Firstly, Medline has decided not to keep the abstract of the most pro-Elmiron study. I interpret this as a negative comment on the study:
Nickel JC, Forrest J, Barkin J, Payne C, Mosbaugh P.
Safety and efficacy of up to 900 mg/day polysulfate sodium (elmiron) in patients with interstitial cystitis. Urology. 2001 Jun;57(6 Suppl 1):122-3. No abstract available.
Elmiron IS associated with bleeding
Arch Intern Med. 2002 Jul 22;162(14):1644-5.
Comment in:
* Arch Intern Med. 2003 Jan 13;163(1):119; authors reply 119-20.
Massive bleeding on a bladder protectant: a case report of pentosan polysulfate sodium-induced coagulopathy.
Gill S, Naiman SC, Jamal A, Vickars LM.
Department of Medicine, University of British Columbia, Vancouver, Canada.
Pentosan polysulfate sodium (Elmiron; Alza Pharmaceuticals, Mountain View, Calif) is an oral preparation of pentosan polysulfate used in the symptomatic management of interstitial cystitis. While pentosan polysulfate has a known heparin-like effect in its parenteral form, there have been no previous reports of coagulopathy with oral use. We present an interesting case of inadvertent systemic anticoagulation resulting in serious bleeding complications in a young woman taking oral pentosan polysulfate for interstitial cystitis.
PMID: 12123410 [PubMed - indexed for MEDLINE]
J Physiol Pharmacol. 1999 Mar;50(1):111-9.
Experimental studies on the anticoagulant and antithrombotic effects of sodium and calcium pentosan polysulphate.
Giedrojc J, Radziwon P, Klimiuk M, Bielawiec M, Breddin HK, Kloczko J.
Department of Haematology, University Medical School, Bialystock, Poland.
"¦. Na-PPS and Ca-PPS markedly prolonged clotting time "¦.
PMID: 10210159 [PubMed - indexed for MEDLINE]
Ann Oncol. 1996 Nov;7(9):939-44.
A phase I study of pentosan polysulfate sodium in patients with advanced malignancies.
Lush RM, Figg WD, Pluda JM, Bitton R, Headlee D, Kohler D, Reed E, Sartor O, Cooper MR. Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
BACKGROUND: Pentosan polysulfate is a semi-synthetic sulfated heparinoid polysaccharide which has been used as an anticoagulant for nearly thirty years in Europe .... RESULTS: Thirteen patients with advanced stage metastatic cancer were enrolled ... All patients experienced a progressive prolongation of their aPTT and PT [clotting times]. Furthermore, all patients experienced at least grade I thrombocytopenia. One patient developed grade III liver abnormalities ... and another patient developed grade IV thrombocytopenia while receiving the same regimen.
Clin Cancer Res. 1997 Dec;3(12 Pt 1):2347-54.
Phase I trial of orally administered pentosan polysulfate in patients with advanced cancer.
Marshall JL, Wellstein A, Rae J, DeLap RJ, Phipps K, Hanfelt J, Yunmbam MK, Sun JX, Duchin KL, Hawkins MJ.
Lombardi Cancer Research Center, Georgetown University Hospital, Washington, DC 20007, USA. [email protected]
"¦. Patients diagnosed with advanced, incurable malignancies who met standard Phase I criteria and who did not have a history of bleeding complications were enrolled, in cohorts of three, to receive PPS p.o. t.i.d., at planned doses of 180, 270, 400, 600, and 800 mg/m2 "¦. 20 of the 21 patients had evidence of grade 1 or 2 gastrointestinal (GI) bleeding. These toxicities became evident at a much earlier time point as the dose was increased, but their severities were similar at all dose levels "¦. Pharmacokinetic analysis suggested marked accumulation of PPS upon chronic administration
Anesthesiology. 2001 Nov;95(5):1307.
Epidural hematoma after epidural steroid injection: a possible association with use of pentosan polysulfate sodium.
Siddiqui MN, Ranasinghe JS, Siddiqui S.
Publication Types:
* Letter
PMID: 11685018 [PubMed - indexed for MEDLINE]
Elmiron can induce thrombocytopenia:
Ann Hematol. 1996 Jul;73(1):51-2.
