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1 November 1994 | Volume 121 Issue 9 | Pages 676-683
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
Results: Of 793 retrieved citations, 120 contained original reports on 186 interactions. The weighted
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.
Author and Article Information
From McMaster University; Centre for Evaluation of Medicines, St. Joseph's Hospital; the Hamilton Civic Hospitals Research Centre, Hamilton, Ontario, Canada.
REVIEW
Interactions of Warfarin with Drugs and Food
statistic. 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.
Grant Support: In part by Hamilton Civic Hospitals Research Centre and The Centre for Evaluation of Medicines, St. Joseph's Hospital, Ontario, Canada. Dr. Wells is the recipient of a McLaughlin scholarship from the University of Ottawa. Dr. Hirsh is a Distinguished Research Professor of the Heart and Stroke Foundation of Canada and is a Trillium Award recipient from the Ministry of Health.
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