基于FAERS数据库的4种磷酸二酯酶5抑制剂安全性分析

Safety of four phosphodiesterase 5 inhibitors based on the FAERS database

目的对真实世界不良事件报告数据进行挖掘,分析4种磷酸二酯酶5(PDE5)抑制剂的上市后安全性特征。方法检索美国食品药品监督管理局(FDA)不良事件报告系统(FAERS),分别收集2012年第二季度至2022第三季度以西地那非、他达拉非、伐地那非和阿伐那非为首要怀疑药物的不良事件(ADE)报告数据,并进行系统-器官分类(SOC)和首选术语(PT)标准化映射分析,根据报告比值比(ROR)法和信息成分分析(IC)法筛选出药品不良反应(ADR)的有效不相称测定信号,并对高强度信号进行分析。结果共纳入西地那非ADE报告27695例、他达拉非16683例、伐地那非718例、阿伐那非222例,4种药物ADE报告的SOC主要类型较为类似。在高强度ADR信号方面,整体信号强度(按ROR值)为西地那非>他达拉非>伐地那非,未检测出阿伐那非的有效ADR信号。其中西地那非ADR信号主要集中于生殖系统并出现多个恶性皮肤肿瘤相关ADR信号,他达拉非的恶性皮肤肿瘤相关ADR信号强度明显高于其他药物、且其大部分高强度信号尚未被说明书收载,伐地那非则主要为生殖系统疾病和眼器官疾病。结论4种PDE5抑制剂的ADE整体分布具有一致性,但具体ADR信号特征方面存在一定差异,临床应用时应予以针对性关注,并重点建议对伐地那非和西地那非药品说明书中的ADR信息进行及时补充更新。

Objective To mine real-world adverse event report data and analyze the post-marketing safety characteristics of four phosphodiesterase 5(PDE5)inhibitors.Methods By searching the FDA Adverse Event Reporting System(FAERS),data on adverse drug event(ADE)reports of sildenafil,tadalafil,vardenafil,and avanafil as first suspected drugs were collected from the second quarter of 2012 to the third quarter of 2022,respectively,and standardized map analysis of systematic organ classification(SOC)and preferred term(PT)was performed.Valid disproportional measures signals of adverse drug reaction(ADR)were screened according to report-odds ratio(ROR)and information component(IC),and high-intensity ADR signals were analyzed.Results A total of 27695 cases of sildenafil ADE,16683 cases of tadalafil,718 cases of vardenafil and 222 cases of avanafil were found and included.The major types of SOC reported on the 4 drugs were similar.In terms of high-intensity ADR signals,the overall signal intensity(of ROR value)from largest to smallest was sildenafil,tadalafil,vardenafil,while no valid signal of avanafil was detected.The ADR signals of sildenafil were mainly concentrated in the reproductive system with multiple malignant skin tumor related ADR signals.The signal intensity of ADR related to malignant skin tumors of tadalafil was significantly higher than that of other drugs,and most of its high-intensity signals were not yet included in the specification.Vardenafil was mainly represented by diseases of reproductive system and eye organs.Conclusion The ADR signal strength of the four PDE5 inhibitors showed a decreasing trend with the time of marketing,but there were considerable differences in the specific characteristics.Targeted attention should be paid to the clinical application,and it is recommended to timely supplement and update the ADR information in the instructions of vardenafil and sildenafil.