基于山东省药品不良反应监测中心数据库的奥美拉唑不良反应风险信号挖掘

Risk signal mining of omeprazole adverse reactions based on the database of Shandong Provincial Center for Adverse Drug Reaction Monitoring

目的对奥美拉唑不良反应风险信号进行挖掘和评价,为临床安全使用该药提供参考。方法对山东省药品不良反应监测中心2018年1月至2021年12月收到的所有奥美拉唑不良反应报告进行数据清洗,收集患者性别、年龄,给药途径,不良反应累及系统/器官、临床表现及转归情况等信息;采用报告比值比(ROR)法、比例报告比值比(PRR)法和英国药品和保健品管理局(MHRA)综合标准法对与奥美拉唑相关的不良反应风险信号进行挖掘和评价。ROR法和PRR法的风险信号判断标准为报告数≥3,ROR或PRR的95%置信区间(CI)下限>1;MHRA综合标准法的风险信号判断标准为报告数≥3,PRR≥2且χ^(2)≥4。结果以奥美拉唑为怀疑药物的报告共2706份,其中严重不良反应234例(8.7%);男性1270例(46.9%),女性1432例(52.9%);中位年龄58岁,其中<18岁者86例,18~60岁1417例,>60岁1203例;奥美拉唑不良反应共累及17个系统/器官,按报告数排名前5位的依次为胃肠系统[1412例次(37.6%)]、皮肤及其附件[883例次(23.5%)]、神经系统[716例次(19.1%)]、呼吸系统[269例次(7.2%)]及全身系统[207例次(5.5%)];不良反应中位发生时间为用药后30 min,发生在用药后1 d内的有1710例(63.2%);1595例(58.9%)患者痊愈,1098例(40.6%)好转,无死亡病例。ROR法和PRR法分别挖掘出风险信号27个,MHRA综合标准法21个;采用ROR法挖掘出的信号强度排名前5位的不良反应分别为胃肠胀气、头痛、便秘、舌麻木和关节疼痛;采用PRR法挖掘出的信号强度排名前5位的不良反应分别胃肠胀气、头痛、便秘、舌麻木和眩晕;采用MHRA综合标准法挖掘出的信号强度排名前5位的不良反应分别为胃肠胀气、头痛、便秘、腹胀和口干。27个风险信号中,说明书未提及的有胸闷、寒战、紫绀、口麻木、全身颤抖、舌麻木。结论奥美拉唑不良反应涉及多个系统/器官,常见不良反应有胃肠胀气、头痛、便秘等,胸闷、寒战、紫绀、口麻木、全身颤抖、舌麻木等风险信号在说明书中未记载,临床应予以警惕并及时干预。

Objective To mine and evaluate the adverse reaction risk signals of omeprazole,and provide reference for the safe application of the drug.Methods Data cleansing on all adverse reactions of omeprazole collected in the Shandong Provincial Center for Adverse Drug Reaction Monitoring database fromJanuary 2018 to December 2021 was performed,and information on patients′gender,age,drug administration routes,and the systems/organs involved,clinical manifestations,and outcomes of adverse reactions was collected.The risk signals of adverse reactions associated with omeprazole were mined and evaluated using reporting odds ratio(ROR),proportional reporting ratio(PRR),and Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard methods.The risk signal judgment criteria for ROR and PRR methods were the number of reports≥3,and the lower limit of 95%confidence interval(CI)of ROR or PRR>1,and that of MHRA method was the number of reports≥3,PRR≥2,andχ^(2)≥4.Results A total of 2706 adverse reaction reports with omeprazole as suspect drug were entered,including 234 severe adverse reactions(8.7%).Of them,1270 were male(46.9%)and 1432 female(52.9%);the median age was 58 years,including 86 patients under 18 years old,1417 cases between 18‑60 years old,and 1203 cases over 60 years old.A total of 17 systems or organs were involved in adverse reaction related to omeprazole,and the top 5 were gastrointestinal system[1412 cases(37.6%)],skin and its accessories[883 cases(23.5%)],nervous system[716 cases(19.1%)],respiratory system[269 cases(7.2%)],and systemic system[207 cases(5.5%)].The median occurrence time of adverse reactions from medication was 30 minutes,and 1710 cases(63.2%)occurred within 1 day after medication.After treatments,1595 patients(58.9%)recovered,1098 patients(40.6%)wereimproved,and no deaths were reported.Twenty‑seven risk signals were mined by ROR and PRR methods,respectively,and 21 by MHRA method.The top 5 adverse reactions in signal intensity mined using the ROR method were gastrointestinal bloating,headache,constipation,tongue numbness,and joint pain;the top 5 adverse reactions in signal intensity mined using the PRR method were gastrointestinal bloating,headache,constipation,tongue numbness,and dizziness;the top 5 adverse reactions in signal intensity mined using the MHRA method were gastrointestinal bloating,headache,constipation,bloating,and dry mouth.Among them,the signals not mentioned in the labels were chest tightness,chills,cyanosis,mouth numbness,overall trembling,and tongue numbness.Conclusions The adverse reactions of omeprazole involve multiple systems/organs,and common adverse reactions include gastrointestinal bloating,headache,constipation,etc.Risk signals such as chest tightness,chills,cyanosis,numbness of the mouth,trembling of the whole body,and numbness of the tongue are not recorded in the labels,which should be vigilant and intervened in time in clinics.