二肽基肽酶-4抑制剂上市后药品不良反应信号挖掘与分析  

Signal Mining and Analysis of Adverse Drug Reaction of DPP-4 Inhibitors After Marketing

作　　者：王虎 董文娟 周春巧 张雪林 丁晓莉 王松 刘海林 WANG Hu;DONG Wenjuan;ZHOU Chunqiao;ZHANG Xuelin;DING Xiaoli;WANG Song;LIU Hailin(The First People′s Hospital of Chongqing Liang Jiang New Area,Chongqing,China 401121;Institute of Materia Medica,College of Pharmacy,Army Medical University,Chongqing,China 400038)

机构地区：[1]重庆两江新区第一人民医院,重庆401121 [2]中国人民解放军陆军军医大学药学院药物研究所,重庆400038

出　　处：《中国药业》2022年第17期105-110,共6页China Pharmaceuticals

基　　金：重庆市技术创新与应用发展专项面上项目[cstc2019jscx-msxmX0096]。

摘　　要：目的 促进二肽基肽酶-4(DPP-4)抑制剂西格列汀、沙格列汀、阿格列汀、利格列汀的临床安全、合理用药。方法 采用计算机检索美国食品药物管理局不良事件报告系统2004年1月1日至2021年3月31日西格列汀、沙格列汀、阿格列汀、利格列汀的药品不良反应(ADR)报告,采用报告比值比(ROR)法检测4种DPP-4抑制剂的ADR信号,重点关注ROR较高、药品说明书尚未提及及文献报道较少的ADR信号。结果 共纳入63 944份ADR报告,分别为西格列汀48 265份、沙格列汀6 969份、阿格列汀1 654份、利格列汀7 056份。4种DPP-4抑制剂在内分泌疾病,新陈代谢与营养不良,血管病,肝胆疾病,胃肠道疾病,肾脏和泌尿系统疾病,良性、恶性肿瘤及不明新生物(包括囊肿和息肉)中ADR信号均较强。其中,胃食管静脉曲张方面,沙格列汀(ROR=15.67)和阿格列汀(ROR=13.53)ADR信号均较强;阿格列汀血栓性脑梗死(ROR=114.03)ADR信号较强;西格列汀坏死性胰腺炎ADR信号较强(ROR=8.03);抗利尿激素分泌异常方面,沙格列汀(ROR=2.10)和阿格列汀(ROR=6.66)ADR信号均较强,但该类ADR药品说明书及相关文献中均未提及。结论 临床医务人员应加强对DPP-4抑制剂西格列汀、沙格列汀、阿格列汀、利格列汀主要ADR差异性的认识,重点关注药品说明书中未提及及文献报道较少、但发生率又较高的ADR。应用该类药物时须考虑患者的合并症、疾病史及潜在ADR,从而促进临床安全、合理用药。Objective To promote the safe and rational use of dipeptidyl peptidase-4(DPP-4) inhibitors such as sitagliptin,saxagliptin,alogliptin and linagliptin in the clinic.Methods The adverse drug reaction(ADR) reports of sitagliptin,saxagliptin,alogliptin and linagliptin from January 1,2004 to March 31,2021 in the the US Food and Drug Administration Adverse Event Reporting System(FAERS) were searched by the computer. The ADR signals of the above four DPP-4 inhibitors were detected by the reporting odds ratio(ROR) method,focusing on the ADR signals with a high ROR,not mentioned in the drug instructions and less reported in the studies.Results A total of 63 944 ADR reports were obtained,including 48 265 reports of sitagliptin,6 969 reports of saxagliptin,1 654 reports of alogliptin and 7 056 reports of linagliptin. The ADR signals of the above four DPP-4inhibitors were strong in the endocrine diseases,metabolism and malnutrition,vascular diseases,hepatobiliary diseases,gastrointestinal diseases,kidney and urinary system diseases,benign and malignant tumors,unknown new organisms(including cysts and polyps).Among them,the ADR signals of saxagliptin(ROR = 15. 67) and alogliptin(ROR = 13. 53) were strong in the gastroesophageal varicosis. The ADR signal of alogliptin was strong in the thrombotic cerebral infarction(ROR = 114. 03). The ADR signal of sitagliptin(ROR = 8. 03) was strong in the necrotizing pancreatitis. The ADR signals of saxagliptin(ROR = 2. 10) and alogliptin(ROR = 6. 66) were strong in the abnormal secretion of antidiuretic hormone,which were not mentioned in the drug instructions and relevant studies.Conclusion Clinical staff should strengthen the understanding of the differences of the main ADR of DPP-4 inhibitors such as sitagliptin,saxagliptin,alogliptin and linagliptin,and focus on the ADR that is not mentioned in the drug instructions,less reported in the studies but has a high incidence. The complications,history of disease of patients,and potential ADR of DPP-4 inhibitors should be considered when usin

关 键 词：二肽基肽酶-4抑制剂 西格列汀 沙格列汀 阿格列汀 利格列汀 药品不良反应 信号挖掘 

分 类 号：R95[医药卫生—药学] R977.15