What is Mesna
Mesna (sodium 2-mercaptoethanesulfonate) is a cytoprotective agent that prevents hemorrhagic cystitis by neutralizing acrolein, the toxic metabolite of ifosfamide and cyclophosphamide that damages the bladder lining. 1
Mechanism and Clinical Use
Mesna is a synthetic sulfhydryl compound that works by binding to and detoxifying acrolein in the urinary tract, preventing urothelial damage. It is FDA-approved specifically to reduce the incidence of ifosfamide-induced hemorrhagic cystitis 1. The drug is concentrated in the bladder where it exerts its protective effect locally.
Primary Indications
For Ifosfamide Therapy
Mesna is recommended to decrease the incidence of ifosfamide-associated urothelial toxicity 2. This recommendation applies to all patients receiving ifosfamide chemotherapy, as the risk of hemorrhagic cystitis without prophylaxis is substantial.
For Cyclophosphamide Therapy
Mesna plus saline diuresis (or forced saline diuresis alone) is recommended to decrease urothelial toxicity associated with high-dose cyclophosphamide in the setting of stem-cell transplantation 2. This is particularly important in the bone marrow transplant setting where cyclophosphamide doses are highest.
Dosing Regimens
Standard-Dose Ifosfamide (< 2.5 g/m²/day)
For short infusions, the total daily mesna dose equals 60% of the ifosfamide dose, given as:
- 20% of ifosfamide dose IV 15 minutes before ifosfamide
- 20% at 4 hours after ifosfamide
- 20% at 8 hours after ifosfamide 2
For continuous ifosfamide infusions:
- 20% bolus at start
- 40% continuous infusion for 12-24 hours after ifosfamide completion 2
FDA-Approved Oral Regimen
The recommended approach is an IV bolus of 20% of the ifosfamide dose at the time of ifosfamide administration, followed by oral mesna tablets at 40% of the ifosfamide dose given at 2 and 6 hours after each ifosfamide dose 2. The total daily mesna dose equals 100% of the ifosfamide dose. This regimen demonstrated less than 5% incidence of grade 3-4 hematuria in controlled trials 2.
Important caveat: If a patient vomits within 2 hours of taking oral mesna, repeat the dose or give IV mesna instead 2.
High-Dose Cyclophosphamide
For stem cell transplantation, mesna is typically given as continuous infusion at 100% of the cyclophosphamide dose. Recent evidence suggests continuous infusion is superior to intermittent bolus dosing, with one study showing 5.6% versus 27.8% incidence of hemorrhagic cystitis (p=0.01) 3. High-dose mesna protocols (320% of cyclophosphamide dose) combined with hyperhydration have shown HC incidence of 31.4% with only 11.5% grade 3 and no grade 4 events 4.
Clinical Efficacy
The evidence demonstrates clear benefit for ifosfamide prophylaxis. In controlled studies, mesna reduced hemorrhagic cystitis from 31-100% in control groups to 0-6% with standard mesna regimens 1. For cyclophosphamide, mesna was equally effective as continuous bladder irrigation in preventing severe hemorrhagic cystitis (18% grade 3-4 in both groups), but with significantly less patient discomfort (2% vs 84%) and fewer urinary tract infections (14% vs 27%) 5.
Critical Limitations
Mesna does not prevent hemorrhagic cystitis in all patients, nor does it prevent or alleviate any other adverse reactions or toxicities associated with ifosfamide or cyclophosphamide 1. It is not indicated for hematuria due to other causes such as thrombocytopenia 1.
The optimal dosing for very high-dose ifosfamide has not been established, and more frequent/prolonged mesna regimens may be necessary given the longer half-life of ifosfamide at these doses 2.
Important Safety Considerations
Serious hypersensitivity reactions including anaphylaxis can occur with mesna, even after multiple uneventful doses 1. Patients must be instructed to stop mesna immediately and seek emergency care if they develop fever, facial swelling, difficulty breathing, rash, or feeling faint.
Severe dermatologic reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome have been reported 1.
The multi-dose vials contain benzyl alcohol (10.4 mg/mL), which is associated with serious adverse reactions in premature neonates and low-birth-weight infants 1.
Adjunctive Measures
Patients should drink 1-2 liters of fluid daily during mesna therapy 1. Adequate hydration remains essential even with mesna prophylaxis. Patients should be instructed to report if urine turns pink or red, as this indicates potential hemorrhagic cystitis requiring evaluation 1.