This is a fixed-dose combination of a uroprotective agent (Mesna) and an alkylating antineoplastic agent (Ifosfamide). Mesna is specifically included to prevent the dose-limiting urotoxic side effects, particularly hemorrhagic cystitis, caused by Ifosfamide's toxic metabolites (acrolein). Ifosfamide is a prodrug requiring hepatic activation. The combination is a cornerstone of several high-intensity chemotherapy regimens used primarily for solid tumors and sarcomas in the Indian oncology setting.
Adult: Ifosfamide: 1.2 to 2.0 g/m²/day IV over 30-120 minutes for 3-5 consecutive days every 3-4 weeks. High-dose regimens use up to 5 g/m²/day. Mesna: Dose is a percentage of the ifosfamide dose. Standard: 60% of ifosfamide dose given as IV bolus at 0 hours (with ifosfamide), 4 hours, and 8 hours post-ifosfamide. Alternative: 20% of ifosfamide dose given IV concurrently, followed by continuous IV infusion of 40% of ifosfamide dose over 12-24 hours.
Note: Administer in a hospital setting under supervision of an oncologist. Pre-hydrate with 1-2L of IV fluids (e.g., Dextrose 5% or Normal Saline). Ifosfamide is given as an IV infusion over 30 minutes to several hours. Mesna is given as IV bolus injections or infusion as per schedule. Maintain high urine output (>100 mL/hr) during and for at least 24 hours after therapy. Monitor urine for blood (dipstick) each day.
Ifosfamide is a prodrug activated by hepatic microsomal enzymes to 4-hydroxyifosfamide, which spontaneously forms the active alkylating agent, isophosphoramide mustard, and the toxic byproduct, acrolein. Isophosphoramide mustard cross-links DNA strands, inhibiting DNA replication and transcription, leading to cell death. Acrolein causes direct chemical irritation and damage to the urothelium, leading to hemorrhagic cystitis. Mesna provides specific, local detoxification in the urinary tract. It is rapidly oxidized to dimesna in plasma, which is filtered by the glomerulus. In the renal tubules, dimesna is reduced back to free mesna, which binds to and inactivates acrolein, forming a stable, non-toxic thioether compound that is excreted.
Pregnancy: Category D. Ifosfamide is teratogenic and embryotoxic. Can cause fetal harm. Contraindicated, especially in first trimester. 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, somnolence, and other neurotoxic effects.
| Allopurinol | May increase risk of ifosfamide-induced neurotoxicity. | Moderate |
| CYP3A4 Inducers (e.g., Phenobarbital, Phenytoin, Rifampicin, Carbamazepine) | Increase metabolism of ifosfamide to active/toxic metabolites, potentially increasing efficacy and toxicity (myelosuppression, neurotoxicity). | Major |
| CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin) | Decrease activation of ifosfamide, potentially reducing efficacy. | Major |
| Warfarin | Ifosfamide may enhance anticoagulant effect; monitor INR closely. | Moderate |
| Nephrotoxic drugs (e.g., Aminoglycosides, Amphotericin B, Cisplatin) | Additive risk of renal impairment. | Major |
| Myelosuppressive drugs (other chemotherapy, clozapine) | Additive bone marrow suppression. | Major |
| CNS Depressants (e.g., Benzodiazepines, Opioids) | May exacerbate ifosfamide-induced neurotoxicity (sedation, confusion). | Moderate |
| Live Vaccines | Risk of disseminated infection due to immunosuppression. | Major |
Same composition (Mesna (1gm) + Ifosfamide (NA)), different brands: