基于FAERS数据库的替扎尼定不良事件信号挖掘研究

Research on signal mining of adverse events of tizanidine based on FAERS database

目的 基于美国食品药品管理局不良事件报告系统(FAERS)数据库对替扎尼定不良事件(ADE)进行信号挖掘,探索ADE的发生特点,为临床安全应用替扎尼定提供参考。方法 运用报告比值比法和综合标准法分析FAERS数据库2004年第1季度至2022年第2季度的替扎尼定ADE报告数据。利用《国际医学用语词典》对ADE信号挖掘结果进行汉化及系统归类。结果 获得替扎尼定ADE报告数7 135份,涉及患者1 732例,涉及ADE共1 304种。基于2种ADE信号挖掘方法,在首选语(PT)层级共获得177个信号。药品说明书中未记载的PT信号有32个,包括钾消耗性肾病、心脏呼吸骤停、胎儿生长受限等。1 732例患者中,发生ADE的女性例数是男性的2.37倍(1 057例vs. 446例),年龄在40~64岁的人群占比较大(36.03%),报告人员以消费者占比最大(32.79%),累及的系统/器官主要有各类神经系统疾病、精神病类等。替扎尼定相关ADE的中位发病时间为75 d(四分位间距:28~223 d),但需警惕开始用药1年后仍有ADE发生的可能(13.38%)。结论 临床应用替扎尼定时应充分关注其钾消耗性肾病、自杀既遂等ADE的发生及女性、40~64岁等重点人群。

Objective Based on U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the signal mining of tizanidine adverse drug events(ADEs)was conducted to explore the occurrence characteristics of ADE,hoping to provide references for the safe clinical application of tizanidine.Methods The reporting odds ratio(ROR)and medicines and healthcare products regulatory agency methods(MHRA)were used to analyse the ADE of tizanidine using FAERS registration data from the first quarter of 2004 to the second quarter of 2022.After valid signals were obtained,the MedDRA was used for translation and system organ classification.Results A total of 7135 reports of tizanidine ADE were obtained,including 1732 patients,1304 ADE types were involved.According to the results of 2 ADE signal mining methods,at the preferred term(PT)level,177 signals were detected.There were 32 PT signals not included in the drug instructions,including potassium wasting nephropathy,cardio-respiratory arrest,and foetal growth restriction etc.In 1732 patients,the number of ADE cases of female was 2.37 times that in male(1057 vs.446),and the age group between 40 and 64 accounted for a large proportion(36.03%).The highest proportion(32.79%)reported by consumers.The system organ class involved mainly included various neurological diseases and psychosis.The median time to onset of tizanidine-related ADEs was 75 d(interquartile range:28-223 d),but it was necessary to be vigilant that ADE may still occur 1 year after starting the drug(13.38%).Conclusion This study aims to suggest that clinical application of tizanidin-related ADE should be paid full attention to the occurrence of ADE such as potassium-wasting nephropathy and suicidally completed,as well as key populations such as women and patients of 40-64 years old.