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:
- 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)
Mesna dosing
| Aspect | Ifosfamide | Cyclophosphamide |
|---|---|---|
| When mesna is mandatory | All ifosfamide regimens, any dose. | Typically with high‑dose IV (e.g., transplant, PBSC mobilization, some vasculitis/autoimmune protocols); not routinely for low‑dose oral unless specific risk factors. |
| General mesna:drug ratio (IV) | Total mesna usually 60–100% of daily ifosfamide dose depending on regimen and route. | Total mesna generally 60–160% of daily cyclophosphamide dose (wider range, highly protocol‑dependent). |
| Standard short‑infusion regimen (IV only) | Classic schedule: 60% of ifosfamide dose as mesna, given as 20% at 0, 4, and 8 hours relative to each ifosfamide dose. | Common approach (off‑label, varies): 60% of cyclophosphamide dose total, e.g., 20% at 0, 4, and 8 hours; some centres use higher totals (e.g., up to 100%) for very high doses. |
| Standard IV–oral regimen | FDA‑validated option: 20% IV at time 0, then 40% PO at 2 h and 40% PO at 6 h; total mesna = 100% of ifosfamide dose (for standard doses <2 g/m²/day). | Many guidelines mirror ifosfamide: 40% of cyclophosphamide dose PO at 0, 2, and 6 h (total 120%), but this is institution‑driven, not uniformly standardized. |
| Continuous‑infusion regimens | Often: 20% of total ifosfamide dose as IV bolus at start, then 40% as continuous infusion during ifosfamide, continuing 12–24 h after; total typically ≥60–100% of ifosfamide dose. | High‑dose cyclophosphamide continuous/extended infusion regimens may use similar strategy: IV bolus + continuous mesna aiming for ≥100% cumulative mesna relative to cyclophosphamide; details are protocol‑specific. |
| Oral‑only regimens | Less common; typically reserved for selected ambulatory regimens with reliable PO intake, still keeping total mesna ≥100% of ifosfamide dose with divided dosing over 8–12 h. | Frequently used in vasculitis/autoimmune protocols (e.g., pulse cyclophosphamide) with fixed oral doses (e.g., 400 mg PO 2 h before, 2 and 6 h after), approximating a % of the cyclophosphamide dose. |
| Key clinical points | Mesna is non‑negotiable with ifosfamide; ensure mesna schedule covers the entire period of metabolite excretion and extends several hours beyond the last ifosfamide dose. | Indication and intensity are more variable; mesna is most critical in high‑dose settings or in patients with added bladder risk factors. Hydration and frequent voiding are essential adjuncts. |
Adverse Effects
- Generally well tolerated
- Rare: nausea, vomiting, diarrhea, rash
- Can cause unpleasant odor in urine
Pharmacist Considerations
- Timing: Administer before chemo and continue per protocol to ensure adequate bladder protection
- Hydration: Must be adequately hydrated to maximize urinary excretion of toxic metabolites
- Monitoring: Watch for hematuria, signs of bladder irritation despite MESNA
- Formulation choice: IV vs oral depending on regimen and patient status
- 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
Synonyms
2-mercaptoethane sulfonate sodium