基于FAERS数据库的儿童唑类抗真菌药物相关肝损伤研究  

Research on Liver Injury Related to Azole Antifungals in Children Based on FAERS Database

作　　者：朱正怡[1] 倪映华[1] 高鹏[1] 黄凌斐[1] 杨巨飞[1] 缪静 ZHU Zhengyi;NI Yinghua;GAO Peng;HUANG Lingfei;YANG Jufei;MIAO Jing(Department of Pharmacy,Children’s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China;Research Center for Clinical Pharmacy,Zhejiang University,Hangzhou 310058,China)

机构地区：[1]浙江大学医学院附属儿童医院药剂科,国家儿童健康与疾病临床医学研究中心,杭州310052 [2]浙江大学临床药学研究中心,杭州310058

出　　处：《中国现代应用药学》2024年第24期3440-3446,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：浙江省医学会临床医学专项资金项目(2022ZYC-Z23)。

摘　　要：目的基于美国食品药品监督管理局不良事件报告系统数据库(FDA Adverse Event Reporting System,FAERS)分析研究儿童唑类抗真菌药物的肝损伤不良事件,为临床安全使用提供参考。方法提取氟康唑、伊曲康唑、伏立康唑、泊沙康唑、艾沙康唑的不良事件报告,并采用比例失衡法、综合标准法及多项伽马泊松分布缩减法进行不良事件信号挖掘,对儿童肝损伤相关报告进行分析。结果共提取5种唑类抗真菌药物的儿童肝损伤报告360份,伏立康唑和氟康唑报告数最多,分别为185例和87例。除伊曲康唑外,报告年龄主要分布于>12岁儿童(43.06%)。发生肝损伤的时间主要集中在30 d内,常见报告的合用药物包括两性霉素B、甲氨蝶呤、环孢素等。所有唑类药物均检出肝损伤的阳性信号,信号值较高的是伏立康唑的脂肪性肝炎(6例,ROR 172.80,PRR 171.85,EBGM0547.65)和艾沙康唑的急性肝衰竭(8例,ROR 77.49,PRR 65.01,EBGM0530.21),其中脂肪性肝炎为新的信号。结论唑类抗真菌药物均有致儿童肝损伤风险,发生时间主要集中在30 d内,合用肝毒性药物和相互作用药物可能增加肝损伤风险,具体临床表型和风险因素仍需临床研究验证。OBJECTIVE To study and analyze liver injury associated with azole antifungals in children based on the FDA Adverse Event Reporting System(FAERS),aiming to provide reference for clinical drug safety.METHODS Adverse event reports of fluconazole,itraconazole,voriconazole,posaconazole and isavuconazole were extracted.Disproportionality analysis,comprehensive standard method and Multi-item Gamma Poisson Shrinker method were used to detect adverse event signals,with further analysis conducted on liver injury reports associated with azole antifungals in children.RESULTS A total of 360 liver injury reports related to 5 azole antifungals in children were extracted.Voriconazole and fluconazole were reported most frequently,with 185 and 87 cases respectively.Adolescents comprised the majority of the reports(43.06%),except for itraconazole.The onset of liver injury primarily occurred within 30 d.The most commonly reported concomitant medications were amphotericin B,methotrexate,and cyclosporine.Positive signals for liver injury were detected in all azole antifungals.The top signal was steatohepatitis with voriconazole(6 cases,ROR 172.80,PRR 171.85,EBGM0547.65)and acute liver failure with isavuconazole(8 cases,ROR 77.49,PRR 65.01,EBGM0530.21).Steatohepatitis was a new signal.CONCLUSION All azole antifungals have the risk of causing liver injury in children,primarily occurring within 30 d.Co-administration of hepatotoxic or interacting drugs may increase the risk of liver injury,specific phenotypes and risk factors still need to be verified by clinical studies.

关 键 词：唑类抗真菌药物 肝损伤 儿童 FDA不良事件报告系统 不良事件 

分 类 号：R969.3[医药卫生—药理学]