Dapsone-induced methemoglobinemia and hemolytic anemia

The treatment of two common adverse effects of dapsone (methemoglobinemia and hemolytic anemia) is discussed, and a case of acute dapsone intoxication is described. A pregnant 29-year-old woman was admitted to an emergency room three hours after ingesting 50 tablets of dapsone (100 mg each) and six alcoholic drinks. One hour after admission 50 g of activated charcoal was given p.o., and 65 mg of methylene blue was given i.v. The patient was found to have a methemoglobin concentration of 25.1%. Arterial blood gases while the patient was breathing 4 L/min of oxygen by nasal cannula were PO₂, 136 mm Hg (72.1% saturation); PCO₂, 28.9 mm Hg; bicarbonate content, 18.9 mmol/L; and pH, 7.42. Oxygen therapy was changed to 100% oxygen by face mask, 50 g of activated charcoal in sorbitol was administered p.o., and another 65 mg of methylene blue was given i.v. Two more 50-g doses of activated charcoal in sorbitol were given (18.5 and 22 hours after dapsone ingestion). Methylene blue 130 mg was given 14 hours after dapsone ingestion, and 65 mg was given 21, 36, and 55.5 hours after ingestion. Methemoglobin concentrations never rose above 20% after the sixth dose of methylene blue. On hospital days 2 and 3, laboratory values were consistent with a diagnosis of hemolytic anemia; the patient received two units of packed red blood cells. The hematocrit decreased over the next three days to 23.9%, and the patient received four units of packed red blood cells. On day 8 oxygen therapy was changed to oxygen 2 L/min by nasal cannula, and on day 10 the patient was breathing room air. Oral doses of activated charcoal have been used to treat acute dapsone poisoning. Methylene blue acts as a cofactor for the nicotinamide adenine dinucleotide phosphate system to convert methemoglobin to hemoglobin. Methylene blue, however, sometimes aggravates the adverse effects of dapsone, particularly in patients with glucose 6-phosphate dehydrogenase deficiency. Total methylene blue dosages exceeding 4 mg/kg are more likely to aggravate the methemoglobinemia and possibly cause or aggravate an acute hemolytic state. Most cases of dapsone-induced methemoglobinemia and hemolysis resolve when the offending drug is discontinued. When methylene blue is required for symptomatic patients with an elevated methemoglobin concentration (more than 30%), careful monitoring of drug dosage and clinical progress is indicated.