of stroke or peripheral vascular disease) or to diabetes
mellitus with at least 1 additional risk factor [microalbuminuria, hypertension, elevated total cholesterol levels, low high-density lipoprotein (HDL) cholesterol levels,
smoking]. Moreover, it reduces total mortality as well as the need for revascularizations, and delays the start and the progression of congestive heart failure. In
diabetic and nondiabetic patients, it significantly reduces the occurrence of microalbuminuria and diminishes the risk of development of nephropathy. These effects
occur both in hypertensive and in normotensive patients.
Pharmacodynamics: Ramipril is a product which, after absorption from the gastrointestinal tract, is hydrolysed in the liver to from the active ACE inhibitor, ramiprilat,
which is a potent and long-acting ACE inhibitor.
Administration of ramipril causes an increase in plasma renin activity and a decrease in plasma concentrations of angiotensin II and aldosterone. The beneficial
haemodynamic effects resulting from ACE inhibition are consequences of the reduction in angiotensin II causing dilatation of peripheral vessels and reduction in
vascular resistance. There is evidence suggesting that tissue ACE particularly in the vasculature, rather than circulating ACE, is the primary factor determining the
haemodynamic effects.
Angiotensin-converting enzyme is identical with kininase II, one of the enzymes responsible for the degradation of bradykinin. There is evidence that ACE inhibition by
ramipril appears to have some effects on the kallikrein-kinin prostaglandin systems. It is assumed that effects on these systems contribute to the hypotensive and
metabolic activity of ramipril.
Administration of Cardace to hypertensive patients results in reduction of both supine and standing blood pressure. The antihypertensive effects is evident within 1-2
hrs after the drug intake; peak effect occurs 3-6 hrs after drug intake and has been shown to be maintained for at least 24 hrs after usual therapeutic doses.
Pharmacokinetics: Following oral administration, ramipril is rapidly absorbed from the gastrointestinal tract, and peak plasma concentrations of ramipril are reached
within 1 hr. Peak plasma concentrations of the active metabolite, ramiprilat, are reached within 2-4 hrs.
Plasma concentrations of ramiprilat decline in a polyphasic manner. The effective t½ of ramiprilat after multiple-once daily administration of ramipril is 13-17 hrs for
ramipril 5-10 mg and markedly longer for lower doses of ramipril 1.25-2.5 mg. This difference is related to the long terminal phase of the ramiprilat concentration-time
curve observed at very low plasma concentrations. This terminal phase is independent of this dose indicating a saturable capacity of the enzyme to bind ramiprilat.
Steady-state plasma concentrations of ramiprilat after once-daily dosing with the usual dose of ramipril are reached by about the 4th day of treatment.
Ramipril is almost completely metabolized and the metabolites are excreted mainly via the kidneys. In addition to the bioactive metabolite, ramiprilat, other inactive
metabolites have been identified including diketopiperazine ester, diketopiperazine acid and conjugates.
Pharmacology: Cardura exerts its vasodilator effect via selective blockade of a1-adrenoceptors located in the vasculature.
Administration of Cardura to hypertensive patients causes a clinically significant reduction in blood pressure as a result of a reduction in systemic vascular resistance.
With once-daily dosing, clinically significant reductions in blood pressure are present throughout the day and at 24 hrs post-dose. A gradual reduction in blood
pressure occurs with maximum reduction usually occurring 2-6 hrs after dosing. In patients with hypertension, blood pressures during treatment with Cardura were
similar in both the supine and standing positions. Unlike nonselective a-adrenoreceptor-blocking agents, tolerance has not been observed in long-term therapy with
Cardura. Elevations of plasma renin activity and tachycardia were seen infrequently in sustained therapy.
Cardura, in addition to its antihypertensive effect, produce favorable effects on blood lipids, with a significant increase in the HDL/total cholesterol ratio and significant
reductions in total triglycerides and total cholesterol. It therefore confers an advantage over diuretics and ß-adrenoceptor-blocking agents which adversely affect these
parameters. Based on the established association of hypertension and blood lipids with coronary heart disease, the favorable effects of doxazosin therapy on both
blood pressure and lipids indicate a reduction in risk of developing coronary heart disease.
Treatment with Cardura has been shown to result in regression of left ventricular hypertrophy, inhibition of platelet aggregation and enhanced tissue plasminogen
activator capacity. Additionally, Cardura improves insulin sensitivity in patients who have impairment.
Cardura has been shown to be free of adverse metabolic effects and is suitable for use in patients with asthma, diabetes, left ventricular dysfunction and gout.
Administration of Cardura to patients with symptomatic benign prostatic hyperplasia (BPH) results in a significant improvement in urodynamics and symptoms. The
effect in BPH is thought to result from selective blockade of the a-adrenoceptors located in the prostatic muscular stroma, capsule of the prostate and bladder neck.
Pharmacokinetics: Absorption: After oral administration of therapeutic doses, Cardura is well absorbed with peak blood levels occurring at about 2 hrs.
Pharmacokinetic studies in patients with renal impairment have shown no significant alterations compared to patients with normal renal function. There are only
limited data in patients with liver impairment nor studies of the effects of drugs known to influence hepatic metabolism (eg, cimetidine).
Biotransformation/Elimination: The plasma elimination is biphasic with the terminal elimination half-life being 22 hrs and hence, this provides the basis for once-daily
dosing. Cardura is extensively metabolized with <5% excreted as unchanged drug.
Pharmacotherapeutic Group: Antiandrogen. ATC Code: L02BB03.
Pharmacology: Pharmacodynamics: Bicalutamide is a nonsteroidal antiandrogen, devoid of other endocrine activity. It binds to androgen receptors without activating
gene expression and thus, inhibits the androgen stimulus. Regression of prostatic tumours results from this inhibition. Clinically, discontinuation of Casodex can result
in antiandrogen withdrawal syndrome in a subset of patients.
Casodex 50 mg is a racemate with its antiandrogenic activity being almost exclusively in the (R)-enantiomer.
Casodex 150 mg was studied as a treatment for patients with localised (T1-T2, N0 or NX, M0) or locally advanced (T3-T4, any N, M0; T1-T2, N+, M0) nonmetastatic
prostate cancer in a combined analysis of 3 placebo controlled, double-blind studies in 8,113 patients, where Casodex was given as immediate hormonal therapy or as
adjuvant to radical prostatectomy or radiotherapy (primarily external beam radiation). At 9.7 years median follow-up, 36.6% and 38.17% of all Casodex- and placebo-
treated patients, respectively, had experienced objective disease progression.
A reduction in risk of objective disease progression was seen across most patient groups but was most evident in those at highest risk of disease progression.
Therefore, clinicians may decide that the optimum medical strategy for a patient at low risk of disease progression particularly in the adjuvant setting following radical
prostatectomy, may be to defer hormonal therapy until signs that the disease is progressing.
No overall survival difference was seen at 9.7 years median follow-up with 31.4% mortality (HR=1.01; 95% CI 0.94-1.09). However, some trends were apparent in
exploratory subgroup analyses.
Data on progression-free survival and overall survival over time based on Kaplan-Meier estimates for patients with locally advanced disease are summarized in Tables
1 and 2. (See Tables 1 and 2.)
For patients with localized disease receiving Casodex alone, there was no significant difference in progression free survival. There was no significant difference in
overall survival in patients with localized disease who received Casodex as adjuvant therapy, following radiotherapy (HR=0.98; 95% Cl 0.8-1.2) or radical prostatectomy
(HR=1.03; 95% Cl 0.85-1.25). In patients with localized disease, who would otherwise have been managed by watchful waiting, there was also a trend toward
decreased survival compared with placebo patients (HR=1.15; 95% Cl 1-1.32). In view of this, the benefit-risk profile for the use of Casodex is not considered favorable
in patients with localized disease.
In a separate programme, the efficacy of Casodex 150 mg for the treatment of patients with locally advanced nonmetastatic prostate cancer for whom immediate
castration was indicated, was demonstrated in a combined analysis of 2 studies with 480 previously untreated patients with nonmetastatic (M0) prostate cancer. At
56% mortality and a median follow-up of 6.3 years, there was no significant difference between Casodex and castration in survival (HR=1.05; CI 0.81-1.36); however,
equivalence of the 2 treatments could not be concluded statistically.
