Gol. Obat, PIO n AHFS 2004 Indikasi: AHFs 2005, hal 855 n PIO Mek. Kerja a to Z drug fact 2003 Farmakokinetik: ahfs 2004 hal 885 Dosis: ahfs 2004 hal 855, pio Kontraindikasi: BNF 57, 2009, hal 592, mayler hal 654 ES & toksisitas: ES (BNF 57, 2009, hal 592-593) Interaksi Obat: A to Z Drug Facts, 2003
Contoh sediaan yg beredar dipasaran: AHFS 2004, hal 855 3.2. Pra formulasi Formula umum: sediaan : Zat aktif Pengisotonis Pelarut: NaOH (dibuat terpisah) WFI
A. Perhitungan Buat table: Nama zat aktif, delta TF, dan C (%), delta TF.C - Tonisitas Acetazolamide Penurunan titik beku:W: o,52-Tb x C/ 0,576= 0,52-0,13x10%/0,576= 0,900
NaOH pH 9.2; POH=4,8__[OH]=10 -4.8 __[NaOH]= 1/1 x [OH-]___M NaOH=0,0000158___mol NaOH=0,0000158 M x 5 ml=0,0000792 mmol__ massa NaOH= 7,924x10-5 mol x 40 = 0,0032 B. Penimbangan Akan dibuat sediaan injeksi acetalomide dengan kekuatan sediaan 500 mg sebanyak 500 vial
DAFTAR PUSTAKA Ditjen POM Departemen Kesehatan RI. 1995. Farmakope Indonesia. Edisi ke empat. Jakarta: Departemen Kesehatan RI.
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AcetaZOLAMIDE
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This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or standards of non-Merck sources. Medication Safety Issues Sound-alike/look-alike issues: AcetaZOLAMIDE may be confused with acetoHEXAMIDE Diamox Sequels may be confused with Diabinese, Dobutrex, Trimox Pronunciation
Use: Unlabeled/Investigational
Pregnancy Risk Factor
Pregnancy Considerations
Lactation
Contraindications
Warnings/Precautions
Adverse Reactions
Metabolism/Transport Effects
Drug Interactions
Storage
Reconstitution
Compatibility
Mechanism of Action
Pharmacodynamics/Kinetics (a set a ZOLE a mide) U.S. Brand Names Diamox Sequels Generic Available Yes Canadian Brand Names Apo-Acetazolamide Diamox Pharmacologic Category Anticonvulsant, Miscellaneous Carbonic Anhydrase Inhibitor Diuretic, Carbonic Anhydrase Inhibitor Ophthalmic Agent, Antiglaucoma Pharmacologic Category Synonyms AED, Miscellaneous Anti-epileptic Drug, Miscellaneous Miscellaneous Anticonvulsant CAI CAI Diuretic Carbonic Anhydrase Inhibitor, Diuretic Antiglaucoma Agent, Ophthalmic Glaucoma Treatment, Ophthalmic Use: Labeled Indications Treatment of glaucoma (chronic simple open-angle, secondary glaucoma, preoperatively in acute angle-closure); drug-induced edema or edema due to congestive
Mental Health: Effects on heart failure (adjunctive therapy); centrencephalic epilepsies (immediate release dosage form); prevention or amelioration of symptoms associated with acute mountain sickness Use: Unlabeled/Investigational Metabolic alkalosis; respiratory stimulant in COPD; urine alkalinization Pregnancy Risk Factor C Pregnancy Considerations Teratogenic in animal studies, however, there are no adequate and well-controlled studies in pregnant women. Lactation Enters breast milk/not recommended (AAP rates compatible) Contraindications Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation; hepatic disease or insufficiency; decreased sodium and/or potassium levels; adrenocortical insufficiency, cirrhosis; hyperchloremic acidosis, severe renal disease or dysfunction; severe pulmonary obstruction; long-term use in noncongestive angle- closure glaucoma Warnings/Precautions Concerns related to adverse effects: CNS effects: Impairment of mental alertness and/or physical coordination may occur. Psychiatric Treatment
Nursing: Physical Assessment/Monitoring
Dosage Forms
Pricing: U.S. (www.drugstore.com)
Extemporaneously Prepared
References
International Brand Names
