A 14-year-old girl on the MAP regimen develops confusion, hallucinations and mutism two days after starting high-dose ifosfamide infusion. Metabolic causes are excluded. The specific antidote for ifosfamide-induced encephalopathy is:

• A Naloxone
• B Leucovorin
• C Flumazenil
• D Methylene blue ✓

Explanation

Ifosfamide metabolite chloroacetaldehyde inhibits mitochondrial oxidative phosphorylation and depletes glutathione, producing a hyperammonaemic encephalopathy. Intravenous methylene blue is the established antidote and usually produces dramatic improvement within hours. Leucovorin rescues methotrexate toxicity, not ifosfamide toxicity. Naloxone and flumazenil treat opioid and benzodiazepine overdose respectively. Severe cases may require haemodialysis, and further ifosfamide cycles are avoided after an episode.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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