Post-marketing safety of pentosan polysulfate sodium: a 21-year pharmacovigilance analysis of the FAERS database

TL;DR

A 21-year analysis of safety reports shows that pentosan polysulfate sodium is linked to long-term risks like vision-threatening eye issues and gender-specific side effects.

Contribution

The study reveals new safety signals for pentosan polysulfate sodium, including long-latency maculopathy and gender-specific adverse events.

Findings

Pentosan polysulfate sodium is strongly associated with pigmentary maculopathy, particularly in females.

Psychiatric adverse events like depression and anxiety were identified as significant non-ocular safety signals.

Adverse events typically occurred after a median of 1,715 days, with a decreasing risk over time.

Abstract

To characterize the post-marketing safety profile of pentosan polysulfate sodium (PPS) using the FDA Adverse Event Reporting System (FAERS) database.

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.

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.

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.

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