中国药物警戒 ›› 2021, Vol. 18 ›› Issue (5): 483-488.
DOI: 10.19803/j.1672-8629.2021.05.17

• 安全与合理用药 • 上一篇    下一篇

他克莫司与伏立康唑联合使用不良反应信号挖掘与分析

曹鑫1,2,3, 孙玉泉4, 黄贵民5, 冉仲阳4, 崔向丽2,*   

  1. 1首都医科大学药学院,北京 100069;
    2首都医科大学附属北京友谊医院药学部,北京 100050;
    3首都儿科研究所附属儿童医院药学部,北京 100020;
    4北京航空航天大学数学科学学院,北京 100191;
    5首都儿科研究所儿童健康大数据中心,北京 100020
  • 收稿日期:2019-12-10 出版日期:2021-05-15 发布日期:2021-05-12
  • 通讯作者: *崔向丽,女,博士,主任药师,临床药学与药事管理。E-mail:cui10@163.com
  • 作者简介:曹鑫,女,本科,主管药师,临床药学。
  • 基金资助:
    国家自然科学基金（81603197）;国家卫健委卫生技术评估重点实验室2019年度开放基金（FH019-02）;北京市医院管理中心2020年培育项目（PG2020002）;首都卫生发展科研专项（首发2020-1-2024）

Signal Mining and Analysis of Adverse Reactions Induced by Tacrolimus and Voriconazole

CAO Xin1,2,3, SUN Yuquan4, HUANG Guimin5, RAN Zhongyang4, CUI Xiangli2,*   

  1. 1College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China;
    2Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;
    3Department of Pharmacy,Children's Hospital, Capital Institute of Pediatrics, Beijing 100020, China;
    4Mathematics Science Institute, Beihang University, Beijing 100191, China;
    5Child Health Big Data Center, Capital Institute of Pediatrics, Beijing 100020, China
  • Received:2019-12-10 Online:2021-05-15 Published:2021-05-12

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摘要： 目的 利用美国食品药品监督管理局（Food and Drug Administration,FDA） 不良事件报告系统（FDA adverse event reporting system,FAERS）,挖掘与分析免疫抑制剂他克莫司与伏立康唑联合使用的不良反应信号,以期为临床联合用药提供参考。方法 检索2010年1月1日至2019年12月31日FAERS数据库中他克莫司与伏立康唑不良事件报告,利用比例失衡法（measures of disproportionality）中的报告比值比法（reporting odds ratio, ROR）和比例报告比值比法（proportional reporting ratio, PRR）,比较他克莫司与伏立康唑联合应用与两药单用的可疑不良反应信号;比较两药联合应用的不良反应与两药说明书中不良反应,筛选新的不良反应。结果 共纳入他克莫司组不良反应报告52 572例,伏立康唑组不良反应报告8 789例,他克莫司与伏立康唑联合使用组不良反应报告1 229例。两者联用与他克莫司组对比,ROR和PRR都>2的不良反应信号共84个;两药联用与伏立康唑组对比,ROR和PRR都>2的不良反应信号共56个;与他克莫司和伏立康唑说明书中不良反应对比,新出现的不良反应有6种。结论 他克莫司与伏立康唑联用后与两者单用相比不良反应信号较多,建议临床合用时监测血药浓度。

关键词: 他克莫司, 伏立康唑, 不良反应报告系统, 比例报告比值比法, 报告比值比

Abstract: Objective To mine and analyze signals of adverse reactions due to the combined use of immunosuppressive agents tacrolimus and voriconazole by using the FDA ( Food and Drug Administration) adverse event reporting system (FAERS) and to provide reference for clinical combined medication. Methods Adverse event reports related to tacrolimus and voriconazole collected in the FAERS database between January 1, 2010 and December 31, 2019 were retrieved using measures of disproportionality. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to compare the suspected adverse reaction signals of tacrolimus and voriconazole used alone or in combination. Adverse reactions that arose from the combination of the two drugs were compared with those specified in the instructions of the two drugs in order to screen out new adverse reactions. Results A total of 52 572 adverse reaction reports of tacrolimus, 8 789 adverse reaction reports of voriconazole, and 1 229 adverse reaction reports of tacrolimus combined with voriconazole were retrieved. When the combined use of the two drugs was compared to tacrolimus used alone, it was found that there were 84 adverse reactions, both ROR and PRR of which were greater than 2, compared with 56 adverse reactions for voriconazole. Compared with the adverse reactions specified in instructions of tacrolimus and voriconazole, there were 6 new adverse reactions involved. Conclusion The combination of tacrolimus and voriconazole may induce far more adverse reactions than single use, which deserves clinical attention.

Key words: tacrolimus, voriconazole, adverse event reporting system, proportional reporting ratio, reporting odds ratio

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