Elmiron (also known as pentosan polysulfate sodium or PPS) is a drug prescribed for over 25 years to treat painful bladder syndrome or interstitial cystitis. This chronic bladder disease includes significant bladder or pelvic pain, incontinence, and dyspareunia. The condition afflicts millions of women in the United States and a much smaller number of men.
Elmiron is manufactured by Janssen Pharmaceuticals, Inc., a division of Johnson & Johnson, and is touted as the “only oral medication FDA approved to treat the bladder pain or discomfort of interstitial cystitis (IC).” The drug was approved for “compassionate use” by the FDA in 1986 and given regulatory approval of the governmental safety oversight agency in 1996. In 2018, it was estimated that sales of Elmiron exceeded $150 million annually.
There have been recent concerns that patients taking Elmiron, especially long-term , are at a higher risk for developing eye problems. The first reports of pigmentary maculopathy (damage to the macula in the eye, which provides central vision) associated with long-term use of Elmiron appeared in the medical literature a few years ago. It is believed, however, that the drug’s manufacturer may have known of this risk much earlier than that.
Over 100 adverse event reports for eye-related injuries (including maculopathy) were filed with the FDA by the manufacturer from 1997 to 2019, with most of the safety reports being categorized as “serious.” During this same time period, the drug did not include an adequate warning to patients and their doctors regarding the potential for vision loss and eye damage associated with long-term and high-dose use of Elmiron.
The drug’s warning label for Elmiron was updated in Canada in April of 2020 to reflect the following critical safety information:
- In the post-market setting, pigmentary maculopathy has been reported with chronic use of Elmiron. Visual symptoms included difficulty reading and prolonged dark adaptation.
- Patients, particularly those with chronic use of Elmiron, should have regular ophthalmic examinations for early detection of pigmentary maculopathy.
- If pigmentary maculopathy is confirmed, Elmiron treatment discontinuation should be considered.
That same warning, however, was not immediately added to the warning label for the drug in the United States, a subject explored through discovery efforts as the litigation against Janssen Pharmaceuticals proceeds. Finally, in June of 2020, changes were made to enhance the warnings in the United States on the Elmiron package insert/warning label. This latest enhancement to the warning label by the drug manufacturer now notes:
Pigment changes in the retina of the eye (also referred to as pigmentary maculopathy in medical journal articles) have been reported with long-term use of ELMIRON® . While the cause of the pigmentary changes is unclear, continued long term dosing with ELMIRON® may be a risk factor. The consequences of these pigmentary changes in the retina are not fully understood. Visual symptoms that have been reported include: difficulty reading, slow adjustment to low or reduced light environments, and blurred vision. If you already have retinal pigment changes from other causes, it may be difficult to distinguish future retinal pigment changes if they occur. Call your doctor (including your eye doctor) if you notice any changes in your vision. Throughout your treatment, regular eye examinations that include retinal examinations are suggested for early detection of retinal/macular changes. Your doctor will discuss with you when to get your first eye examination and follow up exams, and whether the treatment should be continued since these changes may be irreversible and may progress even after stopping treatment.
The studies published so far have found that patients tended to be white women with an average age of 60 and that the most common symptoms of Elmiron-induced maculopathy included:
- Blurred vision
- Difficulty reading
- Prolonged ability of eyes to adjust to darkness
- Difficulty seeing objects close up
- Dimming of vision
- Spot of vision loss in central field of vision (paracentral scotoma)
- Metamorphosia (visual defect that causes linear objects to appear curved or rounded).
On examination, eye specialists have noted varying signs of the drug-induced eye disease include:
- Parafoveal Pigmented Deposits – abnormal blood vessels around the macula
- Vitelliform Deposits – round, yellowish lesions underneath the macula
- Hyperpigmented or dark spots near the retina
- Atrophy of the retinal pigment epithelium
Many patients in these studies were initially diagnosed with macular degeneration, retinal deterioration, pattern dystrophy, atypical maculopathy, macular retinopathy, or age-related macular degeneration, which is a tremendous safety concern since patients may have lost vision due to a failure to timely attribute their maculopathy to Elmiron rather than genetic or age-related conditions.
Current research indicates that PPS maculopathy appears to be limited to patients taking Elmiron and has not been seen in interstitial cystitis patients receiving other types of medication or treatment. The studies have noted this distinct drug-induced eye disease in patients taking Elmiron for 3 to 22 years (with the average duration of use of the drug being 16-17 years in patients with maculopathy). Recent data noted that 11% of patients in a large study group had signs of PPS maculopathy (when taking doses of 500 to 999 grams of Elmiron daily), and that the incidence of maculopathy was 42% in IC patients taking higher doses (1500 gram of PPS daily).
Patients taking Elmiron are urged to consult with their prescribing physician to reassess, given the the latest research, whether the benefits of high-dose or chronic use of Elmiron outweigh the potential ocular adverse effects. Also, patients have been advised to consult with an eye specialist to undergo annual screening, imaging, and monitoring for eye toxicity if they choose (after consultation with their healthcare providers) to remain on the medication.
Below is a summary of some recent studies and medical literature publications on Elmiron-related eye damage:
- Wang D, Au A, Gunnemann F, et al. Pentosan-associated maculopathy: prevalence, screening guidelines, and spectrum of findings based on prospective multimodal analysis. Canadian Journal of Ophthalmology. 2020 Apr 1;55(2):116-125 – A large cross-sectional study that links the prevalence of PPS-associated maculopathy to imaging findings and establishing guidelines to be followed during an eye exam. The study noted a 20% prevalence of drug-induced maculopathy in the cohort tested.
- Mishra K, Patel TP, Singh MS. Choroidal Neovascularization Associated with Pentosan Polysulfate Toxicity. Ophthalmology Retina. 2020 Jan 4(1):111-113 – This case study details an instance of choroidal neovascularization (development of pathological blood vessels in the choroid of the eye) leading to vision loss in a patient on long term Elmiron.
- Pearce WA, Chen R, Jain N. Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium. Ophthalmology. 2018;125(11):1793-1802 – One of the first medical journal articles correlating use of long-term pentosan polysulfate (also sold as Elmiron) with a variant of macular degeneration known as pigmentary maculopathy. The study noted drug-induced eye damage in 24% of patients and that effect appeared to be dose-related.
- Doiron RC, Bona M, Nickel JC. Possible drug-induced, vision-threatening maculopathy secondary to chronic pentosan polysulfate sodium (Elmiron®) exposure. Canadian Urological Association Journal. 2020;14(2) – A recent journal publication further investigating the potential link between Elmiron and irreversible vision damage.
- Vora RA, Patel AP, Yang SS, Melles R. A case of pentosan polysulfate maculopathy originally diagnosed as stargardt disease. American Journal of Ophthalmology Case Reports. 2020 Mar;17:100604 – A case report in which the eye damage caused by Elmiron mimicked a similar eye pathology known in the literature as Stargardt disease (an inherited form of juvenile macular degeneration).
- Shah R, Shah R. Pentosan Polysulfate Maculopathy. Retinal Physician. 2019 Sept. – A broad overview of emerging reports of maculopathy secondary to Elmiron use, and theories on the level of population exposure (on the scale of thousands, as the drug has been on the market for decades).