Orfarin Drug Interactions



Orion Pharma


Full Prescribing Info
Drug Interactions
Warfarin interacts with many drugs. Drugs may reduce the absorption or enterohepatic circulation of warfarin (cholestyramine). Drugs may induce (antiepileptics or antituberculotics) or inhibit the hepatic metabolism of warfarin (e.g. amiodarone or metronidazole). In certain instances cessation of inhibition or induction of liver enzymes can also change the balance of warfarin therapy. Certain drugs may displace warfarin from the plasma protein bonds, which increases the free fraction and, unless the patient has some liver disease or some other medication inhibiting warfarin metabolism, this generally enhances the elimination of warfarin.
The best known pharmacodynamic interactions are associated with the simultaneous use of drugs affecting the platelets (acetylsalicylic acid, clopidogrel, ticlopidine, dipyridamole, most of the non­steroidal anti­-inflammatory drugs, but not the coxibs). Primary and secondary hemostasis predisposes the patient to severe bleeding complications. Penicillins in large doses may have the same effect. Vitamin K­-dependent synthesis of the coagulation factors is reduced and the warfarin effect is potentiated by certain drugs, such as anabolic steroids, azapropazone, erythromycin, and some cephalosporins. An ample supply of dietary vitamin K reduces the warfarin effect. Correspondingly, reduced absorption of vitamin K due to e.g. diarrhoea may potentiate the warfarin effect. In patients with inadequate supply of vitamin K, antibiotics may reduce the ability of the intestinal bacteria to produce vitamin K2, which leads to an enhanced warfarin effect. Heavy use of alcohol with concomitant hepatic failure potentiates the warfarin effect. The quinine contained in Tonic-­water may also potentiate the warfarin effect.
Cranberry juice and other cranberry products may potentiate the effect of warfarin and therefore concomitant use should be avoided.
If the patient needs relief of pain while on warfarin, paracetamol or opiates are recommended.
Warfarin may potentiate the effect of oral sulphonylurea antidiabetics.
The following drugs have been reported to potentiate or reduce the warfarin effect: Increased effect: acetylsalicylic acid, allopurinol, amiodarone, amoxicillin, argatroban, azapropazone, azithromycin, bezafibrate, cabecitabine, carboxyuridine, celecoxib, clarithromycin, chloral hydrate, cefamandole, cefalexin, cefmenoxime, cefmetazole, cefoperazone, cefuroxime, cimetidine, ciprofloxacin, clofibrate, codeine, cyclophosphamide, dexstropropoxyphene, (dextro)thyroxine, digoxin, disulfiram, doxycycline, erythromycin, etoposide, fenofibrate, feprazone, fluconazole, fluorouracil, flutamide, fluvastatin, fluvoxamine, gatifloxacin, gemfibrozil, grepafloxacin, ifosfamide, indometacin, influenza vaccine, interferon alpha and beta, isoniazid, itraconazole, ketoconazole, latamoxef, leflunomide, lepirudin, levofloxacin, lovastatin, metolazone, methotrexate, metronidazole, miconazole (also oral gel), moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, omeprazole, oxyphenbutazone, paracetamol (the effect evident after 1 to 2 weeks of continuous use), phenylbutazone, piroxicam, proguanil, propafenone, propranolol, quinine, quinidine, rofecoxib, roxithromycin, simvastatin, sulfafurazole, sulfamethizole, sulfamethoxazoletrimethoprim, sulfaphenazole, sulfinpyrazone, sulfofenur, sulindac, (anabolic and androgenic) steroid hormones, tamoxifen, tegafur, tetracycline, tolmetin, tramadol, trastuzumab, troglitazone, valproic acid, vitamin A, vitamin E, zafirlukast.
There are reports suggesting that noscapine as well as glucosamine with or without chondroitin sulphate may increase the INR in patients on warfarin.
Decreased effect: azathioprine, (barbiturates), carbamazepine, chlordiazepoxide, chlortalidone, cloxacillin, ciclosporin, dicloxacillin, disopyramide, griseofulvin, mercaptopurine, mesalazine, mitotane, nafcillin, nevirapine, phenobarbital, primidone, rifampicin, spironolactone, trazodone, vitamin C.
Herbal medications can either potentiate the warfarin effect, e.g. ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis, contains coumarins), papaya (Carica papaya) or danshen (Salvia miltiorrhiza, decreases the warfarin elimination), or reduce it, e.g. ginseng (Panax spp.). The effect of warfarin can be reduced by concomitant use of the herbal preparation St John's wort (Hypericum perforatum). This is due to induction of drug metabolizing enzymes by St John's wort. Herbal preparations containing St John's wort should therefore not be combined with warfarin. The inducing effect may persist for as long as 2 weeks after cessation of treatment with St John's wort. If a patient is already taking St John's wort check the INR and stop St John's wort. Monitor INR closely as this may rise on stopping St John's wort. The dose of warfarin may need adjusting.
Ingestion of vitamin K containing foodstuffs during warfarin treatment should be as steady as possible. The most abundant vitamin K sources are green vegetables and leaves, such as: amaranth leaf, avocado, broccoli, Brussels sprout, cabbage, canola oil, chayote leaf, chives, coriander, cucumber skin (but not cucumber without skin), endives, kale leaf, kiwifruit, lettuce leaf, mint leaf, mustard greens, olive oil, parsley, peas, pistachio nuts, purple seaweed laver, spinach leaf, spring onion, soybeans, soybean oil, tea leaves (but not tea), turnip greens, or watercress.
Topical preparations containing methyl salicylate should be used with care in patients on warfarin and excessive usage is to be avoided as potentially dangerous drug interaction can occur.
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