pentosan polysulfate sodium (Rx)

1-10%

Alopecia (4%)

Diarrhea (4%)

Nausea (4%)

Headache (3%)

Abdominal pain (2%)

Indigestion (2%)

Postmarketing Reports

Rectal hemorrhage

Elevated LFTs

Anemia

Leukopenia

Partial thromboplastin time increased

Prothrombin time increased

Thrombocytopenia

Optic neuritis

Retinal hemorrhage

Pigmentary changes in the retina

Contraindications

Hypersensitivity

Cautions

Alopecia is associated with pentosan polysulfate and with heparin products; alopecia began within the first 4 weeks of treatment in clinical trials; ninety-seven percent (97%) of cases of alopecia reported were alopecia areata, limited to a single area on the scalp

The drug has not been studied in patients with hepatic insufficiency; because there is evidence of hepatic contribution to elimination of drug, hepatic impairment may have an impact on pharmacokinetics of the drug; exercise caution when using drug in this patient population

Retinal pigmentary changes

• Pigmentary changes in retina, reported as pigmentary maculopathy, identified with long-term use of drug
• Although most cases occurred after 3 years of use or longer, cases have been seen with a shorter duration of use; while the etiology is unclear, cumulative dose appears to be a risk factor
• Visual symptoms in reported cases included difficulty reading, slow adjustment to low or reduced light environments, and blurred vision
• Visual consequences of pigmentary changes are not fully characterized
• Use caution in patients with retinal pigment changes from other causes in which examination findings may confound appropriate diagnosis, follow-up, and treatment
• Obtain detailed ophthalmologic history in all patients prior to starting treatment; consider testing if there is a family history of hereditary pattern dystrophy, genetic
• For patients with pre-existing ophthalmologic conditions, a comprehensive baseline retinal examination (including color fundoscopic photography, ocular coherence tomography (OCT), and auto-fluorescence imaging) is recommended prior to starting therapy
• A baseline retinal examination (including OCT and autofluorescence imaging) is suggested for all patients within six months of initiating treatment and periodically while continuing treatment; if pigmentary changes in retina develop, re-evaluate risks and benefits of continuing treatment, since these changes may be irreversible
• Follow-up retinal examinations should be continued given that retinal and vision changes may progress even after cessation of treatment

Anticoagulant effects

• The drug 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 reported
• 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, tPA, 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 therapy
• Exercise caution when administering therapy in patients who have a history of heparin-induced thrombocytopenia

Pregnancy Category: B

Lactation: not known if excreted in breast milk, use caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Low molecular weight heparin-like compound; elicits weak anticoagulant (1/15 activity of heparin) and fibrinolytic effects

MOA in cystitis unknown; drug appears to attach to the bladder wall mucosa where it may act as a buffer to protect tissues from irritating substances in the urine

Pharmacokinetics

Absorption: 6%

Half-Life, Elimination: 4.8 hr

Distribution: Uroepithelium of the genitourinary tract with lesser amounts found in the liver, spleen, lung, skin, periosteum, and bone marrow

Metabolism: Spleen and liver; partial depolymerization in the kidney to a large number of metabolites

Excretion: Feces (58% as unchanged drug) Urine (6% primarily as metabolites)