What is the recommended dose of primaquine (an antimalarial medication) for patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Primaquine Dosing in G6PD Deficiency

For patients with G6PD deficiency, the recommended primaquine dosing for radical cure of P. vivax malaria is 0.75 mg/kg weekly (maximum 45 mg) for 8 weeks with close monitoring for hemolysis, specifically for those with intermediate G6PD deficiency (30-70% activity) and non-Mediterranean variant (A-).1

Primaquine Dosing Based on G6PD Status

G6PD Testing Requirements

• Quantitative G6PD testing should be performed before administering primaquine to any patient 1
• Primaquine should not be used in patients with severe G6PD deficiency (<30% activity) or Mediterranean variant (B-) due to very high risk of severe hemolysis 1
• Do not use primaquine if G6PD activity is <70% according to some guidelines 1

Dosing Recommendations

• For intermediate G6PD deficiency (30-70% activity) with non-Mediterranean variant (A-):

  • Weekly primaquine at 0.75 mg/kg (maximum 45 mg) for 8 weeks 1
  • Close monitoring for hemolysis is mandatory 1

• For normal G6PD activity:

  • Standard dosing: 30 mg base per day for 14 days 1

Monitoring for Hemolysis

• Signs of hemolysis typically appear after day 3 and as late as day 8 of primaquine dosing 2

• Early indicators of hemolysis include:

  • Dark urine
  • Hemoglobin drop >20% from baseline
  • Fatigue, dizziness, or shortness of breath 2

• Regular monitoring should include:

  • Physical examination
  • Urine inspection for darkening
  • Serial hemoglobin measurements 2

Special Considerations

Variant-Specific Risk

• The African variant (A-) has mild deficiency and is relatively resistant to severe primaquine-induced hemolysis 1
• The Mediterranean variant (B-) has very high risk of severe hemolysis even with extended dosing regimens 1

Contraindications

• Primaquine is contraindicated in:
  • Pregnant or breastfeeding women 1
  • Patients with severe G6PD deficiency 1
  • Patients with unknown G6PD status where testing is unavailable 3

Management of Hemolytic Events

• If hemolysis occurs:

  • Immediately discontinue primaquine 2
  • Monitor hemoglobin levels closely 2
  • Consider hospitalization for severe cases 2
  • Blood transfusion may be required for significant anemia (Hb <7-8 g/dL) 3, 2

• Alternative treatments when primaquine cannot be used:

  • Ascorbic acid (Vitamin C) is the treatment of choice for methemoglobinemia in G6PD deficiency 1
  • Avoid methylene blue in G6PD deficiency as it may worsen hemolysis 1

Evidence on Safety

• Studies show that even with standard dosing (15 mg/day for 14 days), approximately one-third of G6PD-deficient patients may experience clinically concerning declines in hemoglobin 3
• Some patients may require blood transfusion even with standard dosing 3, 2
• In populations with high G6PD prevalence, standard primaquine regimens carry significant risk of acute hemolytic anemia without G6PD testing 3

Clinical Pitfalls to Avoid

• Do not administer primaquine without G6PD testing when possible 3, 4
• Do not assume mild symptoms are not concerning - hemolysis can progress rapidly 2
• Avoid other medications that can cause oxidative stress in G6PD-deficient patients receiving primaquine 4
• Do not rely on a single hemoglobin measurement - serial monitoring is essential 2
• Remember that G6PD testing may be inaccurate during acute hemolysis, leading to false-normal results 4