OBJECTIVE: To review the mechanisms and clinical significance of adverse 
interactions between warfarin and nonsteroidal anti-inflammatory drugs (NSAIDs) 
and discuss how these interactions can be avoided.
DATA SOURCES: Previous studies of interactions between warfarin and NSAIDs or 
reports of adverse interactions were identified from a MEDLINE search (1976 to 
present) and from the reference lists of pertinent articles.
STUDY SELECTION AND DATA EXTRACTION: All articles were considered for inclusion 
in the review. Pertinent information was selected for discussion.
DATA SYNTHESIS: All NSAIDs can prolong bleeding time by inhibiting platelet 
function. High-dose aspirin has a direct hypoprothrombinemic effect. 
Phenylbutazone and its analogs enhance the hypoprothrombinemic effect of 
warfarin through a pharmacokinetic interaction by inhibiting the hepatic 
metabolism of warfarin. Mefenamic acid also enhances the anticoagulant effect of 
warfarin, but the mechanism is not known. The clinical relevance of protein 
binding displacement in the interaction between warfarin and NSAIDs has been 
overstated, although a significant one may be more likely in the presence of 
high concentrations of NSAIDs in patients with slow elimination of warfarin 
(e.g., those with severe heart failure or impaired liver function). NSAIDs can 
induce gastrointestinal bleeding, which is likely to be more severe if warfarin 
is also given.
CONCLUSIONS: The combined use of warfarin and NSAIDs is generally discouraged 
because of the increased risk of bleeding in these patients. In patients 
receiving warfarin who also require NSAIDs, phenylbutazone and its analogs, 
high-dose aspirin, mefenamic acid, excessive use of topical methyl salicylate, 
and NSAIDs that are associated with a higher risk of bleeding peptic ulcers 
should be avoided. Patients should be closely monitored for anticoagulant 
control and bleeding complications during the combined use of warfarin and 
NSAIDs.