基于FAERS的六种酪氨酸激酶抑制剂代表药物不良反应信号挖掘与分析  

Mining and analysis of ADR signals of six representative TKI drugs based on FAERS

作　　者：吴倩 刘丽慧 王婷 聂晶 吴记勇 WU Qian;LIU Lihui;WANG Ting;NIE Jing;WU Jiyong(Pharmacy Department,Shandong Second Provincial General Hospital,Jinan China)

机构地区：[1]山东省第二人民医院药学部,山东济南250022

出　　处：《山东医药》2025年第1期59-64,共6页Shandong Medical Journal

基　　金：聚火优才全国药学服务青年项目(CMEAPC2023043)。

摘　　要：目的对美国食品药品监督管理局不良事件呈报系统(FAERS)中酪氨酸激酶抑制剂(TKI)代表药物的不良反应(ADR)信号进行挖掘与分析,为临床合理用药提供参考。方法用OpenVigil2.1平台挖掘FAERS,收集2004年3月—2022年9月六种TKI(伊马替尼、吉非替尼、达沙替尼、舒尼替尼、索拉非尼、阿帕替尼)的ADR报告。采用报告比值比法、比例报告比值比法分析六种TKI代表药物的ADR信号,并按照发生频次和信号强度进行排序。结果六种TKI代表药物共检索到105052份ADR报告,其中舒尼替尼最多(38498份)。按发生频次排序,六种TKI代表药物所致ADR均累及皮肤及皮下组织类疾病和胃肠系统疾病,在呼吸系统、胸及纵隔疾病中伊马替尼引起胸腔积液的发生频次位于第7位。伊马替尼出现染色体和细胞等遗传学分析异常风险信号,吉非替尼出现线粒体谷草转氨酶升高等风险信号,达沙替尼可能引起乳糜胸,舒尼替尼引起睫毛颜色变化,索拉非尼引起掌跖角化病。结论六种TKI代表药物风险信号所提示的ADR和累及系统与药品说明书一致,但风险信号提示的伊马替尼引起的胸腔积液、舒尼替尼引起的眼部ADR等在药品说明书中未提及。Objective To mine and analyze the adverse drug reaction(ADR)signals associated with representative tyrosine kinase inhibitors(TKIs)drugs in the US Food and Drug Administration Adverse Event Reporting System(FAERS),with the aim of providing insights for rational drug use in the clinical practice.Methods ADR reports of six TKI(imatinib,gefitinib,dasatinib,sunitinib,sorafenib and rivoceranib)from March 2004 to September 2022 were collected by using FAERS and the data platform of OpenVigil 2.1.Reporting odds ratio(ROR)and proportional reporting ratio(PRR)were used to analyze the ADR signals of these six representative TKI drugs,and we ranked them according to their frequency and signal intensity.Results A total of 105,052 ADR reports were retrieved from six representative TKIs,with sunitinib accounting for the highest number of reports(38,498).In terms of frequency,ADRs associated with the six TKIs predominantly affected the skin and subcutaneous tissues,as well as the gastrointestinal system.Among respiratory,thoracic,and mediastinal diseases,imatinib ranked 7th in the occurrence of pleural effusion.Imatinib was linked to risk signals related to abnormal genetic analysis,including chromosomal and cellular alterations.Gefitinib showed risk signals such as elevated mitochondrial aspartate aminotransferase levels.Dasatinib might cause chylothorax,sunitinib might result in eyelash discoloration,and sorafenib might lead to palmoplantar keratoderma.Conclusions The ADRs and affected systems indicated by the risk signals of the six representative TKIs are consistent with those described in the package inserts.However,risk signals such as pleural effusion caused by imatinib and ocular ADRs caused by sunitinib are not mentioned in the package inserts.

关 键 词：酪氨酸激酶抑制剂 药物不良反应 美国食品药品监督管理局不良事件呈报系统 数据挖掘 

分 类 号：R979.1[医药卫生—药品]