Tiopronin safety in cystinuria: first real-world pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS): an EAU YAU and Endourology sections review

Abstract

BackgroundCystinuria is a rare genetic disorder that causes recurrent cystine stones and significant morbidity, particularly in children. Tiopronin, the main pharmacologic therapy when conservative measures fail, reduces cystine precipitation and excretion; however, real-world safety data remain scarce.MethodsWe evaluated tiopronin's adverse-event profile using the FDA Adverse Event Reporting System (FAERS) by reviewing reports from Q1 2014 to Q1 2025. After deduplication per FDA guidance, only cases in which tiopronin was recorded as the primary suspect drug were included. Adverse events were coded using MedDRA version 28.0 at the Preferred Term and System Organ Class levels, and disproportionality analysis was performed with Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, and Multi-item Gamma Poisson Shrinker algorithms.ResultsA total of 1,838 unique cases were identified, with 69.6% involving pediatric patients. Most reports originated from the United States (99.4%) and were submitted by physicians (86.5%). Significant safety signals emerged in seven System Organ Classes and 67 Preferred Terms. In addition to expected cystinuria-related events, we detected unlabelled signals such as hyposmia, skin atrophy, breath odour, tongue discoloration, and incorrect dosage administered, the latter being particularly relevant in children.ConclusionThis first FAERS-based pharmacovigilance study of tiopronin identified both known and novel safety signals, underscoring challenges in pediatric dosing and the need for enhanced pharmacovigilance, accurate treatment oversight, and improved education for families and clinicians. Limitations include underreporting, incomplete data, and potential confounding by indication.Graphical abstractA higher-resolution version of the Graphical abstract is available as Supplementary information