University of Minnesota, Minneapolis, MN, USA.
Curr Med Res Opin. 2010 Jan;26(1):239-51. doi: 10.1185/03007990903426787.
To review the safety profile of tramadol hydrochloride (tramadol) in the treatment of chronic osteoarthritis pain, with specific reference to the incidence of adverse events (AEs) reported in large clinical trials.
An extensive review of published clinical trials with tramadol was conducted, using literature searches in MEDLINE and EMBASE (since 1997) and the key search terms: tramadol, immediate-release (IR), extended-release (ER), sustained-release (SR), chronic pain, and osteoarthritis. Studies were included based on appropriate study design, appropriately reported safety data, and chronic osteoarthritis as a pain condition. Secondary analyses of previously published pain studies were excluded.
Fifteen studies met the inclusion criteria. The most common AEs reported across all tramadol formulations were nausea, dizziness, constipation, vomiting, somnolence, and headache. Most AEs were mild to moderate in severity and occurred more commonly during initial treatment than during maintenance treatment. Differences in the rates of selected gastrointestinal and central nervous system AEs were seen between long-acting and immediate-release tramadol formulations, both within individual studies and across all studies. AEs appeared to be dose-dependent in fixed-dose studies.
This review provides a robust base for descriptive assessment of AEs associated with long-acting tramadol formulations. Although the actions of different tramadol formulations are biologically similar, differences in pharmacokinetics, drug-release patterns, and availability may influence the incidence of AEs associated with tramadol. Because of the limitations of a qualitative safety analysis across studies with different populations and study designs, any observed differences should be interpreted with caution, but these differences may help educate healthcare providers about tramadol treatment in patients with chronic osteoarthritis pain and help them select the optimal dose for specific patients.
综述盐酸曲马多（曲马多）治疗慢性骨关节炎疼痛的安全性概况，特别参考大型临床试验报告的不良事件（AE）发生率。
使用 MEDLINE 和 EMBASE（自 1997 年起）中的文献检索，对曲马多的已发表临床试验进行了广泛的回顾，并使用了以下关键搜索词：曲马多、速释（IR）、缓释（ER）、控释（SR）、慢性疼痛和骨关节炎。纳入研究的标准为：适当的研究设计、适当报告的安全性数据以及慢性骨关节炎作为疼痛病症。排除了先前发表的疼痛研究的二次分析。
符合纳入标准的研究有 15 项。所有曲马多制剂报告的最常见 AE 为恶心、头晕、便秘、呕吐、嗜睡和头痛。大多数 AE 的严重程度为轻度至中度，在初始治疗期间比维持治疗期间更常见。长效和速释曲马多制剂在个别研究和所有研究中均观察到选定的胃肠道和中枢神经系统 AE 的发生率存在差异。在固定剂量研究中，AE 似乎与剂量有关。
本综述为描述性评估长效曲马多制剂相关 AE 提供了可靠依据。尽管不同曲马多制剂的作用在生物学上相似，但药代动力学、药物释放模式和可利用性的差异可能会影响与曲马多相关的 AE 发生率。由于在具有不同人群和研究设计的研究之间进行的定性安全性分析存在局限性，因此应谨慎解释任何观察到的差异，但这些差异可能有助于教育医疗保健提供者有关慢性骨关节炎疼痛患者的曲马多治疗，并帮助他们为特定患者选择最佳剂量。