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Sulfa allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonylurea allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe. Discontinue if signs of hypersensitivity are noted. Disease-related concerns: Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control. Hepatic impairment: Use with caution in patients with hepatic dysfunction; in cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy. Respiratory acidosis: Use with caution in patients with respiratory acidosis. Special populations: Elderly: Use with caution in the elderly; may be more sensitive to side effects. Other warnings/precautions: I.M. administration: Painful because of the alkaline pH of the drug; use by this route is not recommended. Adverse Reactions Frequency not defined. Cardiovascular: Flushing Central nervous system: Ataxia, confusion, convulsions, depression, dizziness, drowsiness, excitement, fatigue, fever, headache, malaise Dermatologic: Allergic skin reactions, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria Endocrine & metabolic: Electrolyte imbalance, growth retardation (children), hyperglycemia, hypoglycemia, hypokalemia, hyponatremia, metabolic acidosis Gastrointestinal: Appetite decreased, diarrhea, melena, nausea, taste alteration, vomiting Genitourinary: Crystalluria, glycosuria, hematuria, polyuria, renal failure Hematologic: Agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura Hepatic: Cholestatic jaundice, fulminant hepatic necrosis, hepatic insufficiency, liver function tests abnormal Local: Pain at injection site Neuromuscular & skeletal: Flaccid paralysis, paresthesia Ocular: Myopia Otic: Hearing disturbance, tinnitus Miscellaneous: Anaphylaxis Metabolism/Transport Effects Inhibits CYP3A4 (weak) Drug Interactions Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy Alpha-/Beta-Agonists: Carbonic Anhydrase Inhibitors may decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Dipivefrin. Risk C: Monitor therapy Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Risk C: Monitor therapy Anticonvulsants (Barbiturate): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Barbiturate). Specifically, osteomalacia and rickets. Risk C: Monitor therapy Anticonvulsants (Hydantoin): Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Anticonvulsants (Hydantoin). Specifically, osteomalacia and rickets.Risk C: Monitor therapy Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy Brinzolamide: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Brinzolamide. Risk X: Avoid combination CarBAMazepine: Carbonic Anhydrase Inhibitors may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants.Exceptions: Olopatadine, Ophthalmic. Risk C: Monitor therapy Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Flecainide: Carbonic Anhydrase Inhibitors may decrease the excretion of Flecainide. Risk C: Monitor therapy Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives.Risk C: Monitor therapy Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents.Risk C: Monitor therapy Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy Ketorolac, Systemic: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification Memantine: Carbonic Anhydrase Inhibitors may decrease the excretion of Memantine.Risk C: Monitor therapy Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Risk D: Consider therapy modification Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Primidone: Carbonic Anhydrase Inhibitors may enhance the adverse/toxic effect of Primidone. Specifically, osteomalacia and rickets. Carbonic Anhydrase Inhibitors may decrease the serum concentration of Primidone. Risk C: Monitor therapy Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy QuiNIDine: Carbonic Anhydrase Inhibitors may decrease the excretion of QuiNIDine. Risk C: Monitor therapy RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Risk D: Consider therapy modification Trientine: Carbonic Anhydrase Inhibitor Diuretics may decrease the serum concentration of