Nonsteroidal antiinflammatory drug use in patients receiving warfarin: emphasis on nabumetone

Phenylbutazone has been clearly demonstrated to interact pharmacokinetically and clinically with warfarin, although several other nonsteroidal antiinflammatory drugs (NSAIDs) also have the potential to interact with warfarin to cause alterations in prothrombin time. Aspirin is known to inhibit platelet aggregation irreversibly, whereas nonaspirin NSAIDs are thought to inhibit platelet aggregation reversibly. In contrast, nabumetone was not shown to cause significant inhibition of platelet aggregation, which may be related to the fact that nabumetone preferentially inhibits the prostaglandin synthase-2 isozyme instead of the prostaglandin synthase-1 isozyme. Furthermore, in studies in patients and normal volunteers stabilized on warfarin, nabumetone did not cause alterations in the prothrombin time or international normalized ratio. Based on data evaluating the concomitant use of nabumetone and warfarin, the relative lack of platelet inhibition, and the relatively lower risk of nabumetone-induced gastrointestinal mucosal damage as assessed by radiolabeled chromium-51 fecal blood loss studies and endoscopic evaluations, nabumetone may be preferred if concomitant therapy with warfarin is indicated.