When you’ve been told that a medication is approved by the US FDA, wouldn’t you assume that testing has been performed to prove that it is not only safe but effective? Did this happen for Elmiron® (aka pentosan polysulfate sulfate – PPS) , the only FDA approved oral medication for IC/BPS, that has been now associated with retinal damage, blindness and inflammatory bowel disease?

A new investigative report has raised critical questions about the original approval of Elmiron®.(1) A staggering 18 years after its approval, the after market, follow-up study showed that this medication performed no better than placebo.(2) Dr. Curtis Nickel, the lead investigator in that study, said “I thought the next day it would be over for Elmiron®…Doctors would stop prescribing it. The FDA would order it off the market.” Yet, it is still available today.

Could the eyesight of patients now suffering from pigmentary maculopathy been saved had this research been performed in a more timely way? I believe so. Let’s take a look at what the investigation and related lawsuits revealed.

Approval Timeline

1985 – Orphan Drug Status

Developed in 1985, Elmiron® was initially designated as an “orphan drug,” a status usually reserved for treatments for rare diseases. This allowed the owner of Elmiron® at the time (Medical Marketing Specialists) to save money by giving them tax credits, exemption from fees and the potential of seven years market exclusivity after approval.(3) This status does not mean that the drug is safe or effective.

1986 – Compassionate Use

The following year, Elmiron® was first made available to IC patients on a “compassionate use” basis. This program allows patients with a serious or immediately life-threatening diseases to gain access to an investigational product for treatment when no comparable alternative therapies are available. However, the FDA states that medications approved for compassionate use “may, or may not, be effective in the treatment of the condition, and use of the product may cause unexpected serious side effects.” (4) For nine years, this is how IC patients usually received the medication.

1991 – New Drug Application to the FDA

The new owner of Elmiron®, Baker Cummins Pharmaceuticals (now Baker Norton, a subsidiary of IVAX), applied for New Drug Approval based in June of 1991 based on two studies. The first (E-001) was rejected by the FDA as a failed study. The second (E-002), a study of 148 patients, was questionable at best because only one researcher and study site, that run by the patent holder of Elmiron®, showed success.

1992 – First Denial

In February of 1992, FDA Division Director Wiley Chambers MD issued the first non-approvable letter, citing serious flaws with the submitted studies and encouraging Baker Norton to conduct another study. They said:

One purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences. Based on the analyses submitted to date for studies E-001 and E-002, there appears to be significant investigator interaction. The results obtained by the first investigator listed in each study are significantly different than the results obtained by each of the other investigators in the studies. In the absence of an adequate explanation for these differences, studies E-001 and E-002 cannot be considered to be adequate and well-controlled. It is recommended that an additional clinical investigation utilizing investigators not included in previous studies be conducted and submitted as part of any resubmission of this application.(5)

Their specific concern was that only the patent holder, a doctor at UC-San Diego, showed remarkable success, reporting that 10 out of 15 patients (66.7%) treated with Elmiron® were “better.” No other investigator showed that same success rate and when the data was combined, the other six investigators only reported 23% of their patients better. FDA staff expressed concern about the financial interest of the patent holder.(5)

1993 – Another Submission of the original studies

In March of 1993, FDA staff met with Baker Norton, encouraging an additional study to prove the Elmiron® was effective. The study design was discussed in depth though the FDA allowed Baker Norton to resubmit the original studies with re-analysis of the data from E-001 and E-002. This was submitted to the FDA in July 1993. (5)

1994/1995 – Second Formal Denial

The FDA issued a second letter denying the approval of Elmiron® as a new drug in October of 1994, requesting again that an additional study be performed to show effectiveness and safety. They noted that if the results were clearly positive, that it could support approval. (5)  In February 1995, FDA and Baker Norton met again. The FDA asked, again, for a new study. Baker Norton resisted, stating that their first two trials were valid. The FDA was unconvinced, stating:

We indicated that we need replication of an adequate study. This is in part needed in order to show that other physicians can safely (emphasis mine) use the product. So far, their data shows that one physician can use Elmiron; the results from the other physicians do not show improvement.(5)

Baker Norton suggested including the data from patients using it for “compassionate use” show success. On August 31, 1995, Baker Norton formally submitted this new, less rigorous data to the FDA.

1996 – Formal FDA Approval As A New Drug

The FDA approved Elmiron’s new drug application based upon the new compassionate use data. Please note that this new data was not equivalent to a formal study.

