Summary of some common drug interactions

seen in Aged Care Homes

Jenny Gowan Consultant pharmacist
NEVDGP February 2011

1 Potassium supplements & potassium-sparing drugs
eg Potassium chloride plus
K sparing diuretics eg spironolactone (Aldactone, Spiractin)
OR ACE inhibitors
AND/OR Angiotensin Receptor Blockers (ARBs)

2 (a) Betablockers & verapamil
eg verapamil (Anpec, Cordilox, Isoptin, Veracaps) plus
* Other calcium channel blocking agents such as amlodipine (Norvasc), diltiazem (Cardizem),
felodipine (Agon, Felodur, Plendil), lercanidipine (Zanidip), nifedipine (Adalat ), nimodipine
(Nimotop) require care with concomitant betablocker administration. Additive myocardial
depressant effects may lead to bradycardia and heart failure

(b)Betablockers plus asthma
Betablockers are contraindicated for people with asthma unless benefits in
CCF>risk

(c)Betablockers plus oral hypoglycaemics
Use with caution and advise that sweating may be disguised and tachycardia
absent during a hypoglycaemic episode 3
rd
line treatment

Warfarin (Coumadin, Marevan- do not change brands)
Care with aspirin, clopidogrel and warfarin close monitoring
ALWAYS CHECK WARFARIN FOR INTERACTIONS
NB Clinically significant increased warfarin activity is noted with the following drugs:
allopurinol, amiodarone, antiinfective agents eg ciprofloxacin, co-trimoxazole, erythromycin,
fluconazole, griseofulvin, ketoconazole, metronidazole, miconazole (Daktarin oral Gel),
paracetamol, rifabutin, rifampicin, aspirin (high dose), gemfibrozil, statins, tamoxifen, terbinafine,
vitamin A, E ; and decreased warfarin activity is noted with: carbamazepine, cholestyramine,
phenytoin.
* Care all NSAIDS (including COX-2 inhibitors)- potentially increased bleeding time; also
paracetamol may affect INR doses >3.5G/week. Check all herbal medicines, vitamins and
minerals

4 (a) Digoxin & Potassium depleting agents
Hypokalaemia (low potassium) causes increased sensitivity of the myocardium to digoxin.
(b) Digoxin and other agents
Digoxin levels increased by verapamil, diltiazem, nifedipine, amiodarone, erythromycin etc.
Particular care with doses above 0.125mg of digoxin

5 Change of pH on absorption and excretion
5(a)Absorption
Antacids (containing sodium bicarbonate), H
2
-antagonists, Proton-pump inhibitors , Ural or
Citravescent
plus drugs which require an acid medium to be effective
eg Calcium carbonate,itraconazole (Sporanox), ketoconazole (Nizoral)
Quinolones eg ciprofloxacin (Ciproxin), norfloxacin (Noroxin)
Doxycycline -levels decreased with calcium, magnesium, sodium, zinc
5(b) Excretion
eg Urinary alkalisers:
Decreased effects- nitrofurantoin, lithium
Increased effects- amphetamines

6 Combinations of drugs with anticholinergic side effects
eg tricyclic antidepressants eg amitriptyline, oxybutynin, antipsychotic agents eg
or
(first generation) antihistamines with anticholinergic side effects.
Anticholinergics will negate the effect of cholinesterase inhibitors eg donepezil

7 Combinations of CNS depressant drugs- excess sedation, falls
eg sedatives, phenothiazines, benzodiazepines, antipsychotics, opioid analgesics,
sedating antihistamines


8 NSAIDS, diuretics, ACEI, ARBs- Triple whammy effect
Decreased diuretic and antihypertensive effect with diuretics, antihypertensive
agents and NSAIDS including COX-2s

9 Antidepressants
9(a) MAOIS & food & drugs eg pseudoephedrine

9(b) Combinations of antidepressants
Check and consider wash out times- watch for serotonergic effects
Wash out periods for antidepressants (AMH 2010)
Cat A
Fluoxetine, phenelzine,
tranylcpromine
Long t1/2 No tapering
>10 14 days before new agent
Cat B
TCAs, SSRIs ( except
fluoxetine), mianserin,
mirtazapine
Intermediate t1/2 24-48 hrs Slow withdrawal
Wait 2-4 days before next agent
Cat C
Duloxetine, moclobemide,
venlafaxine , desvenlafaxine
Short t1/2 ( inc metabolites)
<18 hrs
Venlafaxine- slow withdrawal
Moclobemide- withdrawal
symptoms not reported
Wait 1-2 days before next agent

