Is dapsone (diaphenylsulfone) safe to use in patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Dapsone Use in G6PD Deficiency

Dapsone should be avoided in patients with G6PD deficiency due to the significant risk of hemolysis and potentially life-threatening anemia. 1, 2

Mechanism of Risk

• Dapsone, particularly its metabolite dapsone hydroxylamine (DDS-NOH), causes oxidative stress in red blood cells 3
• G6PD-deficient individuals have:
  • Decreased ability to mitigate oxidative stress due to lower NADPH levels
  • Impaired pentose phosphate pathway function
  • Increased susceptibility to hemolysis when exposed to oxidative agents 3, 4

Evidence Supporting Contraindication

• FDA labeling explicitly states that hemolysis may be exaggerated in individuals with G6PD deficiency, and dapsone should be given with caution to these patients 1
• Dapsone is listed among medications that should be prohibited in G6PD-deficient individuals according to evidence-based reviews 5
• The American Academy of Dermatology guidelines note that patients with G6PD deficiency should be observed for signs and symptoms of hemolysis when using dapsone 6
• Management guidelines for G6PD deficiency indicate that dapsone can cause significant hemolysis in G6PD-deficient individuals 2

Clinical Manifestations of Dapsone-Induced Hemolysis

• Acute hemolysis symptoms include:
  • Anemia
  • Fatigue
  • Back or abdominal pain
  • Jaundice
  • Hemoglobinuria 4
• Research shows G6PD-deficient patients have significantly lower hematocrit levels after dapsone treatment 7
• Severe cases may require blood transfusion (10.2 times higher risk in G6PD-deficient patients) 7

Monitoring and Management

If dapsone must be used in a G6PD-deficient patient due to lack of alternatives:

• Perform baseline G6PD activity testing before initiating therapy 2
• Monitor for signs of hemolysis including darkening of urine, pallor, and fatigue 2
• Conduct serial hemoglobin measurements to track potential hemolysis 2
• Discontinue dapsone immediately if signs of hemolysis develop 2
• Be prepared to provide supportive care including IV hydration and blood transfusion if needed 2

Alternative Medications

• Tetracyclines, penicillins, cephalosporins, and macrolides are considered safe options for G6PD-deficient patients 2
• For dermatologic conditions where dapsone might be indicated, consider alternative therapies based on the specific condition

Important Caveats

• The risk of hemolysis appears to be dose-related 1, 8
• Topical dapsone may present less risk than oral formulations, but caution is still warranted
• Hyperbilirubinemia may occur more frequently in G6PD-deficient patients taking dapsone 1
• Drug interactions (particularly with trimethoprim) can increase dapsone levels, potentially exacerbating risk 1

Documentation

• G6PD status should be prominently documented in medical records to prevent inadvertent prescription of contraindicated medications 2
• Patients should be educated about their G6PD status and provided with a list of medications to avoid

In conclusion, the weight of evidence strongly suggests avoiding dapsone in patients with G6PD deficiency whenever possible. When no alternatives exist, extremely close monitoring for hemolysis is essential.