基于FAERS的盐皮质激素受体拮抗剂不良事件信号挖掘  

Signal Mining of Adverse Events Induced by Mineralocorticoid Receptor Antagonists Based on FAERS

作　　者：胡功利 王仲书[1] 陈力[2] HU Gongli;WANG Zhongshu;CHEN Li(The Fourth People's Hospital of Zigong,Zigong,Sichuan,China 643000;West China Second University Hospital,Sichuan University,Chengdu,Sichuan,China 610041)

机构地区：[1]四川省自贡市第四人民医院,四川自贡643000 [2]四川大学华西第二医院,四川成都610041

出　　处：《中国药业》2024年第18期108-113,共6页China Pharmaceuticals

基　　金：四川省自贡市重点科技计划项目[2022ZCYGY19]。

摘　　要：目的 促进盐皮质激素受体拮抗剂(MRA)的临床安全使用。方法 提取美国食品和药物管理局不良事件报告系统(FAERS)2018年第1季度至2023年第1季度上报的3种MRA(螺内酯、依普利酮及非奈利酮)相关药品不良事件(ADE)报告,采用监管活动医学词典中的系统器官分类(SOC)和首选语(PT)进行归类,采用报告比值比(ROR)法与英国药品和保健品管理局(MHRA)综合标准法挖掘ADE信号并进行分析。结果 获得以3类药物为首要怀疑药物的ADE报告35 908份,其中螺内酯27 792份、依普利酮6 734份、非奈利酮1 382份。涉及患者5 930例,其中螺内酯4 455例、依普利酮1 052例、非奈利酮423例;男女比例相当(49.45%比50.55%),以> 65岁患者居多(49.07%)。ADE上报者主要为医师(35.48%)和消费者(24.74%),上报国家主要为美国(37.37%),使用口服剂型的患者最多(47.89%)。PT层级共产生ADE信号467个,其中螺内酯312个、依普利酮136个、非奈利酮19个,包括高钾血症、急性肾损伤、低钠血症、颈静脉压降低等。共涉及26个SOC,其中螺内酯26个、依普利酮20个、非奈利酮8个,包括代谢及营养类疾病、肾脏及泌尿系统疾病、心脏器官疾病、各类检查等。结论 MRA常见ADE信号及其累及系统器官与相应药品说明书基本一致,但要警惕药品说明书中未记载的ADE,如先天性延髓性肌萎缩、慢性心力衰竭、颈静脉压升高、肌痛等。Objective To promote the safe use of mineralocorticoid receptor antagonists(MRAs)in clinical practice.Methods The adverse drug event(ADE)reports induced by three MRAs(spironolactone,eplerenone,finerenone)reported from the first quarter of 2018 to the first quarter of 2023 in the FDA Adverse Event Reporting System(FAERS)were extracted.The systematic organ classification(SOC)and preferred term(PT)in the Medical Dictionary for Regulatory Activities were used for classification,the ADE signals were mined and analyzed by the reporting odds ratio(ROR)and the Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard methods.Results A total of 35908 ADE reports were obtained with the above three MRAs as the primary suspected drugs,including 27792 reports of spironolactone,6734 of eplerenone and 1382 of finerenone.A total of 5930 patients were involved,including 4455 cases of spironolactone,1052 of eplerenone and 423 of finerenone;the proportions of males and females were comparable(49.45%vs.50.55%),the majority of patients were over 65 years(49.07%).ADEs were reported mainly by physicians(35.48%)and consumers(24.74%),mainly from the United States(37.37%),and the patients using oral dosage forms were the most(47.89%).A total of 467 ADE signals were generated at the PT level,including 312 of spironolactone,136 of eplerenone,and 19 of finerenone,involving hyperkalemia,acute kidney injury,hyponatremia,and decreased jugular venous pressure,etc.A total of 26 SOCs were involved,including 26 of spironolactone,20 of eplerenone,and eight of finerenone,involving metabolic and nutritional diseases,kidney and urinary system diseases,heart organ diseases,various examinations,etc.Conclusion The common ADE signals and the involved systems/organs of MRAs are basically consistent with those in the corresponding drug instruction,but we should be alert to the ADEs not recorded in drug instruction,such as congenital bulbar muscular atrophy,chronic heart failure,elevated jugular vein pressure,myalgia,etc.

关 键 词：盐皮质激素受体拮抗剂 螺内酯 依普利酮 非奈利酮 药品不良事件 信号挖掘 报告比值比法 英国药品和保健品管理局综合标准法 

分 类 号：R969.3[医药卫生—药理学] R977.1[医药卫生—药学]