INTERACTIONS OF WARFARIN WITH DRUGS AND FOOD

Purpose: To evaluate the quality of studies about drugs and food inter actions with warfarin and their clinical relevance. Data Sources: MEDL INE and TOXLINE databases from 1966 to October 1993 using the Medical Subject Headings warfarin, drug interactions, and English only. Study Selection: Ail articles reporting original data on drug and food inter actions with warfarin. Data Extraction: Each report, rated independent ly by at least two investigators (using causality assessment), receive d a summary score indicating the level of assurance (level 1 = highly probable, level 2 = probable, level 3 = possible, and level 4 = doubtf ul) that a clinically important interaction had or had not occurred. I nter-rater agreement was assessed using a weighted kappa statistic. Re sults: Of 793 retrieved citations, 120 contained original reports on 1 86 interactions. The weighted kappa statistic was 0.67, representing s ubstantial agreement. Of 86 different drugs and foods appraised, 43 ha d level 1 evidence. Of these, 26 drugs and foods did interact with war farin. Warfarin's anticoagulant effect was potentiated by 6 antibiotic s (cotrimoxazole, erythromycin, fluconazole, isoniazid, metronidazole, and miconazole); 5 cardiac drugs (amiodarone, clofibrate, propafenone , propranolol, and sulfinpyrazone); phenylbutazone; piroxicam; alcohol (only with concomitant liver disease); cimetidine; and omeprazole. Th ree patients had a hemorrhage at the time of a potentiating interactio n (caused by alcohol, isoniazid, and phenylbutazone). Warfarin's antic oagulant effect was inhibited by 3 antibiotics (griseofulvin, rifampin , and nafcillin); 3 drugs active on the central nervous system (barbit urates, carbamazepine, and chlordiazepoxide); cholestyramine; sucralfa te; foods high in vitamin K; and large amounts of avocado. Conclusions : Many drugs and foods interact with warfarin, including antibiotics, drugs affecting the central nervous system, and cardiac medications. M any of these drug interactions increase warfarin's anticoagulant effec t.