基于FAERS数据库的新型四环素类药物不良事件信号挖掘研究

Data mining of adverse event of novel tetracycline-class drugs based on the FAERS database

目的基于美国食品药品管理局不良事件报告系统(FAERS)对新型四环素类药物奥马环素及依拉环素的相关不良事件(ADE)进行数据挖掘,为其临床安全使用提供参考。方法收集2018年第1季度至2024年第2季度FAERS中奥马环素与依拉环素的ADE报告数据。采用《国际医学用药词典》的系统/器官分类(SOC)和首选术语(PT)进行标准化处理与分类,采用报告比值比(ROR)法、英国药品和保健品管理局的综合标准(MHRA)法、贝叶斯置信区间递进神经网络(BCPNN)法和多项伽玛泊松分布缩减(MGPS)法进行ADE信号检测。结果以奥马环素为首要怀疑药品的ADE报告共616份,涉及的SOC中以各类损伤、中毒及手术并发症的报告最多。依拉环素的ADE报告85份,SOC以全身性疾病及给药部位各种反应最多。奥马环素采用MHRA法、ROR法、BCPNN法及MGPS法检测均为阳性信号的PT有32个,依拉环素为9个。奥马环素的常见ADE包括胃肠道ADE及肝酶升高,依拉环素的常见ADE为胰脂肪酶升高及胰腺炎。奥马环素说明书中未提及的ADE包括耳毒性及舌头着色,依拉环素说明书中未提及的ADE包括乳酸酸中毒、纤维蛋白原降低。结论基于FAERS进行ADE信号挖掘有利于发现新型四环素类药物新的ADE,其中奥马环素所致耳毒性及舌头着色,依拉环素所致乳酸酸中毒及纤维蛋白原降低说明书未记载,临床使用中应注意监测。

Objective To evaluate the clinical safety of the new tetracycline drugs,omadacycline and eravacycline,by analyzing adverse events(ADE)reported in FDA Adverse Event Reporting System(FAERS),to provide reference for clinical safety.Methods Extract ADE report data submitted to FAERS from first quarter 2018 to second quarter 2024.Signals were categorized and analyzed using system organ class(SOC)and preferred terms(PT)of Medical Dictionary for Regulatory Activities(MedDRA).Signal detection methods included the reporting odds ratio(ROR)method,Medicines and Healthcare products Regulatory Agency(MHRA)method,the Bayesian confidence interval propagation neural network(BCPNN)method and the multi-item gamma Poisson shrinker(MGPS)method.Results A total of 616 ADE cases were reported in which omadacycline was identified as the primary suspect drug,and the highest number of SOCs involved were reports of various types of injuries,poisonings,and surgical complications.While 85 cases were linked to eravacycline,and the SOCs were most frequent for systemic diseases and various reactions at the site of administration.Using the MHRA,ROR,BCPNN,and MGPS methods,omadacycline showed 32 positive signal PTs,while eravacycline showed 9.Omadacycline was frequently associated with ADE such as gastrointestinal disturbances and elevated liver enzyme levels.In contrast,eravacycline was commonly linked to increased lipase levels and pancreatitis.Notably,certain ADE were absent from the omadacycline prescribing information,including ototoxicity and tongue discoloration.Similarly,lactic acidosis and reduced fibrinogen levels were absent from the eravacycline preseribing information.Conclusion Using FAERS for ADE signal mining helps identify new side effects of tetracycline drugs.Omadacycline may cause ototoxicity and tongue discoloration,while eravacycline is linked to lactic acidosis and fibrinogen reduction,none of which are on product labels,and these effects should be monitored in clinical practice.