Guideline for the treatment and prophylaxis of Ifosfamide induced Encephalitis.

Ifosfamide is an alkylating agent used to treat a range of solid and haematological malignancies. Its use can lead to central nervous system (CNS) toxicity in 10-30% (mean 12%) of patients after intravenous administration.

The onset of symptoms occurs between 12 and 146 hours after the start of administration. CNS toxicity is increased by 50% with oral administration due to differences in metabolism between the two routes. Methylthioninium chloride (Proveblue®) is not licensed for the treatment of ifosfamide induced encephalopathy (IIE), so its use is off-label. Its mechanism of action is unclear, it is proposed that its activity as an electron acceptor reduces the formation of the toxic metabolite chloroacetaldehyde.