Pentosan (Systemic)


VA CLASSIFICATION
Primary: GU900

Commonly used brand name(s): Elmiron.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Anti-inflammatory, local (interstitial cystitis)—

Indications

Accepted

Cystitis, interstitial (treatment)—Pentosan is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis {01} {02} {03} {04} {05} {08}. It may improve symptoms such as urinary urgency and urinary frequency, including nocturia {02} {03} {04}. Symptoms of interstitial cystitis exacerbate and remit, with days up to years between episodes {07}.
—In clinical trials, approximately one fourth to one third of patients receiving pentosan reported an improvement in bladder pain and discomfort after 3 months of therapy {06} {09}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    4000 to 6000 {01}

Mechanism of action/Effect:

The exact mechanism of action is not known, but pentosan has been found to adhere to the bladder wall mucosal membrane, which may act as a buffer to prevent irritating solutes from reaching the cells {01}.


Other actions/effects:

Pentosan has anticoagulant (1/15 the activity of heparin) and fibrinolytic effects {01}.

Absorption:

Approximately 3% of different administered doses {01}.

Distribution:

Pentosan is distributed to the uroepithelium of the genitourinary tract, with lesser amounts found in the bone marrow, liver, lung, periosteum, skin, and spleen {01}.

Biotransformation:

Pentosan undergoes depolymerization in the kidney; 68% of the drug undergoes desulfation in the liver and the spleen 1 hour after intravenous administration; both depolymerization and desulfation can be saturated with continued dosing {01}.

Half-life:


Elimination:

Intravenous: 24 hours after a 40-mg dose {01}.

Oral: 4.8 hours for the unchanged drug {01}.


Elimination:
    Renal, 3.5% with a single dose; 11% with multiple doses, with 3% of that as the unchanged drug {01}.


Precautions to Consider

Carcinogenicity

Studies to determine the carcinogenic potential of pentosan have not been done in humans or animals {01}.

Mutagenicity

Pentosan was not clastogenic or mutagenic when tested in the mouse micronucleus test or the Ames test {01}.

Pregnancy/Reproduction
Fertility—
Reproductive studies in mice and rats using intravenous daily doses of 15 mg per kg of body weight (mg/kg) and in rabbits using 7.5 mg/kg (0.42 and 0.14 times the daily oral human doses of pentosan based on body surface area, respectively) did not reveal evidence of impaired fertility {01}.

Pregnancy—
Studies have not been done in humans {01}.

Reproductive studies in mice and rats using intravenous daily doses of 15 mg/kg and in rabbits using 7.5 mg/kg (0.42 and 0.14 times the daily oral human doses of pentosan based on body surface area, respectively) did not reveal any harm to the fetus {01}. Direct in vitro bathing of cultured mouse embryos with pentosan at a concentration of 1 mg per mL may cause reversible limb bud abnormalities {01}.

FDA Pregnancy Category B {01}.

Breast-feeding

It is not known whether pentosan is distributed into breast milk {01}.

Pediatrics

No information is available on the relationship of age to the effects of pentosan in pediatric patients. Safety and efficacy have not been established.


Geriatrics


Studies performed in patients with interstitial cystitis have not demonstrated geriatrics-specific problems that would limit the usefulness of pentosan in the elderly.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Medications/therapies that increase the risk of hemorrhage, such as:
Alteplase, recombinant or
Anticoagulants, coumarin-derivative or
Aspirin, high dose or
Heparin or
Streptokinase    (concurrent use with pentosan may increase the risk of hemorrhage; patients should be monitored for signs of hemorrhage {01}; if hemorrhage occurs, pentosan should be discontinued {10})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]), serum and
Alkaline phosphatase, serum and
Aspartate aminotransferase (AST [SGOT]), serum and
Gamma-glutamyl transpeptidase, serum and{05}
Lactate dehydrogenase, serum    (increases in values of up to 2.5 times the normal values have occurred in 1.2% of patients taking pentosan; increases usually appeared 3 to 12 months after initiation of therapy, and were not associated with jaundice or other clinical signs or symptoms; these increases were transient, remained unchanged, or, rarely, progressed with continued use {01})


Partial thromboplastin time (PTT) and
Prothrombin time (PT)    (increases have been reported in fewer than 1% of patients taking pentosan; however, PTT and PT were unaffected in one study using up to 1200 mg of pentosan a day for 8 days {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Any condition in which risk of hemorrhage is present, such as:
Aneurysms or
Diverticula or
Gastrointestinal ulceration or
Hemophilia or
Polyps or
Thrombocytopenia or thrombocytopenia, heparin-induced, history of    (since pentosan has weak anticoagulant activity, an additive effect may occur; patients with these conditions should be evaluated carefully before beginning pentosan therapy {01})


Hepatic insufficiency or
Spleen disorders    (since pentosan is desulfated by the liver and the spleen, bioavailability of the parent or active metabolites may be increased; pentosan should be used cautiously in patients with these conditions {01})


Sensitivity to pentosan, structurally related compounds, or excipients{01}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Alanine aminotransferase (ALT [SGPT]), serum and
Aspartate aminotransferase (AST [SGOT]), serum     (determinations recommended every 6 months during treatment {12})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare—incidence £ 1%
{01}    
Allergic reaction{01} (skin rash or hives){01}
    
amblyopia (vision impairment)
    
anemia {01}{05}(unusual tiredness and weakness)
    
dyspnea {01}(difficulty in breathing)
    
ecchymosis {01}(unusual bleeding or bruising)
    
leukopenia {01}(chills; fever; sore throat)
    
thrombocytopenia {01}(unusual bleeding or bruising)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Abdominal pain —incidence 2%{01}
    
alopecia (hair loss)—incidence 4%{01}
    
diarrhea —incidence 4%{01}{03}{05}
    
dizziness —incidence 1%{01}
    
dyspepsia (stomach upset)—incidence 2%{01}{05}
    
headache —incidence 3%{01}{02}
    
nausea —incidence 4%{01}{02}{03}
    
skin rash —incidence 3%{01}

Note: Alopecia may begin within the first 4 weeks of treatment; 97% of reported cases were limited to a single area on the scalp {01}.