In a combined analysis of 2 studies with 805 previously untreated patients with metastatic (M1) disease at 43% mortality, Casodex 150 mg was demonstrated to be
less effective than castration in survival time (HR=1.3; CI 1.04-1.65), with a numerical difference in estimated time to death of 42 days (6 weeks) over a median survival
time of 2 years.
Bicalutamide is a racemate with its antiandrogen activity being almost exclusively in the (R)-enantiomer.
Pharmacokinetics: Bicalutamide is well absorbed following oral administration. There is no evidence of any clinically relevant effect of food on bioavailability.
The (S)-enantiomer is rapidly cleared relative to the (R)-enantiomer, the latter having a plasma elimination half-life (t½) of about 1 week.
On daily administration of Casodex, the (R)-enantiomer accumulates about 10-fold in plasma as a consequence of its long t½, which also makes it suitable for once
daily dosing.
Steady-state plasma concentrations of the (R)-enantiomer of approximately 22 mcg/mL are observed during daily administration of Casodex 150 mg and 9 mcg/mL
during daily administration of Casodex 50 mg. At steady state, the predominantly active (R)-enantiomer accounts for 99% of the total circulating enantiomers.
The pharmacokinetics of the (R)-enantiomer are unaffected by age, renal impairment or mild to moderate hepatic impairment. There is evidence that for subjects with
Pharmacotherapeutic Group: Anti-inflammatory and antirheumatic products, nonsteroids, acetic acid derivatives and related substances. ATC Code: M01AB05.
Pharmacology: Mechanism of Action: Cataflam contains the potassium salt of diclofenac, a nonsteroidal compound with pronounced analgesic, anti-inflammatory and
antipyretic properties. Inhibition of prostaglandin biosynthesis, which has been demonstrated in experiments, is considered to be fundamental to its mechanism of
action. Prostaglandins play a major role in causing inflammation, pain and fever.
Cataflam tablets have a rapid onset of action which makes them particularly suitable for the treatment of acute painful and inflammatory conditions.
Diclofenac potassium in vitro does not suppress proteoglycan biosynthesis in the cartilage at concentrations equivalent to the concentrations reached in humans.
Pharmacodynamics: Cataflam has been found to exert a pronounced analgesic effect in moderate and severe pain. In the presence of inflammation eg, due to trauma
or following surgical interventions, it rapidly relieves both spontaneous pain and pain on movement and diminishes inflammatory swelling and wound oedema.
Clinical studies have also revealed that in primary dysmenorrhoea, diclofenac is capable of relieving pain and reducing the extent of bleeding.
In migraine attacks, Cataflam has been shown to be effective in relieving headache and in improving the accompanying symptoms of nausea and vomiting.
Pharmacokinetics: Absorption: Diclofenac is rapidly and completely absorbed from Cataflam tablets. The absorption sets in immediately after administration and the
same amount is absorbed as from an equivalent dose of diclofenac sodium enteric-coated tablets.
Mean peak plasma concentrations of 3.8 micromol/L are attained 20-60 min after ingestion of one 50-mg tablet. Ingestion together with food has no influence on the
amount of diclofenac absorbed, although onset and rate of absorption may be slightly delayed.
The amount absorbed is linear in proportion to the size of the dose.
Since about ½ of diclofenac is metabolized during its 1st passage to the liver (first-pass effect), the AUC is about half as large following oral or rectal administration as it
is following a parenteral dose of equal size.
Pharmacokinetic behaviour does not change after repeated administration. No accumulation occurs, provided the recommended dosage intervals are observed.
Distribution: 99.7% of diclofenac binds to serum proteins, mainly to albumin (99.4%). The apparent volume of distribution calculated is 0.12-0.17 L/kg.
Diclofenac enters the synovial fluid, where maximum concentrations are measured 2-4 hrs after the peak plasma values have been reached. The apparent t½ for
elimination from the synovial fluid is 3-6 hrs. Two hrs after reaching peak plasma levels, concentrations of diclofenac are already higher in the synovial fluid than in the
plasma, and they remain higher for up to 12 hrs.
Biotransformation: Biotransformation of diclofenac takes place partly by glucuronidation of the intact molecule, but mainly by single and multiple hydroxylation and
methoxylation, resulting in several phenolic metabolites (3'-hydroxy-, 4'-hydroxy-, 5-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy-diclofenac), most of which are
converted to glucuronide conjugates.
Two of these phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.
Elimination: Total systemic clearance of diclofenac from plasma is 263±56 mL/min (mean value ±SD). The terminal t½ in plasma is 1-2 hrs. Four of the metabolites,
including the 2 active ones, also have short plasma half-lives of 1-3 hrs. One metabolite, 3'-hydroxy-4'-methoxy-diclofenac, has a longer plasma half-life. However, this
metabolite is virtually inactive.
About 60% of the administered dose is excreted in the urine as the glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted
to glucuronide conjugates. Less than 1% is excreted as unchanged substance. The rest of the dose is eliminated as metabolites through the bile in the faeces.
Characteristics in Patients: No relevant age-dependent differences in the drug's absorption, metabolism or excretion have been observed.
In patients suffering from renal impairment, no accumulation of the unchanged diclofenac can be inferred from the single-dose kinetics when applying the usual
dosage schedule. At a creatinine clearance of <10 mL/min, the calculated steady-state plasma levels of the hydroxy metabolites are about 4 times higher than in
normal subjects. However, the metabolites are ultimately cleared through the bile.
In patients with chronic hepatitis or nondecompensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.
Toxicology: Preclinical Safety Data: Preclinical data from acute and repeated-dose toxicity studies, as well as from genotoxicity, mutagenicity and carcinogenicity
studies with diclofenac, revealed no specific hazard for humans at the intended therapeutic doses. There was no evidence that diclofenac had a teratogenic potential
Pharmacology: Clonidine acts primarily on the central nervous system, resulting in reduced sympathetic outflow and a decrease in peripheral resistance, renal vascular
resistance, heart rate and blood pressure. Renal blood flow and glomerular filtration rate remain essentially unchanged. Normal postural reflexes are intact and
therefore, orthostatic symptoms are mild and infrequent.
During long-term therapy, cardiac output tends to return to control values, while peripheral resistance remains decreased. Slowing of the pulse rate has been
observed in most patients given clonidine, but the drug does not alter normal hemodynamic response to exercise.
MIMS Class ATC Classification Regulatory Classification
Topical Antifungals & Antiparasites D11AC08 - sulfur compounds ; Belongs to the W
class of medicated shampoos.
Antivirals J05AF05 - lamivudine ; Belongs to the class of G
nucleoside and nucleotide reverse transcriptase
inhibitors. Used in the systemic treatment of viral
infections.
ACE Inhibitors/Direct Renin Inhibitors C09AA01 - captopril ; Belongs to the class of ACE
inhibitors. Used in the treatment of
cardiovascular disease.
ACE Inhibitors/Direct Renin Inhibitors C09AA09 - fosinopril ; Belongs to the class of ACE
inhibitors. Used in the treatment of
cardiovascular disease.
ACE Inhibitors/Direct Renin Inhibitors C09AA01 - captopril ; Belongs to the class of ACE
inhibitors. Used in the treatment of
cardiovascular disease.
Intravenous & Other Sterile Solutions B05BB01 - electrolytes ; Belongs to the class of
solutions affecting the electrolyte balance used in
I.V. solutions.
Antacids, Antireflux Agents & Antiulcerants A02BA02 - ranitidine ; Belongs to the class of H2-
receptor antagonists. Used in the treatment of
peptic ulcer and gastro-oesophageal reflux
disease (GERD).
Antacids, Antireflux Agents & Antiulcerants A02AX - Antacids, other combinations ; Used in
the treatment of acid-related disorders.
Antacids, Antireflux Agents & Antiulcerants A02AF02 - ordinary salt combinations and
antiflatulents ; Belongs to the class of antacids
with antiflatulents.
Penicillins J01CR02 - amoxicillin and enzyme inhibitor ; G
Belongs to the class of penicillin combinations,
including beta-lactamase inhibitors. Used in the
systemic treatment of infections.
Agents Affecting Bone Metabolism M05BA08 - zoledronic acid ; Belongs to the class G
of bisphosphonates. Used in the treatment of
bone diseases.
