Elmiron

Soluble in water

Soluble in water to 50% at pH 6

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including pentosan polysulfate sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Pentosan polysulfate sodium/

Toxicology & Carcinogenesis Studies of Elmiron (CAS NO 37319-17-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies). Technical Report Series No. 512 (2004) NIH Publication No. 04-4446 U.S. Department of Health and Human Services, National Toxicology Program, Research Triangle Park, NC 27709

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

Store at controlled room temperature 15 deg - 30 °C (59 deg - 86 °F).

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for Elmiron (6 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for Elmiron (9 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

The effect of pentosan polysulfate sodium on warfarin pharmacokinetics and pharmacodynamics was investigated in healthy subjects. Warfarin was titrated to an international normalized ratio between 1.4 and 1.8. Subjects continued their titrated dose of warfarin and received pentosan polysulfate sodium 100 mg or placebo every 8 hours for 7 days. The Cmax of R- and S-warfarin was approximately 840 to 890 ng/mL and 680 to 730 ng/mL, respectively, and was similar in the absence and presence of pentosan polysulfate sodium. The half-life for R- and S-warfarin was 52 to 56 hours and 36 to 40 hours, respectively. Prothrombin time, partial thromboplastin time, and the international normalized ratio for warfarin + placebo and warfarin + pentosan polysulfate sodium were comparable. The AUC(INR) indicated no treatment effect (P = .772); however, there was a period effect. Analysis of variance for the treatments by period indicated no treatment effect (P > .1). Adverse events were mild and included headache, epistaxis, and rash. Most adverse events were unrelated to treatment and were seen during warfarin titration. Pentosan polysulfate sodium did not affect warfarin pharmacokinetics or pharmacodynamics.

The risk of hemorrhage may be increased when pentosan polysulfate sodium is used concurrently with drugs that affect hemostasis (e.g., oral anticoagulants, heparin, nonsteroidal anti-inflammatory agents (NSAIAs), thrombolytic agents [e.g., alteplase]). Patients receiving such concomitant therapy should be monitored for hemorrhage.

IDENTIFICATION AND USE: Elmiron (Pentosan polysulfate) is a white powder. Elmiron is a weak anticoagulant (1/15 the activity of heparin). it is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis. It is also used in veterinary medicine. HUMAN STUDIES: Elmiron, a highly sulfated, semisynthetic pentose polysaccharide with properties similar to heparin, is used for the treatment of interstitial cystitis. Overdose of Elmiron has not been reported. Based upon the pharmacodynamics of the drug, toxicity is likely to be reflected as anticoagulation, bleeding, thrombocytopenia, liver function abnormalities, and gastric distress. A case of severe thrombocytopenia and ischemic stroke following Elmiron treatment has been reported. The development of thrombocytopenia was reported in 25 patients receiving either heparin or Elmiron over a 7 month period. Based on platelet aggregation studies it was suggested that an immune allergic reaction to the anticoagulants occurred. ANIMAL STUDIES: Elmiron was orally administered once daily via gavage, 5 days per week, for up to 2 years. The dosages administered to mice were 56, 168 or 504 mg/kg. The dosages administered to rats were 14, 42, or 126 mg/kg for males, and 28, 84, or 252 mg/kg for females. Elmiron was carcinogenic to mice but not rats. Increased incidences of liver hemangiosarcoma, hepatocellular neoplasms (predominantly adenomas), and malignant lymphomas revealed carcinogenic activity of Elmiron in female mice. Reproduction studies have been performed in mice and rats with intravenous daily doses of 15 mg/kg, and in rabbits with 7.5 mg/kg. These studies did not reveal evidence of impaired fertility or harm to the fetus from Elmiron. Elmiron sodium was not clastogenic or mutagenic when tested in the mouse micronucleus test or the Ames test (Salmonella typhimurium).

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for elmiron is available.[Available from, as of February 1, 2019: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

/SIGNS AND SYMPTOMS/ Overdose has not been reported. Based upon the pharmacodynamics of the drug, toxicity is likely to be reflected as anticoagulation, bleeding, thrombocytopenia, liver function abnormalities, and gastric distress.

/CASE REPORTS/ 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.

/CASE REPORTS/ 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.

/CASE REPORTS/ 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.

For more Human Toxicity Excerpts (Complete) data for Elmiron (9 total), please visit the HSDB record page.

