Safety evaluation of irinotecan: a real-world disproportionality analysis using FAERS and JADER databases during the time period 2004-2024

作者：Siyu Lou, Huayou Chen, Zhiwei Cui, Xiyuan Zhang, Chengyu Zhu, Linmei Zhou, Yingyong Ou, Fan Zou · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1516449 · 被引用次数：10 · 研究领域：Pharmacovigilance and Adverse Drug Reactions、Drug-Induced Hepatotoxicity and Protection、Cancer therapeutics and mechanisms

Introduction: Irinotecan is a widely used chemotherapeutic agent for treating colorectal, pancreatic, and ovarian cancers. Despite its therapeutic efficacy, the safety profile of irinotecan necessitates continuous pharmacovigilance due to its association with severe adverse drug events (ADEs). Given its global use, cross-national signal detection may reveal region-specific risks or unrecognized adverse effects. Methods: We conducted a retrospective pharmacovigilance analysis of irinotecan-associated ADEs using two large spontaneous reporting systems: the U.S. FDA Adverse Event Reporting System (FAERS) and the Japan Adverse Drug Event Report (JADER) database. ADE reports between 2004 and 2024 were extracted. Disproportionality analyses were performed using four methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and Multi-item gamma Poisson shrinker (MGPS). Results: A total of 11,344 ADE reports from FAERS and 7,822 from JADER were identified. These reports involved 27 system organ classes (SOCs). In FAERS, the most frequently affected SOC was gastrointestinal disorders (n = 6,888), while in JADER it was blood and lymphatic system disorders (n = 3,389). Disproportionality analysis revealed 388 and 67 preferred terms (PTs) significantly associated with irinotecan in FAERS and JADER, respectively, with 38 overlapping signals. These included both expected ADEs (e.g., neutropenia, diarrhea, thrombocytopen...