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2 063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。
Abstract
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 2 063 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
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Key words
chloroquine /
American Adverse Events Reporting System /
novel coronavirus pneumonia /
adverse drug event /
signal detection
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参考文献
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脚注
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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)
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