2014 – Long Awaited Study Shows It Doesn’t work

A staggering eighteen years after the FDA approval, the Elmiron Study Group published the results of the long awaited, large, double-blind, placebo-controlled study of Elmiron v placebo that the FDA had asked for. It showed no benefit.(2) Again, Dr. Nickel believed that Elmiron would be removed from the market after the study was published.

This then raises the key question. Would patients have taken a medication, in some cases for many years, had they known it didn’t work? Might this information have saved the eye sight of patients now struggling with pigmentary maculopathy, as well as those who have developed inflammatory bowel disease?

Elmiron® Safety History

Elmiron has been prescribed enthusiastically to hundreds of thousands of IC patients over the years.(1) Given the now strong association with retinal disease and inflammatory bowel disorders, let’s take a look at safety data.

Eye Disorders

Late 1980’s/Early 1990’s – Two patients who used Elmiron® in compassionate use data showed eye changes. .(5)

  • A 32 year old white female without a prior history of eye trauma, hypertension, diabetes or previous significant ophthalmologic history complained of experiencing blurred vision.
  • A 21 year old white female without any history of ophthalmological problems, head trauma, diabetes, or any previous neurological symptoms experienced a “filmy sensation over the left eye.”

1991 – A study showed that pentosan polysulfate affected fibroblast growth factors in the eye and inhibited the regrowth and proliferation of retinal pigment epithelial cells, “impairing an important physiological pathway for retinal health.” (6)

1997 – Adverse event reports grow – 488 reports of serious adverse events, eight with changes in vision, were filed with the FDA and are available in the FAER’s database.

1998 – 2020 – Hundreds of additional reports of serious adverse events were filed with the FDA.

2018 – Emory Eye Center Believes That They Have Found A Disease Related to Elmiron® Use

Researchers at the Emory Eye Center published a case series of six IC patients who had taken Elmiron® who had demonstrable changes in the structure and function of their retinas. They had difficulty reading, seeing in darkness, blurred version, etc. The patient with the most severe symptoms was actually the youngest at 37. Diagnosed with IC at 23, she was on Elmiron for years and begin showing changes in her vision at the age of 30. (7)

The Emory team wrote a letter to the Editor of the Journal of Urology to raise awareness among urologists.

We wish to alert readers to a concerning new observation of vision threatening retinal changes associated with long-term exposure to [Elmiron]. We recently reported our findings of retinal pigmentary changes in six patients undergoing long-term therapy with [Elmiron]. These patients primarily described difficulty reading and/or trouble adjusting to dim lighting. Each patient had received a standard dosage of [Elmiron], ranging from 200 to 400 mg daily, for a median duration of 15.5 years. . . . Examination findings in patients with this condition are suggestive of injury to the retina and the underlying retinal pigment epithelium. . . . After extensive investigations, which included molecular testing for hereditary retinal disease, we found these cases to resemble no other retinal disease.(8)

2019 – Research Validates Retinal Disease

Several studies were released in 2019 showing an association between Elmiron® and eye disease.(9,10,11,12) In addition, regulators in Europe and Canada updated their information to warn about the risk of pigmentary maculopathy, encouraging patients to have regular ophthalmologic examinations. (13,14)

A deeply concerning case study profiled a patient whose retinal disease progressed, years after stopping the medication. This was the first of several studies which show progression after stopping the medication. (15)

A second case study was published of a patient who had been misdiagnosed with another eye disease that was determined to be pigmentary maculopathy.(16)

2020 – More Research & Black Box Warning Added

Eye researchers at UCLA found a 20% prevalence of maculopathy in patients using PPS, concluding that there was a significant risk of retinal toxicity for patients using the medication and that severity correlated with long term use. (17) Researchers at Emory release their first study showing that it appeared that the maculopathy continues to evolve even after stopping the medication, in some cases for many years. (18)

In June of 2020, the FDA approved a label change for Elmiron® that included a formal warning of retinal pigmentary changes.(19)

2022 – IC Guidelines Updated To Include Warning of Eye Damage

In 2022, the American Urologic Association Guidelines for IC/BPS were updated to include strong warnings about the risk of retinal disease, encouraging patients to have retinal examinations annually. (20 – See Guideline Statement 15)

2025 – Where We Are Today

As of March 31, 2025, 5,785 cases have been filed within the FDA’s Adverse Event Reporting System (FAERS – fis.fda.gov), including 4,692 reports of “serious” adverse events and 48 fatalities associated with Elmiron®/pentosan use.(21) The great majority of these reports (3,094) relate to eye and retinal damage however several other potentially serious reactions are on the record, notably numerous reports of stomach and GI symptoms (diarrhea) which correlate with recent findings that Elmiron® use is also associated with the development of inflammatory bowel disease.

