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Ocular Toxicity Associated With Pentosan Polysulfate Sodium

      To The Editor:
      Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common disorder that affects 7.9 million adult women in the United States.
      • Berry S.H.
      • Elliott M.N.
      • Suttorp M.
      • et al.
      Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States.
      Pentosan polysulfate sodium (PPS) is the only Food and Drug Administration-approved oral medication for treating IC/BPS. A recent study within the Kaiser Permanente Northern California (KPNC) system suggested that a substantial number of patients with IC/BPS (up to 42%) take long-term PPS.
      • Vora R.A.
      • Patel A.P.
      • Melles R.
      Prevalence of maculopathy associated with long-term pentosan polysulfate therapy.
      A bilateral pigmentary maculopathy associated with long-term use of PPS (Figure, panel A) has been described recently, with the initial report published in November 2018.
      • Pearce W.A.
      • Chen R.
      • Jain N.
      Pigmentary maculopathy associated with chronic exposure to pentosan polysulfate sodium.
      Subsequent reports in the ophthalmology literature have corroborated this association between the use of PPS and a progressive maculopathy, potentially leading to severe, irreversible loss of vision.
      • Vora R.A.
      • Patel A.P.
      • Melles R.
      Prevalence of maculopathy associated with long-term pentosan polysulfate therapy.
      ,
      • Wang D.
      • Au A.
      • Gunnemann F.
      • et al.
      Pentosan-associated maculopathy: prevalence, screening guidelines, and spectrum of findings based on prospective multimodal analysis.
      Although a recent administrative claims report did not identify an association between use of PPS and maculopathy, the mean duration of PPS use among study subjects was less than 1 year, and PPS maculopathy typically develops after many years of exposure to PPS.
      • Vora R.A.
      • Patel A.P.
      • Melles R.
      Prevalence of maculopathy associated with long-term pentosan polysulfate therapy.
      ,
      • Pearce W.A.
      • Chen R.
      • Jain N.
      Pigmentary maculopathy associated with chronic exposure to pentosan polysulfate sodium.
      ,
      • Ludwig C.A.
      • Vail D.
      • Callaway N.F.
      • Pasricha M.V.
      • Moshfeghi D.M.
      Pentosan polysulfate sodium exposure and drug-induced maculopathy in commercially insured patients in the United States.
      Commonly prescribed by urologists, these potential ocular side effects of PPS were also described recently within the urology literature.
      • Doiron R.C.
      • Bona M.
      • Nickel J.C.
      Possible drug-induced, vision-threatening maculopathy secondary to chronic pentosan polysulfate sodium (Elmiron®) exposure.
      Figure thumbnail gr1
      Figure(A) Fundus autofluorescence imaging shows advanced speckled autofluorescence changes in a patient with pentosan polysulfate sodium (PPS) maculopathy (left) compared with an unaffected person (right). (B) Medical specialty profile of PPS prescribers within Mayo Clinic.
      At Mayo Clinic Rochester, Minnesota, we recently identified 4 cases of PPS maculopathy. All affected patients were women 43 to 63 years of age who had been taking the medication for longer than 5 years. Two patients had PPS prescriptions most recently renewed by their primary medical care providers, which stimulated our interest in investigating the profile of the PPS prescribers. We performed a system-wide review of electronic medical records within Mayo Clinic (including Mayo Clinic in Minnesota, Florida, and Arizona, as well as the Mayo Clinic Health System) and identified 319 prescriptions of PPS submitted in the past 36 months. More than one-half of all PPS prescriptions were from non-urologists, with more than one-third being submitted by general medical physicians: internal medicine and family medicine (Figure, panel B).
      The KPNC study highlighted the significant prevalence of PPS-associated maculopathy in 23% of patients taking PPS.
      • Vora R.A.
      • Patel A.P.
      • Melles R.
      Prevalence of maculopathy associated with long-term pentosan polysulfate therapy.
      The progressive nature and threat of permanent loss of central vision warrants increased awareness of PPS maculopathy among all prescribers.
      • Wang D.
      • Au A.
      • Gunnemann F.
      • et al.
      Pentosan-associated maculopathy: prevalence, screening guidelines, and spectrum of findings based on prospective multimodal analysis.
      Our data indicate that general medical practitioners are commonly prescribing or renewing this medication. Yet, there is a paucity of reports regarding PPS ocular toxicity in the general medical literature, and we believe that a rapid increase in awareness among all clinicians will be important to reduce the risk of irreversible loss of vision.
      Caution should be exercised in renewing prescriptions for patients on long-term PPS pharmacotherapy. Because of the recent recognition of this ocular pathology, and incomplete understanding of its development and progression, no official screening guidelines have yet been established. However, based on the available data, some authors have recommended ophthalmic screening of patients when the cumulative PPS dose approaches or exceeds 500 g.
      • Wang D.
      • Au A.
      • Gunnemann F.
      • et al.
      Pentosan-associated maculopathy: prevalence, screening guidelines, and spectrum of findings based on prospective multimodal analysis.
      We also encourage discussion of this side effect with patients, a review of past medical and ocular history, inquiry regarding any visual symptoms or changes, and prompt ophthalmologic referral in case of any concerns—even at low doses—to allow for early detection of maculopathy, which may reduce the risk of irreversible loss of vision.

      References

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        Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States.
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        • Patel A.P.
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        Prevalence of maculopathy associated with long-term pentosan polysulfate therapy.
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        Pigmentary maculopathy associated with chronic exposure to pentosan polysulfate sodium.
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        • Wang D.
        • Au A.
        • Gunnemann F.
        • et al.
        Pentosan-associated maculopathy: prevalence, screening guidelines, and spectrum of findings based on prospective multimodal analysis.
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        • Ludwig C.A.
        • Vail D.
        • Callaway N.F.
        • Pasricha M.V.
        • Moshfeghi D.M.
        Pentosan polysulfate sodium exposure and drug-induced maculopathy in commercially insured patients in the United States.
        Ophthalmology. 2020; 127: 535-543
        • Doiron R.C.
        • Bona M.
        • Nickel J.C.
        Possible drug-induced, vision-threatening maculopathy secondary to chronic pentosan polysulfate sodium (Elmiron®) exposure.
        Can Urol Assoc J. 2020; 14: 10-11