基于欧洲药品不良事件数据库对洛匹那韦/利托那韦不良事件的快速挖掘和分析

A quick data mining and analysis of lopinavir/ritonavir(LPV/r)adverse events based on Eudravigilance Medicines Safety Database

目的:本研究通过数据挖掘技术对洛匹那韦/利托那韦(LPV/r)上市后的药品不良事件(ADEs)报告进行真实世界研究,为临床对早期ADEs的识别及处理提供参考。方法:选择不同层级的MedDRA术语,提取欧洲药品不良事件报告数据库(Eudravigilance,EV)中所有LPV/r相关ADE报告进行分析。结果:截止到2020年2月1日,EV数据库共收录LPV/r相关ADE报告3 753例,发生药品相关不良事件5 833例次。在性别构成上,男性(54. 5%)高于女性(37. 5%),年龄集中在18~64岁(69. 0%),上报人群以"医务人员上报"为主(82. 8%);对ADEs报告进行重点系统分类(SOC),多累及胃肠道系统、肝胆系统、神经系统、营养代谢系统、心血管系统等。本研究采用首选术语(preferred term,PT)进行各系统报告查询,结果显示LPV/r相关ADE侵犯胃肠道系统,常表现为腹泻205例(22. 4%)、呕吐135例(14. 7%)、恶心124例(13. 5%)以及严重的胰腺炎89例(9. 7%)及胃肠道出血57例(6. 2%)等;肝胆系统主要表现为肝功能异常93例(14. 7%)、肝功能指标变化及黄疸67例(10. 6%);神经系统主要涉及轻度头痛199例(31. 6%)、头昏70例(11. 1%)症状,值得注意的是,LPV/r可诱发癫痫发作54例(8. 6%)及周围神经病变33例(5. 2%);其他系统严重者可引起:血糖下降21例(3. 3%)、低血压163例(28. 5%)、血压升高50例(8. 7%)、高钾血症10例(1. 6%)、房室传导阻滞36例(6. 3%)、深静脉血栓形成17例(3. 0%)、心电图QT间期延长16例(2. 8%)、贫血168例(37. 3%)、急性肾损伤129例(32. 3%)等。结论:临床使用LPV/r的过程中,除密切关注腹泻、皮疹、头痛等轻度不良事件外,也应警惕其诱发的胃肠道出血、癫痫发作、低血压、血栓形成、QT间期延长、急性肾损伤、严重的肝脏损伤等严重不良事件。

Objective:This study used data mining to conduct real-world research on adverse drug events(ADEs)after LPV/r was launched on the market,providing a reference for clinical identification and treatment of early ADEs.Methods:MedDRA terminology in different levels of the reproductive system were selected,and all LPV/r-related ADE reports were extracted from the European Drug Adverse Event Reporting Database(Eudravigilance).Results:Until February 1,2020,3753 reports of LPV/r-related ADEs were collected in Eudravigilance,with5833 drug-related adverse events.In terms of gender composition,males(54.5%)are higher than females(37.5%),and the age is concentrated between 18~64 years(69.0%).The reporting population is mainly"medical staff reporting"(82.8%).The ADE reports are focused on the system classification,much involving the following systems:gastrointestinal system,hepatobiliary system,nervous system,nutritional metabolism system,and cardiovascular system,etc.This research uses PT terminology to query each system report,showing that LPV/r-related ADEs invaded the gastrointestinal system and often manifested as diarrhea 205(22.4%),vomiting 135(14.7%),nausea124(13.5%),and severe of pancreatitis 89(9.7%)and gastrointestinal bleeding 57(6.2%),etc.Liver and gallbladder system mainly showed abnormal liver function 93(14.7%),changes in liver function indicators and jaundice 67(10.6%).Nervous system mainly involved symptoms of mild headache 199(31.6%),dizziness 70(11.1%).It is worth noting that LPV/r induced seizures 54(8.6%)and peripheral neuropathy 33(5.2%).Other severe system effects:21(3.3%)decrease in blood glucose,163(28.5%)hypotension,50(8.7%)increase in blood pressure,10(1.6%)hyperkalemia,36(6.3%)AV block,deep vein thrombosis 17(3.0%),electrocardiogram QT interval prolongation 16(2.8%),anemia 168(37.3%),acute kidney injury 129(32.3%),etc.Conclusion:In the clinical use of LPV/r,we should be alert to gastrointestinal bleeding,seizures,hypotension,thrombosis,prolonged QT interval,acute serious adverse events such as kidney injury and severe liver injury,in addition to some mild adverse events such as diarrhea,rash,and headache,etc.