Lai Xiaolong, Jin Liuyin, Zhou Yixia, Li Yang, Sheng Lindan, Xie Guomin, Fang Jianjiang
Department of Emergency, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, 315040, China.
Lishui Second People's Hospital, Lishui, China.
BMC Pharmacol Toxicol. 2025 May 26;26(1):110. doi: 10.1186/s40360-025-00940-0.
As a novel anti-influenza agent, baloxavir marboxil lacks real-world safety data in large populations. Therefore, this study aimed to investigate adverse drug events (ADEs) associated with baloxavir marboxil by analyzing the Food and Drug Administration Adverse Event Reporting System (FAERS) database.
Adverse event reports involving baloxavir marboxil were extracted from the FAERS database spanning the fourth quarter of 2018 to the third quarter of 2023. Demographic characteristics and reporter profiles were analyzed to characterize the exposed population. A disproportionality analysis was performed using four validated pharmacovigilance algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). These complementary approaches were employed to detect, prioritize, and validate potential safety signals.
Analysis of 8,824,675 ADE reports from the FAERS database identified 1,654 cases (0.19%) associated with baloxavir marboxil. Pediatric patients (< 18 years) exhibited the highest ADE reporting rate. Geospatial analysis revealed marked clustering, with 98.97% of reports originating from the United States (63.2%) and Japan (35.77%). We detected 47 significant safety signals spanning 27 System Organ Classes (SOCs), including established reactions such as pneumonia (n = 90) and vomiting (n = 77). Novel signals emerging from the analysis comprised hemorrhagic diathesis (n = 3), rhabdomyolysis (n = 25), hepatic dysfunction (n = 13), and cardiorespiratory arrest (n = 7). Notably, bleeding-related events (e.g., ischemic colitis, IC025 = 5.03) and neurological complications (e.g., febrile delirium, IC025 = 9.12) demonstrated statistically significant associations.
This pharmacovigilance study identifies previously undercharacterized safety signals associated with baloxavir marboxil, including hemorrhagic complications, liver dysfunction, rhabdomyolysis, and life-threatening cardiorespiratory events. Pediatric populations and patients on anticoagulants may require heightened monitoring. While these findings provide critical pharmacovigilance insights, our study is inherently constrained by the spontaneous reporting system, which introduces potential underreporting, reporting biases, and confounding factors. Future research could employ more rigorous prospective study designs, integrating clinical trials and epidemiological studies, to more accurately assess the safety risks of baloxavir marboxil.
作为一种新型抗流感药物，玛巴洛沙韦在大量人群中缺乏真实世界的安全性数据。因此，本研究旨在通过分析美国食品药品监督管理局不良事件报告系统（FAERS）数据库，调查与玛巴洛沙韦相关的药物不良事件（ADEs）。
从2018年第四季度至2023年第三季度的FAERS数据库中提取涉及玛巴洛沙韦的不良事件报告。分析人口统计学特征和报告者资料，以描述暴露人群的特征。使用四种经过验证的药物警戒算法进行不成比例分析：报告比值比（ROR）、比例报告比（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项目伽马泊松收缩器（MGPS）。采用这些互补方法来检测、优先排序和验证潜在的安全信号。
对FAERS数据库中的8,824,675份ADE报告进行分析，确定了1,654例（0.19%）与玛巴洛沙韦相关的病例。儿科患者（<18岁）的ADE报告率最高。地理空间分析显示出明显的聚集性，98.97%的报告来自美国（63.2%）和日本（35.77%）。我们检测到47个显著的安全信号，涵盖27个系统器官类别（SOCs），包括已确定的反应，如肺炎（n = 90）和呕吐（n = 77）。分析中出现的新信号包括出血素质（n = 3）、横纹肌溶解（n = 25）、肝功能障碍（n = 13）和心肺骤停（n = 7）。值得注意的是，出血相关事件（如缺血性结肠炎，IC025 = 5.03）和神经系统并发症（如高热谵妄，IC025 = 9.12）显示出统计学上的显著关联。
这项药物警戒研究确定了与玛巴洛沙韦相关的先前未充分描述的安全信号，包括出血并发症、肝功能障碍、横纹肌溶解和危及生命的心肺事件。儿科人群和服用抗凝剂的患者可能需要加强监测。虽然这些发现提供了关键的药物警戒见解，但我们的研究固有地受到自发报告系统的限制，该系统存在潜在的报告不足、报告偏倚和混杂因素。未来的研究可以采用更严格的前瞻性研究设计，整合临床试验和流行病学研究，以更准确地评估玛巴洛沙韦的安全风险。
