What is the treatment for dapsone (diaphenylsulfone)-induced methemoglobinemia?

Treatment of Dapsone-Induced Methemoglobinemia

The first-line treatment for dapsone-induced methemoglobinemia is intravenous methylene blue at a dose of 1-2 mg/kg administered over 3-5 minutes, which may be repeated if symptoms don't resolve within 30 minutes, up to a maximum total dose of 7 mg/kg. 1

Primary Treatment Algorithm

1. Initial Assessment

   • Confirm methemoglobinemia diagnosis (look for cyanosis unresponsive to oxygen, chocolate-brown colored blood, and "saturation gap" between pulse oximetry and arterial blood gas analysis)
   • Check severity of symptoms (mild: asymptomatic or minimal symptoms; severe: altered mental status, respiratory distress, shock)
   • Rule out G6PD deficiency before administering methylene blue 1

2. First-Line Treatment

   • Administer methylene blue 1-2 mg/kg IV over 3-5 minutes 1
   • May repeat dose after 30 minutes if symptoms persist
   • Maximum total dose: 7 mg/kg 1
   • Consider methylene blue infusion rather than bolus dosing for severe persistent cases 2

3. Adjunctive Therapies

   • Ensure adequate glucose availability (essential for methylene blue effectiveness) 1
   • Provide intravenous hydration 1
   • Administer oxygen supplementation 1
   • Consider ascorbic acid (vitamin C) administration:
     • High-dose vitamin C (10g IV every 6 hours) can be effective when methylene blue is unavailable 3

4. For Refractory Cases

   • Consider exchange transfusion (81.6% survival rate in refractory cases) 1
   • Consider hyperbaric oxygen therapy 1
   • Multiple doses of activated charcoal may help reduce dapsone absorption and enterohepatic recirculation 2, 4

Special Considerations

• G6PD Deficiency: Methylene blue is contraindicated in patients with G6PD deficiency as it can worsen hemolysis 1
• Monitoring: Closely monitor methemoglobin levels after treatment and watch for rebound phenomenon (increased MetHb levels after completion of therapy) 1
• Hemolytic Anemia: Monitor for delayed hemolytic anemia, especially in patients with high methemoglobin levels at presentation, and be prepared to administer blood transfusions if needed 5, 4
• Pregnancy: Methylene blue is teratogenic and should be used only when benefits outweigh risks; exchange transfusion may be preferred if time and matched blood are available 1

Common Pitfalls to Avoid

• Failure to recognize G6PD deficiency before administering methylene blue 1
• Inadequate glucose availability, which can hinder the effectiveness of methylene blue treatment 1
• Overlooking concurrent conditions such as anemia or pneumonia that may precipitate symptomatic methemoglobinemia 5
• Discontinuing monitoring too early, as dapsone has a long half-life and can cause rebound methemoglobinemia 1, 5
• Not considering methylene blue infusion for severe persistent cases, which may help control methemoglobin levels and reduce total dose needed 2

Dapsone-induced methemoglobinemia can be life-threatening but has good outcomes when promptly recognized and appropriately treated with methylene blue and supportive care 6, 5.