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,1,2 Bruce Parsons,3 Chunming Li,4 Feng Xia5 1Pharmacology, Pharmacy and Anaesthesiology Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; 2Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, Australia; 3Medical Affairs/Global Innovative Products, Pfizer, New York, NY, USA; 4Global Innovative Products Statistics, Pfizer, Madison, NJ, USA; 5Safety Surveillance and Risk Management, Worldwide Safety and Regulatory, Worldwide Research and Development, Pfizer, New York, NY, USA 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 highlights its safety in patients with postoperative pain. Keywords: Parecoxib, postoperative pain, safety