Bowel Disorders

(Editors Note: I was an IC support group leader at the time that Elmiron® was approved and diarrhea was commonly discussed. Some suggested that it was the result of the capsule itself rather than the medication and patients were advised to remove the medication from the capsule to reduce the diarrhea. I do not remember who provided this information.)

1998 – First reports of diarrhea and nausea begin to be reported to the FAERS database.

2005 – Case Studies Show Bowel Symptoms Resolved After Stopping Elmiron

Gastroenterologists in the Texas A&M University Health System published two case studies which they believed showed a causal relationship between PPS use and colitis.(22)

  • A 29 year old woman developed bloody diarrhea and cramping abdominal pain one month after starting PPS. A sigmoidoscopy found small ulcers and friable tissue (i.e. red, bleeding tissue). A colonoscopy revealed colitis extending from her rectum to the transverse colon. Biopsies confirmed active colitis. Her symptoms completely resolved when she discontinued PPS use. A repeat endoscopy and biopsies found a total resolution of the colitis.
  • A 59 year old female with a history of IBS developed increased diarrhea and lower left quadrant abdominal pain two weeks after starting PPS. A colonoscopy also revealed ulcerations. Biopsies confirmed moderately active colitis, with some fibrosis (thickening) and necrosis (tissue death). Treatments commonly used for colitis (i.e. mesalamine, prednisone) were not effective. Her abdominal pain and diarrhea improved after PPS was stopped and, like the previous case, further testing revealed a resolution of the colitis.

2014 – Study Participants Experienced GI Complications

Most of the adverse events reported in the 2014 clinical trial were reported as moderate gastrointestinal symptoms. 31 patients in the Elmiron arms of the study dropped out because of their GI symptoms.(2)

2015 – Case Study Reveals Colitis that Improved After Stopping the Medication

Researchers at the University of Missouri and UC Irvine published a case study of a 32 year old female with IC who had struggled with diarrhea for seven months. She had abdominal cramping and loose bloody stools with approximately 20 bowel movements per day. They attempted treatment with several medications (mesalamine, prednisone, rifaximin, dicyclomine, amitryptiline) over a year with no improvement. However, when Elmiron® was discontinued, her symptoms resolved over a few weeks. A new colonoscopy found normal tissue. They concluded that “Elmiron may rarely induce colitis and rectal bleeding. Providers should be aware of this potential side effect, especially at higher doses.” (23)

2022 – Report of Dysplasia

Researchers at the Oregon Health and Science University, searched electronic medical records at two care centers to identify patients using PPS and who had a diagnosis of Crohn’s disease or ulcerative colitis. They found thirty patients who met their criteria, ten of whom had colonic dysplasia. Dysplasia is an area of the lining of the colon where the cells become abnormal and could become cancerous over time. Six (60%) of these patients required colectomy while three discontinued the drug and achieved healing.

These authors said “The presence of mucosal inflammation is a known risk for the development of colorectal cancer. Dysplasia is a precursor for IBD-related colorectal neoplasia; thus, early identification is critical.” They note that in their study PPS users have a significantly higher rate dysplasia at 33% than the 4% observed in the general IBD population.(24)

2023 – Emory Researchers Suggest Strong Association

In May 2023, the original team at Emory released a concerning study. The first section involved thirteen IC/BPS patients with pigmentary maculopathy who had enrolled in a four year prospective study of their ocular and systemic health prior to any concerns about bowel disease. They each had a high, cumulative exposure to pentosan. All experienced GI symptoms while on PPS. Twelve were female, one was male. Median age was 62 years. Median duration of use of PPS was 14 years (9 to 18). Eleven patients (84.6%) experienced bowel symptoms after beginning PPS use with a median time of 4.9 years (3.5 to 6.2). Symptoms included diarrhea, abdominal pain, stool with mucus and blood, tenesmus (feeling like you need to have a bowel movement even when the bowel is empty), fecal urgency and fecal incontinence. Only two of these participants had bowel symptoms prior to starting PPS… one with lactose intolerance and the other with IBS. All 11 underwent at least one colonoscopy and all received a diagnosis of IBD or IBS. Biopsy and microscopic examination found abnormal mucosal changes. The second section evaluated 219 patients with IC who were seen at the Emory Eye Center and PPS use was a statistically significant predictor of IBD or IBS/IBD. No other medications were associated with this risk.(25)

