基于上海市临床药事质量控制中心数据库的药物性肝损伤药物警戒信号检测

Pharmacovigilance Signal Monitoring of Drug-induced Liver Injury Based on Shanghai Quality Control Center of Hospital Pharmaceutical Administration Database

目的:发现上海地区人群中疑似肝损伤报告相关的药物,为临床合理应用提供参考。方法:采用上海市临床药事质量控制中心数据库中上海市44家医院的药品不良反应(ADR)数据,筛选2017年1月1日~2018年12月31日与药物性肝损伤(DILI)相关的ADR病例,并应用报告比值比(ROR)法进行信号检测,分析药物和肝脏ADR信号之间的相关性。结果:获取ADR报告27171份,与DILI相关的ADR报告918份(3.38%),女性发生DILI的风险高于男性(P<0.0001)。经ROR法检测得到35种药物与肝损伤可能相关。按ROR由大到小排名前10位的药物依次是奥氮平、阿托伐他汀、甲氨蝶呤、丙戊酸、对乙酰氨基酚、喹硫平、瑞舒伐他汀、利福平、伏立康唑和甲巯咪唑。此外,与肝损伤可能相关的35种药物中,氯氮平、乙胺丁醇、润燥止痒胶囊、美金刚和低分子肝素钙的药品说明书中没有发现肝损伤的相关风险提示。结论:在临床实践中,应重视监测各类药物与肝损伤之间的关系。利用ROR法进行ADR信号的数据挖掘,发现氯氮平、乙胺丁醇、润燥止痒胶囊、美金刚和低分子肝素钙存在潜在的DILI风险信号,并且这在过去的研究中并未得到证实。为了进一步证实这种潜在的相关性,需要未来更深入的临床研究。

Objective:To find out drugs related suspected liver injury reports in Shanghai population,and provide reference for rational clinical application.Methods:Cases of drug-induced liver injury(DILI)were screened between 1 st January 2017 to 31 st December 2018 by using adverse drug reaction(ADR)data from 44 hospitals in Shanghai,China.The detected signals that drugs related liver injury were analyzed by using reporting odds ratio(ROR).Results:The 27171 of ADR cases were extracted.The 918(3.38%)of them were related between drugs and liver injury,and the risk of DILI in women was higher than that in men(P<0.0001).The 35 of ADR signals related liver injury were filtered by using ROR,and the top 10 drugs of ROR followed by olanzapine,atorvastatin,methotrexate,valproic acid,paracetamol,quetiapine,rosuvastatin,rifampin,voriconazole and methimazole.In addition,there were no references or cases in instructions of clozapine,ethambutol,runzaozhiyang capsule,memantine and low molecular weight heparin calcium which detected signals of potential liver injury risk.Conclusion:We should be attention to monitor relation between drugs and liver injury in clinical practical.Clozapine,ethambutol,runzaozhiyang capsule,memantine,and low molecular weight heparin calcium have potential DILI risks based on Shanghai Quality Control Center of Hospital Pharmaceutical Administration database that have not been confirmed in previous studies.In future,more in-depth preclinical and clinical studies are need to recognize this correlation further.