Iphosphamide is a chemotherapeutic that is used in the treatment of many cancer types. It causes encephalopathy in as many as 27% of patients. Drug interactions increase the probability of encephalopathy. Aprepitant, which is used in the prevention of chemotherapy-induced nausea and vomitus, is one of the problematic drugs. The treatment of encephalopathy includes discontinuation of iphosphamide, the use of methylene blue and correction of electrolytes. If iphosphamide is still useful, methylene blue can be used prophylactically to prevent encephalopathy.