The hepatic safety and tolerability of the novel cyclooxygenase-2 inhibitor celecoxib.

Celecoxib is a cyclooxygenase- (COX)-1-sparing inhibitor of COX-2 that is indicated for the treatment of osteoarthritis and rheumatoid arthritis. Many agents used for treating these diseases, both symptom-modifying and disease-modifying, are associated with the potential for hepatotoxicity. This article presents an analysis of the hepatic effects of celecoxib in 14 controlled studies of patients with arthritis (2 to 24 weeks' duration), in a long-term, open-label safety study (as long as 2 years), in 11 studies of patients receiving treatment for pain after oral or orthopedic surgery (up to 5 days' duration), and in five pharmacology studies. The overall incidence of hepatic adverse events in arthritis patients receiving celecoxib was similar to that for placebo but significantly lower than in the combined group of patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs). The most commonly reported hepatic adverse events were elevations in liver transaminase levels, most of which occurred in patients receiving diclofenac. Similarly, clinically significant elevations of transaminase levels occurred more frequently with NSAIDs than with celecoxib. A pharmacology study performed in patients with mild or moderate hepatic impairment showed that celecoxib did not produce any clinically relevant changes from baseline in creatinine clearance, alanine aminotransferase, or bilirubin values in these settings. In the four interaction studies performed with drugs metabolized in the liver, none of the adverse events was hepatic in nature, and no clinically relevant liver function test abnormalities occurred. In conclusion, this analysis suggests that celecoxib has a very low potential for hepatic toxicity, even after exposures of as long as 2 years at therapeutic doses.