Unless methemoglobinemia is severe or symptomatic, treatment is purely for cosmetic or psychological reasons. Various agents can reduce the methemoglobin levels to within the reference range (~1%) or at least to acceptable levels (5-10%).
Methylene blue is the first-line antidotal therapy. Ascorbic acid and riboflavin have been used. N -acetylcysteine reduces methemoglobin levels but is not yet approved for the treatment of methemoglobinemia. Cimetidine can be used in dapsone-induced methemoglobinemia. Hyperbaric oxygen and exchange transfusion should be considered when methylene blue treatment is ineffective or contraindicated.
Antidotes (eg, methylene blue) are used to counteract methemoglobinemia, acting as cofactors in the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent methemoglobin reductase system. Cimetidine may be used in dapsone-induced methemoglobinemia.
Methylene blue increases the activity of nicotinamide adenine dinucleotide (NADH)-methemoglobin reductase in red blood cells (RBCs), assisting in the conversion of ferric (Fe3+) to ferrous (Fe2+) iron. It is available as a 1% solution (10 mg/mL). Most patients require only 1 dose. Resolution of toxicity should be seen within 1 hour, often within 20 minutes.
The US Food and Drug Administration (FDA) warns against using methylene blue concurrently with serotonergic psychiatric drugs, unless such usage is indicated for life-threatening or urgent conditions. Methylene blue may increase central nervous system (CNS) serotonin levels as a result of monoamine oxidase (MAO)-A inhibition, increasing the risk of serotonin syndrome.
Vitamins, Water Soluble
Vitamins are essential for normal metabolic functioning of the body. Important: they act as cofactors in erythrocyte glutathione reductase and NADH dehydrogenase.
Ascorbic acid is an antioxidant and coenzyme for reduction. It may be helpful in the treatment of congenital methemoglobinemia if used daily and on a continual basis. Although it can occasionally reduce the cyanosis associated with chronic methemoglobinemia, it has no role in the treatment of acute acquired methemoglobinemia.
Riboflavin can reduce the cyanosis associated with chronic methemoglobinemia but has no role in the treatment of acute severe acquired methemoglobinemia.
Histamine H2 Antagonists
Cytochrome P-450 inhibitors are recommended only for patients with methemoglobinemia secondary to dapsone.
Cimetidine inhibits conversion of dapsone to its oxidizing metabolite, dapsone hydroxylamine, by the P-450 system, thereby preventing further development of dapsone-induced methemoglobinemia.
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