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.
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.
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.