Incidence rare—incidence £ 1%
{01}    
Anorexia {01}(loss of appetite)
    
conjunctivitis {01}(irritated or red eyes)
    
constipation {01}
    
epistaxis {01}(nosebleed)
    
esophagitis {01}(difficulty in swallowing)
    
flatulence {01}(stomach gas)
    
gastritis {01}(stomach upset)
    
gum hemorrhage {01}(bleeding gums)
    
heartburn {01}
    
mouth ulcer {01}(sores in mouth)
    
pharyngitis {01}(dryness of throat; pain upon swallowing)
    
photosensitivity {01}(increased sensitivity of skin to sunlight)
    
pruritus {01}(itching)
    
rhinitis {01}{03}(runny nose)
    
tinnitus {01}(ringing in the ears)
    
urticaria {01}(skin rash)
    
vomiting {01}





Overdose
For information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
To decrease absorption—Gastric lavage {01}.

Supportive care—Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Pentosan (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to pentosan, structurally related compounds, or excipients
Other medications, especially alteplase, recombinant; anticoagulants, coumarin-derivative; aspirin, high dose; heparin; or streptokinase
Other medical problems, especially aneurysms, diverticula, gastrointestinal ulceration, hemophilia, polyps, or thrombocytopenia

Proper use of this medication
Taking on empty stomach with a full glass (8 ounces) of water 1 hour before or 2 hours after meals

May require up to 3 to 6 months of therapy to feel effects

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Possibility of increased bleeding time

Following any dietary instructions


Side/adverse effects
Signs of potential side effects, especially allergic reaction, amblyopia, anemia, dyspnea, ecchymosis, leukopenia, thrombocytopenia, and alopecia


General Dosing Information
The clinical value and risks of treatment for longer than 6 months are not known {01}.

Diet/Nutrition
Pentosan should be taken with a full glass (8 ounces) of water at least 1 hour before or 2 hours after meals {01}.

Some patients with interstitial cystitis may benefit by avoiding acidic foods and beverages such as alcohol, caffeinated and citrus beverages, chocolate, spices, and tomatoes {07}. However, this recommendation is not universal; patients should avoid foods or beverages that aggravate their condition {11}.


Oral Dosage Form

PENTOSAN POLYSULFATE SODIUM Capsules

Usual adult dose
Cystitis, interstitial (treatment)
Oral, 100 mg three times a day {01}. If there is no improvement and no side/adverse effects have been reported after three months, pentosan therapy may be continued for another three months {01}.


Usual pediatric dose
Safety and efficacy have not been established.

Strength(s) usually available
U.S.—


100 mg (Rx) [Elmiron]{01}{13}

Canada—


100 mg (Rx) [Elmiron]{08}{14}

Packaging and storage:
Store below 40 ºC (104 ºF), preferably between 15 and 30 ºC (59 and 86 ºF), unless otherwise specified by the manufacturer {01}.

Auxiliary labeling:
   • Take on empty stomach.



Developed: 02/11/1998
Revised: 05/20/1998



References
  1. Elmiron package insert (Baker Norton Pharmaceutricals, Inc.—US), Rev 8/96, Rec 12/96.
  1. Mulholland SG, Hanno P, Parsons CL, et al. Pentosan polysulfate sodium for therapy of interstitial cystitis. Urology 1990; 35(6): 552-8.
  1. Parsons CL, Benson G, Childs S, et al. A quantitatively controlled method to study prospectively interstitial cystitis and demonstrate the efficacy of pentosanpolysulfate. J Urol 1993; 150: 845-8.
  1. Parsons CL, Mulholland SG. Successful therapy of interstitial cystitis with pentosanpolysulfate. J Urol 1987; 138: 513-6.
  1. Fritjofsson Å, Juhlin R, Persson BE, et al. Treatment of ulcer and nonulcer interstitial cystitis with sodium pentosanpolysulfate: a multicenter trial. J Urol 138: 508-12.
  1. Baker Norton Pharmaceuticals. Interstitial cystitis and Elmiron product monograph. Rec 12/96.
  1. National Institute of Diabetes and Digestive and Kidney Diseases home page. Interstitial cystititis. Available from: URL: http://www.niddk.nih.gov. Accessed 9/12/97.
  1. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialities. 32nd ed. Ottawa: Canadian Pharmaceutical Association; 1997 p. 525.
  1. Personal communication, 1997.
  1. Reviewer consensus, 1998.
  1. Panelists comments, 1998.
  1. Panelist comment, 1998.
  1. Elmiron package insert (Alza Corporation—US), New 2/98, Rec 2/98.
  1. Personal communication from Alza Corporation, 1998.
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