A comparison of renal-related adverse drug reactions between rofecoxib andcelecoxib, based on the World Health Organization Uppsala Monitoring Centre safety database

Background: Two isoforms of cyclooxygenase (COX) have been identified, both of them inhibited by traditional nonsteroidal anti-inflammatory drugs (NSA IDs). Inhibition of COX-2 has been associated with the therapeutic effects of NSAIDs, whereas inhibition of COX-1 is believed to be the cause of the a dverse gastrointestinal effects associated with NSAID therapy. When adminis tered at therapeutic doses, new COX-2-specific inhibitors inhibit only the COX-2 isoform. Objective: This study sought to compare renal safety signals between the CO X-2-specific inhibitors rofecoxib and celecoxib, based on spontaneous repor ts of adverse drug reactions (ADRs) in the World Health Organization/Uppsal a Monitoring Centre (WHO/UMC) safety database through the end of the second quarter 2000. Methods: Disproportionality in the association between a particular drug an d renal-related ADR was evaluated using a bayesian confidence propagation n eural network method in which a statistical parameter, the information comp onent (IC) value, was calculated for each drug-ADR combination. In this met hod, an IC value significantly greater than 0 implies that the association of a drug-ADR pair is stronger than background; the higher the IC value, th e more the combination stands out from the background. The ratio of actual to expected numbers of ADRs was also used to assess disproportionality. Results: As with traditional NSAIDs, both COX-2-specific inhibitors were as sociated with renal-related ADRs. However, the adverse renal impact of rofe coxib was significantly greater than that of celecoxib. IC values were sign ificantly different for the following comparisons: water retention (1.97 ro fecoxib vs 1.18 celecoxib; P<0.01); abnormal renal function (2.38 vs 0.70; P<0.01); renal failure (2.22 vs 1.09; P<0.01); cardiac failure (2.39 vs 0.4 8; P<0.01); and hypertension (2.15 vs 1.33; P<0.01). In an additional analy sis, celecoxib was shown to have a similar renal safety profile to that of diclofenac and ibuprofen. Conclusions: Based on spontaneous ADR reports in the WHO/UMC safety databas e at the end of the second quarter 2000, this analysis indicates that rofec oxib has significantly greater renal toxicity than celecoxib or traditional NSAIDs. This negative renal impact may have the potential to increase the risk for serious cardiac and/or cerebrovascular events.