Page 118 - 2019年11月第30卷第21期

·药物与临床·

基于美国FDA不良事件报告系统的硫唑嘌呤相关死亡事件数据

挖掘研究 Δ

吴 斌 ，吴逢波，何治尧，徐 珽（四川大学华西医院临床药学部，成都 610041）
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中图分类号 R969.3 文献标志码 A 文章编号 1001-0408（2019）21-2993-05
DOI 10.6039/j.issn.1001-0408.2019.21.22

摘 要 目的：基于美国FDA不良事件报告系统（FAERS），对硫唑嘌呤相关死亡事件进行数据挖掘，为临床安全使用硫唑嘌呤提
供参考。方法：下载2004年第一季度至2018年第四季度共60个季度的FAERS数据，经过Medex_UIMA_1.3.7系统进行药品名称
标准化、《ICH国际医学用语词典》不良事件系统分类等数据清洗后，提取硫唑嘌呤相关死亡事件，采用报告比值比法（ROR）和比
例报告比值法（PRR）进行信号检测。对硫唑嘌呤相关死亡事件患者的基本信息、报告者信息、报告的时间分布和国家分布、信号
检测结果、直接/间接死亡患者用药剂量和合并用药，以及间接死亡患者报告频率进行分析。结果：共提取到硫唑嘌呤不良事件报
告记录39 695条，其中直接死亡事件报告707条，间接死亡事件报告3 219条；死亡者中位年龄55岁；医师和其他卫生专业人员报
告共占 77.38％；硫唑嘌呤口服给药报告占已知给药途径报告例数的 90.40％（647/715）。“胎儿死亡”（ROR＝4.16，PRR＝4.16）和
“新生儿死亡”（ROR＝4.99，PRR＝4.99）检测出信号。在死亡病例中，老年患者约占30％；存在硫唑嘌呤超禁忌症、超剂量使用情
况；在合并用药中，免疫抑制类药物使用频率最高；在间接死亡病例中，感染事件报告频率最高（3 122例次）。结论：应重视硫唑嘌
呤潜在的致死风险，严格把握硫唑嘌呤禁忌症和剂量，关注老人、儿童特殊人群用药；建议硫唑嘌呤使用前完善基因检测，以精准
用药。
关键词 硫唑嘌呤；不良事件报告系统；死亡；数据挖掘

Data Mining of Azathioprine Related Death Events Based on FDA Adverse Event Report System
WU Bin，WU Fengbo，HE Zhiyao，XU Ting（Dept. of Pharmacy，West China Hospital，Sichuan University，
Chengdu 610041，China）

ABSTRACT OBJECTIVE：To mine the data of azathioprine related death events based on FDA Adverse Event Report System
（FAERS），and to provide reference safe use of azathioprine in clinic. METHODS：Totally 60 quarters of FARES data were
downloaded from 2004Q1 to 2018Q4. After drug names standardized by Medex_UIMA_1.3.7 and adverse events classified by
MedDRA，death events related to azathioprine were extracted. The safety signals were detected by using ROR and PRR methods.
The death events related to azathioprine were analyzed in respects of patient’s general information，reporter’s information，time
and country distribution of reports，signal detection results，dose and drug combination of direct and indirect death，reported
frequency of indirect deaths. RESULTS：A total of 39 695 azathioprine related death events were gathered，including 707 direct
death reports and 3 219 indirect death reports. The media age was 55 years in dead. Physicians and other health professionals
reports took up 77.38％ . Azathioprine administered orally took up 90.40％ （647/715） in reported cases of known route of
adiministration.“Fetal death”（ROR＝4.16，PRR＝4.16）and“neonatal death”（ROR＝4.99，PRR＝4.99）were detected as signal.
About 30 percent of the death reports were the old patients. There were cases using azathioprine beyond contraindications or
maximum dosage. Among drug combination，immunosuppressive drugs were used most frequently. Infection events were reported
most frequently in indirect deaths （3 122 reports）. CONCLUSIONS：The potential death risk of azathioprine should be paid
attention to，and the contraindications and dosage of azathioprine should be strictly controlled. Great importance should be paid
attention to medication for special population of the elderly and children. It is suggested that genetic testing and precise drug use
should be perfected before using azathioprine.
KEYWORDS Azathioprine；Adverse event reporting system；Death；Data mining

本 本 栏栏 目目 协协 办办 目（No.川干研2018-104）
Δ 基金项目：2018年四川省卫生健康委员会干部保健科研课题项
重庆希尔安药业有限公司 ＊主管药师，硕士。研究方向：临床药学、循证药学。电话：
028-85422965。E-mail：binw83@hotmail.com
地址：重庆市合川工业园区希尔安路168号 # 通信作者：主任药师，博士。研究方向：医院药学、临床药学、循
电话：023-67893732 邮编：401520
证药学。电话：028-85422965。E-mail：tingx2009@163.com

中国药房 2019年第30卷第21期 China Pharmacy 2019 Vol. 30 No. 21 ·2993 ·