2025 – Patient Reports Widespread Polyps on Colonoscopy

An IC patient who had severe retinal disease who was also found to have extensive polyps in her bowel. In the past two years, she’s had seven colonoscopies, each of which have found more polyps. Her gastroenterologist suggested that she could have a genetic disorder causing polyp growth but genetic testing found none. Dr. Jain (Emory) confirmed (26) by email that multiple patients that he is working with have also been diagnosed with excessive polyp growth. In a support group meeting we did on June 9th 2025, two patients shared that they, too, had this occur with one having her bowel later removed. “Carpet polyps” or laterally spreading tumors usually require surgical resection. (27)

2026 – Case Series Finds Significant Risk of Severe Polyposis in Maculopathy Patients

A disturbing new paper from UCLA has expanded our knowledge of the effects of pentosan/Elmiron® in the bowel. Eight patients (16 eyes) diagnosed with PPS maculopathy who also underwent GI evaluation between 2019 and 2025. Colonoscopy revealed severe adenomatous polyposis in 6 of the 8 patients (75%), with 3 requiring partial or total colectomy and 2 undergoing endoscopic resection. One patient developed ulcerative colitis, and 2 additional patients were diagnosed with Crohn’s disease or microscopic colitis. The median latency to GI diagnosis was 10 years after PPS initiation. The authors concluded that “PPS maculopathy patients are at risk of concomitant colonic disease, including severe polyposis and dysplasia. The frequent detection of asymptomatic polyposis underscores the importance of colonoscopy screening in exposed patients, even in the absence of GI symptoms. Heightened interdisciplinary awareness and long-term surveillance are warranted to mitigate the vision- and life-threatening consequences of PPS toxicity.” (28)

FDA Failures

Why have scientific standards at the FDA become lax? The FDA did have very rigorous standards that a pharmaceutical company had to meet to get their medication approved. This changed in the 1980’s when patients and care providers were desperate for new treatments that could save the lives of those who were dying rapidly from AIDS. The FDA fast tracked some approvals based on preliminary/supplementary data (i.e. simple lab studies) rather than providing evidence that the medication had actually worked on patients.

Big pharma took this has opportunity to bring more products to market on what is essentially flimsy evidence. Clinical trials cost big bucks, after all. Not surprisingly, their campaign contributions increased leading to Congress passing what some consider a disastrous bill, the Prescription Drug User Fee Act which “explicity directed the FDA to allow approvals based on lower standards” according to the LEVER investigative report.

Dr. Gregg Gonsalves, a professor of epidemiology at the Yale School of Public Health, told an FDA advisory committee in 1993: “We opened Pandora’s Box and Pharma exploited it… unleashing drugs with well-documented toxicities onto the market, without obtaining rigorous data on their clinical efficacy.”

From January 2013 through December 2022, the FDA approved 429 drugs based on inadequate evidence, and have allowed medications to remain on the market even after studies have shown that they are not effective. In fact, 73% of these drugs were sold to patients without evidence that they worked. In 2022, the US Department of Health and Human services revealed that more than one-third of drugs approved on an accelerated pathway have never seen a study confirming that they were effective. If they are done at all (some haven’t been done) these “post market” studies can take years to be conduct.

This appears to be the case of Elmiron®, which appears to have been approved on these more relaxed standards. FDA staff found the two original studies lacking and that only one physician appeared to have success, the physician who had a financial interest in the drug. FDA repeatedly asked for a new study. Then, it was approved based on marginal data and released to the IC patient population who took it assuming that testing proving that it was safe and effective had been done.

Who Monitors Safety Data?

We must also ask whose responsibility was it to monitor the safety data? There was very clear and compelling data emerging from the FAERS database that both eye and bowel issues were persistent. The fundamental flaw in FAERS and the MAUDE database for medical device complications is that the FDA gathers the information but appears to rarely act on it, leaving us to ask how many adverse events and fatalities must be reported before someone in authority takes responsibility and begins to ask probing questions about safety?

What role do pharmaceutical companies have in tracking safety data over time? This is the question that is currently dispute in hundreds of lawsuits filed by patients struggling with retinal damage. Many patients have received six figure settlements rather than proceeding to trial.

Justifiable Rage

Talk with any patients who have lost their sight or had their bowel removed, their rage is undeniable. They are furious that they were given a medication under what appears to be a false promise, or perhaps implication, of effectiveness. Their careers have been destroyed. There is deep, distressing worry about their future, including the cost of care if and/or when they may need assistance with daily activities.

Laura MacMillan was diagnosed with IC in 2001 and, two years later, severe colitis. In 2013, her vision began to change and progressively dimmed though her eye doctor could not determine why it was happening or provide any treatment. In 2021, she learned that retinal disease had been linked with Elmiron®. She had been on the medication for 20 years. After stopping the medication, her colitis symptoms disappeared thankfully but her eye symptoms persist. Today, she can’t work, drive or even see the players on a baseball field.

