Mesna Administration with Cyclophosphamide
For high-dose cyclophosphamide (≥1500 mg/m²/day) in stem-cell transplantation settings, administer mesna plus aggressive saline diuresis to prevent hemorrhagic cystitis. 1
Dosing and Administration Method
High-Dose Cyclophosphamide (Stem-Cell Transplantation)
The American Society of Clinical Oncology specifically recommends mesna combined with saline diuresis or forced saline diuresis for high-dose cyclophosphamide in stem-cell transplantation. 1 While the guideline does not specify exact mesna dosing for cyclophosphamide, the evidence provides two validated approaches based on cyclophosphamide administration method:
For bolus/short infusion cyclophosphamide:
- Administer mesna as intermittent IV bolus at 20% of the cyclophosphamide dose every 6 hours 2
- Continue for at least 12-24 hours after cyclophosphamide completion 3
For continuous infusion cyclophosphamide:
- Give initial mesna bolus at 20% of total cyclophosphamide dose 2
- Follow with continuous mesna infusion at equivalent dose to cyclophosphamide (100% dose matching) 2
- Continue infusion for 12-24 hours after cyclophosphamide completion 3
Critical Timing Considerations
The continuous infusion method provides superior bladder protection because it maintains constant urinary free thiol concentrations, whereas bolus dosing every 6 hours creates periods where alkylating metabolites are elevated but free thiols are diminished. 2 This gap in protection occurs between 4-6 hours after each mesna bolus when urinary free thiols fall to pre-treatment levels while cyclophosphamide metabolites remain elevated. 2
Dilution and Preparation
- Mesna and cyclophosphamide can be mixed together in the same dextrose 5% infusion bag 4
- When refrigerated at 4°C, admixtures remain stable for 48 hours 4
- At room temperature, infuse within 6 hours to prevent significant drug degradation 4
- pH stability is critical—solutions stored at room temperature show significant pH drops (>4 units) by 96 hours 4
Essential Supportive Measures
Hydration is mandatory and equally important as mesna:
- Administer 2-3 liters of IV fluids over 24 hours to dilute toxic metabolites 3, 5
- Instruct patients to urinate frequently, especially immediately upon waking, to prevent overnight acrolein accumulation in the bladder 5
- Forced diuresis with >8 glasses of water daily is recommended 5
Monitoring Requirements
- Observe patients for at least 12 hours post-infusion for hematuria, nausea/vomiting, and electrolyte disturbances 3
- Monitor urine output and appearance for signs of hemorrhagic cystitis 5
- Monthly urine monitoring for red blood cells is recommended for patients on cyclophosphamide 5
Special Populations Requiring Mesna
Mesna should be strongly considered (even if not routinely used) in patients with: 6
- High cumulative cyclophosphamide doses (>30 g total)
- Restricted fluid intake capability
- Neurogenic bladder
- Concurrent oral anticoagulant therapy
- Chronic kidney disease
Important Caveats
For standard-dose cyclophosphamide in non-transplant settings, the evidence for routine mesna use is insufficient. 6 The guideline only firmly recommends mesna for high-dose cyclophosphamide in stem-cell transplantation. 1
Mesna hypersensitivity can mimic vasculitis flares with fever, arthralgia, myalgia, tachycardia, ECG changes, erythroderma, and bullous lesions appearing approximately 3 weeks after initiation. 7 This delayed hypersensitivity reaction can be confused with disease activity in patients being treated for vasculitis.
The risk of hemorrhagic cystitis correlates directly with cumulative cyclophosphamide dose, with bladder cancer risk particularly elevated above 36 g cumulative dose and remaining elevated for years after discontinuation. 6