Elmiron

The Truth

Interstitial cystitis is a diagnosis given to patients with chronic bladder pain in the absence of another identifiable cause. Not much is known about the exact cause of interstitial cystitis, but through damage, injury, improper formation or other issues with tissues and nerves, the bladder and pelvic region of the body become constantly painful. This type of chronic pain can greatly deteriorate a patient’s mood and quality of life. Symptoms can vary day by day and often have a gradual onset with no identifiable triggering event. Other interstitial cystitis symptoms include bladder and pelvic tenderness, frequent urination, fatigue, pain during sexual intimacy and sexual dysfunction.

Amitriptyline, a tricyclic antidepressant also sold under the brand name Elavil, is typically used as a first-line treatment for addressing interstitial cystitis symptoms. Amitriptyline is routinely used for a variety of nerve-related or otherwise atypical pain conditions and issues, including the complex of symptoms presented by interstitial cystitis. A “first-line” treatment means that through clinical evidence amitriptyline has been known to resolve the symptoms of interstitial cystitis for most patients. Elmiron was created, ostensibly, to address the smaller percentage of patients who don’t respond to amitriptyline. 

Elmiron is, as noted, the only oral medication developed specifically to treat interstitial cystitis. Elmiron differs from other interstitial cystitis pain management medications in the way it interacts with the bladder. Rather than blocking pain signals to the brain, Elmiron is designed to provide relief by binding to the inner wall of the bladder known as the urothelium, providing a layer of insulation and protection from potentially irritating chemical components of urine.

Manufactured by Janssen Pharmaceuticals, Elmiron (pentosan polysulfate sodium) was first approved to treat interstitial cystitis by the FDA in 1996 in capsule form. Although the patent expired in 2010, no generic version of Elmiron is available.

The only other medication option specifically intended for interstitial cystitis, RIMSO-50 (dimethylsulfoxide), is administered directly into the bladder, usually by a catheter in a process known as intravesical therapy. 

Long-term users of Elmiron have suffered a variety of side effects including a type of retina damage that could lead to permanent blindness if left untreated.

Studies + Science

Elmiron Side Effects: Initial FDA Clinical Trials 

Elmiron is prescribed to be taken three times a day for up to 90 days at a time. According to Elmiron’s official packaging as provided by the FDA, if no serious adverse events are present, patients may receive a 90-day extension on their prescriptions. The FDA notes that patients should be reevaluated after six months since “The clinical value and risks of continued treatment in patients whose pain has not improved by six months is not known.”

Elmiron has been associated with a wide range of side effects. Side effects reported by the FDA from the first clinical trial include: 

• Insomnia
• Headache
• Depression
• Dizziness
• Hyperkinesia (muscle spasm)
• Nausea 
• Diarrhea 
• Dyspepsia (indigestion)
• Abdominal pain
• Rhinitis (nasal congestion and/or sneezing)
• Increased sweating 
• Rash
• Liver function abnormalities
• Vaginitis (vaginal inflammation)

Side effects from the second clinical trial in which Elmiron was used for up to a year include:

• Alopecia, inflammatory disorders that result in hair loss (4% of patients)

Up to 1% of patients reported the following:

• Conjunctivitis (“pink eye”)
• Tinnitus (noise or ringing in the ear)
• Optic neuritis (inflammation of the optic nerve)
• Amblyopia (“lazy eye”)
• Retinal hemorrhage

Elmiron Side Effects: Post-Market Reports to the FDA and Pigmentary Maculopathy

According to the FDA Adverse Event Reporting System (FAERS), 2,236 cases of side effects while using Elmiron have been reported. Of those, 1,442 were flagged as serious symptoms. 

The most common symptom, representing approximately 10% of reports, is alopecia. Other common side effects reported include pain, diarrhea, headaches, nausea, dizziness and abdominal pain. 

More than 110 visual symptoms have been associated with Elmiron through FAERS and 3% of reports describe maculopathy. Maculopathies are conditions related to the macula, a small region in the back of the eye, roughly in the center behind the lens. 

