基于美国FDA不良事件报告系统数据库的多西环素儿童相关不良事件风险信号挖掘

Signal mining of risk of doxycycline-related adverse events in children based on US FDA Adverse Event Reporting System database

目的了解儿童使用多西环素相关不良事件(AE)风险信号,为安全使用该药提供参考。方法收集美国FDA不良事件报告系统(FAERS)数据库2004年第1季度至2023年第3季度以多西环素为首要怀疑药物的儿童AE报告,采用《国际医学用语词典》26.1版首选术语(PT)和系统器官分类(SOC)对AE进行标准化和分类。采用报告比值比(ROR)法进行多西环素AE风险信号挖掘,AE报告数≥3且ROR的95%置信区间(CI)>1定义为风险信号,并对其进行描述性分析。结果共收集到儿童使用多西环素相关AE报告637份,涉及107个PT和21个SOC。AE报告数居前10位(含并列)的PT依次为呕吐、抑郁、吞咽困难、赫克斯海默反应、硬化性胆管炎、头痛、溃疡性结肠炎、食管溃疡、恶心、食管炎、自杀想法,其中抑郁、赫克斯海默反应、硬化性胆管炎、溃疡性结肠炎、自杀想法为说明书未记载的不良反应。信号强度居前10位的PT依次为赫克斯海默反应、光照性指甲松离、醒前幻觉、食管溃疡、食管损伤、睡前幻觉、玻璃体炎、指甲剥离、硬化性食管炎、糜烂性食管炎,其中赫克斯海默反应、醒前幻觉、睡前幻觉、玻璃体炎、硬化性胆管炎为说明书未记载的不良反应。精神疾病为该药说明书不良反应中未涉及的SOC。结论多西环素儿童相关AE主要为呕吐、吞咽困难、食管溃疡、恶心、食管炎等药品说明书已记载的不良反应。此外,多西环素还可能导致赫克斯海默反应、硬化性胆管炎、溃疡性结肠炎、精神疾病等药品说明书未记载的AE。

Objective To understand the adverse event(AE)risk signal of doxycycline in children and provide reference for the safe use of the drug in clinic.Methods AE reports of children with doxycy⁃cline as primary suspect drug were collected from the US FDA Adverse Event Reporting System(FAERS)database during the 1st quarter of 2004 to the 3rd quarter of 2023.AEs were standardized and classified according to the preferred term(PT)and system organ class(SOC)in Medical Dictionary for Regulatory Activities 26.1.The AE risk signals of doxycycline were mined using reporting odds ratio(ROR)method.An AE with reports≥3 and the lower limit of the 95%CI of ROR>1 was defined as a risk signal.Descriptive analysis on the risk signals was performed.Results A total of 637 AE reports related to doxycycline in children were collected,involving 107 PTs and 21 SOCs.The top 10 PTs in the number of reports(including juxtaposition)were vomiting,depression,dysphagia,Jarisch⁃Herxheimer reaction,cholangitis sclerosing,headache,colitis ulcerative,oesophageal ulcer,nausea,oesophagitis,and suicidal ideation.Among them,depression,Jarisch⁃Herxheimer reaction,cholangitis sclerosing,colitis ulcerative and suicidal ideation were not recorded in labels.The top 10 PTs in signal intensity were Jarisch⁃Herxheimer reaction,photoonycholy⁃sis,hypnopompic hallucination,oesophageal ulcer,oesophageal injury,hypnagogic hallucination,vitritis,onycholysis,cholangitis sclerosing,erosive oesophagitis.Among them,Jarisch⁃Herxheimer reaction,hypno⁃pompic hallucination,hypnagogic hallucination,vitritis and cholangitis sclerosing were not recorded in labels.Psychiatric disorders were not covered by adverse reactions in the label.Conclusions The main AEs of doxycycline in children are vomiting,dysphagia,oesophageal ulcer,nausea,oesophagitis,all of which are recorded in the drug label.In addition,doxycycline may also cause AEs that are not recorded in drug label,such as Jarisch⁃Herxheimer reaction,sclerosing cholangitis,ulcerative colitis,and psychiatric disorders.