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Pentosan Polysulfate

A Review of its Use in the Relief of Bladder Pain or Discomfort in Interstitial Cystitis

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Summary

Abstract

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.

Tolerability

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.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Kahn BS, Stanford EJ, Mishell DR, et al. Management of patients with interstitial cystitis or chronic pelvic pain of bladder origin: a consensus report. Current Medical Research & Opinion 2005; 21(4): 509–16

    Article  Google Scholar 

  2. Parsons CL. Evidence-based strategies for recognizing and managing IC. Contemp Urol 2003 Feb; 15(2): 22–35

    Google Scholar 

  3. Curhan GC, Speizer FE, Hunter DJ, et al. Epidemiology of interstitial cystitis: a population based study. J Urol 1999 Feb; 161(2): 549–52

    Article  PubMed  CAS  Google Scholar 

  4. Butrick CW. Interstitial cystitis and chronic pelvic pain: new insights in neuropathology, diagnosis, and treatment. Clinical Obstetrics & Gynecology 2003; 46(4): 811–23

    Article  Google Scholar 

  5. Chancellor MB, Yoshimura N. Treatment of interstitial cystitis. Urology 2004 Mar; 63 (3 Suppl 1): 85–92

    Article  PubMed  Google Scholar 

  6. Evans RJ. Treatment approaches for interstitial cystitis: multimodality therapy. Reviews in Urology 2002; 4 Suppl. 1: S16–20

    PubMed  Google Scholar 

  7. Ortho-McNeil Pharmaceutical I. Elmiron® 100 mg (pentosan polysulfate sodium) capsules [online]. Available from URL: http://www.orthoelmiron.com [Accessed 2006 Jan 5]

  8. Parsons CL. The therapeutic role of sulfated polysaccharides in the urinary bladder. Urol Clin North Am 1994 Feb; 21(1): 93–100

    PubMed  CAS  Google Scholar 

  9. Kalota SJ, Stein PC, Parsons CL. Prevention of acrolein-induced bladder injury by pentosanpolysulfate. J Urol 1992 Jul; 148(1): 163–6

    PubMed  CAS  Google Scholar 

  10. Parsons CL, Forrest J, Nickel JC, et al. Effect of pentosan polysulfate therapy on intravesical potassium sensitivity. Urology 2002 Mar; 59(3): 329–33

    Article  PubMed  Google Scholar 

  11. Russell AL. Glycoaminoglycan (GAG) deficiency in protective barrier as an underlying, primary cause of ulcerative colitis, Crohn’s disease interstitial cystitis and possibly Reiter’s syndrome. Med Hypotheses 1999 Apr; 52(4): 297–301

    Article  PubMed  CAS  Google Scholar 

  12. Sadhukhan PC, Tchetgen M-B, Rackley RR, et al. Sodium pentosan polysulfate reduces urothelial responses to inflammatory stimuli via an indirect mechanism. J Urol 2002 Jul; 168(1): 289–92

    Article  PubMed  CAS  Google Scholar 

  13. Barnes PJ, Karin M. Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 1997 Apr; 336(15): 1066–71

    Article  PubMed  CAS  Google Scholar 

  14. Chiang G, Patra P, Letourneau R, et al. Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis. J Urol 2000 Dec; 164(6): 2119–25

    Article  PubMed  CAS  Google Scholar 

  15. Chiang G, Patra P, Letourneau R, et al. Pentosanpolysulfate (Elmiron) is a potent inhibitor of mast cell histamine secretion. Adv Exp Med Biol 2003; 539(Pt B): 713–29

    PubMed  Google Scholar 

  16. National Toxicology Program Public Health Services, National Institutes of Health, US Department of Health and Human Services. NTP technical report on the toxicology and carcino-genesis studies of Elmiron (Cas No. 37319-17-8) in F344/N rats and B6C3F1 mice (Gavage Studies). Natl Toxicol Program Tech Rep Ser 2004 May; 512: 7–289

    Google Scholar 

  17. Zaslau S, Riggs DR, Jackson BJ, et al. In vitro effects of pentosan polysulfate against malignant breast cells. Am J Surg 2004 Nov; 188(5): 589–92

    Article  PubMed  CAS  Google Scholar 

  18. Simon M, McClanahan RH, Shah JF, et al. Metabolism of [3H]pentosan polysulfate sodium (PPS) in healthy human volunteers. Xenobiotica 2005 Aug; 35(8): 775–84

    Article  PubMed  CAS  Google Scholar 

  19. Faaij RA, Srivastava N, van Griensven JMT, et al. The oral bioavailability of pentosan polysulphate sodium in healthy volunteers. Eur J Clin Pharmacol 1999 Feb; 54(12): 929–35

    Article  PubMed  CAS  Google Scholar 

  20. Modi NB, Kell S, Simon M, et al. Pharmacokinetics and pharmacodynamics of warfarin when coadministered with pentosan polysulfate sodium. J Clin Pharmacol 2005 Aug; 45(8): 919–26

    Article  PubMed  CAS  Google Scholar 

  21. Nyska A, Nold JB, Johnson JD, et al. Lysosomal-storage disorder induced by elmiron following 90-days gavage administration in rats and mice. Toxicol Pathol 2002; 30(2): 178–87

