Summary of some common drug interactions seen in Aged Care Homes

Transcription

1 Summary of some common drug interactions seen in Aged Care Homes Jenny Gowan Consultant pharmacist NEVDGP February 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 (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) & Potassium depleting agents Hypokalaemia (low potassium) causes increased sensitivity of the myocardium to digoxin. (b) and other agents 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)

2 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 Long t1/2 Fluoxetine, phenelzine, tranylcpromine Cat B TCAs, SSRIs ( except fluoxetine), mianserin, mirtazapine Cat C Duloxetine, moclobemide, venlafaxine, desvenlafaxine Intermediate t1/ hrs Short t1/2 ( inc metabolites) <18 hrs No tapering >10 14 days before new agent Slow withdrawal Wait 2-4 days before next agent 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

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

4 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:

5 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) None known B 2 (riboflavine) B 3 (niacin) B 6 (pyridoxine) B 12 (cyanocobalamin) Oral contraceptives Phenothiazines Tricyclics Isoniazid Levodopa Phenytoin Hydralazine Isoniazid Biquanides (metformin,phenformin) Methotrexate 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 Folic acid (vitamin B c) C ( ascorbic acid) D (cholecalciferol) E (α-tocopherol) Phenytoin Al containing antacids in pts with kidney failure Nicotine Oral contraceptives Smoking Antacids Calcitriol Calcitonin, etidronate, pamidronate Isoniazid, rifampicin Phenytoin Anticoagulants Antihypertensives (some) Cholestyramine Decreased plasma concentration of phenytoin 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 Hypermagnesaemia Vit D toxicity May antagonise effects Decreased Vit D levels Calcium and folate levels reduced Increased Vitamin D Increased anticoagulant response Decreased response to iron therapy K (phytomenadione) Anticoagulants Decreased effect of warfarin

6 Table 2: Drug interactions with some minerals Interacting drug Calcium Calcitriol (Rocaltrol) Etidronate (Didronel) salts Phenytoin Quinolones eg ciprofloxacin,, norfloxacin, ofloxacin Tetracyclines Magnesium Potassium Thiazides Verapamil & other Ca channel blockers Antacids Bisphosphonates Levodopa Methyldopa Penicillamine Quinolones Tetracyclines Thyroxine Diuretics Quinolones Tetracyclines ACE inhibitors Angiotensin II receptor antagonists, for example irbesartan Cyclosporin Diuretics- loop, thiazides - potassium sparing diuretics Laxatives Liquorice Effect Hypercalcaemia Increased risk of hypercalcaemia Decreased absorption etidronate Decreased calcium absorption quinolones* tetracyclines* Increased risk of hypercalcaemia Reduced effect of verapamil 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 tetracyclines Decreased effect of thyroxine Increased excretion of magnesium quinolones tetracyclines 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 *Separate doses by two hours Quinolones Oral contraceptives Penicillamine Tetracyclines quinolones * May reduce zinc levels Reduced absorption of penicillamine tetracyclines *

7 Table 3: Some potential herb-drug interactions Herb Drug Comment- possible effects Alfalfa Cyclosporin Interfers with immunosuppression Angelica, Anise Arnica flower, Asafoetida Astraglalus Cyclosporin Interfers with immunosuppression Black cohosh Borage seed oil, Bromelain Caffeine Clozapine Lithium Theophylline Increased clozapine levels Decreased lithium levels Increased theophylline evels Capsaicin ACEI Increased risk of cough Celery Chamomile Coenzyme Q-10 Dandelion Loop diuretics Thiazide diuretics Interference with diuretic activity Danshen, Devil s claw Dong Quai Echinacea 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 Feverfew Aspirin NSAIDs Decreased NSAID effectiveness Garlic, Ginger Ginkgo biloba Antidiabetic agents Aspirin, NSAIDs Increased risk of hypoglycaemia Ginseng Loop diurectics MAOIs Decreased diuresis Insomnia Grapefruit juice Amlodipine, felodipine Benzodiazepines Buspirone Cisapride Clomipramine Cyclosporine Itraconazole Oestrogens Statins (except pravastatin) Saquinivir Decreased anticoagulant effect Increased Delayed effects Decreased levels Increased effects Green tea Decreased anticoagulant effect Guar gum Metformin Decreased hypoglycaemic effect

8 Hawthorn Increased effect Horse chestnut Horse radish Thyroxine Abnormal thyroid function Ispaghula Lithium Decrease in lithium levels Kava Alprazolam Increase lethargy Kelp Thyroxine Possible hypothyroidism L-Tryptophan MAOIs Serotonergic syndrome Licorice Sibutramine Cyclosporine MAOIs K sparing diuretics Additive effetcs Interfers with immunosuppression Hypokalaemia- risk of digoxin toxicity Increased activity Hypokalaemia Meadow sweet Melatonin Fluvoxamine Nifedipine of melatonin Interfers with antihypertensive effect Nettle Onion Papain Arley Passion flower Pectin Plantain HMG-CoA Reductase Inhibitors Decreased effect of HMG- CoA Reducatse Inhibitors Carbamazepine Decreased effect of carbamazepine Decreased digoxin effect Lithium decreased lithium absorption Quassia Quinine Carbamazepine Increased carbamazepine levels Increased digoxin levels Red Clover Aspirin Oestrogens & OCs St John s Wort Anticonvulsants, bupropion, digoxin, HIV drugs, immunosuppressives,, MAOIs, OCs, pseudoephrine,ssris SNRIs theophylline, TCA, triptans eg sumatriptan, warfarin Decreased efficacy of oestrogens Monitor or avoid Saw palmetto Oestrogens, Ocs Increased adverse effects Soy Oestrogens, Ocs Raloxifene, Tamoxifen Oestrogen excess? Interference Sweet clover Turmeric Uva ursi Loop & thiazide diuretics Interference with activity Valerian Benzodiazepine, opiates Prolongation of sedation Yohimbe Tricyclic antidepressants May cause hypertension