基于FAERS和JADER数据库的甲磺酸雷沙吉兰不良事件信号挖掘与分析

Mining and analysis of adverse event signals of rasagiline mesylate based on the FAERS and JADER databases

摘要

目的: 对甲磺酸雷沙吉兰的药品不良事件(adverse drug event,ADE)进行挖掘与分析,以提升临床用药的合理性及安全性。方法: 从美国FDA不良事件报告系统(FDA adverse event reporting system,FAERS)和日本药品不良事件报告系统(Japanese adverse drug event report database,JADER)搜索并提取2006年5月—2024年9月甲磺酸雷沙吉兰上市以来的不良事件报告,联合使用报告比值比(reporting odds ratio,ROR)法、比例报告比(proportional reporting ratio,PRR)法进行数据处理及分析,筛选出阳性信号后,与说明书进行对比,挖掘出潜在新的药物不良反应。结果: 2个数据库分别筛选出以甲磺酸雷沙吉兰为首要怀疑药物的ADE报告7 303和1 263份,获得阳性信号122和45个,累及系统16和10个。发生不良事件女性略多于男性,以老年患者(年龄≥65岁)占比最高,大多数病例发生不良反应在用药后1个月内。FAERS数据库中报告数位于前3位的ADE信号为跌倒、震颤、头晕,相关性位于前3位的ADE信号为性变态(ROR=266.23,PRR=266.08)、突发睡眠(ROR=167.63,PRR=166.97)、脑灌注不足(ROR=129.75,PRR=129.62)。JADER数据库中报告数位于前3位的ADE信号为幻觉、幻视、跌倒,相关性位于前3位的ADE信号为直立性低血压(ROR=226.93,PRR=216.91)、血压波动(ROR=212.31,PRR=208.63)、突发睡眠(ROR=181.89,PRR=179.60),主要涉及各类神经系统疾病、精神类疾病、各类损伤、中毒及操作并发症、血管与淋巴管类疾病等。发现了47个未被说明书收录的ADE,包括感染性吸入性肺炎、大脑梗死、快速眼动睡眠行为障碍、主动脉夹层等安全警戒信号。结论: 临床在使用甲磺酸雷沙吉兰时,除关注说明书中已提及的ADE外,还需重视新的可疑ADE,必要时采取干预措施,以保证患者用药安全有效。

Abstract

Objective: To explore and analyze the adverse drug events (ADEs) of rasagiline mesylate after its launch, in order to improve the safety and rationality of clinical medication. Methods: Adverse event reports of rasagiline mesylate from May 2006 to September 2024 were searched and extracted from the FDA Adverse Event Reporting System (FAERS) in the United States and the Japanese Adverse Drug Event Report Database (JADER). The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were used to process and analyze the data. Positive signals were screened and compared with the instructions to identify potential new drug adverse reactions. Results: A total of 7 303 and 1 263 ADE reports with rasagiline mesylate as the primary suspected drug were screened from the two databases, respectively, and 122 and 45 positive signals were obtained, involving 16 and 10 SOCs. There were slightly more female patients than male patients who experience adverse events, with the highest proportion being elderly patients (aged ≥65 years). Most cases experienced adverse reactions within one month after medication. The top three reported ADE signals in the FAERS database were falls, tremors, and dizziness, while the top three correlated ADE signals were sexual abnormalities (ROR=266.23, PRR=266.08), sudden sleep (ROR=167.63, PRR=166.97), and cerebral hypoperfusion (ROR=129.75, PRR=129.62). The top three ADE signals reported in the JADER database were hallucinations, visual hallucinations, and falls. The top three ADE signals with high correlation were orthostatic hypotension (ROR=226.93, PRR=216.91), blood pressure fluctuations (ROR=212.31, PRR=208.63), and sudden sleep (ROR=181.89, PRR=179.6). It mainly involved various neurological diseases, mental illnesses, various injuries, poisoning and operational complications, vascular and lymphatic diseases, etc. Forty-seven ADEs not included in the instruction manual were identified, including safety warning signals such as infectious aspiration pneumonia, cerebral infarction, rapid eye movement sleep behavior disorder, aortic dissection, etc. Conclusion: When using rasagiline mesylate in clinical practice, in addition to paying attention to the ADEs already mentioned in the instructions, it is also necessary to pay attention to new suspected ADEs, and take intervention measures when necessary to ensure the safe and effective use of the drug for patients.

关键词

甲磺酸雷沙吉兰 / FAERS数据库 / JADER数据库 / 不良事件 / 报告比值比法 / 比例报告比法 / 数据挖掘

Key words

rasagiline mesylate / FAERS database / JADER database / adverse drug events / reporting odds ratio method / proportional reporting ratio method / data mining