Pentosan polysulfate-induced thrombocytopenia: a case diagnosed with an ELISA test used for heparin-induced thrombocytopenia.
Gironell A, Altes A, Arboix A, Fontcuberta J, Munoz C, Marti-Vilalta JL.
Department of Neurology, Hospital de Sant Pau, Barcelona, Spain.
We report a patient who developed severe thrombocytopenia and ischemic stroke following pentosan polysulfate treatment. An ELISA test employed in type-II heparin-induced thrombocytopenia was highly positive. To our knowledge, this is the first case in which this test has been performed in a pentosan polysulfate-induced thrombocytopenia (PIT). Our data suggest that the antibody against pentosan polysulfate-platelet complex also cross-reacts with heparin-platelet factor 4 complex. Due to its greater sensitivity and wider availability, this ELISA test should be used in cases where PIT is suspected.
PMID: 8695727 [PubMed - indexed for MEDLINE]
Am J Hematol. 1994 Mar;45(3):252-7.
Pentosan polysulfate-induced thrombocytopenia and thrombosis.
Tardy-Poncet B, Tardy B, Grelac F, Reynaud J, Mismetti P, Bertrand JC, Guyotat D.
Department of Hematology, CHU Hopital Nord, Saint-Etienne, France.
Pentosan polysulfate is a low-molecular-weight sulfated polysaccharide used as an antithrombotic drug. We present two patients who developed thrombocytopenia and venous thrombosis during treatment with pentosan polysulfate. The relationship between pentosan polysulfate and thrombocytopenia is supported by platelet aggregation and serotonin release tests. In the light of the literature and our two cases, it appears that pentosan polysulfate alone as standard heparin and low-molecular-weight heparin can induce thrombocytopenia and thrombosis. Platelet counts should therefore be periodically monitored during pentosan polysulfate treatment. In the case of pentosan polysulfate-induced thrombocytopenia, it seems that heparin or low-molecular-weight heparin should not be instituted during the acute phase even if platelet aggregation studies are negative, because of their low sensitivity. After remission of thrombocytopenia, whether or not glycosaminoglycans can be reinstituted, at least temporarily, after antibody had disappeared is still an open question.
Publication Types:
* Review * Review of Reported Cases
PMID: 7507640 [PubMed - indexed for MEDLINE]
Elmiron shows toxicity at high doses in rats:
Toxicol Pathol. 2002 Mar-Apr;30(2):178-87.
Lysosomal-storage disorder induced by elmiron following 90-days gavage administration in rats and mice.
Nyska A, Nold JB, Johnson JD, Abdo K.
Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. [email protected]
Elmiron, a highly sulfated, semisynthetic pentose polysaccharide with properties similar to heparin, is used for the treatment of interstitial cystitis. .... Significant organ weight increases were seen in the liver, lungs, and spleen of both species and the kidneys of rats, mainly in groups treated with 250 mg/kg/day and above. Hematological analysis indicated increases for both species in the white blood cell and lymphocyte counts. Sites of toxicity identified histopathologically were the rectum, liver, mesenteric and mandibular lymph nodes (both sexes), spleen (mice only), and lungs and kidneys (rats only). Lesions consisted mainly of infiltration into multiple tissues of vacuolated histiocytes, which, by histochemical investigation, indicated the presence of neutral and acidic mucins and lipidic material within the vacuoles.
PMID: 11950161 [PubMed - indexed for MEDLINE]
Elmiron promotes prion formation (Mad Cow Disease):
EMBO J. 2001 Feb 1;20(3):377-86.
Sulfated glycans and elevated temperature stimulate PrP(Sc)-dependent cell-free formation of protease-resistant prion protein.
Wong C, Xiong LW, Horiuchi M, Raymond L, Wehrly K, Chesebro B, Caughey B.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories/NIH, 903 South 4th Street, Hamilton, MT 59840, USA.
"¦. Heparan sulfate and pentosan polysulfate stimulated PrP-res formation [encouraged prion formation]. Conversion was stimulated further by increased temperature. Both elevated temperature and pentosan polysulfate promoted interspecies PrP conversion.
PMID: 11157745 [PubMed - indexed for MEDLINE
