When research first revealed that pentosan polysulfate (brand name: Elmiron), the only oral medication approved by the FDA for interstitial cystitis, was linked to retinal disease (1), many hoped that using it as a bladder instillation would be safer.

Unfortunately, new research has challenged that assumption. A recently published study has identified the first reported case of pigmentary maculopathy in a patient who received pentosan polysulfate through bladder instillations, not oral use.(2)

Equally concerning, the risk may not be limited to bladder treatments. Three patients who received subcutaneous injections of pentosan polysulfate for arthritis have also developed pigmentary maculopathy, raising broader concerns about its effects on retinal health across multiple routes of administration.(3)

Low Exposure to Medication Linked to Damage

What makes these cases particularly alarming is the very low level of exposure involved. The authors noted, “This is the lowest known exposure for PPS toxicity to date,” with the bladder instillation patient receiving a cumulative dose of just 5.8 grams.

Earlier research suggested that long-term use and high cumulative doses were the primary risk factors for retinal disease. A clear dose-response relationship has been reported, with higher exposure linked to more severe damage. For example:

  • 500–999 grams: 12.7% incidence of maculopathy
  • 1000–1500 grams: 30% incidence
  • 1500 grams: 41.7% incidence (4)

Given this, it is alarming that patients in these newer reports developed retinal damage after dramatically lower exposures. Prior to this, the lowest documented exposure was approximately 435 grams over three years.(5)

Notably, in the original ICN survey of patients using pentosan polysulfate, 12% reported vision and retinal changes within the first year—a timeframe associated with much lower cumulative exposure.(6)

Do Other Medications Increase the Risk?

Another critical question is whether the combination of other medications with pentosan polysulfate increases the risk of retinal damage. In this latest study, researchers found that patients using pentosan polysulfate in combination with amitriptyline or nortriptyline—with or without cyclosporine—were more likely to develop moderate-to-severe maculopathy, particularly at higher cumulative doses over longer periods.*

This is especially concerning because these medications have been prescribed together for decades as part of a “multimodal” treatment strategy.(7) More research is urgently needed to confirm this association and to understand why these combinations may increase risk.

Inflammatory Bowel Disease Implications

There is also growing concern about the role of pentosan polysulfate in bowel disease. The first reported case appeared in 2005,(8) and subsequent studies have suggested that bowel symptoms may improve after discontinuing the medication.(9,10)

Researchers at the Emory Eye Institute observed that many patients with retinal disease also experienced gastrointestinal symptoms. In a 2023 case series of 13 patients:

  • 84.6% developed symptoms suggestive of IBD or IBS
  • Most had abnormal mucosal changes in the colon
  • Some required colectomy due to disease severity
  • All showed improvement after stopping pentosan polysulfate (11)

One of the most troubling findings has been the development of polyposis, where abnormal polyp growth can spread extensively across the bowel. In a recent ICN patient meeting, eight out of 22 patients required bowel resection due to uncontrolled polyp growth.

This raises urgent questions: Is polyposis dose-dependent? Could drug combinations amplify this risk? What are the long-term consequences for patients? Clearly, we need more research to understand how and why this is occurring.

A Path Forward

Later this spring, we hope to launch the first formal registry of patients who have used Elmiron to document bowel complications. The goal is to generate sufficient data to:

  • Encourage an update to the Black Box warning
  • Support a formal FDA review
  • Improve patient safety and awareness

Many patients who have been harmed continue to ask a difficult question: Why is this medication still on the market—and why are its risks still being minimized by some urologists? There is still much we don’t fully understand about how pentosan polysulfate affects the body.

Our goal is simple:

👉 Better data
👉 Better warnings
👉 Better protection for patients

References: 

  1. Osborne J. Long-term Pentosan Use May Be Linked To Eye Disease. IC Network. Dec 10, 2019
  2. Qin S, et al. Pigmentary Maculopathy in Patients with IC: Association with Pentosan Polysulfate and Other Therapies. Ophthalmology Science Volume 6, Number 1, January 2026
  3. Fung A, et al. Pentosan polysulfate macuopathy following subcutaneous injections for arthritis. JAMA Opthalmol Case Reports. 2026 Feb 1;144(2):185-191
  4. Vora RA, et al. Prevalence of maculopathy associated with long-term pentosan polysulfate therapy. Opthalmology. 2020;127:835-836
  5. Barnet JM, et al. Potential new-onset of clinically detectable pentosan polysulfate years after drug cessation.  Retin Cases Brief Rep. 2022;16:724-726
  6. Osborne J. Long Term Elmiron Use Linked To Eye Disease. IC Optimist. Fall 2018: 11-14
  7. Clemens JQ, Erickson DR, Varela NP, Lai HH. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome. J Urol. 2022;208(1):34-42.
  8. Conkling B, et al. Pentosan Drug Induced Colitis. Am J Gastroenterol. 100:S202. September 2005
  9. Almashhrawi, A, et al. Elmiron-induced Colitis: A Rare Complication. Am J Gastroenterol. 11;S151, October 2015.
  10. Anderson J, et al. Pentosan Polysulfate-Associated Dysplasia in Inflammatory Bowel Disease: A Case Series. Am J Gastroenterol. 117:S15, December 2022
  11. Jung E, et al. Colopathy Associated with Pentosan Polysulfate Use Front Pharmacolactions 2025 Jul 28:16:1494467.