, Volume 66, Issue 6, pp 821-835
Date: 17 Sep 2012

Pentosan Polysulfate

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Pentosan polysulfate (pentosan polysulfate sodium; ELMIRON®), a heparin-like, sulfated polysaccharide, is used to manage bladder pain and discomfort in adults with interstitial cystitis (IC). Preliminary clinical models suggest that pentosan polysulfate repairs damaged glycosaminoglycan (GAG) layers lining the urothelium and in vitro data suggest it may provide an anti-inflammatory effect in patients with IC. Pentosan polysulfate shows beneficial effects in a proportion of patients with IC in terms of the improvement of a patient’s overall condition and the relief of pain, and it is a generally well tolerated therapy. It is the only US FDA-approved oral treatment for the relief of bladder pain or discomfort associated with IC, and data support its role as an important option in the treatment of patients with IC.

Pharmacological Properties

Pentosan polysulfate is a semi-synthetic, sulfated polysaccharide, which is chemically and structurally similar to heparin and GAG. One theory is that the drug binds to and repairs the GAG layer on the bladder epithelium, thus reducing permeability in damaged parts of the barrier and preventing toxins from the urine irritating the uroepithelium.

An in vitro study has shown that pentosan polysulfate may also reduce inflammation associated with IC by inhibiting the inflammatory response and by reducing histamine secretion through inhibition of connective tissue and mucosal mast cells.

In animal studies, pentosan polysulfate showed no clear evidence of drugrelated carcinogenic activity in rats; however, carcinogenic activity was observed in mice exposed to the drug.

The bioavailability of pentosan polysulfate is very low (≤3%). The maximum plasma concentration of pentosan polysulfate occurs within ≈2 hours of oral administration. Pentosan polysulfate was distributed in humans to areas including the uroepithelium of the genitourinary tract, bone marrow, lung, liver, periosteum, skin and spleen in a radiolabelling study. The liver and spleen are the sites of desulfation and the kidney is the site of depolymerisation of pentosan polysulfate, although a large amount of unchanged drug is excreted in the faeces (≈52%) and a small amount in the urine. The elimination half-life of pentosan polysulfate, after a single oral <15mg radiolabelled dose supplemented with a 300mg dose, is ≈26.5 hours.

Pentosan polysulfate has no effect on the pharmacokinetics of warfarin and no other drug interactions have been examined.

Therapeutic Efficacy

In well designed, randomised, placebo-controlled trials in patients with moderate or severe IC, pentosan polysulfate was more effective than placebo, with significantly (both p ≤ 0.04) greater proportions of pentosan polysulfate recipients (28% and 32%) than placebo recipients (13% and 16%) showing a substantial overall improvement of their condition.

In a randomised, nonblind study with ciclosporin and a randomised, double-blind pilot study with hydroxyzine in patients who had at least moderate IC symptoms, pentosan polysulfate was shown to be less effective than ciclosporin and not significantly different from hydroxyzine at improving the symptoms of IC.

Noncomparative studies of long-term treatment with pentosan polysulfate showed improvement in IC symptoms (mostly severe) over time. A significant reduction in pain was also observed over time in some patients.

In a small, nonblind study, combination therapy with pentosan polysulfate and heparin was more effective than pentosan polysulfate alone in improving the symptoms of IC. The concomitant use of pentosan polysulfate and hydroxyzine in a pilot study, however, conferred no advantage over either drug alone.


Pentosan polysulfate 100mg three times daily was generally well tolerated, with adverse events usually being mild in severity. In three randomised, double-blind studies and two noncomparative, long-term studies, the most commonly reported adverse events with pentosan polysulfate were nausea, diarrhoea and headache. Alopecia (1–5% incidence) was reported in three studies. In addition, the incidence of rectal haemorrhage was 4% in one dose-ranging study.

Pentosan polysulfate treatment generally had no significant effect on laboratory parameters. In a long-term study (up to 35 months) abnormal liver function tests occurred in 2% of patients.

Various sections of the manuscript reviewed by: J. Barkin, Humber River Regional Hospital, Toronto, Ontario, Canada; T.R. Einarson, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; P. Hanno, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA; B. Kahn, Department of Obstetrics and Gynecology, Scripps Clinic and Research Institute, La Jolla, California, USA; J.C. Nickel, Department of Urology, Queens University, Kingston, Ontario, Canada; J. Sairanen, Department of Urology, Helsinki University Hospital, Helsinki, Finland; A. van Ophoven, Department of Urology, University of Münster, Münster, Germany.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘pentosan polysulfate’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘pentosan polysulfate’ or ‘pentosanpolysulfate’ and ‘interstitial cystitis’. Searches were last updated 4 April 2006.
Selection: Studies in patients with interstitial cystitis who received pentosan polysulfate. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Pentosan polysulfate, interstitial cystitis, glycosaminoglycan, pharmacodynamics, pharmacokinetics, therapeutic use.