Ifosfamide is a substrate for both CYP3A4 and CYP2B6.

CYP3A4 inducers (e.g., carbamazepine, phenytoin, fosphenytoin, phenobarbital, rifampin, St. John’s Wort) may increase metabolism of Ifosfamide to its active alkylating metabolites and increase formation of the neurotoxic/nephrotoxic metabolite chloroacetaldehyde. Closely monitor patients for toxicities and consider dose adjustment.

CYP3A4 inhibitors (e.g., ketoconazole, fluconazole, itraconazole, sorafenib, aprepitant, fosaprepitant, grapefruit juice) may decrease the metabolism of Ifosfamide to its active alkylating metabolites, possibly decreasing effectiveness.

Ifosfamide should be administered intravenously at a dose of 1.2 g/m² per day for 5 consecutive days. Treatment is repeated every 3 weeks or after recovery from hematologic toxicity (Platelets ≥100,000/mL, WBC ≥4,000/mL).

To prevent bladder toxicity, Ifosfamide should be given with extensive hydration consisting of at least 2 liters of oral or intravenous fluid per day. A protector such as Mesna should also be used to prevent hemorrhagic cystitis.

Ifosfamide should be administered as a slow intravenous infusion lasting a minimum of 30 minutes. Although Ifosfamide has been administered to a small number of patients with compromised hepatic and/or renal function, studies to establish optimal dose schedules in such patients have not been conducted.

Ifosfamide is contraindicated in patients with known hypersensitivity to ifosfamide and in patients with urinary outflow obstruction.

Adverse reactions and frequencies are based on 30 publications describing clinical experience with fractionated administration of Ifosfamide as monotherapy with a total dose of 4 to 12 g/m² per course. Because clinical trials are conducted under widely varying conditions, adverse reaction rates cannot be directly compared and may not reflect rates observed in clinical practice.

Pregnancy: Category D. Ifosfamide can cause fetal harm when administered to a pregnant woman. Fetal growth retardation and neonatal anemia have been reported following exposure to ifosfamide-containing regimens during pregnancy. Animal studies indicate gene mutations and chromosomal damage in vivo.

Women should not become pregnant and men should not father a child during therapy and for up to 6 months after therapy.

Nursing Mothers: Ifosfamide is excreted in breast milk. Women must not breastfeed during treatment.

Pediatric Use: Safety and effectiveness have not been established.

Geriatric Use: Use cautiously, reflecting reduced organ function and comorbidities. Half-life may increase with age. Monitor renal function carefully.

Renal Impairment: Ifosfamide and metabolites are substantially excreted by the kidney; patients with renal impairment may have greater risk of toxicity.

Myelosuppression & Immunosuppression: Ifosfamide may cause severe leukopenia, neutropenia, thrombocytopenia, and anemia, increasing risk of life-threatening infections and sepsis. Monitor CBC regularly.

CNS Toxicity: Neurotoxicity such as confusion, hallucinations, seizures, somnolence, and coma have been reported. Symptoms usually resolve within 48–72 hours of discontinuation but may persist. Discontinue if encephalopathy develops.

Renal & Urothelial Toxicity: Ifosfamide is both nephrotoxic and urotoxic. Hydration and mesna co-administration are essential.

Fertility: Ifosfamide can cause amenorrhea, azoospermia, and sterility in both sexes.

 Overdose may cause enhanced toxicities including severe myelosuppression, neurotoxicity, and urotoxicity. Supportive and symptomatic treatment should be provided. There is no specific antidote.

Store the vial in the original carton at 2°–8°C. Protect from light. Keep out of reach of children.