10 10(a)Antacids plus other drugs orally administered drugs
Separate by 2 hours whenever possible eg particular caution with digoxin, doxcycline
oral hypoglycaemics, phenytoin, theophylline, thyroxine, warfarin
10(b) Calcium, iron, zinc
Separate from other medications eg quinolones, tetracyclines, bisphosphonates , strontium

11 Care with drugs which have narrow therapeutic indices-
Antiarrhythmics- amiodarone, mexilitine, etc
Anticoagulants-, warfarin,
Anticonvulants- carbamazepine, phenytoin, sodium valproate
cyclosporin,
digoxin
gentimicin, tobramycin
lithium- ACEI, ARBs, NSAIDs, Thiazide diuretics (Increased effect of Li)
Potassium, Ural, (Decreased effect of Li )
Methotrexate - avoid with aspirin& NSAIDS if high dose MTX, ciprofloxacin, cyclosporine,
doxycyline, folic acid on same day, PPIs ( high dose MTX) , trimethoprim. Co-trimoxazole,
theophylline

12. NB Care- erythromycin, tramadol have many interactions
eg erythromycin (and clarithromycin) interacts with carbamazepine, cyclosporin,digoxin
theophylline, warfarin and others (azithromycin and roxithromycin less but caution)

eg tramadol interacts with drugs that reduce seizure threshold eg SSRIs, TCAs,
antipsychotics; carbamazepine (decreased activity of tramadol), ondansetron ( decreased analgesic
effect of tramadol) , Warfarin (increased INR). Possible serotonergic syndrome with pethidine.
Protease inhibitors, St Johns Wort, and other antidepressants ( eg SSRIs, SNRIs, TCAs. MAOIs,
moclobemide )

13 Oral contraceptives
Oestrogen metabolism increased by carbamazepine, phenytoin, griseofulvin,
rifampicin. Broad spectrum antibiotics may also be implicated

14 Alcohol
Disulfiram- like reaction possible with ketoconazole, metronidazole, tinidazole
Minimise alcohol intake with drugs having a depressant effect eg BZD, sedating
antihistamines, phenothiazines, metformin, sulfonylureas

15 Grapefruit juice- 200mLs
Increases levels of alprazolam, amlodipine (about 40%), carbamazepine, clomipramine,
cyclosporin, felodipine (over 200%),atrovastatin, simvastatin, (not pravastatin or
rosuvastatin), midazolam, nifedipine (approx 40%), saquinavir, tacrolimus, triamzolam.

16 Combinations of drugs with similar side effects
eg hypotensive additive effects;
Postural hypotension- antihypertensives, oxazepam, bromocriptine, anti-Parkinson
drugs, antipsychotics etc

17 Combinations of drugs with opposing actions
eg cholinesterases with anticholinergics; dopamine agonist with dopamine antagonist
eg levodopa & metoclopramide

18 OTC products, vitamins & minerals, herbal products
Check: Alcohol, antacids, sugars, sodium, potassium, iron, aspirin, NSAIDs,
antihistamines, vitamins, herbal products etc

19 Drugs which may contribute to serotonin syndrome
Class Drugs
Antidepressants

Desvenlafaxine, duloxetine, St Johns wort, MAOIs (including moclobemide),
SSRIs, TCAs, venlafaxine
Opioids Dextromethorphan, fentanyl, pethidine, tramadol
Stimulants Hallucinogenic amphetamines, phentermine, sibutramine
5Ht
1
agonists Sumatriptan, naratriptan, zolmitriptan
Others Illicit drugs (LSD, ecstasy, cocaine), selegiline, linezolid, llithium, methylene
blue


20 Clopidogrel and PPIs?
Possible inhibition of metabolism to active form with inhibitors of CYP2C19 or genetic lack of
CYP2C19*2. Now shown to be a minor concern

21 Drugs which may prolong QT interval
Class Drugs
Antiarrhythmics Amiodarone, disopyramide, sotalol
Antipsychotics Amiulpride, droperidol, haloperidol, pimozide, ziprasidone
Anti-infectives Atazanavir, chloroquine, clarithromycin, erythromycin, fluconazole, mefloquine,
moxifloxacin, pentamidine, quinine, voricoanzole
Others Arsenic trioxide, cocaqine, dolasetronm methadone, tacrolimus, TCAs, vardenafil

22. Drugs and CYP enzymes
Interactions between drugs that are inducers or inhibitors and those that are substrates
of the same enzyme are theoretically possible. Inhibition of metabolism will result in
higher levels of drug whereas enzyme induction results in lower levels of the drug . eg
risperidone CYP 2D6 substrate & fluoxetine (strong CYP 2D6 inhibitor) - results in
increased levels of risperidone.

