基于OpenFDA挖掘与评价达格列净上市后的不良反应

Analysis of post-marketing adverse drug reactions induced by dapagliflozin based upon OpenFDA

目的:挖掘与评价达格列净上市后的不良反应安全信号,为临床安全合理用药提供参考。方法:检索美国食品药品监督管理局公共数据公开项目(the US Food and Drug Administration Public Data Open Project,OpenFDA)2014年1月至2021年3月期间达格列净不良反应报告数据,采用报告比值比(report odds ratio,ROR)法进行风险信号挖掘。采用国际医学用语词典(Medical Dictionary for Drug Regulatory Activities,MedDRA)的首选系统器官分类(System Organ Classification,SOC)和首选术语(preferred term,PT)对挖掘的信号进行统计分类和分析。结果:共检索到达格列净相关不良反应报告14811例,具有临床参考意义的不良反应风险信号49个,涉及9个系统器官,主要涉及感染和侵染疾病、代谢及营养失调疾病、肾脏和泌尿系统疾病、肿瘤疾病、胃肠紊乱疾病、神经系统疾病、全身性疾病及给药部位各种反应、心血管疾病、心脏疾病。发现达格列净除说明书载入的不良反应外,还存在败血症(ROR=2.60)、急性胰腺炎(ROR=6.21)、胰腺炎(ROR=5.03)、脑梗死(ROR=6.74)、高血压(ROR=2.40)、急性心肌梗死(ROR=1.43)等说明书未提及的阳性风险信号。结论:临床应用达格列净时,除药品说明书中已提到的不良反应外,还需密切关注其败血症、急性胰腺炎、胰腺炎、脑梗死、高血压、急性心肌梗死等风险,以避免因不良反应带来损害。

OBJECTIVE To evaluate the reports of adverse reactions of dapagliflozin and data mining and analysis to provide reference for drug safety in clinical practices.METHODS The data of dapagliflozin adverse reaction reports from January 2014 to March 2021 were retrieved from OpenFDA.Risk signals were mined by reporting odds ratio(ROR).Adverse reactions were counted and classified using preferred system organ class(SOC)and preferred term(PT)of Medical Dictionary for Regulatory Activities(MedDRA).RESULTS A total of 14811 reports of adverse reactions related to dapagliflozin were retrieved.And 49 risk signals had clinical reference significance,involving 9 system organ classes.They were involved in infections&infestations,metabolism&nutrition disorders,kidney&urinary system diseases,neoplasms,gastrointestinal disorders,nervous system disorders,general disorders,administration site reactions,cardiovascular disorders and cardiac disorders.In addition to ADR recorded in package inserts,dapagliflozin also had sepsis(ROR=2.60),acute pancreatitis(ROR=6.21),pancreatitis(ROR=5.03),cerebral infarction(ROR=6.74),hypertension(ROR=2.40),acute myocardial infarction(ROR=1.43)and other positive risk signals not mentioned in package inserts.CONCLUSION During clinical dosing of dapagliflozin,in addition to ADR mentioned in package inserts,great attention should be paid to the risks of sepsis,acute pancreatitis,pancreatitis,cerebral infarction,hypertension and acute myocardial infarction to avoid injury induced by ADR.