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

Management of G6PD Deficiency

The management of Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency primarily involves screening at-risk populations and avoiding medications that can trigger hemolysis, with immediate discontinuation of oxidant drugs if signs of hemolysis occur. 1, 2

Screening and Diagnosis

• Qualitative screening for G6PD deficiency is recommended upon entry into care or before starting therapy with oxidant drugs in patients with predisposing racial or ethnic backgrounds (Mediterranean, African, Indian, or Southeast Asian descent) 3, 1, 2
• Quantitative G6PD testing is specifically required before tafenoquine administration 2
• First-degree relatives of patients with G6PD deficiency should be tested 1, 2

Risk Stratification by Variant

• The African variant (GdA-) affects 10-15% of Black men and women and typically causes milder, self-limited hemolysis 3, 1, 2
• The Mediterranean variant (Gdmed) predominantly affects men from Mediterranean regions, India, and Southeast Asia, and can cause life-threatening hemolysis 3, 1, 2

Medications to Avoid

• Seven medications are definitively contraindicated in G6PD deficiency 4:

  • Dapsone
  • Methylene blue (methylthioninium chloride)
  • Primaquine
  • Rasburicase
  • Nitrofurantoin (though recent evidence suggests it may be safer than previously thought) 5
  • Phenazopyridine
  • Sulfamethoxazole/cotrimoxazole

• For P. vivax or P. ovale malaria requiring radical cure, primaquine should only be used after G6PD testing 2, 6

Monitoring During Treatment with Potentially Hemolytic Drugs

• Before initiating treatment with potentially hemolytic medications, obtain a complete blood count with hemoglobin determination 3, 2
• For G6PD-deficient patients who must receive potentially hemolytic drugs, close hematological monitoring is required (e.g., at day 3 and 8) 6
• The adult dosage of primaquine should not exceed 15 mg base daily for fourteen days, even in G6PD normal patients 6

Warning Signs of Hemolysis

• Immediately discontinue any potentially hemolytic medication if signs of hemolysis occur 1, 2, 6:
  • Darkening of urine (reddish color)
  • Sudden decrease in hemoglobin concentration
  • Back or abdominal pain
  • Jaundice
  • Fatigue or pallor

Special Considerations

• Pregnant women should avoid primaquine as the G6PD status of the fetus may be unknown 6
• Patients with cardiac disease, long QT syndrome, ventricular arrhythmias, or electrolyte abnormalities require ECG monitoring when using primaquine due to potential QT interval prolongation 6
• Recent real-world evidence suggests that some medications previously considered risky (including nitrofurantoin, ciprofloxacin, and hydroxychloroquine) may be safer than previously thought in G6PD-deficient patients 5

Management of Acute Hemolytic Crisis

• Discontinue the offending agent immediately 6
• Provide supportive care including hydration 7
• Monitor hemoglobin levels and renal function 2
• Blood transfusion may be necessary in severe cases 7, 8

Prevention

• The most effective management strategy is prevention of hemolysis by avoiding oxidative stress 9
• Educate patients about their condition and provide a list of medications and foods (particularly fava beans) to avoid 7, 5
• Consider medical alert identification for affected individuals 8