基于FAERS数据库洛拉替尼不良事件信号挖掘与严重不良事件影响因素分析  

Adverse Event Signal Mining and Serious Adverse Event Influencing Factors of Lorlatinib Based on FAERS Database

作　　者：刘中秋 范晓慧 张艳华[1] 张关敏[1] LIU Zhongqiu;FAN Xiaohui;ZHANG Yanhua;ZHANG Guanmin(Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Pharmacy,Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Pharmacy,Jiangbei District of Zhongda Hospital Affiliated to Southeast University,Nanjing 210000,China;Department of Pharmacy,Rizhao People's Hospital,Shandong Province,Rizhao 276823,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所药剂科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [2]东南大学附属中大医院江北院区药学部,南京210000 [3]山东省日照市人民医院药学部,日照276823

出　　处：《医药导报》2023年第9期1412-1417,共6页Herald of Medicine

摘　　要：目的对洛拉替尼不良事件(AEs)进行数据挖掘并探究其致严重AEs的危险因素。方法检索美国食品药品管理局不良事件报告系统(FAERS)数据库,使用openFDA数据平台,收集洛拉替尼自上市至2022年3月31日所致AEs报告信息。根据严重程度分组,通过单因素分析及修正泊松回归模型,分析洛拉替尼致严重AEs的危险因素。结果共获得洛拉替尼AEs报告1986例,其中严重AEs 1468例(73.92%)。检测到AEs信号103个。按发生频次排序,洛拉替尼致水肿报告数最多(49例次),按信号强度排序,游走性血栓性浅静脉炎信号最强[ROR=214.689,95%CI=(88.065,523.376)],且未在说明书中记载。修正泊松回归分析结果显示,发生严重AEs的危险因素为联合使用CYP3A酶系相互作用的药物[RR=1.148,95%CI=(1.009,1.305)]以及低体质量[RR=0.997,95%CI=(0.994,1.000)],使用其他对症治疗药物为保护因素[RR=0.680,95%CI=(0.493,0.938)]。结论建议临床医师及药师对于洛拉替尼说明书中未提及的信号提高关注度,加强对患者联合用药及营养代谢的管理,避免严重AEs的发生,确保患者用药安全。Objective To conduct data mining on adverse events(AEs)of lorlatinib,and to explore the risk factors of serious AEs.Methods The FAERS database was searched,and the openFDA data platform was used to collect the report information of AEs induced by lorlatinib from listing to March 31,2022.Grouped according to severity,the risk factors of severe AEs caused by lorlatinib were analyzed by univariate analysis and a modified Poisson regression model.Results A total of 1986 lorlatinib AEs were reported,including 1468 serious AEs(73.92%).One hundred and three AEs signals were detected.According to the frequency of occurrence,the number of edema reports was the most(49 cases),and according to the signal intensity,the signal of migratory superficial thrombophlebitis was the strongest[ROR=214.689,95%CI=(88.065,523.376)],moreover,none of them was mentioned in drug instructions.Modified Poisson regression analysis showed that the risk factors for the development of severe AEs were the combination of drugs with CYP3A enzyme system interactions[RR=1.148,95%CI=(1.009,1.305)],and low body weight[RR=0.997,95%CI=(0.994,1.000)],however,other symptomatic medications were the protective factors[RR=0.680,95%CI=(0.493,0.938)].Conclusion It was recommended that clinicians and pharmacists should pay more attention to the signals not mentioned in the instructions of lorlatinib,strengthen the management of patient combination drugs and nutrient metabolism,avoid the occurrence of serious AEs,and ensure the safety of the patient's medication.

关 键 词：洛拉替尼 数据挖掘 药品不良事件 FAERS数据库 

分 类 号：R979.1[医药卫生—药品] R969.3[医药卫生—药学]