1561例PPIs相关ADR分析及其肝功能异常风险信号挖掘

The ADR analysis and the risk signal mining on abnormal liver function in 1561 ADR cases of PPIs

目的:了解质子泵抑制剂(PPIs)不良反应发生情况及特点,为临床安全合理用药提供参考依据。方法:回顾性分析解放军药品不良反应监测中心数据库2009年1月–2017年12月PPIs所致不良反应/事件(ADR/ADE),并利用比例报告比法、报告比值比法、英国药品和保健产品管理局的综合标准法和贝叶斯可信区间递进神经网络法4种方法对PPIs相关肝功能异常进行风险信号挖掘。结果:1561例ADR/ADE,累及系统/器官达18个,主要为皮肤及皮肤附件损害523例次(27.04%)、消化系统损害344例次(17.79%)及全身性损害289例次(14.94%);用药目的以治疗为主(94.36%);患者年龄以18~64岁最多(1123例,71.94%),男女比例为1.26:1;70.40%患者于用药后1 d内发生ADR,72.00%ADR持续时间小于1 d。109例严重报告中频次最多的为肝功能异常,经风险信号挖掘,奥美拉唑出现肝功能异常阳性信号。结论:PPIs所致ADR/ADE累及部位广泛,其中奥美拉唑存在肝功能异常风险,临床应重视PPIs安全性问题,按照适应证合理选用,避免PPIs滥用现象的发生。

Objective:To investigate the regularity and characteristics of the adverse drug reactions(ADR)caused by proton pump inhibitors(PPIs),in order to provide a reference for the safe and rational use of drugs.Methods:The ADR/ADE caused by PPIs in the PLA ADR Monitoring Center database from January 2009 to December 2017 were analyzed retrospectively,and the risk signals of abnormal liver function associated with PPIs were mined by the proportional reporting ratio(PRR),the reporting odds ratio,the combinationχ2 test-PRR measure used by the Medicines and Healthcare Products Regulatory Agency,and the Bayesian Confidence Propagation Neural Network.Results:In the 1561 cases of ADR/ADE,18 organs/systems were involved in.Most of the cases were the damage of skin and skin appendage(523 cases,27.04%),lesion of gastrointestinal system(344 cases,17.79%)and systemic lesion(289 cases,14.94%).The primary purpose of drug administration was for treatment(94.36%).Most of the patients were aged from 18 to 64(1123 cases,71.94%),and the proportion of male and female patients was 1.26:1.About 70.40%of ADR/ADE cases occurred within 1 day after the use of the drug,and the duration of 72.00%ADR/ADE cases was less than 1 day.The most frequent of the 109 severe adverse reactions was abnormal liver function.After mining the risk signal,we found that omeprazole generated the positive signal of abnormal liver function.Conclusion:ADR/ADE induced by PPIs involved a wide range of systems,and omeprazole may cause the risk of abnormal liver function.Clinical attention should be paid to the safety of PPIs,and PPIs should be reasonably selected according to the indications and never be abused.