基于FAERS的神经氨酸酶抑制剂药品不良事件信号挖掘

Signal Mining of Adverse Drug Events of Neuraminidase Inhibitors Based on FAERS Database

目的为临床安全使用神经氨酸酶抑制剂提供参考。方法采用OpenVigil 2.1平台检索美国食品和药物管理局不良事件报告系统(FAERS)中2004年第1季度至2022年第3季度奥司他韦、扎那米韦、帕拉米韦的相关药品不良事件(ADE)报告(其中帕拉米韦只有2015年至2022年的数据),采用报告比值比(ROR)法和英国药品和保健品管理局(MHRA)综合标准法挖掘ADE信号,采用《国际医学用语词典(25.0版)》(MedDRA 25.0)中的首选语(PT)对检索到的药品不良反应(ADR)进行编码,按系统器官分类(SOC)进行归类。结果共获得以神经氨酸酶抑制剂为首要怀疑药物的ADE报告14646份,其中奥司他韦12223份、扎那米韦2377份、帕拉米韦46份。共挖掘到ADE信号228个,涉及15个SOC,SOC主要集中在精神病类、胃肠系统疾病、各类神经系统疾病等。发生频次较多的ADR,奥司他韦为呕吐、异常行为、幻觉、失眠、意识模糊状态等,扎那米韦为异常行为、幻觉、谵妄、意识丧失、意识状态改变等,帕拉米韦为休克和急性肾损伤;信号强度较大的ADR,奥司他韦为婴儿痤疮、热性谵妄、病态人格、出血性小肠结肠炎、睡惊症等,扎那米韦为热性谵妄、热性惊厥、眼黏膜皮肤综合征、异常行为、梦话,帕拉米韦为休克和急性肾损伤;未列入药品说明书的ADR,奥司他韦有失眠、上腹痛、攻击、意识丧失、心动过缓等,扎那米韦有意识丧失、意识水平下降、惊厥发作、攻击、激越等。结论临床使用神经氨酸酶抑制剂时,应关注精神病类、胃肠系统疾病和各类神经系统疾病的ADR,以保障患者的用药安全。

Objective To provide a reference for clinic safe use of neuraminidase inhibitors.Methods The OpenVigil 2.1 platform was used to retrieve adverse drug event(ADE)reports related to three neuraminidase inhibitors(oseltamivir,zanamivir,peramivir)in the US Food and Drug Administration Adverse Event Reporting System(FAERS)from the first quarter of 2004 to the third quarter of 2022(with data for peramivir only available from 2015 to 2022).The reporting odds ratio(ROR)method and the Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive method were used to mine ADE signals,the preferred terms(PT)in the MedDRA 25.0 were used for encoding of the searched adverse drug reactions(ADRs)and the system organ classification(SOC)was used for classification.Results A total of 14646 ADE reports were obtained with neuraminidase inhibitors as the primary suspected drug,including 12223 reports of oseltamivir,2377 reports of zanamivir,and 46 reports of peramivir.A total of 228 ADE signals and 15 SOCs were mined,with SOC mainly concentrated in psychiatric disorders,gastrointestinal diseases,various neurological diseases,etc.ADRs with a high frequency of occurrence included vomiting,abnormal behavior,hallucinations,insomnia,and confusion of oseltamivir,abnormal behavior,hallucinations,delirium,loss of consciousness,and changes in the consciousness of zanamivir,and shock and acute kidney injury of peramivir.ADRs with high signal intensity included infantile acne,delirium febrile,pathological personality,hemorrhagic enterocolitis,and sleep disturbances of oseltamivir,delirium febrile,febrile seizures,ocular mucocutaneous syndrome,abnormal behavior,and sleep talk of zanamivir,and shock and acute kidney injury of peramivir.Oseltamivir had insomnia,upper abdominal pain,aggression,loss of consciousness,bradycardia,and other ADRs not listed in the drug instructions.Zanamivir had loss of consciousness,decreased consciousness levels,seizures,aggression,agitation,and other ADRs not listed in the drug instructions.Conclusion When using neuraminidase inhibitors in the clinic,attention should be paid to ADRs in psychiatric,gastrointestinal,and various neurological diseases to ensure the safety of medication for patients.