Trientine. Risk C: Monitor therapy Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy Storage Capsules, tablets: Store at controlled room temperature. Injection: Store vial for injection (prior to reconstitution) at controlled room temperature. Reconstituted solution may be refrigerated (2C to 8C) for 1 week, however, use within 12 hours is recommended. Stability of IVPB solution is 5 days at room temperature (25C) and 44 days at refrigeration (5C). Reconstitution Injection: Reconstitute with at least 5 mL sterile water to provide a solution containing not more than 100 mg/mL. Further dilute in D 5 W or NS for I.V. infusion. Compatibility Stable in dextran 6% in D 5 W, dextran 6% in NS, D 5 LR, D 5 NS, D 5 1/2NS, D 5 1/4NS, D 5 W, D 10 W, LR, NS, 1/2NS. Y-site administration: Variable (consult detailed reference): Diltiazem, TPN. Compatibility when admixed: Compatible: Cimetidine, ranitidine. Incompatible:Multivitamins. Mechanism of Action Reversible inhibition of the enzyme carbonic anhydrase resulting in reduction of hydrogen ion secretion at renal tubule and an increased renal excretion of sodium, potassium, bicarbonate, and water to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons Pharmacodynamics/Kinetics Onset of action: Capsule, extended release: 2 hours; I.V.: 2 minutes Peak effect: Capsule, extended release: 8-12 hours; I.V.: 15 minutes; Tablet: 2-4 hours Duration: Inhibition of aqueous humor secretion: Capsule, extended release: 18-24 hours; I.V.: 4-5 hours; Tablet: 8-12 hours Distribution: Erythrocytes, kidneys; blood-brain barrier and placenta; distributes into milk (~30% of plasma concentrations) Excretion: Urine (70% to 100% as unchanged drug) Dosage Note: I.M. administration is not recommended because of pain secondary to the alkaline pH Children: Glaucoma: Oral: 8-30 mg/kg/day or 300-900 mg/m 2 /day divided every 8 hours I.V.: 20-40 mg/kg/24 hours divided every 6 hours, not to exceed 1 g/day Edema: Oral, I.V.: 5 mg/kg or 150 mg/m 2 once every day Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses, not to exceed 1 g/day; extended release capsule is not recommended for treatment of epilepsy Adults: Glaucoma: Chronic simple (open-angle): Oral: 250 mg 1-4 times/day or 500 mg extended release capsule twice daily Secondary, acute (closed-angle): I.V.: 250-500 mg, may repeat in 2-4 hours to a maximum of 1 g/day Edema: Oral, I.V.: 250-375 mg once daily Epilepsy: Oral: 8-30 mg/kg/day in 1-4 divided doses; not to exceed 1 g/day; extended release capsule is not recommended for treatment of epilepsy Metabolic alkalosis (unlabeled use): I.V. 250 mg every 6 hours for 4 doses or 500 mg single dose; reassess need based upon acid-base status Mountain sickness: Oral: 250 mg every 8-12 hours (or 500 mg extended release capsules every 12-24 hours) Therapy should begin 24-48 hours before and continue during ascent and for at least 48 hours after arrival at the high altitude Note: In situations of rapid ascent (such as rescue or military operations), 1000 mg/day is recommended. Urine alkalinization (unlabeled use): Oral: 5 mg/kg/dose repeated 2-3 times over 24 hours Respiratory stimulant in COPD (unlabeled use): Oral, I.V.: 250 mg twice daily Elderly: Oral: Initial: 250 mg twice daily; use lowest effective dose Dosing adjustment in renal impairment: Cl cr 10-50 mL/minute: Administer every 12 hours Cl cr <10 mL/minute: Avoid use (ineffective) Hemodialysis: Moderately dialyzable (20% to 50%) Peritoneal dialysis: Supplemental dose is not necessary Administration: Oral May be administered with food. May cause an alteration in taste, especially carbonated beverages. Short-acting tablets may be crushed and suspended in cherry or chocolate syrup to disguise the bitter taste of the drug; do not use fruit juices. Alternatively, submerge