Acne Treatment Preparations / Emollients, Cleansers & D11AC30 - others ; Belongs to the class of
Skin Protectives medicated shampoos.
GIT Regulators, Antiflatulents & Anti-Inflammatories A03FA02 - cisapride ; Belongs to the class of G
propulsives. Used in the treatment of functional
gastrointestinal disorders.
Antacids, Antireflux Agents & Antiulcerants A02BA02 - ranitidine ; Belongs to the class of H2- G
receptor antagonists. Used in the treatment of
peptic ulcer and gastro-oesophageal reflux
disease (GERD).
Agents Affecting Bone Metabolism M05BA02 - clodronic acid ; Belongs to the class of G
bisphosphonates. Used in the treatment of bone
diseases.
Antacids, Antireflux Agents & Antiulcerants A02AB01 - aluminium hydroxide ; Belongs to the
class of aluminium-containing antacids.
Surgical Dressings & Wound Care D09AA - Medicated dressings with antiinfectives ;
Used as medicated dressings.
Surgical Dressings & Wound Care D09AA - Medicated dressings with antiinfectives ;
Used as medicated dressings.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Agents Affecting Bone Metabolism M05BA07 - risedronic acid ; Belongs to the class G
of bisphosphonates. Used in the treatment of
bone diseases.
Agents Affecting Bone Metabolism M05BA07 - risedronic acid ; Belongs to the class
of bisphosphonates. Used in the treatment of
bone diseases.
Vitamins & Minerals (Paediatric) A11JB - Vitamins with minerals ; Used as dietary
supplements.
Other Drugs Acting on Musculo-Skeletal System M09AX01 - hyaluronic acid ; Belongs to the class G
of other drugs for disorders of the musculo-
skeletal system.
Vitamins & Minerals (Pre & Post Natal) / Antianemics B03AE10 - various combinations ; Belongs to the B
class of iron in other combinations. Used in the
treatment of anemia.
GIT Regulators, Antiflatulents & Anti-Inflammatories A03AX13 - silicones ; Belongs to the class of other
drugs used for functional bowel disorders.
Supplements & Adjuvant Therapy A11AA03 - multivitamins and other minerals, incl.
combinations ; Belongs to the class of
multivitamins with minerals. Used as dietary
supplements.
Nasal Decongestants & Other Nasal Preparations R01AA05 - oxymetazoline ; Belongs to the class of W
topical sympathomimetic agents used as nasal
decongestants.
Vitamins &/or Minerals / Vitamins & Minerals A11BA - Multivitamins, plain ; Used as dietary
(Paediatric) supplements.
Supplements & Adjuvant Therapy A16AX01 - thioctic acid ; Belongs to the class of B
various alimentary tract and metabolism
products.
Intravenous & Other Sterile Solutions B05AA01 - albumin ; Belongs to the class of blood G
substitutes and plasma protein fractions. Used as
blood substitutes.
Intravenous & Other Sterile Solutions B05AA01 - albumin ; Belongs to the class of blood G
substitutes and plasma protein fractions. Used as
blood substitutes.
Intravenous & Other Sterile Solutions B05AA01 - albumin ; Belongs to the class of blood G
substitutes and plasma protein fractions. Used as
blood substitutes.
Intravenous & Other Sterile Solutions B05AA01 - albumin ; Belongs to the class of blood
substitutes and plasma protein fractions. Used as
blood substitutes.
Intravenous & Other Sterile Solutions B05AA01 - albumin ; Belongs to the class of blood
substitutes and plasma protein fractions. Used as
blood substitutes.
Intravenous & Other Sterile Solutions B05AA01 - albumin ; Belongs to the class of blood
substitutes and plasma protein fractions. Used as
blood substitutes.
Antacids, Antireflux Agents & Antiulcerants A02BA02 - ranitidine ; Belongs to the class of H2-
receptor antagonists. Used in the treatment of
peptic ulcer and gastro-oesophageal reflux
disease (GERD).
Agents Affecting Bone Metabolism M05BA04 - alendronic acid ; Belongs to the class
of bisphosphonates. Used in the treatment of
bone diseases.
Other Dermatologicals / Other Drugs Acting on M02AC - Preparations with salicylic acid
Musculo-Skeletal System derivatives ; Used in the topical treatment of joint
and muscular pains.
Surgical Dressings & Wound Care B02BC08 - calcium alginate ; Belongs to the class
of local hemostatics. Used in the treatment of
hemorrhage.
Supplements & Adjuvant Therapy A11HA05 - biotin ; Belongs to the class of other
plain vitamin preparations. Used as dietary
supplements.
Skin Antiseptics & Disinfectants D08AX08 - ethanol ; Belongs to the class of other
antiseptics and disinfectants. Used in the
treatment of dermatological diseases.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) M01AG01 - mefenamic acid ; Belongs to the class
of non-steroidal antiinflammatory and
antirheumatic products, fenamates.
Antacids, Antireflux Agents & Antiulcerants A02AF02 - ordinary salt combinations and
antiflatulents ; Belongs to the class of antacids
with antiflatulents.
Preparations for Oral Ulceration & Inflammation A01AB11 - various ; Belongs to the class of local
antiinfective and antiseptic preparations. Used in
the treatment of diseases of the mouth.
Preparations for Oral Ulceration & Inflammation A01AB11 - various ; Belongs to the class of local
antiinfective and antiseptic preparations. Used in
the treatment of diseases of the mouth.
Drugs for Bladder & Prostate Disorders D11AX10 - finasteride ; Belongs to the class of
other dermatologicals.
Vitamins & Minerals (Pre & Post Natal) / Antianemics B03AE04 - iron, multivitamins and minerals ;
Belongs to the class of iron in other combinations.
Used in the treatment of anemia.
Agents Affecting Bone Metabolism M05BA04 - alendronic acid ; Belongs to the class G
of bisphosphonates. Used in the treatment of
bone diseases.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) M01AG01 - mefenamic acid ; Belongs to the class
of non-steroidal antiinflammatory and
antirheumatic products, fenamates.
Antacids, Antireflux Agents & Antiulcerants A02AG - Antacids with antispasmodics ; Used in
the treatment of acid-related disorders.
Antacids, Antireflux Agents & Antiulcerants A02AF02 - ordinary salt combinations and B
antiflatulents ; Belongs to the class of antacids
with antiflatulents.
Other Drugs Acting on the Respiratory System R07AA02 - natural phospholipids ; Belongs to the
class of lung surfactants. Used in the treatment of
respiratory diseases.
Oestrogens, Progesterones & Related Synthetic Drugs G03DC01 - allylestrenol ; Belongs to the class of G
estren derivative progestogens used in
progestogenic hormone preparations.
Neurodegenerative Disease Drugs N06DA02 - donepezil ; Belongs to the class of G
anticholinesterases. Used in the management of
dementia.
Other Drugs Acting on the Genito-Urinary System A13A - TONICS ; Used as tonics. G
Parenteral Nutritional Products B05BA01 - amino acids ; Belongs to the class of G
solutions for parenteral nutrition used in I.V.
solutions.
Cholagogues, Cholelitholytics & Hepatic Protectors A05BA - Liver therapy ; Used in liver therapy.
Phlebitis & Varicose Preparations / Anorectal A11AB - Multivitamins, other combinations ; Used B
Preparations as dietary supplements.
Phlebitis & Varicose Preparations / Anorectal C05CA53 - diosmin, combinations ; Belongs to the
Preparations class of bioflavonoids used as capillary stabilizing
agents.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) M01AG01 - mefenamic acid ; Belongs to the class
of non-steroidal antiinflammatory and
antirheumatic products, fenamates.
Vitamins & Minerals (Paediatric) A11AA03 - multivitamins and other minerals, incl.
combinations ; Belongs to the class of
multivitamins with minerals. Used as dietary
supplements.
Androgens & Related Synthetic Drugs G03BA03 - testosterone ; Belongs to the class of
3-oxoandrosten (4) derivative androgens used in
androgenic hormone preparations.
Cancer Hormone Therapy / Other Drugs Affecting G03HA01 - cyproterone ; Belongs to the class of
Hormonal Regulation antiandrogen preparations.
Androgens & Related Synthetic Drugs G03BB01 - mesterolone ; Belongs to the class of
5-androstanon (3) derivative androgens used in
androgenic hormone preparations.
