Pentosan Polysulfate
Also known as: PPS, Elmiron, Pentosan Polysulfate Sodium, SP54
Summary
Pentosan polysulfate sodium (PPS), marketed as Elmiron, is a semi-synthetic sulfated polysaccharide and the only FDA-approved oral medication for treating bladder pain and discomfort associated with interstitial cystitis/bladder pain syndrome (IC/BPS). FDA-approved in 1996, PPS works by adhering to the bladder wall to restore the defective glycosaminoglycan layer, acting as a protective barrier against irritating urinary substances. While clinical trials demonstrate efficacy in reducing pain, urgency, and urinary frequency, long-term use has been associated with a dose-dependent risk of pentosan polysulfate maculopathy (PPSM), a potentially vision-threatening retinal condition that has led to updated FDA labeling and screening recommendations.
Potential Benefits
Treatment of Interstitial Cystitis/Bladder Pain Syndrome
Pentosan polysulfate sodium is highly effective for managing bladder pain syndrome and interstitial cystitis, with systematic reviews demonstrating statistically significant improvement in overall patient response (p < .001), pain reduction (p = .009), and decreased urinary urgency (p = .005) compared to placebo.[1][2] In double-blind, placebo-controlled trials, 38% of patients treated with PPS for three months reported improvement in IC/BPS symptoms.[1][6]
Mechanism of Action and Bladder Protection
PPS works by replenishing the defective mucous (glycosaminoglycan) layer of the bladder wall, restoring epithelial barrier integrity and controlling cell permeability to prevent irritating urinary solutes from reaching epithelial cells.[1][3] The medication binds to the bladder epithelium with sufficient strength to resist bladder washing, providing a protective coating structurally similar to the natural glycosaminoglycan lining.[3][8]
Clinical Efficacy Evidence
Multiple meta-analyses and systematic reviews support PPS efficacy, with seven randomized controlled trials showing clear beneficial effects in reducing pain, urgency, and urinary frequency associated with interstitial cystitis.[2][4][5][6] Treatment duration typically requires at least 3-6 months to achieve maximum therapeutic benefit, with some patients experiencing continued improvement over time.[1][6] The medication demonstrates superior efficacy over placebo in well-designed clinical trials, making it a cornerstone pharmacological agent for IC/BPS management.[1][2][8]
Safety Information
Maculopathy and Retinal Toxicity
The most significant safety concern with long-term PPS use is pentosan polysulfate maculopathy (PPSM), a dose-dependent retinal condition characterized by pigmentary changes, outer retinal atrophy, and potential permanent vision loss.[7][10][11][12][13] Studies demonstrate prevalence rates of 16-20% among PPS users, with risk increasing substantially with cumulative exposure.[10][11] Patients receiving cumulative doses exceeding 2,000 grams face a 7.39-fold increased risk compared to unexposed individuals, while those receiving 1-500 grams show a 1.65-fold increase.[13] The condition can progress even after medication discontinuation, and there is currently no treatment available.[7][10]
FDA Warning and Screening Recommendations
In 2020, the FDA issued a drug labeling change warning about increased risk for retinal pigmentary changes and recommending detailed ophthalmologic evaluation prior to starting treatment.[7][10] Current screening guidelines recommend baseline eye examinations (including optical coherence tomography, near-infrared reflectance, and fundus autofluorescence imaging) within 6 months of starting therapy, followed by annual screening as patients approach 500g cumulative exposure (approximately 4.6 years on standard 300mg daily dosing).[7][11] Patients exceeding 1,500g cumulative exposure face substantially elevated maculopathy risk, with odds ratios reaching 28.33 for exposures above 2,000 grams.[14]
Common Adverse Effects and Contraindications
Gastrointestinal side effects are most common, including rectal hemorrhage (6.3% at 300mg daily dose, 15% at 900mg daily), diarrhea, heartburn, and stomach pain.[1][6] Other notable adverse effects include reversible alopecia (hair loss beginning within 4 weeks of treatment), mildly elevated liver enzymes (1.2% of patients), headache, and rash.[1][6] PPS has weak anticoagulant properties and may increase bleeding risk, with contraindications including aneurysm, hemophilia, active ulcers, low platelet count, and hepatic insufficiency.[1][6] The medication demonstrates poor oral bioavailability (approximately 6%), with most of the dose (84%) excreted unchanged in feces.[9][12]