How is G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency managed?

Management of G6PD Deficiency

The management of G6PD deficiency primarily involves avoiding triggers of hemolysis, particularly medications with high oxidative potential and fava beans, while ensuring proper monitoring during high-risk situations. 1

Diagnosis and Screening

• Quantitative enzyme activity testing is recommended for diagnosis of G6PD deficiency, particularly:
  • Before administering primaquine for malaria
  • In patients with unexplained hemolysis
  • Individuals from high-prevalence regions (Africa, Southern Europe, Mediterranean region, Middle East, South-East Asia, and Oceania) 1, 2
• Point-of-care rapid diagnostic tests and fluorescent spot test (FST) are useful screening methods with high sensitivity for moderate to severe deficiency 1

Medication Management

Medications to Avoid

• High-risk medications that should be avoided in G6PD deficiency:
  • Primaquine (contraindicated in severe G6PD deficiency) 2
  • Dapsone (can cause significant hemolysis) 1
  • Nitrofurantoin 1
  • Methylene blue (contraindicated) 1
  • Rasburicase 3

Safe Alternative Medications

• Safe first-line antibiotics for G6PD-deficient patients:
  • Penicillins
  • Cephalosporins
  • Macrolides
  • Most tetracyclines (avoid in children <8 years) 1

Special Considerations for Specific Medications

• Primaquine:

  • Contraindicated in severe G6PD deficiency 2
  • For mild to moderate deficiency, decision must be based on risk-benefit assessment 2
  • If administered, baseline hematocrit and hemoglobin must be checked before treatment with close monitoring at days 3 and 8 2
  • Contraindicated in pregnancy even if the mother is G6PD normal (fetus may not be) 2

• Antimalarials:

  • Artesunate is preferred over quinine for P. falciparum malaria 1
  • For severe malaria, IV artesunate (2.4 mg/kg at 0,12, and 24 hours, then daily) is first-line 1
  • IV quinine is second-line (20 mg/kg loading dose, then 10 mg/kg every 8 hours) 1

• Other medications:

  • Recent evidence suggests lower risk than previously thought for some medications like sulfamethoxazole/cotrimoxazole 1, 4
  • For methemoglobinemia, use ascorbic acid (0.5-1.0 g/day in divided doses) instead of methylene blue 1, 5

Dietary and Lifestyle Management

• Avoid fava beans - a common dietary trigger for hemolysis 1
• Maintain adequate hydration, especially during illness 1
• Diet recommendations: 60-70% calories from complex carbohydrates, 10-15% from protein 1

Monitoring and Management of Hemolysis

1. Monitor for signs of hemolysis:

   • Darkening of urine
   • Pallor
   • Fatigue 1

2. If hemolysis occurs:

   • Immediately discontinue the offending agent
   • Provide supportive care including IV hydration
   • Blood transfusion for severe anemia 1
   • Serial hemoglobin measurements to track hemolysis 1

3. Documentation:

   • Document G6PD status prominently in medical records
   • Establish monitoring protocol for high-risk situations 1

Special Populations

• Pregnant women:

  • Avoid primaquine due to risk to fetus 1, 2
  • Pregnancy testing recommended before starting primaquine in women of reproductive age 2

• Breastfeeding women:

  • Avoid primaquine or discontinue nursing 1

• Newborns:

  • Screen those from high-risk populations 1
  • Monitor for neonatal jaundice 3, 6

• Heterozygous females:

  • May have intermediate deficiency that can still cause clinical symptoms under severe oxidative stress 1

Pitfalls and Caveats

• G6PD testing has limitations - physicians should be aware of residual risk of hemolysis even with negative testing 2
• Acute hemolytic crisis can be managed effectively if diagnosed promptly 3
• The geographic distribution of G6PD deficiency correlates with past/present malaria endemicity 3, 6
• Methylene blue, the standard treatment for methemoglobinemia, is contraindicated in G6PD deficiency and can worsen hemolysis 5
• Despite precautions on many drug labels, a recent real-world study showed that many medications previously thought risky (including nitrofurantoin, ciprofloxacin, and sulfamethoxazole) were prescribed safely to thousands of G6PD-deficient patients 4