Elmiron®

TR-512: Toxicology and Carcinogenesis Studies of Elmiron® (CASRN 37319-17-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies) (2004 )

09/05/02

No Evidence

No Evidence

Some Evidence

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Elmiron, a highly sulfated, semisynthetic pentose polysaccharide with properties similar to heparin, is used for the treatment of interstitial cystitis. Thirteen-week gavage studies were conducted by administering the drug in deionized water to F344/N rats and B6C3F1 mice once daily, 5 days per week for up to 13 consecutive weeks, at doses of 0, 63, 125, 250, 500, and 1,000 mg/kg body weight. No significant drug-related effects were observed in body weight, survival, clinical, and necropsy results. 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. Transmission electron microscopy identified these vacuoles as lysosomal structures that exhibited a variety of contents. On the basis of our findings, we propose that Elmiron was absorbed through the focally disrupted rectal mucosa, was deposited in the lamina propria, accumulated within macrophages, and then was distributed by these cells or as a free chemical via the lymphatics and blood, to the various organ sites manifesting histiocytic infiltration. The cytoplasmic membrane-bound structures within macrophages were lysosomes containing membranous material of cellular origin and, perhaps, remnants of the deposited test material, Elmiron.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Elmiron (sodium pentosan polysulfate) is used for the relief of urinary bladder pain associated with interstitial cystitis. The National Toxicology Program (NTP) tested this compound because of its orphan drug status and lack of information about its chronic toxicity and carcinogenicity. Groups of 50 male and 50 female F344/N rats were given Elmiron in de-ionized water by gavage at doses of 0, 14, 42, or 126 mg/kg to males and 0, 28, 84, or 252 mg/kg to females once daily, 5 days per week, for up to 2 years. The same numbers of male and female B6C3F1 mice were dosed similarly with 0, 56, 168, or 504 mg/kg. Elmiron administration produced no effect on the body weight of rats, male mice, or low- and mid-dose groups of female mice. The body weights of the high-dose female mice were significantly decreased relative to those of controls. Pairwise comparison showed that survival of all dosed groups of rats and mice was similar to that of the controls. Elmiron was not carcinogenic in F344/N rats. An increased incidence of liver hemangiosarcoma provided evidence of some carcinogenic activity for Elmiron in male B6C3F1 mice. Increased incidences of liver hemangiosarcoma, hepatocellular neoplasms (predominantly adenomas), and malignant lymphomas revealed carcinogenic activity of Elmiron in female B6C3F1 mice. Elmiron administration produced elevated occurrences of nonneoplastic lesions, such as vacuolated histiocytes in the rectum, lung, spleen (males only), and mesenteric lymph node in rats and liver, rectum, mesenteric lymph node, and spleen in mice. Myxomatous change, chronic inflammation, and squamous metaplasia (mice only) were observed in the large intestine, and lymphohistiocytic hyperplasia was found to be increased in the spleen of rats of both sexes treated with the highest dose. In the latter lesion, the histiocytes contained pale, finely granular cytoplasm and were not considered to represent the same change as the vacuolated histiocytes seen in the mesenteric lymph node and rectum. Under the conditions of these 2-year studies, Elmiron was carcinogenic to mice but not rats.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Long term carcinogenicity studies of Elmiron in F344/N rats and B6C3F1 mice have been conducted. In these studies, Elmiron was orally administered once daily via gavage, 5 days per week, for up to 2 years. The dosages administered to mice were 56, 168 or 504 mg/kg. The dosages administered to rats were 14, 42, or 126 mg/kg for males, and 28, 84, or 252 mg/kg for females. The dosages tested were up to 60 times the maximum recommended human dose (MRHD) in rats, and up to 117 times the MRHD in mice, on a mg/kg basis. The results of these studies in rodents showed no clear evidence of drug-related tumorigenesis or carcinogenic risk.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The potential reproductive toxicity of Elmiron (sodium pentosan polysulfate) in Sprague-Dawley rats was evaluated using the Reproductive Assessment by Continuous Breeding protocol. Elmiron has orphan drug status in the U.S. for compassionate treatment of interstitial cystitis. Dose levels were set at 111, 333, and 1000 mg/kg/day (L, M, and H, respectively) based on data obtained from a 90-day gavage study. Body weights of F1 H males and females were significantly decreased as early as Postnatal Day 4 and continued lower as the second generation matured. No breeding, fertility, or necropsy endpoint related to reproduction was altered in either generation. No differences were noted in F0 or F1 epididymal sperm morphology or density, sperm motion parameters, testicular spermatid head counts, percent normal sperm, or F1 estrous cyclicity. Changes suggestive of hypochromic anemia, platelet activation, and hyperproteinemia were noted in F0 hematology (26% increase in platelets in H males and 15% increase in MPV in male groups), F1 hematology (20% increase in platelets in H males and 10% increase in MPV in H males and females), and F1 clinical chemistry (20% increase in globulin in male groups, and a 7% increase in total protein and 22% decrease in A/G in M and H males). Treatment-related increases (10-53%) were noted in kidney, liver, and spleen weights and organ/body weight ratios in most F0 and F1 treated groups. In the F1 generation there was a treatment-related increase in renal pelvis dilatation in males (5, 0, 30, 30% in O, L, M, H) and females (10, 20, 10, and 30% in O, L, M, H) and an increase in uterine dilatation in females (15, 10, 20, and 30 in the O, L, M, H). Dose-related increases in incidence of microscopic findings included hepatocytic cytoplasmic vacuolization, bile duct hyperplasia, renal tubule cytoplasmic vacuolization, and renal tubule degeneration/dilatation. No reproductive toxicity was noted in either generation at doses up to 1000 mg/kg/day.

