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Pentosan polysulfate sodium (PPS), a treatment for interstitial cystitis, has raised concerns for a contraindication of macular disease on long term effects.

A clinical research report in the British Journal of Ophthalmology has indicated that the use of pentosan polysulfate sodium (PPS, registered as “Elmiron”, Janssen Pharmaceuticals) is now associated with a new diagnosis of macular disease at a seven-year follow-up in a large retrospective matched cohort study.  PPR / Elmiron is marketed for the treatment of interstitial cystitis (bladder pain) and the drug has been approved by the FDA in the United States since 1996.  The lead author of the study,  Dr. Nieraj Jain, in Department of Ophthalmology, Emory University School of Medicine, Atlanta, suggests that there may be a growing body of literature linking PPS exposure  with macular disease.  In follow up reporting from Reuters Health (New York), Dr. Jain stated that “our findings confirm that this is a large-scale public safety issue”.


In this study of medical claims in a large US cohort, the research showed that at the 5-year and 7-year follow-up analysis, 0.3% and 0.6% PPS patients progressed to an atypical maculopathy outcome compared with 0.2% and 0.3% control patients, respectively. In addition, 3.4% and 5.4% PPS patients developed the “atypical maculopathy + AMD outcome” compared with 2.9% and 4.1% control patients at 5 and 7 years, respectively. At 5 years, multivariate analysis showed no significant association (p>0.13) however, at 7 years, PPS users had significantly increased odds of having the atypical maculopathy + AMD outcome (OR=1.41, 95% CI 1.09 to 1.83, p=0.009).  As the treatment has been used widely for over 20 years there may be potential risk for a “vision-threatening drug-associated maculopathy” with “thousands of additional patients”, outlined within the current publication.   PPS is a semisynthetic macromolecule, similar to glycosaminoglycans, however it is not clearly understood this may impact on the retina. One suggestion speculates that many metabolites might cause toxicity to the retinal pigment epithelium (RPE), or perhaps the drug might alter the integrity of the interphotoreceptor matrix, which itself is comprised largely of glycosaminoglycans. At present, however, there is simply not enough information to specifically characterise the pharmacology at present.


In concluding their research report, the authors of the current research have stated that “the results of this study are far-reaching, as many thousands of patients have received PPS since its FDA approval in 1996. Further investigations will explore pathogenesis of disease, clarify the spectrum of disease phenotypes and inform screening guidelines”.  While this study is now focused on the US, it is not yet known what the PPS impact will be on the EU.  Elmiron is marketed now in the EMA, although there may be a far shorter history available for the use of the drug in the European Union.  In the EMA, Elmiron received a positive opinion for granting a marketing authorisation from the CHMP on 23 March 2017.