Warfarin is affected by dietary and drug interactions, and almost all enzymes metabolized by hepatic cytochrome P450 interact with warfarin; the international normalized ratio (INR) should be monitored more closely when adding or discontinuing any drug. Some drugs, such as abciximide, inhibit the absorption of warfarin; pautazone, phenylsulfonazone, and pyrazolone displace warfarin from plasma protein binding sites and increase its blood concentration; vincristine, because it inhibits vitamin K-producing bacteria in the intestine, decreases vitamin K absorption and hinders the synthesis of coagulation factors; mecamylguanidine and methotrexate inhibit warfarin metabolism; barbiturates, rifampin, and ashwagandin cause warfarin metabolism is accelerated. The drug-warfarin interactions were classified into four classes according to the degree of sufficient clinical evidence and are listed in Table 1.
I. Drugs
Table 1 Warfarin-drug and food interactions
Type of evidence
Enhancement
Inhibition
No effect
Class I
Alcohol (if combined with liver disease), amiodarone, anabolic steroids, cimetidine, antomin, sulfamethoxazole, erythromycin, fluconazole, isoniazid (600 mg/d), metronidazole, miconazole, omeprazole, protaxon, propafenone, propranolol, phenylsulfonazone
Barbiturates, lidodine, lisdexamfetamine, cholestyramine, eflornithine, penicillin, rifampin, aluminum thioglycollate, foods rich in vitamin K, high consumption of avocado
Alcohol, acidulants, atenolol, butylamine, enoxaparin, fluoxetine, painkillers, metoprolol
Class II
Paracetamol, chloral hydrate, ciprofloxacin, dextropropoxyphene, disulfiram, etraconazole, quinidine, phenytoin, tamoxifen, tetracycline, influenza vaccine
Diclofenac
Ibuprofen, Ketoconazole
Class III
Aspirin, diisopropylpyrimethamine, 5-fluorouracil, ketobuprofen, lovastatin, morethizine, nalidixic acid, fluoperazine, ofloxacin, propoxyphene, chinolide, sodium mebendazole, topical salicylates
Azathioprine, cyclosporine A, aromatic vincristine, trazodone
Class IV
Cephalosporins, vincristine V, gemfibrozil, heparin, anti-inflammatory pain, sulfisoxazole
Diltiazem, tobacco, vancomycin