Kanbayashi Yuko, Kaneko Yuki, Kobayashi Momoko, Wakabayashi Haruka, Shimizu Tadashi, Uchida Mayako
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.
In Vivo. 2025 Jan-Feb;39(1):346-352. doi: 10.21873/invivo.13834.
BACKGROUND/AIM: Despite the seriousness of lung adverse events (AEs) associated with lenvatinib, comprehensive data on these events remain limited. This study was conducted to examine the disproportionality, time to onset, incidence rates, and outcomes of lenvatinib-associated lung AEs using the Japanese Adverse Drug Event Report database.
We analysed data for the period from April 2004 to May 2023. Data on lung AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). Weibull distribution parameters were also calculated.
Among the 2,230,863 reports analysed, 7,684 reports of AEs associated with lenvatinib were identified, including 380 lung AEs. Signals were detected for three lung AEs: tracheal fistula, tracheo-oesophageal fistula, and tracheal haemorrhage. Fatal outcomes were observed for tracheal fistula and tracheal haemorrhage. A histogram of median times to onset indicated that lung AEs associated with lenvatinib occurred 15-111 days after administration. Weibull distributions showed that the incidence of these AEs remained constant throughout the exposure period (random failure type).
The present study highlights post-marketing AEs associated with lenvatinib, with a particular focus on lung AEs. Tracheal fistula and tracheal haemorrhage were identified as AEs with potentially serious outcomes following lenvatinib administration. Monitoring patients for early signs of these AEs is important not only at treatment initiation, but also throughout the entire course of therapy.
背景/目的：尽管与乐伐替尼相关的肺部不良事件（AE）较为严重，但关于这些事件的全面数据仍然有限。本研究旨在使用日本药品不良事件报告数据库，研究乐伐替尼相关肺部AE的不成比例性、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。提取了肺部AE的数据，并使用报告比值比（ROR）估计AE的相对不成比例性。还计算了威布尔分布参数。
在分析的2230863份报告中，确定了7684份与乐伐替尼相关的AE报告，其中包括380份肺部AE报告。检测到三种肺部AE的信号：气管瘘、气管食管瘘和气管出血。气管瘘和气管出血观察到了致命结局。发病中位时间的直方图表明，与乐伐替尼相关的肺部AE在给药后15 - 111天发生。威布尔分布表明，这些AE的发病率在整个暴露期保持恒定（随机失效类型）。
本研究强调了与乐伐替尼相关的上市后AE，尤其关注肺部AE。气管瘘和气管出血被确定为乐伐替尼给药后具有潜在严重后果的AE。不仅在治疗开始时，而且在整个治疗过程中监测患者这些AE的早期迹象都很重要。
