唑来膦酸注射液不良反应信号的挖掘与评价

Data mining and evaluation of adverse drug reaction signals of zoledronic acid injection

目的挖掘和评价唑来膦酸注射液上市后的不良反应(ADR)信号,为临床合理安全用药提供依据。方法采用比例报告比法(PRR)和报告比值比法(ROR)对2004年第1季度至2020年第3季度美国FDA不良事件报告系统(FAERS)中接收的唑来膦酸注射液报告进行ADR信号挖掘。结果检索得到唑来膦酸注射液为怀疑及合并用药的药物不良事件(ADE)报告共50395份,数据进行分析处理后得到1995个阳性信号,主要集中在各种肌肉骨骼及结缔组织疾病(占21.59%)、全身性疾病及给药部位各种反应(占18.04%)、胃肠系统疾病(占9.12%)、感染及侵染类疾病(占6.43%)等方面。在报告频数及信号强度排名前20位的首选术语(PTs)中未在说明书中出现的阳性信号共37个,包括尿路感染(PRR值、χ^(2)值、ROR值的95%CI下限分别为1.94、292.75、1.80)、血25-羟维生素D_(3)升高(PRR值、χ^(2)值、ROR值的95%CI下限分别为79.74、143.16、24.01)、快感缺乏(PRR值、χ^(2)值、ROR值的95%CI下限分别为18.44、15028.18、17.91)等。这37个阳性信号累及器官系统13个,以感染及侵染类疾病占首位。结论使用唑来膦酸注射液时应注意药物可能引起的各种肌肉骨骼疾病、全身性疾病,同时对说明书中未提及的尿路感染、血25-羟维生素D_(3)升高、快感缺乏等新的不良反应也需要引起关注。

Objective To provide reference for rational drug use through mining and evaluating adverse drug reactions(ADR)signals of zoledronic acid injection.Methods The proportional reporting ratio(PRR)and reporting odds ratio(ROR)were used to find the ADR signal of zoledronic acid injection from the first quarter of 2004 to the third quarter of 2020 in the US FDA Adverse Event Reporting System(FAERS).Results Among 50395 adverse reaction reports retrieved related to zoledronic acid injection,1995 risk signals were clinically significant,covering on musculoskeletal and connective tissue disorders(21.59%),general disorders and administration site conditions(18.04%),gastrointestinal disorders(9.12%),and infections and infestations(6.43%).Totally 37 positive ADR signals which were not recorded in the drug instructions were identified among the top 20 preferred terms(PTs)according to frequency and reporting strength,mainly including urinary tract infection(PRR=1.94,χ^(2)=292.75,95%CI lower limit of ROR=1.80),blood 25-hydroxycholecalciferol elevation(PRR=79.74,χ^(2)=143.16,95%CI lower limit of ROR=24.01)and anhedonia(PRR=18.44,χ^(2)=15028.18,95%CI lower limit of ROR=17.91).These 37 positive signals involved 13 systems and organs,with infections and infestations being the first place.Conclusion Musculoskeletal and systemic diseases may be induced by the administration of zoledronic acid injections.Special attention should be paid to newly identified ADRs not listed in the drug instructions,such as urinary tract infection,blood 25-hydroxycholecalciferol elevation and anhedonia.