Many more patients have been sharing their stories, some completely blind, others struggling with vision loss that is progressing over time. For those who have settled their lawsuits early, before research showed that the damage could progress over time, there is regret that they did not ask for or receive lifetime eye care to cover, at least, the cost of additional eye testing. Yet, some settlements allow patients to file additional cases against the company should more health conditions arise. One year after accepting a settlement, a patient still hasn’t received all of her money because Medicare put a $30,000 lien on her case demanding that it be reimbursed for all of the retinal testing she had done.

I believe that Elmiron® was developed with the best of intention to help others. The harsh reality, though, is that the drug companies balked at paying for another clinical trial. Sadly, this groundbreaking investigative report proves that this is, in actuality, a pattern and that many medications are approved without adequate evidence that they work.  This is simply unacceptable.  We must must be steadfast in demanding the FDA require more comprehensive testing and, most importantly, to remove products from the market that have been found to be ineffective and/or associated with severe adverse events.

Elmiron® was widely recommended and used by thousands of patients who are now at risk of progressive retinal disease and inflammatory bowel disease. It’s still on the market today but should it be?

References:

  1. Lenzer J, Brownlee S. FDA Approved And Ineffective. The Lever. June 5, 2025
  2. Nickel JC, et al. Pentosan Polysulfate Sodium For IC/BPS: Insights from a Randomized, Double-Blind Placebo Controlled Study. JUROL. Mar 2015
  3. Designating an Orphan Product: Drugs and Biological Products. US FDA – Accessed 5/6/25
  4. Expanded Access. US FDA. – Accessed 5/6/25
  5. Turner Vs. TEVA Branded Pharmaceutical Products R&D. https://newyork.legalexaminer.com/wp-content/uploads/sites/7/2021/02/2021-2-4-elmiron-turner-complaint_r.pdf
  6. Katrinka H. Leschey, et al. Inhibition of Growth Factor Effects in Retinal Pigment Epithelial Cells, 32 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 1770–1778 (1991)
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  8. Re: FDA BRUDAC 2018 Criteria for Interstitial Cystitis/Bladder Pain Syndrome Clinical Trials: Future Direction for Research: J. C. Nickel and R. Moldwin J Urol 2018; 200: 39–42. Pearce W. et al The Journal of Urology. Published online: August 3, 2018
  9. Jenelle Foote, Adam Hanif, and Nieraj Jain, Chronic Exposure to Pentosan Polysulfate Sodium is Associated with Retinal Pigmentary Changes and Vision Loss, 201 UROLOGY e688 (2019),
  10. Adam M. Hanif and Nieraj Jain, Clinical Pearls for a New Condition. Pentosan Polysulfate Therapy, a Common Treatment for Interstitial Cystitis, Has Been Associated with a Maculopathy, REVIEW OF OPHTHALMOLOGY July 10, 2019
  11. Adam Hanif et al., Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A multicenter Study, 137 JAMA OPHTHALMOLOGY 1275, 1282 (Sep. 5, 2019)
  12. Nieraj Jain et al., Association of Macular Disease with Long-Term Use of Pentosan Polysulfate Sodium: Findings from a U.S. Cohort, BRITISH JOURNAL OF OPHTHALMOLOGY
  13. https://www.ema.europa.eu/en/documents/product-information/elmiron-epar-product-information_en.pdf
  14. https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/health-product-infowatch/health-product-infowatch-october-2019.html#elmiron
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  17. Derrick Wang et al., Pentosan-Associated Maculopathy: Prevalence, Screening Guidelines, and Spectrum of Findings Based on Prospective Multimodal Analysis, CANADIAN JOURNAL OF OPHTHALMOLOGY (in press, published online January 2020),
  18. Rachel Shah et al., Disease Course in Patients With Pentosan Plolysulfate Sodium-Associated Maculopathy After Drug Cessation, JAMA OPHTHALMOLOGY (Published online July 9, 2020).
  19. Elmiron Drug Information Sheet – June 2025
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  21. FAERS Database. Search conducted 06/25 using the terms Elmiron, pentosan polysulfate and pentosan polysulfate sulfate – fis.fda.gov
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  24. Anderson J, et al. Pentosan Polysulfate-Associated Dysplasia in Inflammatory Bowel Disease: A Case Series. Am J Gastroenterol. 117:S15, December 2022
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  26. Personal Correspondance. Email – May 25, 2025
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