基于FDA数据库对氯喹不良反应信号的检测及药物相互作用分析  

Detection and Analysis of Safety Signals of Chloroquine Based Upon FDA Adverse Event Database

作　　者：胡希 洪东升[1,2] 羊红玉 郑东升[1,2] 赵青威 HU Xi;HONG Dong-sheng;YANG Hong-yu;ZHENG Dong-sheng;ZHAO Qing-wei(The First Affiliated Hospital,College of Medicine,Zhejiang University,Hangzhou 310003,China;Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research,Hangzhou 310003,China)

机构地区：[1]浙江大学医学院附属第一医院,杭州310003 [2]浙江省药物临床研究与评价技术重点实验室,杭州310003

出　　处：《中国药学杂志》2020年第9期685-691,共7页Chinese Pharmaceutical Journal

基　　金：国家临床重点专科(临床药学)项目资助;浙江省公益技术研究社会发展项目资助(2016C33142);“十三五”浙江省中医药(中西医结合)重点学科建设计划项目资助(2017-xk-A35);浙江省药学会医院药学专项科研项目资助(2012ZYY02,2019ZYY12)。

摘　　要：目的挖掘和评价氯喹上市后的安全信号,为新型冠状病毒肺炎抗病毒等临床合理用药提供参考。方法检索美国食品药品监督管理局(Food and Drug Administration,FDA)不良事件报告系统(FDA Adverse Event Reporting System,FAERS)数据库2004年01月01日至2020年02月22日收录以氯喹为怀疑药物不良事件(adverse drug events,ADEs)报告,采用报告比值比(ROR)法和贝叶斯可信区间递进神经网络法(BCPNN)检测该药品各种ADEs信号,重点评估口服氯喹对各个脏器系统的安全信号。结果纳入分析的2063份ADEs报告中,以氯喹为怀疑药物的ADEs报告共557份。经检测,发现该药不良反应信号累及多个系统,具有临床参考意义的高风险信号包括:完全性房室传导阻滞(ROR=2.90,IC-2SD=1.64)、心室纤维性颤动(ROR=3.40,IC-2SD=1.27)、失明(ROR=27.51,IC-2SD=0.55)、心源性休克(ROR=6.86,IC-2SD=0.54)和呕吐(ROR=1.70,IC-2SD=1.83)等;另有少见且高危的不良反应信号包括:低钾血症(ROR=4.18,IC-2SD=1.51)、急性肾衰竭(ROR=3.08,IC-2SD=0.30)、高铁血红蛋白血症(ROR=4.37,IC-2SD=0.03)以及发热(ROR=1.80,IC-2SD=1.84)等不良反应尚未被说明书收录,但与文献报道一致,在临床使用中密切注意。临床医务人员在合并用药时应结合氯喹相关不良反应,密切注意患者是否有基础疾病和配伍禁忌,预防不良反应的发生和加重。结论基于FAERS的ADEs信号检测有助于了解氯喹安全性,提高临床医务工作者对氯喹不良反应的认识,在新型冠状病毒肺炎等疾病的治疗中有效预防和避免氯喹相关药害事件。OBJECTIVE To analyze and evaluate the safety signals of chloroquine in the patients,and to provide a valuable reference for rational use in clinic.METHODS Both the reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)were applied to analyze safety signals of chloroquine based upon the adverse drug events(ADEs)data ranging from 2004 to 2020 as reported in the Adverse Event Reporting System(FAERS)database of the Food and Drug Administration(FDA),and to systematically assesse the safety signals of chloroquine phosphate on various organs systems.RESULTS Among the 2063 reports of ADEs studied,557 reports were considered to be mainly caused by chloroquine.The results demonstrated that the high-risk ADEs signals of chloroquine involved various systems,such as atrioventricular block complete(ROR=2.90,IC-2SD=1.64),ventricular fibrillation(ROR=3.40,IC-2SD=1.27),blindness(ROR=27.51,IC-2SD=0.55),cardiogenic shock(ROR=6.86,IC-2SD=0.54),vomiting(ROR=1.70,IC-2SD=1.83).Moreover,some rare ADEs with high-risk signals showed a correlation with chloroquine,including hypokalaemia(ROR=4.18,IC-2SD=1.51),renal failure acute(ROR=3.08,IC-2SD=0.30),methaemoglobinaemia(ROR=4.37,IC-2SD=0.03),and pyrexia(ROR=1.80,IC-2SD=1.84),which were consistent with literature reports.However,these ADEs were not listed in instruction and worth much attention in clinic.Moreover,basic diseases of patients and drug incompatibility need much attention to prevent the occurrence and exacerbation of chloroquine-related adverse reactions.CONCLUSION A comprehensive analysis of the ADEs signals of chloroquine could shed some light on understanding of its safety characteristics and would provide valuable information for rational use of chloroquine in clinic,especially in treatment of COVID-19.

关 键 词：氯喹 美国不良事件报告系统 新型冠状病毒肺炎 药物不良事件 信号检测 

分 类 号：R969.3[医药卫生—药理学]