The safety profile of parecoxib for the treatment of postoperative pain: a pooled analysis of 28 randomized, double-blind, placebo-controlled clinical trials and a review of over 10 years of postauthorization data

Stephan A Schug, Bruce Parsons, Chunming Li, Feng Xia, Stephan A Schug, Bruce Parsons, Chunming Li, Feng Xia

Abstract

Background: Nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors are associated with safety issues including cardiovascular, renal, and gastrointestinal (GI) events.

Objective: To examine the safety of parecoxib, a COX-2 inhibitor, for the management of postoperative pain.

Design: Pooled analysis of 28 placebo-controlled trials of parecoxib and review of postauthorization safety data.

Main outcome measures: Prespecified safety events commonly associated with COX-2 inhibitors and/or NSAIDs. In the clinical trial analysis, the frequency of each event was compared between treatment groups using a chi-square test. In the postauthorization review, the number of confirmed cases, along with outcome, was presented for each event.

Results: In the clinical trial analysis, GI-related events occurred in ~0.2% of patients in the parecoxib and placebo groups. Renal failure and impairment was similar between parecoxib (1.0%) and placebo (0.9%). The occurrence of arterial (parecoxib=0.3%; placebo=0.2%) and venous (parecoxib=0.2%; placebo=0.1%) cardiovascular embolic and thrombotic events was similar between groups. Hypersensitivity reactions including anaphylactic reactions (parecoxib=8.7%; placebo=8.6%), hypotension (parecoxib=2.6%; placebo=2.1%), angioedema (parecoxib=2.5%; placebo=2.8%), and severe cutaneous adverse reactions (0% in both groups) were similar between groups. Incision site or other skin/tissue infections occurred in <0.1% of patients in both groups. The occurrence of these events (total reports/serious reports) in the postauthorization database, based on 69,567,300 units of parecoxib, was as follows: GI ulceration-related events (35/35), renal failure and impairment (77/68), cardiovascular embolic and thrombotic events (66/64), hypersensitivity reactions including hypotension-related events (32/25) and severe cutaneous adverse events (17/17), and masking signs of inflammation (18/18). A majority of reported outcomes were classified as recovered or recovering.

Conclusions: Potentially serious safety events occur infrequently with parecoxib, which high-lights its safety in patients with postoperative pain.

Keywords: Parecoxib; postoperative pain; safety.

Conflict of interest statement

Disclosure Stephan A Schug reports that the Anesthesiology Unit of the University of Western Australia, but not SAS personally, has received research and travel funding, and speaking and consulting honoraria from Pfizer within the last 5 years. Bruce Parsons, Chunming Li, and Feng Xia are full-time employees of and own stock in Pfizer. The authors report no other conflicts of interest in this work.

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