Ifosfamide is a nitrogen mustard alkylating agent and an oxazaphosphorine analog of cyclophosphamide. It is a prodrug requiring hepatic activation via cytochrome P450 (CYP) enzymes, primarily CYP3A4 and CYP2B6, to form active alkylating metabolites, primarily isophosphoramide mustard. It cross-links DNA strands, inhibiting DNA synthesis and function, leading to cell death. It is a cornerstone of combination chemotherapy regimens for various solid tumors and lymphomas in India.
Adult: 1.2 to 2.5 g/m² body surface area per day, administered intravenously over 30 minutes to several hours for 3 to 5 consecutive days. Total dose per cycle typically ranges from 5 to 10 g/m². Dose is ALWAYS part of a specific, protocol-defined combination chemotherapy regimen.
Note: For 1gm vial: Reconstitute with 20-50 mL of Water for Injection or Bacteriostatic Water for Injection. Further dilute in 500-1000 mL of compatible IV fluid (e.g., 0.9% Sodium Chloride Injection, 5% Dextrose Injection) to a final concentration typically between 0.6 to 20 mg/mL. Administer as a slow IV infusion over 30 minutes to several hours. MESNA MUST BE ADMINISTERED CONCURRENTLY. Ensure vigorous hydration (minimum 2 L/day) before, during, and after infusion to dilute urinary metabolites.
Ifosfamide is a prodrug activated in the liver by mixed-function oxidase enzymes. The active metabolites, primarily isophosphoramide mustard, form highly reactive aziridinium ions. These ions alkylate nucleophilic sites on DNA, preferentially at the N-7 position of guanine, leading to intra-strand and inter-strand DNA cross-links. This disrupts DNA replication and transcription, ultimately triggering apoptosis (programmed cell death) in rapidly dividing cells.
Pregnancy: FDA Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. Ifosfamide is teratogenic and embryotoxic. Contraindicated in pregnancy. Effective contraception is required for both males and females during and for at least 6 months after therapy.
Driving: May cause severe drowsiness, dizziness, confusion, and visual disturbances. Patients must be warned not to drive or operate heavy machinery during and for several days after treatment.
| Allopurinol | May increase risk of myelosuppression. | Moderate |
| Warfarin | Ifosfamide may enhance anticoagulant effect, increasing INR and bleeding risk. | Major |
| Phenobarbital, Phenytoin, Carbamazepine | Induce CYP enzymes, potentially increasing activation of ifosfamide to toxic metabolites, increasing risk of neurotoxicity and other adverse effects. | Major |
| Cimetidine | Inhibits CYP enzymes, may decrease activation of ifosfamide, potentially reducing efficacy. | Moderate |
| Cisplatin | Additive nephrotoxicity and ototoxicity. May also reduce ifosfamide metabolism, increasing toxicity. | Major |
| Doxorubicin | Additive cardiotoxicity. Monitor cardiac function. | Major |
| Live vaccines | Risk of disseminated infection due to immunosuppression. Contraindicated. | Major |