基于FAERS数据库的奥司他韦相关药品不良事件的挖掘与分析

Mining and Analysis of Adverse Drug Events of Oseltamivir Based on FAERS Database

目的:挖掘和评价奥司他韦上市后的安全信号,为临床合理用药提供依据。方法:检索美国食品药品监督管理局不良事件报告系统(FAERS)数据库中2004年1月至2022年9月收录的以奥司他韦为首要怀疑对象的药品不良事件(ADE)报告,采用报告比值比法(ROR)和贝叶斯置信区间递进神经网络法(BCPNN)检测ADE信号,重点分析胃肠系统、神经系统、精神病类、肝胆系统等11个系统器官分类(SOC)所涉及的安全信号。结果:收集到以奥司他韦为首要怀疑药物的ADE报告794份(794例患者),其中女性患者所占比例(394例,占49.62%)高于男性患者(297例,占37.41%);年龄<18岁的患者居多(489例,占61.59%);严重不良事件(SAE)共232例(占29.22%)。检出的ADE信号共涉及21个SOC。对重点SOC进行分析发现,神经系统相关ADE中,信号主要集中在惊厥发作(ROR=2.77,IC=1.43)、意识丧失(ROR=2.01,IC=0.99)、言语障碍(ROR=2.67,IC=1.37);精神系统主要表现为异常行为(ROR=30.34,IC=4.74)、幻觉(ROR=20.69,IC=4.22)、失眠(ROR=2.08,IC=1.03)等;奥司他韦侵犯胃肠道主要表现为上腹痛(ROR=2.05,IC=1.01)、呕吐(ROR=6.19,IC=2.48)、出血性小肠结肠炎(ROR=46.35,IC=4.28)等。其他系统高风险信号主要为爆发性肝炎(ROR=10.88,IC=2.70)、急性心力衰竭(ROR=5.89,IC=2.17)、心肌炎(ROR=4.49,IC=1.93)、弥散性血管内凝血(ROR=2.60,IC=1.25)、史-约综合征(ROR=3.44,IC=1.70)、中毒性表皮坏死松解症(ROR=2.06,IC=0.94)等。结论:在患者使用奥司他韦的过程中,除密切关注惊厥发作、异常行为、幻觉、失眠、呕吐、上腹痛等常见ADE外,还应关注爆发性肝炎、急性心力衰竭、弥散性血管内凝血等SAE。

OBJECTIVE:To explore and evaluate the safety signal of oseltamivir after the marketing,so as to provide basis for clinical rational drug use.METHODS:Adverse drug event(ADE)reports with oseltamivir as the first suspected drugs were retrieved from the Food and Drug Administration Adverse Event Reporting System(FAERS)database from Jan.2004 to Sept.2022.Reporting Odds Ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method were sued to detect the ADE signals,mainly included 11 key system organ classification(SOC)such as gastrointestinal,neurological,psychiatric,and hepatobiliary systems.RESULTS:Totally 794 reports of ADE(794 patients)with oseltamivir as the first suspected drug were collected,with a higher proportion of female patients(394 cases,49.62%)than male patients(297 cases,37.41%).The reported ages were all concentrated under 18 years old(489 cases,61.59%),with 232 cases of SAE(29.22%).The detected ADE signals involved a total of 21 SOC.Analysis of key SOC showed that the signals of neurological system-related ADE were mainly convulsive seizures(ROR=2.77,IC=1.43),loss of consciousness(ROR=2.01,IC=0.99),and speech disorders(ROR=2.67,IC=1.37).The main manifestations of psychiatric disorders were abnormal behavior(ROR=30.34,IC=4.74),hallucination(ROR=20.69,IC=4.22),insomnia(ROR=2.08,IC=1.03).The main manifestations of oseltamivir-related gastrointestinal tract were upper abdominal pain(ROR=2.05,IC=1.01),vomiting(ROR=6.19,IC=2.48)and hemorrhagic enterocolitis(ROR=46.35,IC=4.28).Other systemic high-risk signals were mainly hepatitis fulminant(ROR=10.88,IC=2.70),acute heart failure(ROR=5.89,IC=2.17),myocarditis(ROR=4.49,IC=1.93),disseminated intravascular coagulation(ROR=2.60,IC=1.25),Stevens-Johnson syndrome(ROR=3.44,IC=1.70),and toxic epidermal necrolysis(ROR=2.06,IC=0.94).CONCLUSIONS:During the use of oseltamivir,in addition to close attention to common ADE such as convulsive seizures,abnormal behavior,hallucinations,insomnia,vomiting and epigastric pain,SAE such as hepatitis fulminant,acute heart failure,and disseminated intravascular coagulation should be monitored.