Newly identified adverse events for gemcitabine using the food and drug administration adverse event Reporting system

Our research aimed to identify previously undocumented adverse events (AEs) in the gemcitabine drug insert with the goal of informing clinical practice. We extracted adverse events associated with gemcitabine use through 2023 using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Four algorithms (Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Empirical Bayesian Geometric Mean) were employed to detect new AE signals. AEs were considered positive signals only if they were detected by all four algorithms. From 2014 to 2023, a total of 42,360 AEs were reported in 14,905 individuals following gemcitabine use. These AEs totaled 437 preferred terms (PTs) across 20 system organ classes (SOCs). We identified unexpected AEs related to the ocular disorders, the nervous system, and the ear and the labyrinth. The ocular organ system will present with retinopathy, purtscher retinopathy, choroidal effusion, amaurosis, necrotizing scleritis, etc. The nervous system may experience reversible posterior encephalopathy syndrome, cerebellar syndrome, cauda equina syndrome, athetosis, transverse myelitis, etc. The ears and labyrinth may exhibit ototoxicity. Our study identified previously undetected signals following gemcitabine treatment, thereby providing new insights for future medication guidance.

本研究旨在识别吉西他滨（gemcitabine）药品说明书中未记载的不良事件（Adverse Events, AEs），以期为临床实践提供参考依据。本研究借助美国食品药品监督管理局不良事件报告系统（Food and Drug Administration Adverse Event Reporting System, FAERS）数据库，提取了截至2023年与吉西他滨使用相关的不良事件。本研究采用四种算法：报告比值比（Reporting Odds Ratio）、比例报告比值比（Proportional Reporting Ratio）、贝叶斯置信传播神经网络（Bayesian Confidence Propagation Neural Network）以及经验贝叶斯几何平均法（Empirical Bayesian Geometric Mean），以检测新的不良事件信号。仅当某不良事件被上述四种算法均检出时，方可认定为阳性信号。2014年至2023年间，共计14905名患者使用吉西他滨后上报了42360例不良事件，这些不良事件涵盖20个系统器官分类（system organ classes, SOCs）下的437个首选术语（preferred terms, PTs）。本研究识别出与眼部疾病、神经系统以及耳与迷路相关的未记载不良事件：眼部系统可表现为视网膜病变、普尔施特视网膜病变（purtscher retinopathy）、脉络膜积液、黑蒙（amaurosis）、坏死性巩膜炎等病症；神经系统可出现可逆性后部脑病综合征、小脑综合征、马尾综合征、手足徐动症、横贯性脊髓炎等病症；耳及迷路系统则可出现耳毒性反应。本研究成功检出吉西他滨治疗中此前未被发现的不良事件信号，可为未来的临床用药指导提供全新的参考视角。