tablet in 10 mL of hot water and add 10 mL honey or syrup. Administration: I.M. I.M. administration is painful because of the alkaline pH of the drug; use by this route is not recommended. Administration: I.V. I.V.: No specific guidance given by manufacturer, but I.V. push at a rate of up to 500 mg over 3 minutes has been reported in a clinical trial (Mazur, 1999); a study to assess cerebrovascular reserve has used rapid I.V. push of up to 1 g over ?1 minute (Piepgras, 1990) Administration: I.V. Detail pH: 9.2 Monitoring Parameters Intraocular pressure, potassium, serum bicarbonate; serum electrolytes, periodic CBC with differential; monitor growth in pediatric patients Test Interactions May cause false-positive results for urinary protein with Albustix, Labstix, Albutest, Bumintest; interferes with HPLC theophylline assay and serum uric acid levels Dietary Considerations May be taken with food to decrease GI upset. May have additive effects with other folic acid antagonists. Sodium content of 500 mg injection: 47.2 mg (2.05 mEq). Patient Education Take as directed; do not chew or crush long-acting capsule (contents may be sprinkled on soft food). May be administered with food to decrease GI upset. You will need periodic ophthalmic examinations while taking this medication. You may experience drowsiness, dizziness, or weakness (use caution when driving or engaging in tasks that require alertness until response to drug is known); or nausea, loss of appetite, or altered taste (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Monitor serum glucose closely (may cause altered blood glucose in some patients with diabetes, or unusual response to some forms of glucose testing). You may experience increased sensitivity to sunlight (use sunblock, protective clothing, and avoid exposure to direct sunlight). Report unusual and persistent tiredness; numbness, burning, or tingling of extremities or around mouth, lips, or anus; muscle weakness; black stool; or excessive depression. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding. Geriatric Considerations Malaise and complaints of tiredness and myalgia are signs of excessive dosing and acidosis in older adults. Orthostatic hypotension may occur; assess blood pressure. Note renal impairment recommendations; many elderly have Cl cr <50 mL/minute. Dental Health: Effects on Dental Treatment Key adverse event(s) related to dental treatment: Metallic taste (resolves upon discontinuation) Dental Health: Vasoconstrictor/Local Anesthetic Precautions No information available to require special precautions Mental Health: Effects on Mental Status Drowsiness is common, may produce depression less commonly Mental Health: Effects on Psychiatric Treatment Can rarely cause bone marrow suppression, therefore, use cautiously with clozapine and carbamazepine; may increase the excretion of lithium Nursing: Physical Assessment/Monitoring Assess allergy history prior to beginning therapy. Assess effectiveness and interactions of other medications patient may be taking. Monitor for signs of excessive dosing and acidosis (especially in elderly). Measure intraocular pressure at the beginning of therapy and periodically while on this medication. Assess results of laboratory tests, therapeutic effectiveness, and adverse response. Monitor growth in pediatric patients. Monitor blood glucose levels closely if patients have diabetes. Assess knowledge/teach patient appropriate use, possible side effects/appropriate interventions, and adverse symptoms to report. Dosage Forms Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Capsule, extended release: 500 mg Diamox Sequels: 500 mg Injection, powder for reconstitution: 500 mg Tablet: 125 mg, 250 mg Pricing: U.S. (www.drugstore.com) Capsule, 12-hour (AcetaZOLAMIDE) 500 