BACKGROUND: Warfarin is a highly efficacious oral anticoagulant, but its use is 
limited by a well-founded fear of bleeding. Drug and food interactions are 
frequently cited as causes of adverse events with warfarin. We provide an 
updated systematic overview of the quality, clinical effect, and importance of 
these reported interactions.
DATA SOURCES: MEDLINE, TOXLINE, IPA, and EMBASE databases from October 1993 to 
March 2004. Database searches combined the keyword warfarin with drug 
interactions, herbal medicines, Chinese herbal drugs, and food-drug 
interactions.
STUDY SELECTION: Eligible articles contained original reports of warfarin drug 
or food interactions in human subjects. Non-English articles were included if 
sufficient information could be abstracted.
DATA EXTRACTION: Reports were rated independently by 2 investigators for 
interaction direction, clinical severity, and quality of evidence. Quality of 
evidence was based on previously validated causation criteria and study design.
DATA SYNTHESIS: Of 642 citations retrieved, 181 eligible articles contained 
original reports on 120 drugs or foods. Inter-rater agreement was excellent, 
with weighted kappa values of 0.84 to 1.00. Of all reports, 72% described a 
potentiation of warfarin's effect and 84% were of poor quality, 86% of which 
were single case reports. The 31 incidents of clinically significant bleeding 
were all single case reports. Newly reported interactions included celecoxib, 
rofecoxib, and herbal substances, such as green tea and danshen.
CONCLUSIONS: The number of drugs reported to interact with warfarin continues to 
expand. While most reports are of poor quality and present potentially 
misleading conclusions, the consistency of reports of interactions with azole 
antibiotics, macrolides, quinolones, nonsteroidal anti-inflammatory drugs, 
including selective cyclooxygenase-2 inhibitors, selective serotonin reuptake 
inhibitors, omeprazole, lipid-lowering agents, amiodarone, and fluorouracil, 
suggests that coadministration with warfarin should be avoided or closely 
monitored. More systematic study of warfarin drug interactions in patients is 
urgently needed.