Renal effects of etoricoxib and comparator nonsteroidal anti-inflammatory drugs in controlled clinical trials.
Abstract | BACKGROUND: Based on the experience with selective cyclooxygenase (COX)-2 inhibitors, including rofecoxib, valdecoxib, and celecoxib, it was anticipated that etoricoxib, a new selective COX-2 inhibitor, would display mechanism-based, dose-dependent renal adverse effects (AEs) similar to those observed with nonselective non-steroidal anti-inflammatory drugs ( NSAIDs) in long-term treatment. OBJECTIVE: The present analysis examined pooled safety data from the etoricoxib clinical development program with the aim of comparing the renal AE profiles of etoricoxib 60, 90, and 120 mg/d with those of approved therapeutic dosages of the comparator nonselective NSAIDs, naproxen 1000 mg/d and ibuprofen 2400 mg/d, and with that of placebo. METHODS: RESULTS: Data from 4770 patients were included in the analysis. Most patients were women (69.0%-80.3%), and most were white (68.0%-83.3%). The mean (SD) age at baseline ranged from 53.6 (12.1) to 62.2 (8.4) years. Overall, the incidence of renal AEs was low and generally similar between the active-treatment groups. In the placebo; etoricoxib 60-, 90-, and 120-mg; naproxen, and ibuprofen groups, the incidences of hypertension were 2.0%, 4.0%, 3.4%, 4.7%, 2.9%, and 6.6%, respectively, and the incidences of LEE were 1.9%, 3.2%, 1.5%, 1.3%, 2.3%, and 1.8%, respectively. The only significant difference found was the incidence of hypertension with etoricoxib 90 mg/d versus that with placebo (P=0.001); however, the rates of hypertension observed with etoricoxib at any dosage were not clinically meaningfully different versus comparator NSAIDs. Also, LEE was rarely of clinical significance with etoricoxib or comparator NSAIDs; related discontinuations were infrequent in all treatment groups. In addition, the incidences of elevated SCC and CHF were low among active-treatment groups (0.0% to 0.8% and 0.0% to 0.2%, respectively). CONCLUSIONS: Based on this combined data review, the risks for renal AEs (i.e., hypertension, LEE, elevated SCC changes, and CHF) with etoricoxib 60, 90, and 120 mg/d were low, with a shallow dose response, and were generally similar to those found with the comparator NSAIDs naproxen 1000 mg/d and ibuprofen 2400 mg/d.
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Authors | Sean P Curtis, Jennifer Ng, Qinfen Yu, Sumiko Shingo, Gina Bergman, Calogera L McCormick, Alise S Reicin |
Journal | Clinical therapeutics
(Clin Ther)
Vol. 26
Issue 1
Pg. 70-83
(Jan 2004)
ISSN: 0149-2918 [Print] United States |
PMID | 14996519
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Cyclooxygenase Inhibitors
- Pyridines
- Sulfones
- Etoricoxib
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Anti-Inflammatory Agents, Non-Steroidal
(adverse effects)
- Clinical Trials, Phase III as Topic
- Cyclooxygenase Inhibitors
(administration & dosage, adverse effects)
- Dose-Response Relationship, Drug
- Etoricoxib
- Female
- Humans
- Kidney Diseases
(chemically induced)
- Male
- Middle Aged
- Pyridines
(administration & dosage, adverse effects)
- Sulfones
(administration & dosage, adverse effects)
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