Vitamins & Minerals (Pre & Post Natal) / Antianemics B03BB01 - folic acid ; Belongs to the class of folic B
acid and derivatives. Used in the treatment of
anemia.
Vitamins & Minerals (Pre & Post Natal) / Antianemics B03BB01 - folic acid ; Belongs to the class of folic B
acid and derivatives. Used in the treatment of
anemia.
ACE Inhibitors/Direct Renin Inhibitors C09AA05 - ramipril ; Belongs to the class of ACE G
inhibitors. Used in the treatment of
cardiovascular disease.
Antacids, Antireflux Agents & Antiulcerants A02AX - Antacids, other combinations ; Used in
the treatment of acid-related disorders.
Oestrogens, Progesterones & Related Synthetic Drugs G03CA03 - estradiol ; Belongs to the class of
natural and semisynthetic estrogens used in
estrogenic hormone preparations.
Antacids, Antireflux Agents & Antiulcerants A02BA02 - ranitidine ; Belongs to the class of H2-
receptor antagonists. Used in the treatment of
peptic ulcer and gastro-oesophageal reflux
disease (GERD).
Oestrogens, Progesterones & Related Synthetic Drugs G03AC01 - norethisterone ; Belongs to the class
of progestogens. Used as systemic contraceptives.
Psoriasis, Seborrhea & Ichthyosis Preparations D05AC01 - dithranol ; Belongs to the class of
topical antracen derivative agent used in the
treatment of psoriasis.
Emollients, Cleansers & Skin Protectives D02 - EMOLLIENTS AND PROTECTIVES ; Used as
skin emollients and protectants.
Antacids, Antireflux Agents & Antiulcerants A02BA03 - famotidine ; Belongs to the class of
H2-receptor antagonists. Used in the treatment of
peptic ulcer and gastro-oesophageal reflux
disease (GERD).
Nootropics & Neurotonics/Neurotrophics N06BX03 - piracetam ; Belongs to the class of
other psychostimulants and nootropics.
Antacids, Antireflux Agents & Antiulcerants A02AX - Antacids, other combinations ; Used in
the treatment of acid-related disorders.
Cholagogues, Cholelitholytics & Hepatic Protectors A05BA03 - silymarin ; Belongs to the class of
drugs used in liver therapy.
Vitamins & Minerals (Pre & Post Natal) / Antianemics B03BA01 - cyanocobalamin ; Belongs to the class
of vitamin B12 (cyanocobalamin and analogues).
Used in the treatment of anemia.
Agents Affecting Bone Metabolism M05BA03 - pamidronic acid ; Belongs to the class
of bisphosphonates. Used in the treatment of
bone diseases.
Vasoconstrictors C01CA03 - norepinephrine ; Belongs to the class G
of adrenergic and dopaminergic cardiac
stimulants excluding glycosides. Used in the
treatment of heart failure.
Other Drugs Acting on the Respiratory System R07AX - Other respiratory system products ; Used W
in the treatment of respiratory diseases.
Supplements & Adjuvant Therapy A11AA03 - multivitamins and other minerals, incl. B
combinations ; Belongs to the class of
multivitamins with minerals. Used as dietary
supplements.
Other Drugs Acting on Musculo-Skeletal System M01AX21 - diacerein ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) M01AG01 - mefenamic acid ; Belongs to the class
of non-steroidal antiinflammatory and
antirheumatic products, fenamates.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) M01AG01 - mefenamic acid ; Belongs to the class
of non-steroidal antiinflammatory and
antirheumatic products, fenamates.
Vitamins & Minerals (Paediatric) A11AA03 - multivitamins and other minerals, incl. B
combinations ; Belongs to the class of
multivitamins with minerals. Used as dietary
supplements.
Intravenous & Other Sterile Solutions B05BB01 - electrolytes ; Belongs to the class of G
solutions affecting the electrolyte balance used in
I.V. solutions.
Antacids, Antireflux Agents & Antiulcerants A02AF01 - magaldrate and antiflatulents ; Belongs
to the class of antacids with antiflatulents.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) M01AG01 - mefenamic acid ; Belongs to the class G
of non-steroidal antiinflammatory and
antirheumatic products, fenamates.
Emollients, Cleansers & Skin Protectives D11AX - Other dermatologicals ; Used in the G
treatment of dermatological diseases.
Nasal Decongestants & Other Nasal Preparations R01AD12 - fluticasone furoate ; Belongs to the G
class of topical corticosteroids used for
prophylaxis and treatment of allergic rhinitis.
Drugs for Bladder & Prostate Disorders G04CB02 - dutasteride ; Belongs to the class of G
testosterone-5-alpha reductase inhibitors. Used in
the treatment of benign prostatic hypertrophy.
Supplements & Adjuvant Therapy A11HA - Other plain vitamin preparations ; Used B
as dietary supplements.
Drugs for Neuropathic Pain / Anticonvulsants N03AF01 - carbamazepine ; Belongs to the class G
of carboxamide derivatives antiepileptic.
Peripheral Vasodilators & Cerebral Activators / N07CA03 - flunarizine ; Belongs to the class of
Antiemetics antivertigo preparations.
Supplements & Adjuvant Therapy G04BX - Other urologicals ; Used in the treatment
of urological problems.
Antacids, Antireflux Agents & Antiulcerants A02BX - Other drugs for peptic ulcer and gastro- G
oesophageal reflux disease (GORD) ; Used in the
treatment of peptic ulcer and gastro-oesophageal
reflux disease (GERD).
Vitamins &/or Minerals A11JA - Combinations of vitamins ; Used as
dietary supplements.
Nasal Decongestants & Other Nasal Preparations A07EA07 - beclometasone ; Belongs to the class
of corticosteroids acting locally. Used in the
treatment of intestinal inflammation.
Vitamins & Minerals (Paediatric) A11AA03 - multivitamins and other minerals, incl.
combinations ; Belongs to the class of
multivitamins with minerals. Used as dietary
supplements.
Nasal Decongestants & Other Nasal Preparations R01AD01 - beclometasone ; Belongs to the class
of topical corticosteroids used for prophylaxis and
treatment of allergic rhinitis.
Vitamins & Minerals (Pre & Post Natal) / Antianemics B03BB51 - folic acid, combinations ; Belongs to
the class of folic acid and derivatives. Used in the
treatment of anemia.
Supportive Care Therapy / Analgesics (Opioid) N02AX02 - tramadol ; Belongs to the class of
other opioids. Used to relieve pain.
Supplements & Adjuvant Therapy C10AX - Other lipid modifying agents ; Used in the
treatment of hyperlipidemia.
Antacids, Antireflux Agents & Antiulcerants A02BX02 - sucralfate ; Belongs to the class of
other drugs used in the treatment of peptic ulcer
and gastro-oesophageal reflux disease (GERD).
Antacids, Antireflux Agents & Antiulcerants A02AX - Antacids, other combinations ; Used in
the treatment of acid-related disorders.
Antacids, Antireflux Agents & Antiulcerants A02BA01 - cimetidine ; Belongs to the class of H2-
receptor antagonists. Used in the treatment of
peptic ulcer and gastro-oesophageal reflux
disease (GERD).
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) M01AG01 - mefenamic acid ; Belongs to the class
of non-steroidal antiinflammatory and
antirheumatic products, fenamates.
Emollients, Cleansers & Skin Protectives D11AX13 - monobenzone ; Belongs to the class of
other dermatologicals.
Emollients, Cleansers & Skin Protectives D03AX03 - dexpanthenol ; Belongs to the class of G
other cicatrizants. Used in the treatment of
wounds and ulcers.
Antacids, Antireflux Agents & Antiulcerants A02AX - Antacids, other combinations ; Used in
the treatment of acid-related disorders.
Vitamin B-Complex / with C A11DA01 - thiamine (vit B1) ; Belongs to the class
of vitamin B1. Used as dietary supplements.
Preparations for Oral Ulceration & Inflammation R02AA15 - povidone-iodine ; Belongs to the class
of antiseptics used in throat preparations.
Psoriasis, Seborrhea & Ichthyosis Preparations D11AC06 - povidone-iodine ; Belongs to the class
of medicated shampoos.
