Gu Joyce H, Samarneh Mark
Medicine, Lake Erie College of Osteopathic Medicine, Greensburg, USA.
Internal Medicine/Nephrology, Riverside Health System, Yonkers, USA.
Cureus. 2024 Dec 5;16(12):e75180. doi: 10.7759/cureus.75180. eCollection 2024 Dec.
We conducted a large-scale disproportionality analysis of the urotoxicity of cyclophosphamide (CYC) and the related drug ifosfamide (IFO) using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, with data ranging from Q4 2012 to Q2 2024. We compared the reporting odds ratio (ROR) of various urotoxicity manifestations of CYC and IFO across patient populations being treated for antineoplastic, immunosuppressive, and transplantation indications. When a wide range of urotoxicity manifestations was aggregated, we found that transplant patients had an increased relative susceptibility to CYC urotoxicity. For the notable adverse effects of chemical and viral hemorrhagic cystitis, we observed a high ROR in the overall population, but this number decreased when the population was restricted to patients treated for neoplastic or transplant indications, revealing that a significant portion of the ROR is explained by the risk associated with these indications. These conclusions did not hold among patients using the uroprotective agent MESNA, where no association with urotoxicity was found, indicating a protective effect of MESNA. Our research reveals heterogeneous behaviors in the urotoxicity of CYC/IFO across indications and toxicity manifestations, providing healthcare professionals with valuable insights for approaching this important drug adverse event association.
我们使用美国食品药品监督管理局不良事件报告系统（FAERS）数据库，对环磷酰胺（CYC）和相关药物异环磷酰胺（IFO）的泌尿系统毒性进行了大规模不成比例分析，数据范围为2012年第四季度至2024年第二季度。我们比较了CYC和IFO在接受抗肿瘤、免疫抑制和移植适应症治疗的患者群体中各种泌尿系统毒性表现的报告比值比（ROR）。当汇总广泛的泌尿系统毒性表现时，我们发现移植患者对CYC泌尿系统毒性的相对易感性增加。对于化学性和病毒性出血性膀胱炎的显著不良反应，我们在总体人群中观察到较高的ROR，但当人群仅限于接受肿瘤或移植适应症治疗的患者时，这个数字下降了，这表明ROR的很大一部分是由与这些适应症相关的风险所解释的。在使用泌尿系统保护剂美司钠的患者中，这些结论不成立，在这些患者中未发现与泌尿系统毒性有关联，这表明美司钠具有保护作用。我们的研究揭示了CYC/IFO在不同适应症和毒性表现的泌尿系统毒性方面存在异质性行为，为医疗保健专业人员处理这一重要的药物不良事件关联提供了有价值的见解。
