Purpose: To evaluate the quality of studies about drugs and food interactions with warfarin and their clinical relevance.
Data Sources: MEDLINE and TOXLINE databases from 1966 to October 1993 using the Medical Subject Headings warfarin, drug interactions, and English only.
Study Selection: All articles reporting original data on drug and food interactions with warfarin.
Data Extraction: Each report, rated independently by at least two investigators (using causality assessment), received a summary score indicating the level of assurance (level 1 = highly probable, level 2 = probable, level 3 = possible, and level 4 = doubtful) that a clinically important interaction had or had not occurred. Inter-rater agreement was assessed using a weighted κ statistic.
Results: Of 793 retrieved citations, 120 contained original reports on 186 interactions. The weighted κ statistic was 0.67, representing substantial agreement. Of 86 different drugs and foods appraised, 43 had level 1 evidence. Of these, 26 drugs and foods did interact with warfarin. Warfarin's anticoagulant effect was potentiated by 6 antibiotics (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. Three patients had a hemorrhage at the time of a potentiating interaction (caused by alcohol, isoniazid, and phenylbutazone). Warfarin's anticoagulant effect was inhibited by 3 antibiotics (griseofulvin, rifampin, and nafcillin); 3 drugs active on the central nervous system (barbiturates, carbamazepine, and chlordiazepoxide); cholestyramine; sucralfate; 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. Many of these drug interactions increase warfarin's anticoagulant effect.