A fixed-dose combination of the alkylating antineoplastic agent Ifosfamide (2g) with its uroprotective antidote Mesna (100mg). Ifosfamide is a prodrug requiring hepatic activation to form cytotoxic isophosphoramide mustard and acrolein. Mesna is a sulfhydryl compound that binds to and detoxifies acrolein in the urinary tract, preventing hemorrhagic cystitis, a dose-limiting toxicity of Ifosfamide. This combination is a cornerstone of chemotherapy regimens for various solid tumors and lymphomas in India.
Adult: Ifosfamide: 1.2 to 2.0 g/m²/day IV infusion over 3-5 days, repeated every 3-4 weeks. The 2g vial is typically used as part of a calculated body surface area (BSA) dose. Mesna: MUST be given at 20% of the Ifosfamide dose (by weight) at time 0 (concurrent with Ifosfamide), followed by 20% at 4 hours and 8 hours after the start of Ifosfamide infusion. Therefore, for a 2g Ifosfamide dose, total Mesna required is 400mg (200mg at 0, 4, and 8h is another common regimen). The 100mg in this combination is only the initial 5% dose.
Note: For IV infusion only. Ifosfamide is reconstituted and diluted in 500-1000 mL of 0.9% Sodium Chloride or 5% Dextrose. Infuse over 30 minutes to several hours as per protocol. Mesna (from this vial and additional vials) is typically mixed with the same infusion fluid or given separately. HYDRATION: Aggressive hydration with at least 2-3 liters of fluid per day is mandatory to dilute urinary metabolites. Monitor urine output and for hematuria.
Ifosfamide is a prodrug activated by hepatic microsomal enzymes to 4-hydroxyifosfamide, which spontaneously decomposes to phosphoramide mustard and acrolein. Phosphoramide mustard is the active alkylating species that forms cross-links in DNA, primarily at the N-7 position of guanine, leading to DNA strand breaks, miscoding, and inhibition of DNA/RNA synthesis, causing cell death. Acrolein is a toxic metabolite excreted in urine, causing direct damage to the urothelium (hemorrhagic cystitis). Mesna is a thiol compound that is excreted renally. In the kidneys, it is reduced to its free thiol form, which binds specifically and detoxifies acrolein in the bladder, forming a stable, non-toxic thioether, thereby preventing urothelial toxicity without interfering with the antitumor activity of Ifosfamide.
Pregnancy: Category D. Ifosfamide is teratogenic and embryotoxic. Can cause fetal harm. Contraindicated in pregnancy. Effective contraception required for both males and females during and for at least 6 months after therapy.
Driving: Patients must NOT drive or operate machinery during and for several days after treatment due to high risk of dizziness, confusion, and somnolence.
| Allopurinol | May increase risk of Ifosfamide neurotoxicity | Moderate |
| CYP3A4 Inducers (Phenobarbital, Phenytoin, Rifampicin) | Increase metabolism of Ifosfamide to active/toxic metabolites, potentially increasing efficacy and toxicity | Major |
| CYP3A4 Inhibitors (Ketoconazole, Fluconazole, Clarithromycin) | Decrease activation of Ifosfamide, potentially reducing efficacy | Major |
| Warfarin | Ifosfamide may enhance anticoagulant effect; monitor INR closely | Major |
| Cisplatin | Increases risk of nephrotoxicity, ototoxicity, and neurotoxicity; sequence and hydration critical | Major |
| Other Myelosuppressive agents (e.g., Doxorubicin) | Additive bone marrow suppression | Major |
| CNS Depressants (Benzodiazepines, Opioids) | May exacerbate Ifosfamide-induced neurotoxicity (sedation, confusion) | Moderate |
| Live Vaccines | Risk of disseminated infection due to immunosuppression | Major |
Same composition (Mesna (100mg) + Ifosfamide (2gm)), different brands: