School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Clin Pharmacol Ther. 2023 Jul;114(1):201-210. doi: 10.1002/cpt.2918. Epub 2023 May 8.
Eltrombopag is clinically approved for use in immune thrombocytopenia (ITP), chronic hepatitis C-related thrombocytopenia, and aplastic anemia and suitable for children; however, data on its overall safety profile are scarce. This study aimed to explore the clinical features of adverse drug events (ADEs) associated with eltrombopag in different age groups using individual case safety reports (ICSRs) from the World Health Organization database VigiBase and the US Food and Drug Administration Adverse Event Reporting System database from 2008 to 2022 in combination with a meta-analysis of data from randomized clinical trials in the literature from inception to July 28, 2022. We conducted disproportionality analyses by grouping patients into the following age groups: 0-17 (0-23 months, 2-11 years, and 12-17 years), 18-64, and ≥ 65 years. The ADEs about hepatobiliary disorders, thrombosis, skin and subcutaneous tissue disorders, infections, and so on were observed more differently in each age group. Meta-analysis results showed differences in the four system organ classes between adults and children with ITP: infections and infestations, general disorders and administration site conditions, skin and subcutaneous tissue disorders, and investigations. The adverse drug reactions in the latest version of instructions were searched in the databases to analyze their postmarketing safety signal strength. We observed signals of elevated alanine aminotransferase, aspartate aminotransferase, and blood bilirubin levels in all age groups. For children, urinary tract infection and back pain showed signals. Due to the inherent limitations of pharmacovigilance studies, more experiments are needed to assess the risks of eltrombopag in different ages.
依洛尤单抗在免疫性血小板减少症（ITP）、慢性丙型肝炎相关血小板减少症和再生障碍性贫血中的应用已得到临床批准，并且适用于儿童；然而，关于其总体安全性的资料却很少。本研究旨在使用 2008 年至 2022 年间从世界卫生组织数据库 VigiBase 和美国食品药品监督管理局不良事件报告系统数据库中获得的个案安全性报告（ICSR），结合 2022 年 7 月 28 日之前文献中随机临床试验的数据进行荟萃分析，来探讨不同年龄组中与依洛尤单抗相关的药物不良反应（ADE）的临床特征。我们通过将患者分组为 0-17 岁（0-23 个月、2-11 岁和 12-17 岁）、18-64 岁和≥65 岁，来进行不成比例分析。在每个年龄组中，都观察到了关于肝胆疾病、血栓形成、皮肤和皮下组织疾病、感染等的 ADE 存在不同的差异。荟萃分析结果显示，成人和儿童 ITP 之间在四个系统器官类别中存在差异：感染和寄生虫感染、一般疾病和给药部位情况、皮肤和皮下组织疾病以及检查。在数据库中搜索了最新版本说明书中的不良反应，以分析其上市后安全性信号强度。我们观察到在所有年龄组中，丙氨酸氨基转移酶、天冬氨酸氨基转移酶和血胆红素水平升高。对于儿童，尿路感染和背痛显示出信号。由于药物警戒研究的固有局限性，需要进行更多的实验来评估依洛尤单抗在不同年龄的风险。