Antacids, Antireflux Agents & Antiulcerants A02BC03 - lansoprazole ; Belongs to the class of G
proton pump inhibitors. Used in the treatment of
peptic ulcer and gastro-oesophageal reflux
disease (GERD).
Supplements & Adjuvant Therapy A16AX - Various alimentary tract and metabolism B
products ; Used in treatment of alimentary tract
and metabolism problems.
Emollients, Cleansers & Skin Protectives D02AX - Other emollients and protectives ; Used
as skin emollients and protectants.
Supplements & Adjuvant Therapy A11AA03 - multivitamins and other minerals, incl.
combinations ; Belongs to the class of
multivitamins with minerals. Used as dietary
supplements.
Supplements & Adjuvant Therapy V01AA08 - food ; Belongs to the class of allergen
extracts. Used as antigenic substances capable of
producing immediate-type hypersensitivity.
Vitamin B-Complex / with C A11DB - Vitamin B1 in combination with vitamin FC tab: B; amp: G
B6 and/or vitamin B12 ; Used as dietary
supplements.
Other Dermatologicals / Emollients, Cleansers & Skin D02AX - Other emollients and protectives ; Used B
Protectives as skin emollients and protectants.
Emollients, Cleansers & Skin Protectives D02AX - Other emollients and protectives ; Used
as skin emollients and protectants.
Emollients, Cleansers & Skin Protectives D02AX - Other emollients and protectives ; Used W
as skin emollients and protectants.
Vitamins & Minerals (Paediatric) A11AA03 - multivitamins and other minerals, incl.
combinations ; Belongs to the class of
multivitamins with minerals. Used as dietary
supplements.
Vitamins & Minerals (Paediatric) A11AA03 - multivitamins and other minerals, incl.
combinations ; Belongs to the class of
multivitamins with minerals. Used as dietary
supplements.
Emollients, Cleansers & Skin Protectives D02AX - Other emollients and protectives ; Used
as skin emollients and protectants.
Emollients, Cleansers & Skin Protectives D02AX - Other emollients and protectives ; Used
as skin emollients and protectants.
Other Dermatologicals / Surgical Dressings & Wound D03AX05 - hyaluronic acid ; Belongs to the class
Care of other cicatrizants. Used in the treatment of
wounds and ulcers.
Vitamins & Minerals (Pre & Post Natal) / Antianemics B03AE02 - iron, multivitamins and folic acid ; B
Belongs to the class of iron in other combinations.
Used in the treatment of anemia.
Emollients, Cleansers & Skin Protectives D11AX - Other dermatologicals ; Used in the
treatment of dermatological diseases.
Surgical Dressings & Wound Care B02BC08 - calcium alginate ; Belongs to the class
of local hemostatics. Used in the treatment of
hemorrhage.
Other Dermatologicals D11AX11 - hydroquinone ; Belongs to the class of 2% cream:W; 4% Forte cream:G
other dermatologicals.
Vitamins & Minerals (Pre & Post Natal) / Antianemics B03AE10 - various combinations ; Belongs to the B
class of iron in other combinations. Used in the
treatment of anemia.
Vaccines, Antisera & Immunologicals J06AA02 - tetanus antitoxin ; Belongs to the class G
of immune sera. Used in the treatment of acute
infectious diseases caused by toxigenic strains.
Vitamins & Minerals (Paediatric) A11AA03 - multivitamins and other minerals, incl. B
combinations ; Belongs to the class of
multivitamins with minerals. Used as dietary
supplements.
Emollients, Cleansers & Skin Protectives A11HA01 - nicotinamide ; Belongs to the class of
other plain vitamin preparations. Used as dietary
supplements.
Emollients, Cleansers & Skin Protectives D02AX - Other emollients and protectives ; Used
as skin emollients and protectants.
Nasal Decongestants & Other Nasal Preparations R01AX30 - combinations ; Belongs to the class of B
other nasal preparations for topical use.
Trophic Hormones & Related Synthetic Drugs G03GB02 - clomifene ; Belongs to the class of G
synthetic agents used as ovulation stimulants.
Psoriasis, Seborrhea & Ichthyosis Preparations D11AX - Other dermatologicals ; Used in the
treatment of dermatological diseases.
Psoriasis, Seborrhea & Ichthyosis Preparations D02AB - Zinc products ; Used as skin emollients
and protectants.
Infant Nutritional Products V06DB -
Fat/carbohydrates/proteins/minerals/vitamins,
combinations ; Used as general nutrients.
Cough & Cold Preparations / Analgesics (Non-Opioid) & R01BA52 - pseudoephedrine, combinations ;
Antipyretics Belongs to the class of systemic sympathomimetic
preparations used as nasal decongestants.
Cough & Cold Preparations / Analgesics (Non-Opioid) & R01BA52 - pseudoephedrine, combinations ;
Antipyretics Belongs to the class of systemic sympathomimetic
preparations used as nasal decongestants.
Cough & Cold Preparations / Analgesics (Non-Opioid) & N02BE51 - paracetamol, combinations excl.
Antipyretics psycholeptics ; Belongs to the class of anilide
preparations. Used to relieve pain and fever.
Other Drugs Acting on Musculo-Skeletal System M01AX21 - diacerein ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Agents Affecting Bone Metabolism M05BA02 - clodronic acid ; Belongs to the class of
bisphosphonates. Used in the treatment of bone
diseases.
Agents Affecting Bone Metabolism M05BX - Other drugs affecting bone structure and
mineralization ; Used in the treatment of bone
diseases.
Supportive Care Therapy / Agents Affecting Bone M05BA06 - ibandronic acid ; Belongs to the class G
Metabolism of bisphosphonates. Used in the treatment of
bone diseases.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of
other non-steroidal antiinflammatory and
antirheumatic products.
Other Dermatologicals / Muscle Relaxants / Other Eye M03AX01 - botulinum toxin ; Belongs to the class G
Preparations of other agents used as peripherally-acting
muscle relaxants.
Trophic Hormones & Related Synthetic Drugs G03GA04 - urofollitropin ; Belongs to the class of
gonadotropins. Used as ovulation stimulants.
Peripheral Vasodilators & Cerebral Activators N07CA02 - cinnarizine ; Belongs to the class of G
antivertigo preparations.
Nasal Decongestants & Other Nasal Preparations R01AX10 - various ; Belongs to the class of other W
nasal preparations for topical use.
Peripheral Vasodilators & Cerebral Activators N06DX02 - Ginkgo folium ; Belongs to the class of
other anti-dementia drugs.
GIT Regulators, Antiflatulents & Anti-Inflammatories A07EA06 - budesonide ; Belongs to the class of G
corticosteroids acting locally. Used in the
treatment of intestinal inflammation.
Preparations for Oral Ulceration & Inflammation D07AB09 - triamcinolone ; Belongs to the class of G
moderately potent (group II) corticosteroids. Used
in the treatment of dermatological diseases.
Vitamins & Minerals (Pre & Post Natal) / Antianemics B03AE02 - iron, multivitamins and folic acid ;
Belongs to the class of iron in other combinations.
Used in the treatment of anemia.
Topical Anti-Infectives with Corticosteroids D01AC - Imidazole and triazole derivatives ; Used
in the topical treatment of fungal infection.
Antacids, Antireflux Agents & Antiulcerants A02BC03 - lansoprazole ; Belongs to the class of G
proton pump inhibitors. Used in the treatment of
peptic ulcer and gastro-oesophageal reflux
disease (GERD).
Drugs for Erectile Dysfunction & Ejaculatory Disorders G04BE03 - sildenafil ; Belongs to the class of G
drugs used in erectile dysfunction.
Antacids, Antireflux Agents & Antiulcerants A02BC02 - pantoprazole ; Belongs to the class of
proton pump inhibitors. Used in the treatment of
peptic ulcer and gastro-oesophageal reflux
disease (GERD).
Cholagogues, Cholelitholytics & Hepatic Protectors A05B - LIVER THERAPY, LIPOTROPICS ; Used in B
liver therapy.
Penicillins J01CR02 - amoxicillin and enzyme inhibitor ; G
Belongs to the class of penicillin combinations,
including beta-lactamase inhibitors. Used in the
systemic treatment of infections.
ACE Inhibitors/Direct Renin Inhibitors C09AA01 - captopril ; Belongs to the class of ACE
inhibitors. Used in the treatment of
cardiovascular disease.
