Cystosan

• Approved Indication:
• Interstitial Cystitis (IC)/Bladder Pain Syndrome (BPS):
  Indicated for the relief of bladder pain or discomfort associated with interstitial cystitis in adults.
• Clinically Accepted Off-Label Use:
• Osteoarthritis (OA):
  Investigated for intra-articular or oral use in managing symptoms of knee osteoarthritis due to its cartilage-protective and anti-inflammatory effects.

• Route: Oral
• Adults (Interstitial Cystitis):
• Recommended dose: 100 mg orally three times daily, at least 1 hour before or 2 hours after meals.
• Duration: A trial period of 3 months is recommended to evaluate effectiveness. Continued use may be needed for sustained benefit.
• Pediatrics:
• Not recommended. Safety and efficacy have not been established in patients under 18 years.
• Elderly:
• No specific dose adjustments, but monitor closely due to potential increased bleeding risk.
• Renal or Hepatic Impairment:
• Use with caution. No specific dosage recommendations available. Periodic liver and renal function tests are advised.

Pentosan polysulfate sodium (PPS) is a low molecular weight, semi-synthetic heparin-like polysaccharide. Its primary action in interstitial cystitis involves replenishing the glycosaminoglycan (GAG) layer of the urothelium, which acts as a protective barrier against urinary irritants. PPS also exhibits mild anticoagulant, anti-inflammatory, and fibrinolytic activity. It inhibits mast cell degranulation and may prevent the infiltration of inflammatory cells into the bladder wall, thereby reducing pain, urgency, and discomfort.

• Absorption:
  Oral bioavailability is low (~3%). Absorption is enhanced on an empty stomach.
• Distribution:
  Limited systemic distribution. A portion accumulates in the bladder wall, which is the presumed site of action.
• Metabolism:
  Not extensively metabolized. Minor hepatic processing may occur.
• Half-life:
  Approximately 6 hours.
• Elimination:
  Excreted mainly in urine (as both unchanged drug and metabolites) and partly via feces.

• Pregnancy:
• FDA Pregnancy Category C.
  Animal studies have shown adverse fetal effects at high doses. Human data are insufficient. Use only if the potential benefit justifies the risk.
• Lactation:
• Unknown if excreted in human milk. Caution is advised if administered to breastfeeding mothers.

• Class:
• Urinary Tract Protectant
• Glycosaminoglycan (GAG) Replenisher
• Subclass:
• Semi-synthetic polysaccharide derivative

• Hypersensitivity to pentosan polysulfate sodium or any excipients in the formulation
• Active bleeding disorders (e.g., hemophilia)
• History of heparin-induced thrombocytopenia (due to structural similarity)
• Recent gastrointestinal bleeding or peptic ulcer disease

• Ocular toxicity (maculopathy):
  Long-term use may be associated with pigmentary maculopathy. Perform baseline and periodic eye exams in long-term users.
• Bleeding risk:
  Has weak anticoagulant properties. Use with caution in patients taking NSAIDs, aspirin, or anticoagulants.
• Liver function:
  Rare cases of elevated liver enzymes reported. Monitor hepatic function during prolonged therapy.
• Hematologic effects:
  Monitor platelet counts periodically due to rare reports of thrombocytopenia.

• Common (>1%):
• Gastrointestinal: Nausea, diarrhea, dyspepsia, abdominal pain
• Neurological: Headache, dizziness
• Dermatologic: Alopecia (hair loss)
• Uncommon to Rare:
• Bleeding/bruising (e.g., epistaxis, gum bleeding)
• Elevated liver enzymes
• Rash or hypersensitivity reactions
• Visual changes (e.g., pigmentary maculopathy with long-term use)
• Most adverse effects are dose-dependent and reversible upon discontinuation.

• Anticoagulants/Antiplatelet Agents (e.g., warfarin, aspirin, clopidogrel):
  ↑ Risk of bleeding—monitor closely if combined.
• NSAIDs:
  Caution due to additive gastrointestinal and bleeding risks.
• No known CYP450-related drug interactions.
  Does not significantly inhibit or induce major cytochrome enzymes.

• Ophthalmologic concerns (2018–2022):
  Multiple studies and regulatory reports linked long-term use (≥2 years) with maculopathy, prompting updated warnings and recommendations for periodic retinal examinations.
• FDA Labeling Update:
  Safety labeling revised to include risk of pigmentary maculopathy and guidance for baseline ophthalmologic assessments.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Protection: Keep container tightly closed, protected from moisture and direct light
• Special handling: No refrigeration or reconstitution required
• Keep out of reach of children