Generic
Ifosfamide
5 brands available in the market
At a glance
Ifosfamide is used for third-line chemotherapy of germ cell testicular cancer and in combination with other agents for various cancers including blood, breast, lung, ovarian, pancreatic, testicular and lymph node cancers.
Description
Ifosfamide is a prodrug that requires metabolic activation by hepatic cytochrome P450 isoenzymes. It acts as an alkylating agent that causes cross-links in DNA and RNA of cancer cells, stopping their growth and multiplication. It is used alone or in combination with other chemotherapy medicines, radiotherapy and surgery to treat blood cancer, breast, lung, ovarian, pancreatic, testicular and lymph node cancers.
Indications
- Germ cell testicular cancer (third-line chemotherapy)
- Pancreatic cancer
- Ovarian cancer
- Breast cancer
- Non-small cell lung cancer
- Testicular cancer
- Blood cancer
- Lymphoma
- Sarcoma
- Solid tumours
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
Alkylating Agent (Nitrogen Mustard Derivative)
Pharmacology
Ifosfamide is a prodrug that requires metabolic activation by hepatic cytochrome P450 isoenzymes. Activation occurs by hydroxylation at the ring carbon atom forming the unstable intermediate 4-hydroxyifosfamide, which decomposes to yield acrolein and an alkylating isophosphoramide mustard. The exact mechanism is not fully determined, but cytotoxic action is primarily through DNA crosslinks caused by alkylation at guanine N-7 positions.
Mechanism of action
Isophosphoramide mustard alkylates DNA at guanine N-7 positions to form inter- and intra-strand cross-links, resulting in cell death.
Dosage
Adult Dose (Intravenous):
- Germ Cell Testicular Carcinoma: 1.2 g/m2/day for 5 days (slow infusion, minimum 30 minutes); repeat every 3 weeks or after recovery from hematologic toxicity; with mesna and adequate hydration (at least 2 L/day)
- Lymphoma/Sarcoma/Solid Tumours: Regimen 1: 8-12 g/m2 divided over 3-5 days; Regimen 2: 6 g/m2 divided over 5 days; Regimen 3: 5-6 g/m2 (max 10 g) as 24-hour infusion
Renal Dose: CrCl <10 mL/min: Administer 75% of dose
Child Dose: Safety and efficacy not established
Administration
Administered under physician supervision as slow IV infusion (minimum 30 minutes); mesna and adequate hydration required to prevent bladder toxicity.
Missed dose
If you miss a dose, take it as soon as possible; if it is almost time for your next dose, skip the missed dose; do not double the dose.
Side effects
Common Side Effects:
- Nausea
- Vomiting
- Anemia (low RBC count)
- Hair loss
- Decreased WBC count
- Infection
- Blood in urine (hemorrhagic cystitis)
- CNS toxicity (somnolence, confusion, hallucinations, seizures, coma)
Serious: Myelosuppression, sepsis, neurotoxicity, nephrotoxicity
Precautions & warnings
Precautions:
- Ifosfamide may affect your ability to drive (dizziness, drowsiness)
- Causes severe myelosuppression; regular blood tests required (WBC, platelets, hemoglobin)
- Careful monitoring for CNS toxicity (somnolence, confusion, hallucinations, seizures)
- Adequate hydration and mesna required to prevent renal and urothelial toxicity
- Use effective contraception to avoid pregnancy (during treatment and for 6 months after last dose)
- Monitor kidney, liver function and blood cells regularly
Contraindications
Contraindications:
- Hypersensitivity
- Severe bone-marrow depression
- Pregnancy
- Lactation
- Urinary outflow obstruction
Drug interactions
Drug Interactions:
- Enhanced toxicity with allopurinol, cisplatin
- Enhances anticoagulant effect of warfarin
- CYP2A6 inducers (amobarbital, phenobarbital, rifampin) reduce serum levels; inhibitors (isoniazid, miconazole) increase levels
- CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital, rifampin) reduce levels; inhibitors (azole antifungals, clarithromycin, erythromycin) increase levels
Food interactions
Food Interactions: It is unsafe to consume alcohol with Ifosfamide.
Use in pregnancy
Use in Pregnancy: Unsafe; definite evidence of risk to developing baby; fetal growth retardation and neonatal anemia reported; animal studies show embryotoxicity and anomalies; if used during pregnancy or patient becomes pregnant, apprise of potential hazard to fetus.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Excreted in breast milk; due to potential for serious adverse events and tumorigenicity, discontinue nursing.
Pediatric use
Safety and efficacy in pediatric patients have not been established.
Geriatric use
Study of patients 40-71 years indicated elimination half-life increases with age; elderly patients more likely to have decreased renal function; caution in dose selection.
Renal / hepatic impairment
Renal Impairment: CrCl <10 mL/min: Administer 75% of dose; caution in renal impairment; monitor renal function regularly.
Hepatic Impairment: Caution in hepatic impairment; monitor liver function regularly.
Overdose effects
Overdose: May cause myelosuppression, neurotoxicity, nephrotoxicity; provide symptomatic supportive treatment.
Storage conditions
Store vial in original carton at 2°-8°C; protect from light; keep out of reach of children.
Chemical structure
Ifosfamide