基于FAERS数据库的托吡酯不良事件信号挖掘与分析

Mining and analysis of topiramate adverse event signals based upon FAERS database

目的:挖掘托吡酯上市后的不良事件(adverse drug event,ADE)信号,提高对托吡酯安全性的认知。方法:检索了美国食品药品监督管理局不良事件报告系统(FDA Adverse Event Reporting System,FAERS)数据库2014年第3季度至2023年第2季度的数据,使用报告比值比(reporting odds ratio,ROR)和比例报告比(proportional reporting ratio,PRR)法对托吡酯的ADE信号进行挖掘与分析。结果:托吡酯ADE报告12 862份,ADE信号598个。系统器官分类(system organ class,SOC)不成比例分析发现“各种先天性家族性遗传性疾病”(ROR=2.91,PRR=2.88)具有显著性。首选术语(preferred term,PT)分析揭示了托吡酯相关的强度较高的ADE信号,如鼻石症、视觉持续、睫状肌痉挛、主动脉肺动脉间隔缺损以及良性家族性天疱疮等;发生频次较高的ADE信号,如异常感觉、嗜睡、记忆受损、意识模糊状态、肾结石以及认知障碍等。与药品说明书和药物副作用资源(Side Effect Resource,SIDER)数据库对比发现,部分ADE信号保持高度一致,同时也发现了一些新的ADE信号。结论:妊娠期妇女应谨慎使用托吡酯,并关注各种先天性疾病的风险。同时也应警惕相关的“眼器官疾病”“肾脏及泌尿系统疾病”以及说明书中未提及的ADE信号,保障患者用药安全。

OBJECTIVE To enhance the understanding of safety profile of topiramate through analyzing the adverse drug event(ADE) signals reported in the database of FDA Adverse Event Reporting System(FAERS) since its market approval.METHODS Raw data from the database of FAERS were retrieved for the third quarter of 2014 through the second quarter of 2023,focusing upon ADE reports associated with topiramate.Reporting odds ratio(ROR) and proportional reporting ratio(PRR) were employed for identifying positive signals of ADEs related to topiramate.RESULTS A total of 12 862 ADE reports associated with topiramate encompassed 598 distinct ADE signals.A disproportionate analysis of system organ class(SOC) revealed significant association with “Congenital,familial and genetic disorders”(ROR=2.91,PRR=2.88).Preferred term(PT) analysis revealed a number of higher intensity ADE signals associated with topiramate,such as rhinolithiasis,visual perseveration,ciliary muscle spasm,aortopulmonary septal defect and benign familial pemphigus;ADE signals of higher frequency,such as paraesthesia,somnolence,memory impairment,confusional state,nephrolithiasis and cognitive disorder.Lastly,upon comparisons with package inserts and the database of Side Effect Resource(SIDER),some ADE signals showed consistent patterns while novel ADE signals were also identified.CONCLUSION Caution is advised for pregnant women due to an elevated risk of congenital diseases.Additionally,vigilance is recommended for topiramate-associated “eye disorders”,“renal and urinary disorders” and ADE signals not mentioned in package inserts,ensuring the dosing safety of patients.