Elmiron Information
Elmiron ()
Elmiron () Description
Pentosan polysulfate sodium is a semi-synthetically produced heparin-like macromolecular carbohydrate derivative, which chemically and structurally resembles glycosaminoglycans. It is a white odorless powder, slightly hygroscopic and soluble in water to 50% at pH 6. It has a molecular weight of 4000 to 6000 Dalton with the following structural formula:
Elmiron () is supplied in white opaque hard gelatin capsules containing 100 mg pentosan polysulfate sodium, microcrystalline cellulose, and magnesium stearate. It also contains pharmaceutical glaze (modified) in SD-45, synthetic black iron oxide, FD&C Blue No. 2 aluminum lake, FD&C Red No. 40 aluminum lake, FD&C Blue No. 1 aluminum lake, D&C Yellow No. 10 aluminum lake, n-butyl alcohol, propylene glycol, SDA-3A alcohol, and titanium dioxide. It is formulated for oral use.
Elmiron () Clinical Trials
Elmiron () was evaluated in two clinical trials for the relief of pain in patients with chronic interstitial cystitis (IC). All patients met the NIH definition of IC based upon the results of cystoscopy, cytology, and biopsy. One blinded, randomized, placebo-controlled study evaluated 151 patients (145 women, 5 men, 1 unknown) with a mean age of 44 years (range 18 to 81). Approximately equal numbers of patients received either placebo or Elmiron () 100 mg three times a day for 3 months. Clinical improvement in bladder pain was based upon the patient's own assessment. In this study, 28/74 (38%) of patients who received Elmiron () and 13/74 (18%) of patients who received placebo showed greater than 50% improvement in bladder pain (p=0.005).
A second clinical trial, the physician's usage study, was a prospectively designed retrospective analysis of 2499 patients who received Elmiron () 300 mg a day without blinding. Of the 2499 patients, 2220 were women, 254 were men, and 25 were of unknown sex. The patients had a mean age of 47 years and 23% were over 60 years of age. By 3 months, 1307 (52%) of the patients had dropped out or were ineligible for analysis, overall, 1192 (48%) received Elmiron () for 3 months; 892 (36%) received Elmiron () for 6 months; and 598 (24%) received Elmiron () for one year.
Patients had unblinded evaluations every 3 months for the patient's rating of overall change in pain in comparison to baseline and for the difference calculated in "pain/discomfort" scores. At baseline, pain/discomfort scores for the original 2499 patients were severe or unbearable in 60%, moderate in 33% and mild or none in 7% of patients. The extent of the patients' pain improvement is shown in .
At 3 months, 722/2499 (29%) of the patients originally in the study had pain scores that improved by one or two categories. By 6 months, in the 892 patients who continued taking Elmiron () , an additional 116/2499 (5%) of patients had improved pain scores. After 6 months, the percent of patients who reported the first onset of pain relief was less than 1.5% of patients who originally entered in the study (see ).
Elmiron () Indications And Usage
Elmiron () (pentosan polysulfate sodium) is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis.
Elmiron () Contraindications
Elmiron () is contraindicated in patients with known hypersensitivity to the drug, structurally related compounds, or excipients.
Elmiron () Warnings
Elmiron () Precautions
Elmiron () is a weak anticoagulant (1/15 the activity of heparin). At a daily dose of 300 mg (n = 128), rectal hemorrhage was reported as an adverse event in 6.3% of patients. Bleeding complications of ecchymosis, epistaxis, and gum hemorrhage have been reported (see ). Patients undergoing invasive procedures or having signs/symptoms of underlying coagulopathy or other increased risk of bleeding (due to other therapies such as coumarin anticoagulants, heparin, t-PA, streptokinase, high dose aspirin, or nonsteroidal anti-inflammatory drugs) should be evaluated for hemorrhage. Patients with diseases such as aneurysms, thrombocytopenia, hemophilia, gastrointestinal ulcerations, polyps, or diverticula should be carefully evaluated before starting Elmiron () .
A similar product that was given subcutaneously, sublingually, or intramuscularly (and not initially metabolized by the liver) is associated with delayed immunoallergic thrombocytopenia with symptoms of thrombosis and hemorrhage. Caution should be exercised when using Elmiron () in patients who have a history of heparin induced thrombocytopenia.
Alopecia is associated with pentosan polysulfate and with heparin products. In clinical trials of Elmiron () , alopecia began within the first 4 weeks of treatment. Ninety-seven percent (97%) of the cases of alopecia reported were alopecia areata, limited to a single area on the scalp.
Elmiron () has not been studied in patients with hepatic insufficiency. Because there is evidence of hepatic contribution to the elimination of Elmiron () , hepatic impairment may have an impact on the pharmacokinetics of Elmiron () . Caution should be exercised when using Elmiron () in this patient population.
Mildly (
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.
Pentosan polysulfate sodium was not clastogenic or mutagenic when tested in the mouse micronucleus test or the Ames test (). The effect of pentosan polysulfate sodium on spermatogenesis has not been investigated.
