What are the management and treatment options for Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Management of G6PD Deficiency

The primary management of Glucose-6-phosphate dehydrogenase (G6PD) deficiency focuses on preventing hemolytic episodes by avoiding oxidative triggers, with quantitative enzyme activity testing recommended for diagnosis, and close monitoring required when medications with hemolytic potential must be used. 1

Diagnosis and Screening

• Gold standard: Quantitative enzyme activity assay measuring G6PD activity in U/g Hemoglobin
• Screening methods:
  • Fluorescent spot test (FST)
  • Point-of-care rapid diagnostic tests (sensitivity ~100% for severe/moderate deficiency)
• Testing indications:
  • Before administering primaquine for malaria
  • Patients with unexplained hemolysis
  • Individuals from high-prevalence regions (Africa, Southern Europe, Mediterranean region, Middle East, South-East Asia, Oceania)
  • Males of African, Italian, and/or Greek ancestry before dapsone treatment 2, 1

Prevention of Hemolytic Episodes

Medication Management

1. Contraindicated medications:

   • Primaquine in severe G6PD deficiency 3
   • Methylene blue 1
   • Nitrofurantoin (potential risk, though recent evidence suggests lower risk than previously thought) 4
   • Phenazopyridine (potential risk) 4

2. Medications requiring caution:

   • Primaquine in mild to moderate G6PD deficiency (requires close monitoring) 3
   • Dapsone (can cause significant hemolysis) 2
   • Sulfonamides (including sulfamethoxazole/cotrimoxazole) 1

3. Generally safe medications:

   • Penicillins (including amoxicillin, though rare cases of hemolysis reported) 1, 5
   • Cephalosporins
   • Macrolides
   • Tetracyclines (avoid in children <8 years) 2, 1
   • Most quinolones (monitor with ciprofloxacin) 1

Dietary Precautions

• Avoid fava beans (most common dietary trigger) 1, 4
• Maintain adequate hydration, especially during illness

Monitoring and Management of Hemolytic Episodes

Monitoring Protocol

1. Baseline assessment:

   • Complete blood count
   • Document G6PD status prominently in medical records

2. During high-risk situations (infection, medication exposure):

   • Monitor for signs of hemolysis (darkening of urine, pallor, fatigue)
   • Check hemoglobin levels at baseline, day 3, and day 8 when using potentially hemolytic drugs 1, 3
   • Monitor reticulocyte count if hemolysis is suspected

Management of Acute Hemolysis

1. Discontinue the offending agent immediately 3
2. Supportive care:
   • Intravenous hydration
   • Blood transfusion for severe anemia
   • Monitor renal function
   • For methemoglobinemia: ascorbic acid (0.5-1.0 g/day in divided doses) instead of methylene blue 1

Special Considerations

Malaria Treatment

• Use artemisinin-based combination therapies or chloroquine (for sensitive strains) 1
• For P. vivax/P. ovale infections requiring primaquine:
  • Test G6PD status before administration
  • Consider weekly primaquine for intermediate deficiency (>30% < 70%) with close monitoring 1, 3

Pregnancy and Breastfeeding

• Primaquine is contraindicated in pregnancy (risk to G6PD-deficient fetus) 3
• Breastfeeding women should avoid primaquine or discontinue nursing 3
• Screen newborns for G6PD deficiency in high-risk populations

Heterozygous Females

• May have intermediate deficiency with clinical symptoms under oxidative stress
• Require careful monitoring similar to homozygous/hemizygous individuals 1

Patient Education

• Provide list of medications and foods to avoid
• Educate about signs of hemolysis requiring medical attention
• Emphasize importance of informing all healthcare providers about G6PD status 1

Recent real-world evidence suggests that some medications previously thought to be high-risk (including nitrofurantoin, ciprofloxacin, and sulfamethoxazole) may be safer than previously believed, with only 3 out of 71 cases of major hemolysis in G6PD-deficient patients being associated with medications in a large cohort study 4. However, until more definitive evidence emerges, caution remains the prudent approach when prescribing these medications to G6PD-deficient individuals.