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

Management and Treatment of G6PD Deficiency

Screening for G6PD deficiency is strongly recommended before starting therapy with oxidant drugs in patients with predisposing racial or ethnic backgrounds (particularly those from Africa, Mediterranean region, Middle East, Southeast Asia, and Oceania). 1

Diagnosis and Screening

• G6PD deficiency is the most common enzymatic disorder of red blood cells, affecting approximately 400 million people worldwide
• Highest prevalence in:
  • Africa (10-15% of black men and women have GdA- variant)
  • Southern Europe and Mediterranean region
  • Middle East
  • Southeast Asia
  • Central and southern Pacific islands 2
• Two main variants with different clinical implications:
  • GdA- (African variant): Milder, more self-limited hemolysis
  • Gdmed (Mediterranean variant): Can cause life-threatening hemolysis 1

Prevention of Hemolytic Episodes

Medications to Avoid

The following medications have strong evidence for causing hemolysis in G6PD-deficient patients and should be strictly avoided:

1. Dapsone
2. Primaquine
3. Rasburicase
4. Methylene blue (methylthioninium chloride)
5. Nitrofurantoin
6. Phenazopyridine
7. Tolonium chloride (toluidine blue) 3

Special Considerations for Primaquine

If primaquine must be used (e.g., for malaria treatment):

• G6PD testing is mandatory before administration
• Contraindicated in severe G6PD deficiency
• For mild to moderate deficiency:
  • Careful risk-benefit assessment required
  • Baseline hematocrit and hemoglobin must be checked
  • Close hematological monitoring (e.g., day 3 and 8)
  • Discontinue immediately if signs of hemolysis occur (darkening of urine, marked fall in hemoglobin) 4

Management of Acute Hemolytic Crisis

For patients experiencing acute hemolytic crisis:

1. Immediate discontinuation of the offending medication or removal from exposure to the trigger
2. Supportive care:
   • Intravenous hydration
   • Oxygen supplementation if needed
   • Cardiopulmonary support with mechanical ventilation and pressor support if necessary 1
3. Monitoring:
   • Complete blood count
   • Renal function
   • Urinalysis (for hemoglobinuria)
   • ECG monitoring (especially if medications that prolong QT interval are used) 1

Treatment Options for Methemoglobinemia (a complication of G6PD deficiency)

For G6PD-deficient patients with methemoglobinemia:

1. Ascorbic acid (Vitamin C):

   • Treatment of choice when methylene blue is contraindicated
   • Dosing options:
     • Adults: 0.5-10g in various regimens
     • Children: 0.5g every 12 hours or 1g every 4 hours 1

2. Avoid methylene blue:

   • Ineffective in G6PD deficiency
   • Can worsen hemolysis
   • May paradoxically increase methemoglobinemia 1

3. Exchange transfusion:

   • Consider in severe cases unresponsive to other treatments 1

Long-term Management

1. Patient education:

   • Provide list of medications to avoid
   • Educate about signs of hemolysis (dark urine, jaundice, fatigue)
   • Advise on dietary triggers (fava beans)

2. Genetic counseling:

   • Test first-degree relatives of patients with hereditary methemoglobinemia
   • Advise about inheritance patterns (X-linked recessive) 1

3. Regular monitoring:

   • In G6PD-normal patients receiving potentially hemolytic medications, perform routine blood examinations
   • Monitor for hemolysis with complete blood counts and hemoglobin determinations 4

Special Considerations

Malaria Treatment in G6PD-deficient Patients

For uncomplicated P. falciparum malaria:

• Artemether/lumefantrine (AL)
• Atovaquone-Proguanil (A-P)
• Dihydroartemisinin-piperaquine (DHAePPQ) 1

For P. vivax or P. ovale:

• Chloroquine or hydroxychloroquine (first-line)
• For radical cure (anti-relapse treatment):
  • For those with intermediate G6PD deficiency (>30% <70%) and non-Mediterranean variant: weekly primaquine (0.75 mg base/kg, maximum 45 mg) for 8 weeks with close monitoring 1

Perioperative Management

1. Screen patients with suspected G6PD deficiency before surgery
2. Avoid oxidative stressors during perioperative period
3. Safe medications for pain and anxiety management include:
   • Benzodiazepines
   • Codeine/codeine derivatives
   • Propofol
   • Fentanyl
   • Ketamine 2

Important Caveats

• Many compounds have been wrongly cited as causing hemolysis in G6PD-deficient patients when hemolysis was actually due to concurrent infections
• The severity of hemolytic reactions depends on the G6PD variant and the degree of enzyme deficiency
• G6PD deficiency correlates geographically with past/present malaria endemicity, suggesting evolutionary selection pressure 5

Remember that prevention is the most effective management strategy for G6PD deficiency. Careful medication selection and avoidance of known triggers can prevent most hemolytic episodes and associated complications.