基于FDA不良事件数据库对甲巯咪唑与丙硫氧嘧啶药物风险信号的数据挖掘与评价

Data Mining and Evaluation of Pharmacovigilance Risk Signals of Methimazole and Propylthiouracil Based on FDA Adverse Event Database

目的挖掘甲巯咪唑(MMI)及丙硫氧嘧啶(PTU)药物不良事件(ADE)信号,并对其上市后安全性作出评价,为临床合理用药提供参考。方法采用报告比值比(ROR)法对美国食品药品管理局(FDA)公共数据库2004年1月—2016年12月ADE报告进行药品的风险信号挖掘,并分析年龄、性别等对风险信号的影响。结果以MMI和PTU为首要怀疑药品的ADE分别为5367,2133份,相关风险信号分别有536,1053个,ADE信号数量按系统器官分类排序前5位分别为全身性疾病及给药部位反应、血液及淋巴系统、肝胆系统、内分泌系统、医学检查。其中高强度风险信号包括急性肝衰竭(PTU,ROR=15.73;MMI,ROR=2.39);粒细胞缺乏(PTU,ROR=24.1;MMI,ROR=24.6);ANCA阳性血管炎(PTU,ROR=283.10;MMI,ROR=54.60);幼儿先天性皮肤发育不全(PTU,ROR=475.8;MMI,ROR=374.2)等。结论PTU存在严重肝肾损伤、血管炎、血液系统损伤等风险;MMI存在胆道损伤、皮肤损伤、孕期药物影响等风险。建议妊娠期甲状腺功能亢进(甲亢)患者首选PTU,青少年甲亢、皮肤药物敏感患者慎用MMI。

To mine the adverse drug reaction signals of methimazole(MMI)and propylthiouracil(PTU),and evaluate the security to provide reference for clinical medication.Methods The reporting odds ratio(ROR)was used to mine the risk signals from the data in the Open FDA of US Food and Drug Administration(FDA)during 2004-2016,and analyze the impact of age,gender and other effects on the signal.Results MMI and PTU as the primary suspect drug ADE were 5367 copies and 2133 copies,and the relevant signals were 536,1053.The top five ADE signals of system organ class were blood and lymphatic system disorders,general disorders and administration site conditions,hepatobiliary disorders,endocrine disorders,investigations.The high intensity risk signals include acute hepatic failure(PTU,ROR=15.73;MMI,ROR=2.39),agranulocytosis(PTU,ROR=24.1;MMI,ROR=24.6),ANCA positive vasculitis(PTU,ROR=283.10;MM,ROR=54.60),aplasia cutis congenita(PTU,ROR=475.8;MMI,ROR=374.2),etc.Conclusion PTU has the risks of severe renal and hepatic damages,vasculitis and blood system damage,etc;MMI has risks of bile duct and skin injuries,drug exposure during pregnancy,etc.PTU is recommended as the first-line choice for pregnancy with hyperthyroidism.Adolescent and skin sensitive patients using MMI should be strictly observed with caution.