23. Drug/Disease Interactions
eg verapamil in CCF
betablockers in asthma


If in doubt check
NB: The above is a broad checklist. Please check with latest references eg
AUS-DI, Facts & comparisons, eMIMs, Herbs & natural supplements, eTG


CARE: Older people may be more sensitive to adverse effects



Notes:
Table 1: Vitamin and drug interactions
Vitamin Drug Effect
A (retinol) Anticoagulants
Cholestyramine
Acitretin ( Neotigason)
Etretinate (Tigason)
Isotretinoin (Roaccutane)
Increased effect
Decreased vitamin A absorption
Hypervitaminosis A
Hypervitaminosis A
Possible additive toxic effects
B
1
(thiamine)

B
2
(riboflavine)



B
3
(niacin)

B
6
(pyridoxine)



B
12
(cyanocobalamin)




Folic acid (vitamin B
c)
None known

Oral contraceptives
Phenothiazines
Tricyclics

Isoniazid

Levodopa
Phenytoin
Hydralazine
Isoniazid

Biquanides
(metformin,phenformin)
Methotrexate

Phenytoin


May cause deficiencies of B
2



Increased requirements of B
3

Reduced effect of levodopa

Reduced effect of phenytoin

May require B
6
May require B
6


Decreased B
12


Decreased plasma concentration of
phenytoin
C ( ascorbic acid) Al containing antacids in
pts with kidney failure
Corticosteroids

Iron
Nicotine

Oral contraceptives

Smoking
Warfarin
Increased absorption of Al 8-50 times

Vit C may protect against
corticosteroid-induced osteoporosis
Increased absorption of iron
Large doses of ascorbic acid will
reduce plasma levels of nicotine
Changes in high doses vitamin C may
affect efficiency
Decreased absorption of C from the
gut
Possible reduction in warfarin effect
D (cholecalciferol) Antacids
Calcitriol
Calcitonin, etidronate,
pamidronate
Isoniazid, rifampicin
Phenytoin
Hypermagnesaemia
Vit D toxicity
May antagonise effects

Decreased Vit D levels
Calcium and folate levels reduced
Increased Vitamin D
E (-tocopherol) Anticoagulants
Antihypertensives (some)
Cholestyramine
Iron
Increased anticoagulant response


Decreased response to iron therapy
K (phytomenadione) Anticoagulants

Decreased effect of warfarin
Table 2: Drug interactions with some minerals
Interacting drug Effect
Calcium Calcitriol (Rocaltrol)
Digoxin
Etidronate (Didronel)
Iron salts
Phenytoin
Quinolones eg ciprofloxacin, ,
norfloxacin, ofloxacin
Tetracyclines

Thiazides
Verapamil & other Ca channel
blockers
Hypercalcaemia
Increased risk of hypercalcaemia
Decreased absorption etidronate
Decreased iron absorption
Decreased calcium absorption
Decreased serum levels of
quinolones*
Decreased serum levels of
tetracyclines*
Increased risk of hypercalcaemia
Reduced effect of verapamil
Iron Antacids
Bisphosphonates
Levodopa

Methyldopa

Penicillamine

Quinolones

Tetracyclines

Thyroxine
Reduced absorption of iron*
Reduced absorption of iron *
Absorption of levodopa may be
reduced
Reduced absorption of
methyldopa
Reduced absorption of
penicillamine
Decreased serum levesl of
quinolones
Decreased serum levels of
tetracyclines
Decreased effect of thyroxine
Magnesium Diuretics
Quinolones

Tetracyclines
Increased excretion of magnesium
Decreased serum levels of
quinolones
Decreased serum levels of
tetracyclines
Potassium ACE inhibitors
Angiotensin II receptor
antagonists, for example irbesartan
Corticosteroids
Cyclosporin
Diuretics- loop, thiazides
- potassium sparing diuretics
Laxatives

Liquorice
Increased risk of hyperkalamia
Increased risk of hyperkalamia

Increased excretion of potassium
Increased risk of hyperkalaemia
Increased risk of hypokalaemia
Increased risk of hyperkalaemia
Chronic use reduces absorption of
potassium
Reduced potassium also
aggrevates glucose tolerance

Zinc Quinolones

Oral contraceptives
Penicillamine

Tetracyclines
Decreased serum levels of
quinolones *
May reduce zinc levels
Reduced absorption of
penicillamine
Decreased serum levels of
tetracyclines *

