基于中国山东省药品不良反应监测中心和美国FDA不良事件报告系统数据库的注射用砷剂心脏毒性风险信号挖掘  

Signal mining of cardiotoxicity risk in arsenical for injection based on the database of Shandong Provincial Center of Adverse Drug Reaction Monitoring in China and the US FDA Adverse Event Reporting System database

作　　者：衣巧艳 谢彦军[2] 舒雨童 张秋红 戚迎梅 李敏 赵霞[1] 刘逢芹[1] 李霞 韩毅[1] Yi Qiaoyan;Xie Yanjun;Shu Yutong;Zhang Qiuhong;Qi Yingmei;Li Min;Zhao Xia;Liu Fengqin;Li Xia;Han Yi(Department of Pharmacy,the First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,Ji′nan 250014,China;Shandong Provincial Center of Adverse Drug Reaction Monitoring(Shandong Drug Abuse Monitoring Center),Ji′nan 250013,China;College of Pharmacy,Shandong University,Ji′nan 250012,China;Ji′nan Center for ADR and MDAE monitoring,Ji′nan 250000,China)

机构地区：[1]山东第一医科大学第一附属医院(山东省千佛山医院)药学部,济南250014 [2]山东省药品不良反应监测中心(山东省药物滥用监测中心),济南250013 [3]山东大学药学院,济南250012 [4]济南市药品不良反应和医疗器械不良事件监测中心,济南250000

出　　处：《药物不良反应杂志》2024年第3期133-137,共5页Adverse Drug Reactions Journal

基　　金：国家重点研发计划(2020YFC2008303,2020YFC2008306);山东省重点研发计划(2020RKB14165);山东省千佛山医院培育基金(QYPY2020NSFC0813);山东省药品不良反应监测中心委托项目(2022SDADRKY14)。

摘　　要：目的挖掘注射用砷剂心脏不良事件风险信号,提高临床对砷剂心脏毒性的认识。方法采用报告比值比(ROR)法、比例报告比值比(PRR)法和英国药品和保健品管理局(MHRA)综合标准法3种方法对山东省药品不良反应监测中心数据库(山东数据)2003年第1季度至2022年第4季度和美国FDA不良事件报告系统(FAERS)数据库2003年第4季度至2023年第3季度的药物不良反应/事件报告中注射用砷剂心脏毒性风险信号进行挖掘。ROR法和PRR法中,报告数≥3、ROR和PRR值的95%CI下限>1定义为不良事件风险信号;MHRA综合标准法中,报告数≥3、PRR>2且χ^(2)>4定义为不良事件风险信号。结果山东数据中共有注射用砷剂相关报告358例,与亚砷酸氯化钠注射液有关者275例(76.8%),与注射用三氧化二砷(ATO)有关者83例(23.2%);358例报告中25例(7.0%)报告了心脏不良反应,严重者占28.0%(7/25)。FAERS数据库中共有ATO相关报告1294例,其中418例(32.3%)报告了心脏不良事件,严重者占62.2%(260/418)。对山东数据中275例亚砷酸氯化钠注射液报告的数据挖掘结果显示,QT间期延长、胸闷、心悸和心慌为风险信号,其中QT间期延长的信号最强。在FAERS数据中共挖掘出35个心脏不良事件信号,其中QT间期延长和长QT综合征的信号最强;6个心律失常信号(缓慢型心律失常、室上性期前收缩、室性期前收缩、尖端扭转型室速、室性心动过速和房室阻滞)和6个心脏器质性病变信号(心包炎、心内膜炎、心包积液、心肌炎、二尖瓣关闭不全和心脏扩大)的强度也排名较前。结论注射用砷剂与心脏毒性发生的关联性较强,且严重病例占比较高。注射用砷剂的心脏毒性主要影响QT间期,也可表现为多种类型心律失常和某些心脏器质性病变。Objective To explore the adverse cardiac event risk signals in arsenical for injection,improve the clinical understanding of the cardiac toxicity of arsenical.Methods The risk signals of adverse cardiac events associated with arsenical for injection were mined using 3 methods,including reporting odds ratio(ROR)method,proportional reporting ratio(PRR)method,and the Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard method based on data in Shandong Provincial Center of Adverse Drug Reaction Monitoring(Shandong data)in China from the first quarter of 2003 to the fourth quarter of 2022 and the data in US FDA Adverse Event Reporting System(FAERS)database from the fourth quarter of 2003 to the third quarter of 2023.The definition of risk signal in ROR and PRR method was the number of adverse event reports≥3 and the lower limit of 95%confidence interval(CI)of ROR and PRR>1.The definition of risk signals in MHRA comprehensive standard method was the number of adverse event reports≥3,PRR>2,andχ^(2)>4.Results There were a total of 358 reports on arsenical for injection in Shandong data,of which 275(76.8%)were related to arsenious acid and sodium chloride injection,and 83(23.2%)were related to arsenic trioxide for injection.Among the 358 reports,adverse cardiac reactions were reported in 25 reports(7.0%),and severe cases accounted for 28.0%(7/25).There were a total of 1294 reports on ATO in FAERS,and adverse cardiac events were reported in 418 reports(32.3%),of which severe cases accounted for 62.2%(260/418).The signal mining results form 275 reports on arsenious acid and sodium chloride injection in Shandong data showed that QT interval prolonged,chest tightness,cardiopalmus,and palpitations were risk signals.Among them,the signal strength of QT interval prolonged was the strongest.A total of 35 adverse cardiac event signals were mined in FAERS data,of which the signal strength of QT interval prolonged and long QT syndrome were the strongest.In addition,the strength of 6 arrhythmia signals

关 键 词：三氧化二砷 药物不良反应报告系统 心脏毒性 药物警戒 药品说明书 

分 类 号：R95[医药卫生—药学]