mg (100): $299.97 Capsule, 12-hour (Diamox Sequels) 500 mg (60): $314.98 Tablets (AcetaZOLAMIDE) 125 mg (90): $29.99 250 mg (60): $29.99 Extemporaneously Prepared Tablets may be crushed and suspended in cherry, chocolate, raspberry, or other highly- flavored carbohydrate syrup in concentrations of 25-100 mg/mL; simple suspensions are stable for 7 days. For solutions with longer stability, see references for Parastampuria and Alexander. Alexander KS, Haribhakti RP, and Parker GA, Stability of Acetazolamide in Suspension Compounded From Tablets, Am J Hosp Pharm, 1991, 48(6):1241-4. McEvoy G, ed, AHFS Drug Information 96, Bethesda, MD: American Society of Health System Pharmacists, 1996. Parastampuria J and Gupta VD, Development of Oral Liquid Dosage Forms of Acetazolamide, J Pharm Sci, 1990, 79:385-6. References American Academy of Pediatrics Committee on Drugs: The Transfer of Drugs and Other Chemicals Into Human Milk, Pediatrics, 1994, 93(1):137-150. Chapron DJ, Gomolin IH, and Sweeney KR, Acetazolamide Blood Concentrations Are Excessive in the Elderly: Propensity for Acidosis and Relationship to Renal Function, J Clin Pharmacol, 1989, 29(4):348-53. Chapron DJ, Sweeney KR, Feig PU, et al, Influence of Advanced Age on the Disposition of Acetazolamide, Br J Clin Pharmacol, 1985, 19:363-71. Corbett JT, Acetazolamide and Purpura, Br Med J, 1985, 1:1122-3. Heller I, Halevy J, Cohen S, et al, Significant Metabolic Acidosis Induced by Acetazolamide, Arch Intern Med, 1985, 145(10):1815-7. Marik PE, Kussman BD, Lipman J, et al, "Acetazolamide in the Treatment of Metabolic Alkalosis in Critically Ill Patients," Heart Lung, 1991, 20(5 Pt 1):455-9. Mazur JE, Devlin JW, Peters MJ, et al, "Single Versus Multiple Doses of Acetazolamide for Metabolic Alkalosis in Critically Ill Medical Patients: A Randomized, Double-Blind Trial," Crit Care Med, 1999, 27(7):1257-61. Parikh JR, Nolan RL, Bannerjee A, et al, Acetazolamide-Associated Nephrocalcinosis in a Transplant Kidney, Transplantation, 1995, 59(12):1742-3. Piepgras A, Schmiedek P, Leinsinger G, et al, A Simple Test to Assess Cerebrovascular Reserve Capacity Using Transcranial Doppler Sonography and Acetazolamide, Stroke, 1990, 21(9):1306-11. Reiss WG and Oles KS, Acetazolamide in the Treatment of Seizures, Ann Pharmacother, 1996, 30(5):514-9. Rousseau P and Fuentevilla-Clifton A, Acetazolamide and Salicylate Interaction in the Elderly: A Case Report, J Am Geriatr Soc, 1993, 41(8):868-9. Schwenk MH, St. Peter WL, Meese MG, et al, Acetazolamide Toxicity and Pharmacokinetics in Patients Receiving Hemodialysis, Pharmacotherapy, 1995, 15(4):522-7. Shinnar S, Gammon K, Bergman EW Jr, et al, Management of Hydrocephalus in Infancy: Use of Acetazolamide and Furosemide to Avoid Cerebrospinal Fluid Shunts, J Pediatr, 1985, 107(1):31-7. Vaziri ND, Saiki J, Barton CH, et al, Hemodialyzability of Acetazolamide, South Med J, 1980, 73(4):422-3. Wandstrat TL and Phillips J, Pseudotumor Cerebri Responsive to Acetazolamide, Ann Pharmacother, 1995, 29(3):318. Weiss IS, Hirsutism After Chronic Administration of Acetazolamide, Am J Ophthalmol, 1974, 78(2):327-8. International Brand Names Acetadiazol (MX) Acetak (PE) Albox (JP) Apo-Acetazolamide (MY) Azol (TW) Carbinib (PT) Cetamid (PH) Diamox (AE, AR, AT, AU, BD, BE, BG, BH, BR, CH, CL, CO, CY, CZ, DE, DK, EG, ES, FI, FR, GB, GR, HK, HN, HR, ID, IE, IL, IN, IQ, IR, IT, JO, JP, KP, KW, LB, LU, LY, MY, NL, NO, OM, PH, PK, PT, QA, RU, SA, SE, SG, SY, TH, TR, TW, VE, YE, ZA) Diamox Sustets (CO) Diluran (CZ) Diural (UY) Diuramid (PL) Evamox (PK) Fonurit (HU) Glaupax (CH, DE, HR, JP, TH) Huma-Zolamide (HN, HU) Ledamox (JP) Lediamox (PT) Medene (TH) Optamide (PH) Renamid (HR) Stazol (PY) Synomax (IN) Uramox (IL) Zolmide (PH)
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