ACE Inhibitors/Direct Renin Inhibitors C09AA01 - captopril ; Belongs to the class of ACE
inhibitors. Used in the treatment of
cardiovascular disease.
ACE Inhibitors/Direct Renin Inhibitors C09AA01 - captopril ; Belongs to the class of ACE
inhibitors. Used in the treatment of
cardiovascular disease.
ACE Inhibitors/Direct Renin Inhibitors C09AA01 - captopril ; Belongs to the class of ACE
inhibitors. Used in the treatment of
cardiovascular disease.
Drugs for Neuropathic Pain / Anticonvulsants N03AF01 - carbamazepine ; Belongs to the class
of carboxamide derivatives antiepileptic.
Other Antihypertensives / Drugs for Bladder & Prostate C02CA04 - doxazosin ; Belongs to the class of G
Disorders alpha-adrenoreceptor antagonists, peripherally-
acting antiadrenergic agents. Used in the
treatment of hypertension.
Emollients, Cleansers & Skin Protectives D02AE01 - carbamide ; Belongs to the class of
carbamide preparations used as skin emollients
and protectants.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of B
other non-steroidal antiinflammatory and
antirheumatic products.
Other Drugs Acting on Musculo-Skeletal System M01AX25 - chondroitin sulfate ; Belongs to the
class of other non-steroidal antiinflammatory and
antirheumatic products.
Other Drugs Acting on Musculo-Skeletal System M01AX05 - glucosamine ; Belongs to the class of B
other non-steroidal antiinflammatory and
antirheumatic products.
Intravenous & Other Sterile Solutions B05AA01 - albumin ; Belongs to the class of blood
substitutes and plasma protein fractions. Used as
blood substitutes.
Emollients, Cleansers & Skin Protectives D02AX - Other emollients and protectives ; Used
as skin emollients and protectants.
Emollients, Cleansers & Skin Protectives D02AX - Other emollients and protectives ; Used
as skin emollients and protectants.
Other Dermatologicals / Emollients, Cleansers & Skin D02AX - Other emollients and protectives ; Used
Protectives as skin emollients and protectants.
3/28/2017 12:21
2/25/2017 17:52
2/25/2017 17:58
2/25/2017 18:19
Abilify Oral Solution 1 mg/mL 2/25/2017 18:23
150 mL x 1's (Rp512,250/botol)
2/25/2017 18:45
X 2/25/2017 18:47
2/25/2017 18:49
2/25/2017 18:50
X 2/25/2017 19:58
2/25/2017 20:03
2/25/2017 20:06
2/25/2017 20:45
Aclam dry syr button/view.png 2/25/2017 20:48
60 mL x 1's (Rp41,000/botol)
Aclam Forte dry syr button/view.png
60 mL x 1's (Rp60,000/botol)
Aclam FC caplet button/view.png
15's (Rp133,500/pak)
2/25/2017 22:36
2/26/2017 6:48
2/26/2017 6:50
2/26/2017 6:57
2/26/2017 7:02
2/26/2017 7:04
5 mL x 1's (Rp1,400,000/boks)
2/26/2017 7:22
2/26/2017 7:24
2/26/2017 7:26
X 2/26/2017 7:38
2/26/2017 7:44
2/26/2017 7:45
2/26/2017 8:45
X 2/26/2017 9:05
2/26/2017 9:07
X 2/26/2017 9:09
2/26/2017 9:11
2/26/2017 9:13
2/26/2017 9:14
2/26/2017 9:16
2/26/2017 11:25
2/26/2017 11:27
2/26/2017 11:29
2/26/2017 11:34
X 2/26/2017 11:36
2/26/2017 11:38
2/26/2017 13:56
60 mL x 1's (Rp64,170/boks)
X 2/26/2017 14:08
2/26/2017 14:11
2/26/2017 14:13
2/26/2017 14:17
2/26/2017 14:19
Afrin nasal drops 0.25 mg/mL 2/26/2017 14:22
10 mL x 1's
Afrin nasal spray 0.5 mg/mL
button/view.png
15 mL x 1's
2/26/2017 14:24
2/26/2017 14:26
2/26/2017 14:28
2/26/2017 14:33
2/26/2017 14:35
2/26/2017 14:37
2/26/2017 14:39
2/26/2017 14:47
2/26/2017 14:49
X 2/26/2017 14:51
2/26/2017 14:53
X 2/26/2017 14:55
X 2/26/2017 14:57
2/26/2017 14:59
2/26/2017 15:18
X 2/26/2017 15:26
2/26/2017 15:39
X 2/26/2017 15:46
2/26/2017 16:01
2/26/2017 16:38
2/26/2017 16:40
2/26/2017 16:45
2/26/2017 16:47
2/26/2017 18:13
2/26/2017 18:15
X 2/26/2017 18:18
X 2/26/2017 18:19
2/26/2017 18:28
2/26/2017 18:33
X 2/26/2017 18:35
2/26/2017 18:54
2/26/2017 18:57
2/26/2017 18:59
Aleros syr 0.5 mg/mL 2/26/2017 19:02
60 mL x 1's (Rp45,000/botol)
2/26/2017 19:11
2/26/2017 19:13
2/26/2017 19:14
2/26/2017 19:16
2/26/2017 19:18
X 2/26/2017 19:21
2/26/2017 19:22
2/26/2017 19:29
2/26/2017 19:31
2/26/2017 19:34
X 2/26/2017 19:49
2/26/2017 19:51
2/26/2017 19:53
X 2/26/2017 19:55
2/26/2017 19:56
2/26/2017 20:01
2/26/2017 20:03
2/26/2017 20:05
2/26/2017 20:07
2/26/2017 20:08
2/26/2017 20:10
2/26/2017 20:14
2/26/2017 20:17
2/26/2017 20:21
2/26/2017 20:23
2/26/2017 20:28
2/26/2017 20:33
2/26/2017 20:35
X 2/26/2017 20:37
2/26/2017 20:42
2/26/2017 20:44
2/26/2017 20:46
2/26/2017 20:48
2/26/2017 20:51
2/26/2017 20:55
X 2/26/2017 21:06
2/26/2017 21:14
2/26/2017 21:23
2/26/2017 21:35
X 2/26/2017 21:40
X 2/26/2017 21:46
2/26/2017 21:48
2/26/2017 21:57
X 2/27/2017 5:16
2/27/2017 5:17
2/27/2017 5:19
X 2/27/2017 5:21
X 2/27/2017 5:28
2/27/2017 5:30
2/27/2017 5:38
2/27/2017 5:40
2/27/2017 5:42
2/27/2017 5:47
2/27/2017 5:49
2/27/2017 5:51
2/27/2017 5:53
Aminosteril Infant infusion 6 % 2/27/2017 5:55
100 mL x 10 × 1's (Rp66,000/botol)
2/27/2017 5:57
2/27/2017 6:12
2/27/2017 6:14
2/27/2017 6:16
2/27/2017 6:18
2/27/2017 6:19
2/27/2017 6:25
2/27/2017 6:30
2/27/2017 6:32
2/27/2017 6:34
X 2/27/2017 6:36
2/27/2017 6:38
X 2/27/2017 6:39
2/27/2017 6:41