For more Non-Human Toxicity Excerpts (Complete) data for Elmiron (11 total), please visit the HSDB record page.

Evaluation: There is inadequate evidence in humans for the carcinogenicity of pentosan polysulfate sodium. There is sufficient evidence in experimental animals for the carcinogenicity of pentosan polysulfate sodium. Overall evaluation: Pentosan polysulfate sodium is possibly carcinogenic to humans (Group 2B).

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Groups of 50 male and 50 female /rats/ were administered Elmiron in deionized water by gavage at doses of 0, 56, 168, or 504 mg/kg, 5 days per week, for 104 or 105 weeks. Survival of all dosed groups of mice was similar to that of the vehicle control groups. Mean body weights of males were similar to those of vehicle controls. Mean body weights of 504 mg/kg females were progressively less than those of the vehicle controls during the second year of the study. Increased incidences of hemangiosarcomas of the liver and hepatocellular neoplasms were observed in male and female mice. The incidences of hemangiosarcomas in the 504 mg/kg groups exceeded the historical control ranges for males and females; both the trend and the incidence in the 504 mg/kg groups were significant for males. Hemangiosarcomas in males and females were attributed to Elmiron administration. The incidence of hepatocellular adenoma in 504 mg/kg females was significantly increased and exceeded the historical control range; the trends for hepatocellular adenoma and for hepatocellular adenoma or carcinoma (combined) were also significant in females and were attributed to Elmiron administration. There was also a marginal increase in the incidences of hepatocellular neoplasms in male mice, which may have been associated with Elmiron administration. Malignant lymphomas occurred with a positive trend in female mice; the incidence in the 504 mg/kg group was also significantly increased and matched the upper limit of the historical control range. These malignant lymphomas may have been associated with Elmiron administration. Nonneoplastic lesions related to the administration of Elmiron occurred in the liver, rectum, mesenteric lymph node, and spleen of 504 mg/kg mice and to a lesser extent in 168 mg/kg mice. These lesions were similar to those observed in the 3-month study.

Groups of 50 male and 50 female /rats/ were administered Elmiron in deionized water by gavage at doses of 0, 14, 42, or 126 mg/kg to males and 0, 28, 84, or 252 mg/kg to females, 5 days per week, for 104 or 105 weeks. Survival of all dosed groups of rats was similar to that of the vehicle control groups. Mean body weights of all dosed groups were similar to those of the vehicle controls throughout the 2-year study. Microscopically, myxomatous changes were present in the rectum of 56% of 126 mg/kg males and 83% of 252 mg/kg females. The incidences of chronic active focal alveolar inflammation of the lung were increased in all dosed groups. The incidences of histiocytic cellular infiltration of the mesenteric lymph nodes were increased in 42 and 126 mg/kg males and in 84 and 252 mg/kg females, and lymphohistiocytic hyperplasia was present in the spleen of 126 mg/kg males and 252 mg/kg females.

