基于FAERS数据库的3种PDE5Is药物不良事件信号挖掘

Data Mining for Adverse Drug Events of Three Kinds of PDE5Is Based on FAERS Database

目的 基于美国FDA不良事件报告系统(FAERS)数据库,挖掘3种磷酸二酯酶5抑制剂(PDE5Is)药物(西地那非、他达拉非、伐地那非)的不良事件信号,为临床安全用药提供一定的参考。方法 提取FAERS数据库2004年第一季度至2021年第三季度3种PDE5Is药物(西地那非、他达拉非、伐地那非)不良事件(ADE)报告数据,采用报告比值比(ROR)法和比例报告比值(PRR)法对相关报告进行数据挖掘分析。结果 共得到以PDE5Is为主要怀疑药物的ADE报告65 271例,其中西地那非ADE报告39 086例、他达拉非ADE报告20 130例、伐地那非ADE报告6 055例。共挖掘ADE信号1 179个,涉及25个系统器官(SOC)。西地那非主要集中在全身性疾病及给药部位各种反应、生殖系统及乳腺疾病、眼器官疾病等;他达拉非主要集中在全身性疾病及给药部位各种反应、各类神经系统疾病、眼器官疾病等;伐地那非主要集中在生殖系统及乳腺疾病、全身性疾病及给药部位各种反应、各类神经系统疾病等。通过ROR法及PRR法分析发现PDE5Is共同的不良反应有头痛、潮红、鼻塞、视力模糊、血压降低等。但不同PDE5Is之间的不良反应也存在一些区别,西地那非在眼器官疾病系统和恶性肿瘤总报告数和信号强度均较高;他达拉非在肌肉骨骼肌系统的不良反应显著高于西地那非和伐地那非,伐地那非需注意生殖系统、神经系统、眼器官疾病等不良反应。结论 本研究对3种PDE5Is常见ADE信号及其累及系统的挖掘结果与药品说明书具有一致性,证实本研究结果真实可信。

OBJECTIVE To excavate the ADE signals of Three kinds of PDE5 Is(sildenafil, tadalafil, vardenafil) based on FDA adverse event reporting system(FAERS) and provide references for rational drug use in clinic. METHODS The ADEs of three kinds of PDE5 Is reported from the first quarter of 2004 to the third quarter of 2021 were accessed from FAERS database, and the ADE signals of three kinds of PDE5 Is were mined by the method of reporting odds ratio(ROR) and proportional reporting ratio(PRR). RESULTS A total of 65 271 ADE reports with PDE5 Is as the primary suspected drugs were obtained, including 39 086 ADE reports of sildenafil, 20 130 ADE reports of tadalafil and 6 055 ADE reports of vardenafil.All of the reports involved 25 system organs which were classified by system organclass(SOC). The ADE signals of sildenafil were mainly focused on general disorders and administration site conditions, reproductive system and breast disorders, eye disorders, etc. The ADE signals of tadalafil were mainly focused on general disorders and administration site conditions, nervous system disorders, eye disorders, etc. The ADE signals of vardenafil were mainly focused on reproductive system and breast disorders, general disorders and administration site conditions, nervous system disorders, etc. ROR and PRR analysis showed that the common ADE signals of three kinds of PDE5 Is included headache, flushing, nasal congestion, blurred vision and lower blood pressure etc. There were some differences in ADE signals among three kinds of PDE5 Is. Sildenafil had high total number of reports and signal intensity in eye disorders and neoplasms. The adverse reactions of tadalafil in muscle-skeletal system were significantly higher than those of sildenafil and vardenafil. For vardenafil, more attention would be paid to the adverse reactions of reproductive system, nervous system and eye disorders. CONCLUSION In this study, the acquisition of common ADE signals and the involved system organs of ADE of three kinds of PDE5 Is are consistent with the drug instructions, confirming the authenticity of the results.