2/27/2017 6:43
Amoxsan cap 250 mg 2/27/2017 6:47
10 × 10's (Rp147,500/boks)
Amoxsan cap 500 mg
10 × 10's (Rp302,000/boks)
Amoxsan dispersible tab 250 mg
10 × 10's (Rp130,000/boks)
Amoxsan dry syr 125 mg/5 mL
60 mL x 1's (Rp20,710/botol)
Amoxsan Forte dry syr 250 mg/5 mL
60 mL x 1's (Rp29,535/botol)
Amoxsan infusion 1 g
10 × 1's (Rp207,100/boks)
Amoxsan Paed oral drops 100 mg/mL
15 mL x 1's (Rp20,710/botol)
2/27/2017 6:49
2/27/2017 6:51
2/27/2017 6:53
2/27/2017 7:02
2/27/2017 7:04
2/27/2017 7:06
2/27/2017 7:08
2/27/2017 7:09
2/27/2017 7:11
2/27/2017 7:13
2/27/2017 7:15
2/27/2017 7:17
Analsik FC caplet 2/27/2017 7:20
10 × 10's (Rp110,000/boks)
2/27/2017 7:22
X 2/27/2017 7:27
X 2/27/2017 7:29
X 2/27/2017 7:30
2/27/2017 7:45
2/27/2017 7:47
X 2/27/2017 10:50
2/28/2017 5:14
X 2/28/2017 19:42
2/28/2017 19:46
2/28/2017 19:48
2/28/2017 19:49
2/28/2017 19:54
2/28/2017 20:02
2/28/2017 20:09
X 2/28/2017 20:11
X 2/28/2017 21:15
2/28/2017 21:19
2/28/2017 21:21
2/28/2017 21:23
2/28/2017 21:25
2/28/2017 21:31
2/28/2017 21:33
X 2/28/2017 21:36
X 2/28/2017 21:38
2/28/2017 21:40
2/28/2017 21:42
2/28/2017 21:43
2/28/2017 21:45
2/28/2017 21:47
2/28/2017 21:49
2/28/2017 21:50
2/28/2017 21:52
2/28/2017 21:54
2/28/2017 21:56
2/28/2017 21:58
2/28/2017 22:03
X 2/28/2017 22:05
2/28/2017 22:06
2/28/2017 22:08
2/28/2017 22:10
X 2/28/2017 22:12
2/28/2017 22:14
2/28/2017 22:16
2/28/2017 22:17
2/28/2017 22:19
2/28/2017 22:21
2/28/2017 22:23
X 2/28/2017 22:25
2/28/2017 22:27
2/28/2017 22:31
2/28/2017 22:41
2/28/2017 22:43
X 2/28/2017 22:45
X 2/28/2017 22:47
2/28/2017 22:55
2/28/2017 22:56
2/28/2017 22:58
2/28/2017 23:03
Apialys oral drops button/view.png 2/28/2017 23:05
10 mL x 1's (Rp20,000/botol)
Apialys syr button/view.png
100 mL x 1's (Rp18,500/botol)
2/28/2017 23:11
2/28/2017 23:26
2/28/2017 23:28
2/28/2017 23:29
2/28/2017 23:49
2/28/2017 23:54
2/28/2017 23:55
X 3/1/2017 0:07
3/1/2017 0:09
3/1/2017 0:11
3/1/2017 0:19
3/1/2017 0:21
3/1/2017 0:23
X 3/1/2017 0:25
Arespin soln for infusion 4 mg/4 mL 3/1/2017 0:28
(amp) 1's (Rp350,000/boks)
3/1/2017 6:22
X 3/1/2017 6:32
X 3/1/2017 6:37
3/1/2017 6:39
3/1/2017 6:41
X 3/1/2017 6:43
X 3/1/2017 6:45
3/1/2017 6:46
3/1/2017 7:02
3/1/2017 7:04
3/1/2017 7:06
3/1/2017 7:08
3/1/2017 7:10
3/1/2017 7:11
X 3/1/2017 7:13
3/1/2017 7:15
3/1/2017 7:17
3/1/2017 7:19
3/1/2017 7:20
3/1/2017 7:22
3/1/2017 7:24
3/1/2017 7:28
3/1/2017 7:30
3/1/2017 7:32
3/1/2017 7:36
3/1/2017 7:41
3/1/2017 7:46
3/1/2017 7:48
3/1/2017 7:50
3/1/2017 7:52
3/1/2017 7:57
3/1/2017 7:58
3/1/2017 8:06
X 3/1/2017 8:08
3/1/2017 8:10
3/1/2017 8:12
3/1/2017 8:21
X 3/1/2017 8:23
3/1/2017 8:28
3/1/2017 8:30
3/1/2017 8:37
X 3/1/2017 8:46
3/1/2017 8:48
X 3/1/2017 8:56
3/1/2017 9:04
3/1/2017 9:06
3/1/2017 9:08
3/1/2017 9:10
3/1/2017 9:12
X 3/1/2017 9:21
X 3/1/2017 9:22
X 3/1/2017 9:28
3/1/2017 9:30
AV F AZA Acne Foundation cream 20% 3/1/2017 9:33
AV F AZA Acne Foundation cream 20/
30 g x 1's (Rp58,000/kontainer)
X 3/1/2017 9:38
X 3/1/2017 9:40
X 3/1/2017 9:42
3/1/2017 9:44
3/1/2017 9:46
3/1/2017 9:50
X 3/1/2017 9:55
Avocel FC tab 5 mg 3/1/2017 9:58
3 × 10's
X 3/1/2017 10:12
3/1/2017 10:19
3/1/2017 10:20
3/1/2017 10:22
3/1/2017 10:32
3/1/2017 10:37
3/1/2017 10:39
3/1/2017 10:47
3/1/2017 11:03
3/1/2017 11:05
3/1/2017 11:07
3/1/2017 11:13
3/1/2017 11:15
X 3/1/2017 11:20
Bantif Child syr 3/1/2017 11:25
60 mL x 1's (Rp9,450/boks)
3/1/2017 11:38
3/1/2017 11:43
3/1/2017 11:46
3/1/2017 11:50
3/1/2017 11:53
3/1/2017 11:54
Bd-GARD cap 3/1/2017 11:57
30's (Rp230,000/pak)
X 3/1/2017 11:59
3/1/2017 12:01
3/1/2017 12:03
3/1/2017 12:05
3/1/2017 12:06
3/1/2017 12:08
X 3/1/2017 12:10
X 3/1/2017 12:29
X 3/1/2017 12:31
X 3/1/2017 12:35
3/1/2017 12:37
3/1/2017 12:39
X 3/1/2017 12:46
3/1/2017 12:48
3/1/2017 12:50
3/1/2017 12:51
3/1/2017 12:53
3/1/2017 12:55
3/1/2017 12:57
X 3/1/2017 12:59
3/3/2017 18:42
3/1/2017 13:04
X 3/1/2017 13:06
X 3/1/2017 13:08
X 3/1/2017 13:10
X 3/1/2017 13:12
X 3/1/2017 13:14
3/1/2017 13:16
3/1/2017 13:18
X 3/1/2017 13:19
X 3/1/2017 13:21
X 3/1/2017 13:23
3/1/2017 13:25
X 3/1/2017 13:27
X 3/1/2017 13:29
X 3/1/2017 13:31
3/1/2017 13:32
3/1/2017 13:34
3/1/2017 13:36
3/1/2017 13:40
X 3/1/2017 13:41
3/1/2017 13:43
3/1/2017 13:45
3/1/2017 13:47
3/1/2017 13:49
3/1/2017 13:53
3/1/2017 13:55
X 3/1/2017 13:57
X 3/1/2017 13:59
3/1/2017 14:03
3/1/2017 14:05
Berea syr 15 mg/5 mL Berea syr 15 3/1/2017 14:08
mg/5 mL
60 mL x 1's (Rp24,871/botol)
Berea tab 30 mg Berea tab 30 mg
10 × 10's (Rp117,040/boks)
3/1/2017 14:12
3/1/2017 14:14
3/1/2017 14:16
3/1/2017 14:18
3/1/2017 14:20
3/1/2017 14:21
X 3/1/2017 14:23
3/1/2017 14:25
3/1/2017 14:39
3/1/2017 14:41
3/1/2017 14:43
3/1/2017 14:48
3/1/2017 14:50
X 3/1/2017 14:55
3/1/2017 14:57
3/1/2017 14:58
3/1/2017 15:00
3/1/2017 15:02
3/1/2017 15:04
3/1/2017 15:06
3/1/2017 15:07
3/1/2017 15:09
3/1/2017 15:11
3/1/2017 15:19
3/1/2017 15:24
3/1/2017 15:33
3/1/2017 15:35
X 3/1/2017 15:40
3/1/2017 15:42
3/1/2017 15:44
3/1/2017 15:49
3/1/2017 15:54
