阿奇霉素临床应用安全性研究:基于北京市近5年药品不良反应监测数据

Safety analysis of azithromycin clinical application:Data based on 5-year spontaneous reports in Beijing

目的:基于自发呈报的不良反应(ADR)数据,分析阿奇霉素(AZM)致ADR的分布和特点,估算ADR发生风险,为其临床安全使用提供支持。方法:回顾性调取2013年1月至2017年12月,北京市药品不良反应监测中心收到AZM导致ADR的上报数据,采用MedDRA术语集(主要采用SOC、HLT和PT)对ADR描述进行双人标化,定性分析ADR发生特点,定量估算ADR发生风险,根据公式:I=n/[N/(DDD×d)]×100%,假设药品采购量与销售量相等,即N表示5年药品使用量(g),DDD为0.5 g·L^-1(静脉)和0.3 g·L^-1(口服),疗程为5 d,通过风险比(RR)分析静脉与口服途径ADR发生差异。结果:最终纳入分析ADR报告1411例(共计2746例次),5年总采购量为18471715.25 g。女性804例(56.94%),主要用药原因为抗感染治疗(95.75%)。ADR主要累及的器官系统为胃肠系统、皮肤及皮下组织系统和全身性及给药部位各种反应。共收到40例严重ADR,其中6例(15.00%)的患者为儿童,27例(67.50%)的怀疑药品剂型为注射剂,ADR表现主要包括皮疹、速发过敏反应性休克、恶心、肝功能异常和输注部位疼痛等,未收到死亡病例。静脉组ADR发生风险显著高于口服组(RR=111.95,[99.66,125.75]),但因果关系有待进一步证实。结论:基于北京地区5年ADR监测数据,AZM所致ADR主要发生在胃肠道、皮肤及全身或给药部位,严重ADR较为罕见,安全性良好,静脉途径的ADR发生风险显著高于口服途径。应积极探索基于电子病历系统的药物安全性评价研究。

OBJECTIVE To describe the characteristic of adverse reactions(ADR)of azithromycin(AZM)and estimate the risk of ADR based on spontaneous reports data,in order to support for its clinical safety.METHODS The ADR spontaneous reports data of AZM in Beijing was retrospectively collected from January 2013 to December 2017.MedDRA terminology(mainly using SOC,HLT and PT)was used to standardize the ADR description by two reviewers.The characteristics of ADR occurrence were qualitatively analyzed and the risk of ADR occurrence was quantitatively estimated.The incidence of ADR was estimated as I=n/[(N/(DDD×d)]×100%(n=number of ADR cases,N=total quantity(g)of AZM used,DDD denotes defined daily dose of AZM(estimated 0.5 g·d^-1 intravenously,and 0.3 g·d^-1 orally),and d=average duration of AZM therapy(estimated 5 days).The difference in the occurrence of ADR between intravenous and oral routes was analyzed by risk ratio(RR).RESULTS 1411 ADR reports(2746 in total)were finally included in the analysis,and the 5-year total procurement volume was 18471715.25 g.There were 804 females(56.94%),and the main reason for medication was anti-infective treatment(95.75%).The organ systems mainly involved in ADR were gastrointestinal system,skin and subcutaneous tissue system and systemic and administration site reactions.A total of 40 cases of serious ADRs were received,including 6 cases(15.00%)of children and27 cases(67.50%)of suspected drug dosage form injection.The ADR manifestations mainly included rash,anaphylactic shock,nausea,abnormal liver function and infusion site pain.No death cases were received.The risk of ADR occurrence was significantly higher in the intravenous group than in the oral group(RR=111.95,[99.66,125.75]),but the causal relationship needs to be further confirmed.CONCLUSION Based on the 5-year ADR monitoring data in Beijing,AZM-induced ADRs mainly occurred in the gastrointestinal tract,skin and systemic or administration sites,serious ADRs were rare with a good safe profile,and the risk of ADRs by the intravenous route was significantly higher than that by the oral route.Drug safety evaluation studies based on electronic medical record systems should be actively explored.