Urotoxicity of Cyclophosphamide: A Comparison Across Neoplastic, Autoimmune, and Transplant Indications

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.