Cyclophosphamide-Induced Cystitis: Drug of Choice
Mesna is the drug of choice for preventing cyclophosphamide-induced hemorrhagic cystitis, combined with aggressive hydration (2-3 L in 24 hours) and frequent bladder emptying. 1, 2
Prevention Protocol
Mesna Administration
For high-dose cyclophosphamide (≥1500 mg/m²/day), the American Society of Clinical Oncology recommends mesna plus saline diuresis or forced saline diuresis, particularly in stem-cell transplantation settings. 1, 2
- Mesna works by binding to acrolein, the toxic metabolite of cyclophosphamide that causes bladder damage 3, 4
- The European League Against Rheumatism recommends mesna for all patients receiving pulse cyclophosphamide, as hemorrhagic cystitis occurs in up to 6% of patients 5
- The FDA label confirms that mesna may be helpful in preventing or limiting urotoxic effects with cyclophosphamide 6
Specific dosing regimens:
- For ifosfamide: IV bolus at 20% of the ifosfamide dose at time of administration, followed by oral mesna at 40% of the ifosfamide dose at 2 and 6 hours after each dose 1
- Oral mesna is given 4 and 8 hours after cyclophosphamide infusion for 2 doses (20% of cyclophosphamide infusion dose) 3
Hydration Strategy
- Maintain adequate hydration of 2-3 L in 24 hours to dilute toxic metabolites in the urine 1, 2
- Forced diuresis with >8 glasses of water daily is recommended 1
- Hydration with forced diuresis and frequent bladder emptying can reduce the frequency and severity of bladder toxicity 3
Bladder Emptying Protocol
Instruct patients to urinate frequently throughout treatment, with particular emphasis on emptying the bladder immediately upon waking in the morning. 3, 1
- This prevents the acrolein metabolite from dwelling in the bladder overnight, which is when the highest concentration accumulates 3
- Frequent bladder emptying throughout the day is also essential 3
Monitoring Requirements
- Check urinary sediment regularly for the presence of erythrocytes and other signs of toxicity 3
- Monthly monitoring of urine for red blood cells or other abnormalities is recommended for patients on cyclophosphamide 1
- Monitor urine output and appearance for signs of hematuria 1
Important Caveats
If the patient vomits within 2 hours of taking oral mesna, repeat the dose or switch to IV mesna. 1, 2
- Furosemide may be administered as an adjunct to mesna per institutional standards 3
- In overdose situations, cystitis prophylaxis with mesna may be helpful in preventing or limiting urotoxic effects 6
Evidence Considerations
While one older study from 1994 failed to demonstrate benefit of adding mesna to hyperhydration alone 7, and a 1991 randomized trial showed equal efficacy between mesna and hyperhydration 8, current guidelines from the American Society of Clinical Oncology, European League Against Rheumatism, and FDA label all recommend mesna as the standard of care 1, 2, 5, 6. The guideline recommendations supersede these older individual studies, particularly for high-dose regimens where the risk is greatest.