    Article  PubMed  CAS  Google Scholar 

  22. Mulholland SG, Hanno P, Parsons CL, et al. Pentosan polysulfate sodium for therapy of interstitial cystitis: a double-blind placebo-controlled clinical study. Urology 1990 Jun; 35(6): 552–8

    Article  PubMed  CAS  Google Scholar 

  23. Parsons CL, Benson G, Childs SJ, et al. A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate. J Urol 1993 Sep; 150(3): 845–8

    PubMed  CAS  Google Scholar 

  24. Sant GR, Propert KJ, Hanno PM, et al. A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis. J Urol 2003 Sep; 170(3): 810–5

    Article  PubMed  CAS  Google Scholar 

  25. Sairanen J, Tammela TL, Leppilahti M, et al. Cyclosporine A and pentosan polysulfate sodium for the treatment of interstitial cystitis: a randomized comparative study. J Urol 2005 Dec; 174(6): 2235–8

    Article  PubMed  CAS  Google Scholar 

  26. Hanno PM. Analysis of long-term Elmiron therapy for interstitial cystitis. Urology 1997 May; 49 (Suppl. 5A): 93–9

    Article  PubMed  CAS  Google Scholar 

  27. Jepsen JV, Sall M, Rhodes PR, et al. Long-term experience with pentosanpolysulfate in interstitial cystitis. Urology 1998 Mar; 51(3): 381–7

    Article  PubMed  CAS  Google Scholar 

  28. van Ophoven A, Heinecke A, Hertle L. Safety and efficacy of concurrent application of oral pentosan polysulfate and subcutaneous low-dose heparin for patients with interstitial cystitis. Urology 2005 Oct; 66(4): 707–11

    Article  PubMed  Google Scholar 

  29. Nickel JC, Barkin J, Forrest J, et al. Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis. Urology 2005 Apr; 65(4): 654–8

    Article  PubMed  Google Scholar 

  30. Waters MG, Suleskey JF, Finkelstein LJ, et al. Interstitial cystitis: a retrospective analysis of treatment with pentosan polysulfate and follow-up patient survey. J Am Osteopath Assoc 2000 Mar; 100 (3 Suppl): S13–18

    PubMed  CAS  Google Scholar 

  31. Rice L, Kennedy D, Veach A. Pentosan induced cerebral sagittal sinus thrombosis: a variant of heparin induced thrombo-cytopenia. J Urol 1998 Dec; 160(6 Pt 1): 2148

    PubMed  CAS  Google Scholar 

  32. Gill S, Naiman SC, Jamal A, et al. Massive bleeding on a bladder protectant: a case report of pentosan polysulfate sodium-induced coagulopathy. Arch Intern Med 2002 Jul 22; 162(14): 1644–5

    Article  PubMed  Google Scholar 

  33. Tardy-Poncet B, Tardy B, Grelac F, et al. Pentosan polysulfate-induced thrombocytopenia and thrombosis. Am J Hematol 1994; 45(3): 252–7

    Article  PubMed  CAS  Google Scholar 

  34. Siddiqui MN, Ranasinghe JS, Siddiqui S. Epidural hematoma after epidural steroid injection: a possible association with use of pentosan polysulfate sodium [letter]. Anesthesiology 2001 Nov; 95(5): 1307

    Article  PubMed  CAS  Google Scholar 

  35. Wu EQ, Birnbaum H, Mareva M, et al. Interstitial cystitis: cost, treatment and co-morbidities in an employed population. Pharmacoeconomics 2006; 24(1): 55–65

    Article  PubMed  Google Scholar 

  36. Parsons CL, Dell J, Stanford EJ, et al. Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Urology 2002 Oct; 60(4): 573–8

    Article  PubMed  Google Scholar 

  37. Selo-Ojeme DO, Onwude JL. Interstitial cystitis. J Obstet Gynaecol 2004 Apr; 24(3): 216–25

    Article  PubMed  CAS  Google Scholar 

  38. Nickel JC. Interstitial cystitis: a chronic pelvic pain syndrome. Med Clin North Am 2004; 88(2): 467–81

    Article  PubMed  Google Scholar 

  39. Dell JR, Parsons CL. Multimodal therapy for interstitial cystitis. J Reprod Med 2004 Mar; 49 (3 Suppl.): 243–52

    PubMed  CAS  Google Scholar 

  40. Parsons CL. Prostatitis, interstitial cystitis, chronic pelvic pain, and urethral syndrome share a common pathophysiology: lower urinary dysfunctional epithelium and potassium recycling. Urology 2003; 62(6): 976–82

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 1311, New Zealand

    Vanessa R. Anderson & Caroline M. Perry

Authors
  1. Vanessa R. Anderson
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  2. Caroline M. Perry
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Corresponding author

Correspondence to Vanessa R. Anderson.

Additional information

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.

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Anderson, V.R., Perry, C.M. Pentosan Polysulfate. Drugs 66, 821–835 (2006). https://doi.org/10.2165/00003495-200666060-00006

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