Post-marketing withdrawal of analgesic medications because of adverse drug reactions: a systematic review

<b>Introduction</b>: Many analgesics have been withdrawn from the market because of adverse drug reactions. Controversy still surrounds the use of some approved analgesics for pain management. However, the trends and reasons for withdrawal of analgesics when harms are attributed to their use have not been systematically assessed. <b>Areas covered</b>: We conducted searches in PubMed; Embase; Google Scholar; clinicaltrials.gov; WHO databases of withdrawn products; websites of the European Medicines Agency, the US Food and Drug Administration, the UK Medicines and Healthcare products Regulatory Agency; Meyler’s <i>Side Effects of Drugs; Stephens’ Detection of New Adverse Drug Reactions</i>; the <i>Pharmaceutical Manufacturing Encyclopedia</i>; and the <i>Merck Index</i>. We included licensed analgesics that were withdrawn after marketing because of adverse reactions between 1950 and March 2017. We excluded herbal products, non-human medicines, and non-prescription medicines. We used the Oxford Centre for Evidence Based Medicine criteria to document the levels of evidence, and chi-squared tests to compare withdrawal patterns across geographical regions. <b>Expert opinion</b>: Pharmacovigilance systems in low-resource settings should be strengthened. Greater co-ordination across regulatory authorities in assessing and interpreting the benefit-harm balance of new analgesics should be encouraged. Future reporting of harms in clinical trials of analgesics should follow standardized guidelines.

<b>引言</b>：多种镇痛药物因药品不良反应已被撤市，部分已获批的镇痛药物在疼痛管理中的应用仍存在争议。然而，当不良反应归咎于药物使用时，镇痛药物撤市的趋势与原因尚未得到系统性评估。
<b>检索范围</b>：本研究在PubMed、Embase、Google Scholar、clinicaltrials.gov、世界卫生组织（World Health Organization, WHO）撤市产品数据库、欧洲药品管理局（European Medicines Agency）官方网站、美国食品药品监督管理局（US Food and Drug Administration）官方网站、英国药品和医疗产品监管署（UK Medicines and Healthcare products Regulatory Agency）官方网站、《迈勒药物不良反应（Meyler’s Side Effects of Drugs）》、《斯蒂芬斯新不良反应检测（Stephens’ Detection of New Adverse Drug Reactions）》、《制药工业百科全书（Pharmaceutical Manufacturing Encyclopedia）》以及《默克索引（Merck Index）》中开展了文献检索。本研究纳入了1950年至2017年3月期间，因药品不良反应于上市后撤市的获批镇痛药物；排除草药制品、非人用药物及非处方药物。本研究采用牛津循证医学中心（Oxford Centre for Evidence Based Medicine）制定的标准对证据等级进行记录，并采用卡方检验（chi-squared tests）比较不同地理区域的镇痛药物撤市模式。
<b>专家评述</b>：应加强低资源地区的药物警戒系统建设；应鼓励各监管机构在评估与解读新型镇痛药物的获益-风险平衡方面强化协作；未来镇痛药物临床试验的不良反应报告应遵循标准化指南。