Groups of five male and five female rats were administered 0, 33, 111, 333, 1,000, or 3,000 mg Elmiron/kg body weight in deionized water by gavage, 5 days per week, for 16 days. Elmiron administration had no effect on survival or body weight gain. Activated partial thromboplastin time was significantly increased in 3,000 mg/kg rats. Liver weights of 3,000 mg/kg rats were significantly greater than those of the vehicle controls. Hepatocellular cytoplasmic vacuolization occurred in all 3,000 mg/kg females.

Groups of five male and five female mice were administered Elmiron in deionized water by gavage at doses of 0, 33, 111, 333, 1,000, or 3,000 mg/kg, 5 days per week, for 16 days. All mice survived to the end of the study. Mean body weight gains of male mice administered 333 mg/kg or greater were significantly greater than that of the vehicle control group. Liver weights of 1,000 and 3,000 mg/kg males were significantly increased

For more National Toxicology Program Studies (Complete) data for Elmiron (7 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including pentosan polysulfate sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Pentosan polysulfate sodium/

Five healthy male volunteers were given (125)I-labelled pentosan in conjunction with unlabelled pentosan at a dose of 0.1, 1, 7, or 50 mg intravenously. The halflives for doses of 0.1-7 mg ranged from 13 to 18 minutes. At a dose of 50 mg, the half-life was 45 minutes. ...

Following oral administration of a radiolabeled 300- or 450-mg dose of pentosan polysulfate sodium solution, the mean half-life for plasma radioactivity was 27 or 20 hours, respectively.

Orally absorbed pentosan polysulfate sodium undergoes partial desulfation in the liver and spleen and partial depolymerization in the kidneys to form a large number of metabolites. Desulfation and depolymerization pathways can become saturated with continued dosing.

The fraction of pentosan polysulfate sodium that is absorbed is metabolized by partial desulfation in the liver and spleen, and by partial depolymerization in the kidney to a large number of metabolites. Both the desulfation and depolymerization can be saturated with continued dosing.

Sprague-Dawley rats were given (3)H-labelled pentosan orally or intravenously at a dose of 5 mg/kg bw, and killed 1 or 4 hours later, respectively. Autoradiography indicated extensive distribution of radiolabel in the whole animal after intravenous administration, with notable labelling of connective tissues, and low activity in bone and cartilage. There was a high concentration of radiolabel in the urine, and preferential localization of radiolabel to the lining of the urinary tract. After oral administration, the tissue distribution of radiolabel was similar, but activity was lower.

In rabbits given 1.0-1.2 mg pentosan by oral administration, median recovery in the urine was 7.45% (range, 2.1-46.0%) for pentosan of low relative molecular mass, and 0.1% (range, 0.0-0.3%) for pentosan of high relative molecular mass.

In rabbits given 1-1.2 mg of pentosan by intravenous administration, median recovery in the urine was 47.2% (range, 19.7-73.2%) for unfractionated pentosan, 74.6% (range, 31.4-96.3%) for pentosan of low relative molecular mass, and 3.3% (range, 2.5-5.0%) for pentosan of high relative molecular mass.

Excretion of pentosan was studied in 34 female patients with interstitial cystitis who were receiving long-term treatment with pentosan. The median concentration of pentosan in the urine of these patients was 1.2 ug/mL (range, 0.5-27.7 ug/mL). All the pentosan recovered from the urine of these patients was of low relative molecular mass.

For more Absorption, Distribution and Excretion (Complete) data for Elmiron (12 total), please visit the HSDB record page.

Anticoagulants

MEDICATION

MEDICATION (VET)

As a semi-synthetic compound, the polysaccharide backbone of pentosan polysulfate sodium, xylan, is present in beech tree bark. Extracted xylan from beech bark or other plant sources is treated with sulfating agents (e.g. chlorosulfonic acid or sulfuryl chloride). After sulfation, pentosan polysulfate is treated with sodium hydroxide to form a sodium salt of the compound.

Preparation: CH 293566 (1953 to Wander)

In the European Union, other formulations apart from the oral form include ointment, rectal suppository, and injectable solution.

Oral: Capsules,100 mg, Elmiron (Janssen)

Information available in 2005 indicated that Pentosan polysulfate sodium was used in the manufacture of pharmaceutical preparations in the following countries: Argentina, Australia, Austria, Canada, France, Germany, Hong Kong, Hungary, Italy, Portugal, South Africa, Spain, Switzerland, United States (1,2)