Renovascular safety profile of etoricoxib

Abstract

Rofecoxib and celecoxib, the first selective COX-2 inhibitors introduced into the marketplace, have recognized mechanism-based renovascular effects similar to those associated with the non-selective NSAIDs which are dual COX-1 and COX-2 inhibitors. Specifically, edema, blood pressure elevation, attenuation of the effects of anti-hypertensive agents, and acute renal failure were manifest in a small percentage of patients. To assess the renovascular safety of etoricoxib, a new highly selective COX-2 inhibitor. The etoricoxib development program contains information on 3348 patients participating in 8 phase III studies in osteoarthritis, rheumatoid arthritis, chronic low back pain, and surveillance endoscopy. Grouped together, the patients in these studies represent 1491 placebo, 658 etoricoxib 60 mg/day, 889 etoricoxib 90 mg/day, 472 etoricoxib 120 mg/day, 1034 naproxen 1000mg/day, 226 ibuprofen 2400 mg/day treated patients. As part of the program-wide safety survey, lower extremity edema adverse experiences (AEs) and hypertension AEs, as well as discontinuations due to these AEs were analyzed. The overall incidence of lower extremity edema occurred in 28 (1.9%), 21 (3.2%), 13 (1.5%), 6 (1.3%), 24 (2.3%), and 4 (1.8%) of patients in the placebo, 60, 90, 120-mg etoricoxib, naproxen, and ibuprofen groups, respectively. Discontinuations due to lower extremity edema were infrequent in all active treatment groups; in 3 (0.3%), 2 (0.3%), 1 (0.1%), 0 (0.0%), 0 (0.0%), and 1 (0.4%) of patients in the placebo, 60, 90, 120-mg etoricoxib, naproxen, and ibuprofen groups, respectively. Hypertension occurred in 30 (2.0%), 26 (4.0%), 30 (3.4%), 22 (4.7%), 30 (2.9%), and 15 (6.6%) of patients in the placebo, 60, 90, 120-mg etoricoxib, naproxen, and ibuprofen groups, respectively. Few patients discontinued due to hypertension: 0(0.0%), 1(0.2%), 2(0.2%), 2(0.4%), 1(0.1%), and 0 (0.0%) of patients in the placebo, 60, 90, 120-mg etoricoxib, naproxen, and ibuprofen groups, respectively. There were no incidences of acute renal failure in any treatment group. Based on this combined data review, the risk of lower extremity edema and hypertension AEs with etoricoxib was low and generally similar to comparator NSAIDs. There was no compelling evidence of dose-related trends for these AEs with the various etoricoxib doses studied.