Elmiron () Adverse Reactions
Elmiron () was evaluated in clinical trials in a total of 2627 patients (2343 women, 262 men, 22 unknown) with a mean age of 47 [range 18 to 88 with 581 (22%) over 60 years of age]. Of the 2627 patients, 128 patients were in a 3–month trial and the remaining 2499 patients were in a long-term, unblinded trial.
Deaths occurred in 6/2627 (0.2%) patients who received the drug over a period of 3 to 75 months. The deaths appear to be related to other concurrent illnesses or procedures, except in one patient for whom the cause was not known.
Serious adverse events occurred in 33/2627 (1.3%) patients. Two patients had severe abdominal pain or diarrhea and dehydration that required hospitalization. Because there was not a control group of patients with interstitial cystitis who were concurrently evaluated, it is difficult to determine which events are associated with Elmiron () and which events are associated with concurrent illness, medicine, or other factors.
The adverse events described below were reported in an unblinded clinical trial of 2499 interstitial cystitis patients treated with Elmiron () . Of the original 2499 patients, 1192 (48%) received Elmiron () for 3 months; 892 (36%) received Elmiron () for 6 months; and 598 (24%) received Elmiron () for one year, 355 (14%) received Elmiron () for 2 years, and 145 (6%) for 4 years.
Frequency (1 to 4%): Alopecia (4%), diarrhea (4%), nausea (4%), headache (3%), rash (3%), dyspepsia (2%), abdominal pain (2%), liver function abnormalities (1%), dizziness (1%).
Frequency (≤ 1%):
Elmiron () Overdosage
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. (See and sections.) At a daily dose of 900 mg for 32 weeks (n = 127) in a clinical trial, rectal hemorrhage was reported as an adverse event in 15% of patients. At a daily dose of Elmiron () 900 mg for 16 weeks in a clinical trial that enrolled 51 patients in the Elmiron () group and 49 in the placebo group, elevated liver function tests were reported as an adverse event in 11.8% of patients in the Elmiron () group and 2% of patients in the placebo group. In the event of acute overdosage, the patient should be given gastric lavage if possible, carefully observed and given symptomatic and supportive treatment.
Elmiron () Dosage And Administration
The recommended dose of Elmiron () is 300 mg/day taken as one 100 mg capsule orally three times daily. The capsules should be taken with water at least 1 hour before meals or 2 hours after meals.
Patients receiving Elmiron () should be reassessed after 3 months. If improvement has not occurred and if limiting adverse events are not present, Elmiron () may be continued for another 3 months.
The clinical value and risks of continued treatment in patients whose pain has not improved by 6 months is not known.
Elmiron () How Supplied
Elmiron () is supplied in white opaque hard gelatin capsules imprinted "BNP7600" containing 100 mg pentosan polysulfate sodium. Supplied in bottles of 100 capsules.
NDC NUMBER 50458-098-01
Elmiron ()
Elmiron () Patient Leaflet
Questions and Answers About
Elmiron () is used to treat the pain or discomfort of interstitial cystitis (IC). It is not known exactly how Elmiron () works, but it is not a pain medication like aspirin or acetaminophen and therefore must be taken continuously for relief as prescribed.
You should take 1 capsule of Elmiron () by mouth three times a day, with water at least 1 hour before meals or 2 hours after meals. Each capsule contains 100 mg of Elmiron () .
Anticoagulant therapy such as warfarin sodium, heparin, high doses of aspirin or anti-inflammatory drugs such as ibuprofen until you speak with your doctor.
The most common side effects are hair loss, diarrhea, nausea, blood in the stool, headache, rash, upset stomach, abnormal liver function tests, dizziness and bruising.
Call your doctor if these side effects persist or are bothersome or if there is blood in your stool.
If you suspect that someone may have taken more than the prescribed dose of this medicine, contact your local poison control center or emergency room immediately. This medication was prescribed for your particular condition. Do not use it for another condition or give the drug to others.
This leaflet provides a summary of information about Elmiron () . Medicines are sometimes prescribed for uses other than those listed in a Patient Leaflet. If you have any questions or concerns, or want more information about Elmiron () , contact your doctor or pharmacist. Your pharmacist also has a longer leaflet about Elmiron () that is written for health professionals that you can ask to read.
Elmiron () is a Registered Trademark of Teva Branded Pharmaceutical Products R&D, Inc. under license to Ortho-McNeil-Janssen Pharmaceuticals, Inc.
© OMJPI 2002,1998
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Ortho Women's Health & Urology, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.Raritan, New Jersey 08869
Revised June 2010
Elmiron () Principal Display Panel - Mg Bottle Label
Elmiron () is a registered trademarkof IVAX Research, LLC under license toOrtho-McNeil-Janssen Pharmaceuticals, Inc.
Manufactured by:Janssen Ortho LLC, Gurabo, Puerto Rico 00778Manufactured for:Ortho Women's Health & Urology, Division ofOrtho-McNeil-Janssen Pharmaceuticals, Inc.Raritan, New Jersey 08869Revised June 2010
