| アブストラクト | BACKGROUND: Cystinuria 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. METHODS: We 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. RESULTS: A 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. CONCLUSION: This 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. |
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| 投稿者 | Ergul, Rifat Burak; Gurlek, Ismail Taha; Ozervarli, M Firat; Ozcan, Seyda Gul; Pietropaolo, Amelia; Tsaturyan, Arman; Juliebo-Jones, Patrick; Tzelves, Lazaros; Sener, Tarik Emre; Donmez, M Irfan; Oktar, Tayfun; Somani, Bhaskar; Tefik, Tzevat |
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| 組織名 | Department of Urology, Istanbul Faculty of Medicine, Istanbul University,;Istanbul, Turkiye.;EAU Young Academic Urologists (YAU) Urolithiasis and Endourology Working Group;Arnhem, Arnhem, NL-6803, The Netherlands.;Department of Urology, Mus State Hospital, Mus, Turkiye.;Varto Vocational School, Mus Alparslan University, Mus, Turkiye.;Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkiye.;Department of Nephrology, Cerrahpasa Faculty of Medicine, Istanbul;University-Cerrahpasa, Istanbul, Turkiye.;Department of Urology, University Hospitals Southampton, NHS Trust, Southampton,;UK.;Department of Urology, Yerevan State Medical University After M. Heratsi,;Yerevan, Armenia.;Department of Clinical Medicine, University of Bergen, Bergen, Norway.;2nd Department of Urology, Sismanoglio Hospital, National and Kapodistrian;University of Athens, Athens, Greece.;Department of Urology, Marmara University, School of Medicine, Istanbul, Turkiye.;Division of Pediatric Urology, Department of Urology, Istanbul Faculty of;Medicine, Istanbul University, Istanbul, Turkiye.;Istanbul, Turkiye. tzevat.tefik@gmail.com. |
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