Ifosfamide — Drug Monograph

Brand names: Ifex

Drug class: Alkylating Agent

Mechanism of Action

Structural analog of cyclophosphamide; requires hepatic CYP3A4 activation. Active alkylating metabolites cross-link DNA. Also produces chloroacetaldehyde, a neurotoxic metabolite that accumulates in the CNS.

FDA Indications

• Germ cell testicular cancer (third-line and beyond, as part of combination regimens)

Common Side Effects

• Nausea and vomiting (high emetic risk)
• Myelosuppression
• Alopecia
• Hematuria
• Fatigue
• Elevated liver enzymes

Clinical Pearl

Ifosfamide encephalopathy can be reversed with methylene blue 50 mg IV q4–8h — thought to work by preventing the redox cycling of chloroacetaldehyde. High-risk features: prior cisplatin nephrotoxicity, low serum albumin, pelvic disease.

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