3/1/2017 15:58
Bevizil FC caplet 3/1/2017 16:01
25 × 4's (Rp135,000/boks)
3/1/2017 16:03
X 3/1/2017 16:05
3/1/2017 16:07
3/1/2017 16:21
3/1/2017 16:29
Binapro softcap 3/1/2017 16:31
6 × 10's (Rp420,000/boks)
3/1/2017 16:36
X 3/1/2017 16:38
3/1/2017 16:40
3/1/2017 16:50
X 3/1/2017 16:54
X 3/1/2017 17:08
X 3/1/2017 17:10
3/1/2017 17:12
Bioferron chewable tab 3/1/2017 17:15
10 × 3's (Rp30,000/boks)
3/1/2017 17:19
X 3/1/2017 17:24
X 3/1/2017 17:26
3/1/2017 17:28
3/1/2017 17:36
3/1/2017 17:40
3/1/2017 17:41
3/1/2017 17:43
3/1/2017 17:45
3/1/2017 17:47
3/1/2017 17:49
3/1/2017 17:51
3/1/2017 17:53
3/1/2017 18:00
3/1/2017 18:02
3/1/2017 18:04
3/1/2017 18:06
3/1/2017 18:08
3/1/2017 18:10
3/1/2017 18:19
3/1/2017 18:27
3/1/2017 18:40
3/1/2017 18:41
3/1/2017 18:46
Biothicol cap 250 mg 3/1/2017 18:49
10 × 10's (Rp165,000/boks)
Biothicol cap 500 mg
10 × 10's (Rp330,000/boks)
Biothicol dry syr 125 mg/5 mL
60 mL x 1's (Rp18,900/boks)
Biothicol Forte dry syr 250 mg/5 mL
60 mL x 1's (Rp52,250/boks)
3/1/2017 18:57
X 3/1/2017 18:59
3/1/2017 19:01
3/1/2017 19:06
3/1/2017 19:07
3/1/2017 19:09
3/1/2017 19:11
3/1/2017 19:13
3/1/2017 19:15
3/1/2017 19:17
3/1/2017 19:19
3/1/2017 19:21
3/1/2017 19:23
3/1/2017 19:25
3/1/2017 19:38
3/1/2017 19:43
3/1/2017 20:59
Blopress tab 16 mg Blopress tab 16 mg 3/1/2017 21:03
14's (Rp199,760/pak)
28's
Blopress tab 8 mg Blopress tab 8 mg
14's (Rp151,780/pak)
28's
3/1/2017 21:12
3/1/2017 21:14
BMT Gold milk powd BMT Gold milk 3/1/2017 21:16
powd
200 g x 1's (Rp42,000/pak)
400 g x 1's (Rp79,900/kaleng)
800 g x 1's (Rp153,500/boks)
X 3/1/2017 21:26
3/1/2017 21:28
3/1/2017 21:30
3/1/2017 21:31
3/1/2017 21:33
X 3/1/2017 21:35
3/1/2017 21:37
3/1/2017 21:40
3/1/2017 21:42
3/1/2017 21:44
3/1/2017 21:45
3/1/2017 22:02
3/1/2017 22:03
3/1/2017 22:05
X 3/1/2017 22:07
3/1/2017 22:13
3/1/2017 22:15
3/1/2017 22:17
3/3/2017 5:17
30 mL x 1's (Rp15,000/kontainer)
Breathy nasal spray 6.5 mg/mL
30 mL x 1's
3/3/2017 5:42
3/3/2017 5:44
3/3/2017 5:46
1 mL x 5 × 1's (Rp101,598/boks)
Bricasma inhalation powd 0.5 mg
Bricasma inhalation powd 0.5 mg
100 dose x 1's (Rp110,000/boks)
Bricasma respules 2.5 mg/mL Bricasma
respules 2.5 mg/mL
2 × 5's (Rp104,386/karton)
Bricasma tab 2.5 mg Bricasma tab 2.5
mg
10 × 10's (Rp237,424/boks)
X 3/3/2017 5:55
Brilinta FC tab 90 mg Brilinta FC tab 90 3/3/2017 5:58
mg
4 × 14's (Rp805,605/boks)
3/3/2017 6:11
3/3/2017 6:16
3/3/2017 6:18
3/3/2017 6:20
3/3/2017 6:21
3/3/2017 6:26
Broncho-Vaxom Adult cap 7 mg 3/3/2017 6:29
10's
30's
Broncho-Vaxom Childn cap 3.5 mg
Broncho-Vaxom Childn cap 3.5 mg
10's
30's
3/3/2017 7:22
3/1/2017 23:39
3/1/2017 23:41
3/1/2017 23:42
3/1/2017 23:44
3/1/2017 23:46
3/1/2017 23:48
3/1/2017 23:56
3/2/2017 5:40
3/2/2017 5:42
3/2/2017 5:43
X 3/2/2017 5:45
3/2/2017 5:47
3/2/2017 5:49
3/2/2017 5:51
X 3/2/2017 5:52
3/2/2017 5:56
3/2/2017 6:04
3/2/2017 6:06
X 3/2/2017 6:14
X 3/2/2017 6:16
3/2/2017 6:31
3/2/2017 6:32
3/2/2017 7:29
3/2/2017 7:31
3/2/2017 7:33
3/2/2017 7:35
3/2/2017 7:39
X 3/2/2017 7:41
3/2/2017 7:43
3/2/2017 7:45
Caldece effervescent tab 3/2/2017 7:48
1 × 10's (Rp25,000/boks)
3/2/2017 7:56
3/2/2017 7:57
3/2/2017 8:02
X 3/2/2017 8:06
3/2/2017 8:11
X 3/2/2017 8:22
3/2/2017 8:24
3/2/2017 8:43
3/2/2017 8:48
3/2/2017 8:49
3/2/2017 8:51
3/2/2017 8:53
3/2/2017 8:55
3/2/2017 8:57
3/2/2017 8:59
Campto infusion 100 mg/5 mL Campto 3/2/2017 9:03
infusion 100 mg/5 mL
1's (Rp2,779,635/vial)
Campto infusion 40 mg/2 mL Campto
infusion 40 mg/2 mL
1's (Rp1,270,910/vial)
3/2/2017 9:05
3/2/2017 9:07
3/2/2017 9:12
3/2/2017 9:14
3/2/2017 9:22
X 3/2/2017 9:38
3/2/2017 9:58
3/2/2017 15:54
3/2/2017 15:58
3/2/2017 15:59
3/2/2017 16:01
3/2/2017 16:03
3/2/2017 16:05
3/2/2017 16:07
3/2/2017 16:09
3/2/2017 16:10
X 3/2/2017 16:16
3/2/2017 16:18
3/2/2017 16:19
3/2/2017 16:29
3/2/2017 16:33
3/2/2017 16:35
3/2/2017 16:40
X 3/2/2017 16:45
X 3/2/2017 16:59
3/2/2017 17:01
3/2/2017 17:02
3/2/2017 17:04
3/2/2017 17:06
3/2/2017 17:11
X 3/2/2017 17:19
3/2/2017 17:32
3/2/2017 17:38
3/3/2017 19:02
3/2/2017 17:45
3/2/2017 17:47
Cataflam D dispertab 50 mg 3/2/2017 17:51
5 × 10's (Rp173,525/boks)
Cataflam sugar-coated tab 25 mg
5 × 10's (Rp93,265/boks)
Cataflam sugar-coated tab 50 mg
5 × 10's (Rp177,995/boks)
X 3/2/2017 17:53
3/2/2017 17:55
3/2/2017 18:03
3/2/2017 18:05
Cavit D3 tab Cavit D3 tab 3/2/2017 18:08
100's (Rp134,200/pak)
3/2/2017 18:10
3/2/2017 18:21
X 3/2/2017 18:33
3/2/2017 18:35
3/2/2017 18:40
3/2/2017 18:42
Cefacef cap 100 mg 3/2/2017 18:45
3 × 10's (Rp502,500/boks)
Cefacef dry syr 100 mg/5 mL
30 mL x 1's (Rp69,580/boks)
3/2/2017 18:47
3/2/2017 18:49
3/2/2017 18:51
3/2/2017 19:02
3/2/2017 19:07
3/2/2017 19:09
3/2/2017 19:11
3/2/2017 19:13
3/2/2017 19:15
3/2/2017 19:17
Cefila cap 100 mg button/view.png 3/2/2017 19:20
30's (Rp330,000/pak)
Cefila cap 200 mg
10's (Rp170,000/pak)
Cefila cap 50 mg button/view.png
30's (Rp165,000/pak)
Cefila dry syr 100 mg/5 mL
30 mL x 1's (Rp58,000/botol)
3/2/2017 19:32
3/2/2017 19:34