What is pentosan polysulfate used for?

What is Pentosan Polysulfate Used For?

Pentosan polysulfate sodium is FDA-approved specifically for the relief of bladder pain or discomfort associated with interstitial cystitis/bladder pain syndrome (IC/BPS). 1

Primary Indication: Interstitial Cystitis/Bladder Pain Syndrome

Pentosan polysulfate is the only oral medication approved by the FDA for treating bladder pain and discomfort in IC/BPS patients. 1, 2 The American Urological Association (AUA) classifies it as a second-line oral medication with Grade B evidence strength, meaning it has demonstrated efficacy in clinical trials though results have been mixed. 3

Mechanism of Action

Pentosan polysulfate is a low molecular weight, heparin-like sulfated polysaccharide that works through several proposed mechanisms: 1

• Repairs damaged glycosaminoglycan (GAG) layers lining the bladder wall (urothelium), which may be defective in IC/BPS patients 2
• Acts as a buffer on the bladder mucosal membrane to control cell permeability and prevent irritating urinary solutes from reaching bladder cells 1
• Provides anti-inflammatory effects based on in vitro data 2

Clinical Efficacy

The drug demonstrates beneficial effects in a proportion of IC/BPS patients, though not all patients respond: 2

• Treatment duration matters significantly - patients should continue therapy for at least 6 months before assessing full benefit, as longer treatment duration correlates with greater improvement in response rates 4
• Five out of seven randomized controlled trials showed clear benefit of pentosan polysulfate for IC/BPS 5
• Recent multicenter data showed average improvement of 4.93 points on the O'Leary-Santa Interstitial Cystitis Symptom Index compared to 1.66 points with placebo (p=0.014) 6

Dosing

The standard FDA-approved dose is 100 mg three times daily (300 mg total daily), administered with water 1 hour before or 2 hours after meals. 1

Critical Safety Warning: Retinal Toxicity

In 2020, the FDA mandated a new warning label due to risk of retinal pigmentary maculopathy associated with pentosan polysulfate use. 3 This is the most important safety consideration that must be discussed with every patient.

Ophthalmologic Monitoring Requirements

Before starting and during pentosan polysulfate therapy, the following monitoring is mandatory: 3

• Obtain detailed ophthalmologic history prior to initiating treatment
• Perform comprehensive baseline retinal examination for patients with any preexisting eye conditions
• Conduct retinal examination within 6 months of starting treatment
• Perform periodic retinal examinations during continued therapy
• Reevaluate risk-benefit if pigmentary retinal changes develop

Maculopathy Symptoms to Monitor

Patients should be counseled to report: 3

• Difficulty reading
• Slow adjustment to low light environments
• Blurred vision
• Risk correlates with cumulative drug exposure 3

Treatment Context and Approach

Pentosan polysulfate should be used as part of a multimodal treatment strategy for IC/BPS, not as monotherapy. 3 The AUA emphasizes that pain management alone is insufficient - addressing underlying bladder symptoms is essential. 3

Other Second-Line Oral Options for IC/BPS

When pentosan polysulfate is contraindicated or ineffective, alternative second-line oral medications include: 3

• Amitriptyline (started at 10 mg, titrated to 75-100 mg if tolerated)
• Cimetidine
• Hydroxyzine

Overlap with Chronic Prostatitis/Chronic Pelvic Pain Syndrome

For male patients with symptoms overlapping IC/BPS and CP/CPPS, the same oral medications (including pentosan polysulfate) may be effective, though treatment should also include manual physical therapy for pelvic floor tenderness and stress management techniques. 7

Emerging Off-Label Use: Hemorrhagic Cystitis

Preliminary case series data suggest pentosan polysulfate may hasten resolution of hemorrhagic cystitis following allogeneic hematopoietic cell transplant. 8 In a retrospective series of 6 patients, pentosan polysulfate was initiated at a median of 4.5 days after hemorrhagic cystitis onset, with median time to symptom resolution of 9 days. 8 However, this remains an off-label use requiring further study.

Key Clinical Pitfalls to Avoid

• Failing to obtain baseline and periodic ophthalmologic examinations - this is now a critical safety requirement given the 2020 FDA warning 3
• Discontinuing therapy too early - patients need at least 6 months of treatment to assess full therapeutic benefit 4
• Using pentosan polysulfate as monotherapy rather than as part of comprehensive IC/BPS management 3
• Not discussing the retinal toxicity risk with patients before initiating treatment 3