Elmiron Lawsuit

Understanding Elmiron, Interstitial Cystitis, and Pigmentary Maculopathy

by Zachary Coburn, M.D.

Every medication comes with side effects. Physicians and patients have a careful discussion together and only start a medication if the potential benefits outweigh the risks. For example, you would take your Statin medication knowing it reduces your chance of heart attacks and cardiovascular disease despite the hazard of muscle aches. But what if you were considering a medication for which you and your physician did not fully understand the risks of?

Interstitial Cystitis

Elmiron was initially developed for the treatment of interstitial cystitis, a chronic pain syndrome. The condition causes bladder or pelvic pain as well as frequent urination which can have a significant impact on the quality of life for patients. While the exact mechanism of interstitial cystitis is still not yet understood, it may be more common than you think; studies indicate it impacts between 1 and 5.1 out of 100,000 people and possibly up to 12% of women.

Treatment typically begins with lifestyle management and behavioral modification including managing one’s fluid intake and avoiding foods, beverages, or activities that worsen symptoms. In patients for whom these interventions are ineffective, pharmacological management may be considered. Amitriptyline, an anti-depressant, is used off label as the first line medication by many physicians because it has been found to be an effective pain reliever. At higher doses however, it can cause bothersome side effects including dry mouth, urinary retention, low blood pressure, and constipation. There was a need for other medical options for patients.

Elmiron—A New Treatment

Elmiron (Pentosan polysulfate sodium) is manufactured by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson. It was approved by the U.S. Food and Drug Administration in 1996 for the treatment of interstitial cystitis. It is structurally related to the blood thinner heparin and was found to adhere to the bladder wall but the exact mechanism by which it improves the symptoms of interstitial cystitis is not yet known. Two clinical trials were used in the FDA approval of the medication and involved the study of 151 patients over the course of 3 months and nearly 2500 patients over the span of 1 year respectively. Subsequent studies have similarly found Elmiron to improve symptoms in patients although its overall effect is likely somewhat limited. A 2019 meta-analysis of multiple studies found an overall 12% improvement in bladder pain and urinary symptoms in patients.

It has been reported that hundreds of thousands of patients have or are currently still taking the medication. It is important to recognize that the initial referenced studies used in the medication approval process only involved a couple thousand people studied for up to 1 year. When it was first marketed, listed side effects included headache, nausea, diarrhea, and minor bleeding. Long term adverse reactions would not have been disclosed because they were not yet known about because patients had only been studied for 1 year. Post-approval surveillance monitoring as more patients started to take Elmiron several years out suggests that some may be at risk of serious ophthalmological risk that could permanently impact their vision.

Pigmentary Maculopathy and Elmiron

The macula is the central area of the retina and is an important structure of the eye that is responsible for sensing light. Any damage to the macula impacts the ability to see with clarity and color. Disease of the macula is called “maculopathy” and is actually somewhat common. Age-related macular degeneration is the leading cause of adult blindness in the United States. One subtype involves lesions and deposits are found in the macula while the other subtype involves abnormal growth of blood vessels in the retina. In both cases, the addition of these structures crowd out the macula and impair its ability to sense light and, therefore, the ability to see.

Pigmentary maculopathy was first reported in a case series of 6 patients who had been taking Elmiron for several years in 2018. It is described as a unique disease entity in which pale yellow or orange deposits are found in the macula and also block the passage of light. The mechanism for the deposits is not yet fully understood but it has been proposed that either Elmiron or one of its metabolites deposit within the eye like it does in the bladder. It may be difficult to tell the difference between pigmentary maculopathy and age-related macular degeneration on physical exam. It is possible that there are many patients who were erroneously diagnosed with age-related macular degeneration when they actually had pigmentary maculopathy as the two can present with similar symptoms.

More recent studies have continued to demonstrate a possible correlation between pigmentary maculopathy and Elmiron. A Kaiser Permanente Northern California study published in June 2020 examining 475 patients taking Elmiron found an association between dose size and the risk of developing macular disease. Overall about 25% of patients taking >500 grams of medication daily and nearly 42% in the highest consumption group had findings consistent with pigmentary maculopathy. In their study, Elmiron was the only statistically significant factor associated with the maculopathy despite accounting for age, gender, race, weight, and other demographic data.

While studies are still limited, there seems to be a growing body of evidence confirming an association between Elmiron and the development of ophthalmological side effects. Of note, it is still not known to what degree genetics or other factors may be contributing nor what the exact prevalence of ocular side effects are. Janssen Pharmaceuticals now recommends patients who take Elmiron should receive regular eye and retinal examinations.

Understanding the Risks

Even after stopping Elmiron, pigmentary maculopathy has been observed to continue to progress and vision may worsen. Treatment options, beyond cessation of the medication, are unfortunately somewhat limited at this time. The exact degree of risk associated with Elmiron will hopefully be better elucidated as more studies are conducted. Knowing this, how would your discussion with your physician change if you were considering starting Elmiron? Do you think you have been affected by it?