基于FAERS数据库的奈玛特韦/利托那韦片不良事件信号挖掘与分析

Signal mining and analysis of adverse drug events for nirmatrelvir/ritonavir tablets based on FAERS database

目的基于美国食品药品监督管理局不良事件报告系统(FAERS)数据库,挖掘奈玛特韦/利托那韦片组合包装的可疑不良事件(ADE)信号,为临床安全使用奈玛特韦/利托那韦片提供参考。方法收集FAERS数据库2021年第4季度至2022年第4季度奈玛特韦/利托那韦片的ADE报告,采用报告比值比法(ROR)和比例报告比值比法(PRR)进行风险信号挖掘,并利用《监管活动医学词典》(MedDRA)中药物不良反应术语集的系统器官分类(SOC)和首选术语(PT)对ADE报告进行分类和描述。结果获得首要怀疑药物为奈玛特韦/利托那韦片的ADE报告26135例,涉及1859个ADE信号,上报人员多以患者(71.53%)为主,美国(80.91%)上报数量最多。经ROR法和PRR法计算分析得到阳性信号246个,涉及21个SOC。本研究中奈玛特韦/利托那韦片较为常见或相关性较高的ADE信号为腹泻、呕吐、味觉倒错、头晕和肌痛等,与奈玛特韦/利托那韦片药品说明书记载一致;还发现未列入药品说明书的新的潜在风险信号,包括苔舌、舌水疱、鼻充血、流涕、疾病复发、免疫抑制剂水平升高、抗凝药水平降低、产品给用持续时间有误、产品包装混淆和产品剂量混淆等。结论临床在应用奈玛特韦/利托那韦片时,除了关注药品说明书中已记载的ADE信号,还应严密关注药品说明书中未记载的新的潜在ADE信号,以保证患者用药的安全性。

Objective To mine the signals of adverse drug events(ADE)for nirmatrelvir/ritonavir tablets(co-packaged)based on Food and Drug Administration adverse event reporting system(FAERS)database,and to provide reference for safe use of drugs in clinic.Methods The reports on nirmatrelvir/ritonavir-induced ADE were collected from FAERS database from Q42021 to Q42022,and reporting odds ratio(ROR)method and proportional reporting ratio(PRR)method were used for risk signals mining.ADE reports were classified and described using the system organ class(SOC)and preferred term(PT)of the adverse drug reaction nomenclature set in Medical Dictionary for Regulatory Activities(MedDRA).Results A total of 26135 ADE reports on the primary suspected drug nirmatrelvir/ritonavir tables were obtained,involving 1859 ADE signals.The reporting population was mostly patients(71.53%)and the reporting country was mainly the United States(80.91%).After ROR method and PRR method mining,246 positive ADE signals were obtained,involving 21 SOC.The more common or highly correlated ADE signals for nirmatrelvir/ritonavir in this study were diarrhoea,vomiting,dysgeusia,dizziness and myalgia,which were consistent with the nirmatrelvir/ritonavir drug instructions.This study also identified new signals not mentioned in the drug instructions,including coated tongue,tongue blistering,nasal congestion,rhinorrhoea,disease recurrence,increase in immunosuppressant drug level,decrease in anticoagulation drug level,incorrect drug administration duration,product packaging confusion,product dose confusion,etc.Conclusion To ensure patients′safety,when using nirmatrelvir/ritonavir,it was important to pay attention to the ADE signals that had been documented in the drug instruction,as well as new ADE signals that are not mentioned in the drug instruction.