Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
Department of Education and Research Center for Pharmacy Practice, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Japan.
Br J Clin Pharmacol. 2024 Dec;90(12):3348-3354. doi: 10.1111/bcp.16237. Epub 2024 Sep 2.
This study was conducted to examine disproportionality, times to onset, incidence rates and outcomes of lenvatinib-associated cardiac adverse events (AEs) using the Japanese Adverse Drug Event Report database.
We analysed data for the period between April 2004 and May 2023. Data on cardiac AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). Furthermore, Weibull distribution parameters were calculated.
Of the 2 230 863 reports analysed, we identified 7684 reports of AEs associated with lenvatinib, including 317 cardiac AEs. Signals were detected for eight cardiac AEs: hypertension, cardiac failure, myocarditis, myocardial infarction, immune-mediated myocarditis, cardiomyopathy, angina unstable and cardiotoxicity. Among these, fatal outcomes were observed for cardiac failure, myocarditis and myocardial infarction. Histograms of median times to onset for the eight detected cardiac AE signals showed that AEs occurred at a median of 3.5-134.5 days after lenvatinib administration. The Weibull distributions showed that cardiac failure occurred early after administration (early failure type), myocarditis occurred in a dose-dependent manner (wearout failure type), and myocardial infarction occurred constantly throughout the exposure period (random failure type).
We focused on cardiac AEs associated with lenvatinib as post-marketing AEs. Serious outcomes can arise after lenvatinib administration. Patients should be monitored for signs of onset of these AEs not only at the start of administration, but also over an extended period.
本研究旨在使用日本不良药物事件报告数据库，检查仑伐替尼相关心脏不良事件（AE）的不均衡性、发病时间、发病率和结局。
我们分析了 2004 年 4 月至 2023 年 5 月期间的数据。提取了心脏 AE 数据，并使用报告比值比（ROR）估计 AE 的相对不均衡性。此外，还计算了 Weibull 分布参数。
在分析的 2230863 份报告中，我们确定了 7684 份与仑伐替尼相关的 AE 报告，其中包括 317 份心脏 AE。检测到八种心脏 AE 的信号：高血压、心力衰竭、心肌炎、心肌梗死、免疫介导的心肌炎、心肌病、不稳定型心绞痛和心脏毒性。其中，心力衰竭、心肌炎和心肌梗死观察到致命结局。八种检测到的心脏 AE 信号的中位数发病时间直方图显示，AE 在仑伐替尼给药后 3.5-134.5 天中位数时间发生。Weibull 分布表明心力衰竭发生在给药后早期（早期衰竭类型），心肌炎呈剂量依赖性发生（磨损衰竭类型），心肌梗死在整个暴露期持续发生（随机衰竭类型）。
我们关注仑伐替尼相关的心脏 AE 作为上市后 AE。仑伐替尼给药后可能会出现严重后果。患者不仅在开始给药时，而且在延长的时间段内，都应监测这些 AE 的发病迹象。
