Abstract
OBJECTIVE: To characterize the post-marketing safety profile of pentosan polysulfate sodium (PPS) using the FDA Adverse Event Reporting System (FAERS) database. METHODS: This pharmacovigilance study analyzed FAERS data spanning from the first quarter of 2004 to the first quarter of 2025. Disproportionality analysis, using the reporting odds ratio (ROR), was performed to detect adverse drug event (ADE) signals. A gender-specific analysis was also performed. The time-to-onset (TTO) of ADEs was evaluated through descriptive statistics, the Kaplan-Meier method, and Weibull parametric modeling. RESULTS: The study collected 11,471 reports with PPS as the primary suspected drug. The reporting frequency and strongest signals were overwhelmingly concentrated in the 'Eye Disorders' system organ class (SOC), with pigmentary maculopathy demonstrating an exceptionally high ROR. Significant non-ocular signals were also identified, including depression and anxiety. A gender-specific analysis revealed that maculopathy signals were prominently observed among females, while males exhibited distinct associations with gastrointestinal and urinary adverse events. The TTO analysis (n = 297) revealed a median onset time of 1,715 days, with the Weibull model (β = 0.62) indicating a decreasing hazard rate over time. The majority of reported cases (68.1%) were classified as serious adverse events. CONCLUSION: This 21-year real-world analysis confirms that safety signals for PPS show a distinct long-latency risk profile, most critically vision-threatening maculopathy. The study highlights potential psychiatric adverse events not currently documented in the drug's label and reveals gender-specific risk profiles. These findings emphasize the need for vigilant, sustained ophthalmologic screening and broader safety monitoring for all patients receiving PPS therapy.