*Separate doses by two hours




Table 3: Some potential herb-drug interactions
Herb Drug Comment- possible effects
Alfalfa Corticosteroids
Cyclosporin
Interfers with
immunosuppression
Angelica, Anise
Arnica flower, Asafoetida
Warfarin Increased risk of bleeding
Astraglalus Corticosteroids
Cyclosporin
Interfers with
immunosuppression
Black cohosh Iron Decreased iron absorption
Borage seed oil,
Bromelain
Warfarin Increased risk of bleeding
Caffeine Clozapine
Lithium
Theophylline
Increased clozapine levels
Decreased lithium levels
Increased theophylline evels
Capsaicin ACEI Increased risk of cough
Celery Warfarin Increased risk of bleeding
Chamomile Iron
Warfarin
Decreased iron absorption
Increased risk of bleeding
Coenzyme Q-10 Warfarin Increased risk of bleeding
Dandelion Loop diuretics
Thiazide diuretics
Interference with diuretic
activity
Danshen, Devils claw Warfarin Increased risk of bleeding
Dong Quai Warfarin Increased risk of bleeding
Echinacea Corticosteroids
Cyclosporin
Interfers with
immunosuppression
Ephedra Caffeine
MAOIs
Theophylline
Increased CNS effects
Hypertensive crisis
Increased theophylline levels
Evening
primrose oil
Anticonvulsants
Phenothiazines
Tricyclic antidepressants
May lower seizure threhold
Possible additive effects
Fenugreek Warfarin Increased risk of bleeding
Feverfew Aspirin
Iron
NSAIDs
Warfarin
Increased risk of bleeding
Decreased iron absorption
Decreased NSAID effectiveness
Increased risk of bleeding
Garlic, Ginger Warfarin Increased risk of bleeding
Ginkgo biloba Antidiabetic agents
Aspirin, NSAIDs
Warfarin
Increased risk of hypoglycaemia
Increased risk of bleeding
Increased risk of bleeding
Ginseng Loop diurectics
MAOIs
Decreased diuresis
Insomnia
Warfarin Decreased anticoagulant effect
Grapefruit juice Amlodipine,
felodipine
Benzodiazepines
Buspirone
Cisapride
Clomipramine
Cyclosporine
Itraconazole
Oestrogens
Statins (except pravastatin)
Saquinivir
Increased levels
Increased
Delayed effects
Increased levels
Increased levels
Increased levels
Increased levels
Decreased levels
Increased levels
Increased levels
Increased effects
Green tea Warfarin Decreased anticoagulant effect
Guar gum Metformin Decreased hypoglycaemic effect
Hawthorn Digoxin
Iron
Increased effect
Decreased iron absorption
Horse chestnut Warfarin Increased risk of bleeding
Horse radish Thyroxine Abnormal thyroid function
Ispaghula Lithium Decrease in lithium levels
Kava Alprazolam Increase lethargy
Kelp Thyroxine Possible hypothyroidism
L-Tryptophan MAOIs
Sibutramine
Serotonergic syndrome
Additive effetcs
Licorice Corticosteroids
Cyclosporine
Digoxin
MAOIs
K sparing diuretics
Warfarin
Interfers with
immunosuppression
Hypokalaemia- risk of digoxin toxicity
Increased activity
Hypokalaemia
Increased risk of bleeding
Meadow sweet Warfarin Increased risk of bleeding
Melatonin Fluvoxamine
Nifedipine
Increased levels of melatonin
Interfers with antihypertensive
effect
Nettle Iron Decreased iron absorption
Onion Warfarin Increased risk of bleeding
Papain
Arley
Passion flower
Warfarin Increased risk of bleeding
Pectin HMG-CoA Reductase Inhibitors Decreased effect of HMG-
CoA Reducatse Inhibitors
Plantain Carbamazepine

Digoxin
Iron
Lithium
Decreased effect of
carbamazepine
Decreased digoxin effect
Decreased iron absorption
decreased lithium absorption
Quassia Warfarin Increased risk of bleeding
Quinine Carbamazepine
Digoxin
Warfarin
Increased carbamazepine levels
Increased digoxin levels
Increased risk of bleeding
Red Clover Aspirin
Oestrogens & OCs
Increased risk of bleeding
Decreased efficacy of oestrogens
St Johns Wort Anticonvulsants, bupropion ,
digoxin, HIV drugs,
immunosuppressives,
Iron, MAOIs, OCs,
pseudoephrine,SSRIs SNRIs
theophylline, TCA, triptans eg
sumatriptan, warfarin
Monitor or avoid
Saw palmetto Oestrogens, Ocs
Iron
Increased adverse effects
Decreased iron absorption
Soy Oestrogens, Ocs
Raloxifene, Tamoxifen
Oestrogen excess?
Interference
Sweet clover Warfarin Increased risk of bleeding
Turmeric Warfarin Increased risk of bleeding
Uva ursi Loop & thiazide diuretics Interference with activity
Valerian Benzodiazepine, opiates Prolongation of sedation
Yohimbe Tricyclic antidepressants May cause hypertension