Elmiron associated Maculopathy

Elmiron (pentosan polysulfate sodium / “PPS”) was approved by the FDA in 1996 for the treatment of interstitial cystitis (“IC”), also known as “bladder pain syndrome” or “painful bladder syndrome” and it is the only drug approved to treat pain associated with IC.

In recent years, there have been reports of patients who used Elmiron developing vision loss due to Elmiron-related maculopathy. But there were not any warnings about these Elmiron eye problems in the Elmiron Prescribing Information document, or drug label, until June 2020, when the FDA mandated an Elmiron label change. 

Elmiron maculopathy secondary to pentosan polysulfate (PPS) toxicity was first reported in this 2018 Ophthalmology medical journal article. Symptoms most commonly reported were blurred vision, prolonged dark adaptation, and metamorphopsia. The most common presenting diagnoses for these cases were macular or pattern dystrophy and age-related macular degeneration. [Visual acuity (VA)] correlated with degree of foveal atrophy, and in some cases, cystoid macular edema (CME) or choroidal neovascularization. There is one case of CME that was responsive to anti-vascular endothelial growth factor (VEGF) therapy.

On December 15, 2020 a Dear Healthcare Professional Letter titled, “ELMIRON (pentosan polysulfate sodium) and the Risk of Pigmentary Maculopathy“, was issued in Canada by Janssen, Inc. and Health Canada. Its key messages were: (1) Cases of Elmiron pigmentary maculopathy have been reported with long-term use of Elmiron; and, (2) Elmirion is now contraindicated in patients with a previous history of any macular pathology.

Studies on Elmiron associated maculopathy:

• May 2018 – Dr. William A. Pearce and colleagues at the Emory Eye Center published results of a case study of six adult patients who took pentosan polysulfate sodium for IC in Ophthalmology. They found chronic exposure to the drug caused unique pigmentary maculopathy — specifically, injury to the retinal pigment epithelium, a layer of cells that nourishes the retina. 
• April 2019 – Doctors at Emory Eye Center published an expanded study of 10 patients in the Journal of Urology. Researchers noted that patients with a history of IC who did not take pentosan polysulfate sodium did not have the unique form of pigmented maculopathy present in patients who took the drug. They recommended that patients with signs of damage stop taking Elmiron and patients without symptoms undergo an ophthalmic examination with retinal imaging. 
• October 2019 – Researchers at Kaiser Permanente found 140 patients who had taken about 5,000 pentosan polysulfate sodium pills over the course of 15 years. Of those patients, 91 agreed to be examined. Twenty-two out of those 91 patients had signs of toxicity. The toxicity was greater in patients who took more of the drug — 11 percent in patients taking 500 to 1,000 grams and 42 percent in patients taking 1,500 grams or more. 
• November 2019 – Dr. Neiraj Jain and colleagues published a cohort study of data from a large United States medical claims database from 2002 to 2016 in the British Journal of Ophthalmology. They followed data from two groups of pentosan polysulfate sodium users: one group of 3,012 at 5 years and the second group of 1,604 at 7 years. They found pentosan users had significantly increased odds of macular disease at 7 years. 
• November 2019 – Drs. Rachel M. Huckfeldt and Demetrios G. Vavvas published a case report in Ophthalmic Surgery, Lasers and Imaging Retina. They presented the case of a patient whose pentosan-associated maculopathy continued to get worse 6 years after stopping the medication. 
• January 2020 – Drs. Robin A. Vora, Amar P. Patel, and Ronald Melles looked at data for 117 patients with IC who took PPS and found 27 had definite signs of maculopathy. Those who took more than 1,500 g had the highest risk of toxicity. Authors said their findings provided “strong support” to previous studies that linked long-term use of Elmiron to toxic maculopathy.

Pentosan polysulfate sodium is currently marketed globally (North America (United States, Canada and Mexico), Europe (Germany, France, UK, Russia and Italy), Asia-Pacific (China, Japan, Korea, India and Southeast Asia), South America (Brazil, Argentina, Colombia etc.), Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria and South Africa)) by various manufacturers.