The macula contains a high density of photoreceptors and is the area of the eye most responsible for high acuity vision and for  color vision during the day or in lighted areas. Maculopathy is a catch-all term for any condition that affects this functionality of the macula, including conditions such as macular degeneration, retinal dystrophy (nonspecific, chronic damage to the retina), and macular growths that obscure vision. Maculopathies are often associated with age.

A unique maculopathy known as pigmentary maculopathy or PPS maculopathy has been associated with long-term Elmiron use, developing in patients after 14 to 15 years of Elmiron use on average. 

A steadily growing body of evidence seems to indicate that Elmiron could directly contribute to retinal damage and maculopathy, although the exact mechanism behind the damage is still unknown.

A summary of the scientific literature on pigmentary maculopathy including a previously unpublished study presented an American Academy of Ophthalmologists meeting. Of 91 patients who volunteered to be examined for pigmentary maculopathy 22 showed “clear evidence” of the maculopathy described in previous studies. The volunteer patients had taken more than 5,000 Elmiron pills over a 15- year period. However, no control cohort was utilized for comparison, with no causation being established. This does point to a need for further studies with control cohorts to determine if a case for direct causation can be established.

Regulation Recap

According to Janssen Pharmaceuticals and the FDA, two clinical trials were conducted prior to Elmiron’s approval.

First Clinical Trial

The first study was a 12-week, blinded, randomized, controlled trial featuring 151 participants: 145 women, 5 men, and 1 patient of unknown sex. Half of the participants received Elmiron three times a day to treat their interstitial cystitis while the other half received a placebo. 

By “controlling” the study through the use of a control group, researchers minimize bias and ensure randomness to increase confidence that Elmiron was the source of pain relief. “Blinding” the trial means that the patients didn’t know whether they were receiving Elmiron or a placebo (control group). “Randomization” means that no preference was given in dividing participants into the two groups.

Of the 74 patients who received Elmiron, 28 self-reported at least a 50% improvement in their pain. This outcome was regarded as a success and the study is regarded as relatively scientifically sound. 

A downside was that the testing population was relatively small, though not so small as to invalidate the study.

Second Clinical Trial

The second study was an uncontrolled, unblinded, retrospective analysis of 2,499 patients: 2220 women, 254 men, and 25 patients of unknown sex. This study measured Elmiron’s use for up to a year but, in addition to not being controlled through randomization or blinding, the study raises several other areas of concern.

First, a footnote on Janssen’s coverage of the study states: “Trial not designed to detect onset of pain relief.” This is an unusual disclaimer for a medication whose only purpose is to relieve pain. 

Second, the study began with 2,499 patients, but 52% of the patients either dropped out or weren’t eligible to be assessed by the three-month mark. By the one-year mark, only 24% of the patients (598) were still using Elmiron. A high dropout rate such as this can cast doubt on the veracity of the study’s conclusions.

A “D” on the Oxford Scale

Elmiron was reviewed in December 2017 by Aquinox Pharmaceuticals as part of the Bone,

Reproductive and Urologic Drugs Advisory Committee Meeting of the FDA. During that meeting, all existing treatments for interstitial cystitis were reviewed in terms of scientific support. Elmiron received a “D” for effectiveness on the Oxford Scale by that committee. This means that evidence supporting Elmiron’s effectiveness is drawn from “troublingly inconsistent or inconclusive studies of any level.”

Pigmentary Maculopathy Warning 

When Elmiron was released it featured no warnings. On June 16, 2020 however, Janssen Pharmaceuticals added a warning that Elmiron can cause pigmentary maculopathy in long-term users.

The Next Steps

Long-term use of Elmiron may have serious consequences for patients’ eye health and vision. The FDA recommends that patients who have taken Elmiron for longer than six months should consult with a healthcare professional and potentially an ophthalmologist upon recommendation. Asking for alternatives to Elmiron may allow patients to control their interstitial cystitis while reducing their risk of associated adverse events. 

How To File An Adverse Event Report

• Current or former Emiron patients wishing to file an adverse event report with the FDA can do so here. 
• Health care providers can file adverse event reports on behalf of their patients here.