MESNA

Class: Chemoprotective agent (uroprotectant)

Mechanism of Action

• MESNA contains a free thiol (-SH) group that binds and inactivates acrolein, a toxic metabolite of cyclophosphamide and ifosfamide in the urine.
• Prevents hemorrhagic cystitis and urinary tract toxicity by forming a non-toxic stable compound excreted in urine.

Indications

• Prophylaxis of hemorrhagic cystitis during high-dose or standard-dose therapy with:
  • Cyclophosphamide
  • Ifosfamide
• Often used in pediatric and adult regimens:
  • Rhabdomyosarcoma (VAC)
  • Ewing sarcoma (VDC/IE)
  • High-dose cyclophosphamide conditioning for stem cell transplant

Pharmacokinetics

• Route: IV or oral
• Bioavailability: Oral ~50–60%
• Metabolism: Converted to active thiol form in the body
• Excretion: Urinary (rapid)

Dosing

• IV: Usually 20–60% of ifosfamide or cyclophosphamide dose, given before, during, and after chemotherapy infusion
• Oral: Can be used in combination for extended protection
• Pediatric dosing is weight-based or BSA-based

Adverse Effects

• Generally well tolerated
• Rare: nausea, vomiting, diarrhea, rash
• Can cause unpleasant odor in urine

Pharmacist Considerations

1. Timing: Administer before chemo and continue per protocol to ensure adequate bladder protection
2. Hydration: Must be adequately hydrated to maximize urinary excretion of toxic metabolites
3. Monitoring: Watch for hematuria, signs of bladder irritation despite MESNA
4. Formulation choice: IV vs oral depending on regimen and patient status
5. Drug interactions: No major systemic interactions; acts locally in urine

High-Yield Pearls

• MESNA does not protect against systemic toxicity (myelosuppression, neuropathy, cardiotoxicity)
• Always pair with vigorous hydration for maximal protection
• Critical in high-dose cyclophosphamide or ifosfamide regimens used in pediatric sarcomas