Schug Stephan A, Parsons Bruce, Li Chunming, Xia Feng
Pharmacology, Pharmacy and Anaesthesiology Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, Australia.
J Pain Res. 2017 Oct 10;10:2451-2459. doi: 10.2147/JPR.S136052. eCollection 2017.
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.
To examine the safety of parecoxib, a COX-2 inhibitor, for the management of postoperative pain.
Pooled analysis of 28 placebo-controlled trials of parecoxib and review of postauthorization safety data.
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.
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.
Potentially serious safety events occur infrequently with parecoxib, which high-lights its safety in patients with postoperative pain.
非选择性非甾体抗炎药（NSAIDs）和选择性环氧化酶-2（COX-2）抑制剂存在包括心血管、肾脏和胃肠道（GI）事件在内的安全问题。
研究COX-2抑制剂帕瑞昔布用于术后疼痛管理的安全性。
对28项帕瑞昔布安慰剂对照试验进行汇总分析，并审查批准后安全数据。
与COX-2抑制剂和/或NSAIDs通常相关的预先指定的安全事件。在临床试验分析中，使用卡方检验比较各治疗组中每个事件的发生频率。在批准后审查中，列出每个事件的确诊病例数及结果。
在临床试验分析中，帕瑞昔布组和安慰剂组中约0.2%的患者发生胃肠道相关事件。帕瑞昔布组（1.0%）和安慰剂组（0.9%）的肾衰竭和损害情况相似。两组间动脉（帕瑞昔布=0.3%；安慰剂=0.2%）和静脉（帕瑞昔布=0.2%；安慰剂=0.1%）心血管栓塞和血栓形成事件的发生率相似。包括过敏反应（帕瑞昔布=8.7%；安慰剂=8.6%）、低血压（帕瑞昔布=2.6%；安慰剂=2.1%）、血管性水肿（帕瑞昔布=2.5%；安慰剂=2.8%）和严重皮肤不良反应（两组均为0%）在内过敏反应在两组间相似。两组中<0.1%的患者发生切口部位或其他皮肤/组织感染。基于69567300单位帕瑞昔布，批准后数据库中这些事件（总报告数/严重报告数）如下：胃肠道溃疡相关事件（35/35）、肾衰竭和损害（77/68）、心血管栓塞和血栓形成事件（66/64）、包括低血压相关事件（32/25）和严重皮肤不良事件（17/17）在内的过敏反应，以及掩盖炎症迹象（18/18）。大多数报告的结果分类为已恢复或正在恢复。
帕瑞昔布发生潜在严重安全事件的情况很少见，这突出了其在术后疼痛患者中的安全性。
