Safety and effectiveness of methylene blue treatment in patients with methemoglobinemia：An all-patient, post-marketing surveillance

Abstract

Methylene blue has been used globally outside of Japan as a treatment for methemoglobinemia. In Japan, it was specified as a highly necessary drug by the Ministry of Health, Labour and Welfare’s Review Committee on Unapproved and Off-label Drugs with High Medical Needs. Methylene blue intravenous injection 50 mg “Daiichi Sankyo” (MB) was approved in Japan in December 2014. As a condition of approval, post-marketing surveillance was required for all patients with methemoglobinemia who received MB in Japan. The safety and effectiveness of MB based on the post-marketing surveillance data are reported. Of the 46 patients in the safety analysis set, 5 developed adverse drug reactions with a causal relationship to MB, of which 3 were serious hemolytic anemia, which has already been mentioned in the Japanese package insert. In the 41 patients in the effectiveness analysis set, the blood methemoglobin (MetHb) level decreased significantly from pre-treatment (32.4％) to post-treatment (2.0％). MetHb levels decreased by half in 38 patients with a median half-life of 2.7 hours, showing a rapid reduction after starting MB treatment. Regarding the prognosis after MB treatment, 36 patients were recovered, 0 had sequelae, and 5 died. No causal relationship of MB to death was observed in the 5 patients who died. In this all-patient, post-marketing surveillance, MB showed safety and effectiveness in patients with methemoglobinemia in Japan.