基于美国FDA不良事件数据库的利伐沙班不良反应信号挖掘  

ADR Signal Mining of Rivaroxaban Based on FDA Adverse Event Reporting Database

作　　者：吴圆圆 郑淑芬 钟诗龙 WU Yuanyuan;ZHENG Shufen;ZHONG Shilong(School of Biology and Biological Engineering,South China University of Technology,Guangzhou 510006,China;Dept.of Pharmacy,Guangdong Provincial People's Hospital,Guangzhou 510080,China;Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention and Treatment,Guangdong Provincial People’s Hospital,Guangzhou 510080,China)

机构地区：[1]华南理工大学生物科学与工程学院,广州510006 [2]广东省人民医院药学部,广州510080 [3]广东省人民医院广东省冠心病防治研究重点实验室,广州510080

出　　处：《中国药房》2021年第14期1764-1769,共6页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81872934);广东省重点领域研发计划“精准医学与干细胞”重大科技专项基金资助项目(No.2019B020229003)。

摘　　要：目的:挖掘利伐沙班的药品不良反应(ADR)信号,为其临床安全合理使用提供参考。方法:基于美国FDA不良事件报告系统,采用报告比值比法和比例报告比法对FDA公共数据开放项目中于2008年9月-2020年12月上报的利伐沙班ADR报告进行数据挖掘,分析相关ADR报告并映射得到对应的系统器官分类(SOC);同时,统计报告病例的性别、年龄、适应证等基本信息。结果与结论:共提取到相关ADR报告9373236例,其中以利伐沙班为伴随和怀疑药物的ADR报告有102027例;共挖掘得到ADR信号883个,涉及系统器官27个。102027例ADR报告中,女性(41294例,占40.47%)与男性(41071例,占40.26%)比例相当;年龄主要在>50~75岁(29261例,占28.68%)和>75岁(21470例,占21.04%);上报年份主要集中在2018年(18446例,占18.08%);主要上报国家为美国(75390例,占73.89%);严重的ADR报告有35046例(占34.35%),以住院或住院时间延长为主。利伐沙班ADR信号的SOC主要集中在血液和淋巴系统疾病、血管疾病、各类检查及神经系统疾病。在ADR报告数排序前20位的ADR首选术语中,除肺栓塞、急性肾损伤和心房颤动外,其余主要为出血相关的ADR,其中颅内出血是较为严重的ADR。当利伐沙班应用于房颤和预防脑血管意外时易引发颅内出血,当应用于肺栓塞、(深)静脉血栓和血栓形成预防时易引发肺栓塞,临床应密切关注。OBJECTIVE:To excavate the ADR signals of rivaroxaban and provide reference for its safe and rational use in clinic.METHODS:Based on FDA adverse event reporting system(FAERS),the ADRs of rivaroxaban reported from September 2008 to December 2020 in FDA’s Open Data Program were mined using ratio of reports to odds(ROR)and proportional report ratio(PRR).The related ADRs were analyzed,and the corresponding system organ classification(SOC)was mapped.At the same time,the basic information such as gender,age and indications of the patients were statistically reported.RESULTS&CONCLUSIONS:Among 9373236 ADR reports extracted,102027 ADR reports with rivaroxaban as concomitant and suspected drug were obtained;883 ADR signals were mined,involving 27 systems.Among 102027 reports,the proportion of female patients(41294 cases,40.47%)was similar to that of male patients(41071 cases,40.26%).The patients were mainly>50 to 75 years old(29261 cases,28.68%)and>75 years old(21470 cases,21.04%).The reporting year was mainly in 2018(18446 cases,18.08%);main reporting country was the United States(75390 cases,73.89%);there were 35046 cases(34.35%)of severe ADR reports,mainly involving hospital or prolonged hospital stay.The SOC of rivaroxaban ADR singal mainly focused on diseases of the blood and lymphatic system,vascular diseases,various types of examination and nervous system diseases.Among top 20 preferred terms of ADRs with the highest frequency,except for pulmonary embolism,acute kidney injury and atrial fibrillation,the rest were mainly bleeding related ADRs,of which intracranial hemorrhage was the more serious ADR.Intracranial hemorrhage may occur when rivaroxaban is used for the prevention of atrial fibrillation and cerebrovascular accidents,and pulmonary embolism may occur when rivaroxaban is used for the prevention of pulmonary embolism,(deep)venous thrombosis and thrombosis.Great importance should be paid on it.

关 键 词：利伐沙班 美国FDA不良事件报告系统 药品不良反应 信号挖掘 比例报告比法 报告比值比法 

分 类 号：R973.2[医药卫生—药品] R969.3[医药卫生—药学]