Background Encephalopathy is a rare but serious central nervous system toxicity of ifosfamide. Its clinical symptoms are confusion, stupor, seizures, hallucinations and blurred vision.1 The methylene blue (MB) is administered as an antidote to the encephalopathy.
Purpose Description of MB formulation and control quality analysis of the preparation and safety case of encephalopathy associated with ifosfamide in the absence of MB injectable in the pharmaceutical market in the country.
Material and methods Initially the MB solution 10 mg/ml for intravenous administration was prepared. A disposable closed system transfer device with filter 0. 15 µm was used, so as to perform a sterile filtration. Next, an analytical control of drug substance and drug product was carried out in accordance with United States Pharmacopoeia. Finally, the preparation was administrated to the patient.
Results A 60-year-old woman had a uterine leiomyosarcoma in February 2016. The patient received the first cure of doxorubicin (20 mg/m2), ifosfamide (2.5 g/m2) and mesna (2.5 g/m2). On the third day of treatment, the patient had obnubilation and awareness troubles. Ifosfamide-induced encephalopathy was suspected. A treatment with MB was proposed, but unfortunately the product is not marketed in the country. The MB was prepared at the pharmacy with serum glucose 5%: every 1 ml contains 10 mg of drug substance. It has the same visible absorption spectrum as the MB standard solution, contains less than 2.5 USP endotoxin unit per ml, has an osmolality of 308 mmol/Kg, a pH of 4.76 and the preparation was sterile. The drug substance was identified with infrared absorption, The patient received the MB solution in a dose of 6×50 mg day-1. The encephalopathy was resolved with recovery at the neurological level.
Conclusion The MB continues to be an effective antidote for encephalopathy associated with ifosfamide. As was seen in our patient, a dose of 6×50 mg day-1 was sufficient for the management of encephalopathy. Our result is consistent with a previous report.
Reference and/or Acknowledgements 1. Pelgrims J, De Vos F, Van den Brande J, Schrijvers D, Prové A, Vermorken JB. Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature. Brit J Cancer2000;82(2):291–294.
No conflict of interest