Indications for Nebulised Mesna
Nebulised mesna is NOT indicated for prevention of hemorrhagic cystitis in patients undergoing chemotherapy with ifosfamide or cyclophosphamide. The established routes of administration are intravenous, oral, or continuous subcutaneous delivery—nebulisation is not a recognized or guideline-supported method of mesna administration 1, 2.
Standard Indications for Mesna (Non-Nebulised Routes)
Primary Indication: Prevention of Hemorrhagic Cystitis
Ifosfamide-induced hemorrhagic cystitis prevention is the primary FDA-approved indication, with mesna administered as IV bolus (20% of ifosfamide dose) followed by oral doses (40% at 2 and 6 hours post-ifosfamide) for a total daily dose equal to 100% of the ifosfamide dose 2, 3.
High-dose cyclophosphamide (≥1500 mg/m²/day or 2200 mg/m²) requires mesna at a total dose equal to 100% of the cyclophosphamide dose, combined with aggressive saline hydration 1, 4.
Standard-dose cyclophosphamide uses a similar regimen: 20% IV bolus at time of administration, followed by 40% oral doses at 2 and 6 hours 2.
Established Routes of Administration
Intravenous administration is the gold standard, particularly for the initial 20% bolus dose at the time of chemotherapy 1, 2.
Oral administration is used for the subsequent 40% doses at 2 and 6 hours post-chemotherapy, with equivalent efficacy to all-IV regimens (grade 3-4 hematuria <5% in both) 2.
Continuous subcutaneous administration is a practical alternative that avoids IV access requirements and eliminates concerns about oral absorption in patients with severe emesis 5.
Critical Caveats About Route Selection
If a patient vomits within 2 hours of taking oral mesna, the dose must be repeated orally or switched to IV mesna to ensure adequate uroprotection 1, 2.
Mesna alone is insufficient—aggressive hydration (2-3 liters over 24 hours) is mandatory, as neither mesna nor hydration alone adequately prevents hemorrhagic cystitis 1, 2.
The incidence of hemorrhagic cystitis correlates with ifosfamide dosage; when using >2.0 g/m²/day, increased hydration volume, mesna dosage, and duration of mesna infusion are necessary 6.
Why Nebulisation Is Not Used
No guideline from the American Society of Clinical Oncology, American College of Physicians, or National Comprehensive Cancer Network recommends nebulised mesna 1, 2, 4.
The pharmacokinetic profile of mesna requires systemic delivery to achieve adequate urinary concentrations that neutralize acrolein (the toxic metabolite of cyclophosphamide and ifosfamide) in the bladder 3.
Even with standard three-dose mesna protocols, 66.7% of patients show cystoscopic alterations and 100% demonstrate microscopic bladder mucosal changes, indicating that current regimens do not completely prevent bladder damage—nebulisation would likely be even less effective 7.