What is the appropriate dosage and usage of primaquine (an antimalarial medication) for treating malaria, particularly in patients with G6PD (Glucose-6-phosphate dehydrogenase) deficiency?

Primaquine Dosing for Malaria Treatment in G6PD Deficiency

The standard dosage of primaquine for radical cure of vivax malaria is 15 mg base (1 tablet) daily for 14 days, but this must be modified to 7.5 mg weekly for 8 weeks in patients with G6PD deficiency to prevent potentially life-threatening hemolysis. 1

G6PD Testing Requirements

G6PD testing is mandatory before administering primaquine due to the risk of hemolysis in deficient individuals:

• G6PD status assessment must be performed before initiating primaquine therapy 1
• Primaquine should not be prescribed for patients with severe G6PD deficiency 1
• For mild to moderate G6PD deficiency, a risk-benefit assessment is required 1

Dosing Algorithm Based on G6PD Status

For G6PD Normal Patients:

• Standard dose: 15 mg base (1 tablet) daily for 14 days 1
• This is administered concurrently with chloroquine phosphate to eradicate exoerythrocytic parasites 1

For G6PD Deficient Patients:

• Modified dose: 0.75 mg/kg (approximately 45 mg for adults) once weekly for 8 weeks 2, 3
• This weekly regimen is safer in less severe G6PD deficiency variants 4
• Weekly dosing allows for recovery of older erythrocytes between doses

For Unknown G6PD Status (when testing unavailable):

• A risk-benefit assessment must be conducted 1
• Baseline hematocrit and hemoglobin must be checked before treatment 1
• Close hematological monitoring is required (e.g., at day 3 and 8) 1
• Adequate medical support to manage hemolytic risk should be available 1

Monitoring Requirements

For all patients receiving primaquine, especially those with G6PD deficiency:

• Baseline hemoglobin measurement before starting treatment 5, 1
• Follow-up hemoglobin measurements, particularly at days 3 and 8 1
• Monitor for signs of hemolysis:
  • Darkening of urine
  • Marked fall in hemoglobin or erythrocyte count
  • Fatigue, dizziness, or shortness of breath

Special Populations

• Pregnancy: Primaquine is contraindicated in pregnant women 1
• Breastfeeding: A decision should be made whether to discontinue nursing or to discontinue the drug 1
• Children: Dosing should be weight-based; primaquine can be used in appropriate doses 5

Important Precautions

• Discontinue primaquine immediately if signs of hemolysis occur 1
• Hemolytic reactions can be life-threatening in G6PD deficient individuals 6
• Early signs of acute hemolysis typically occur after day 3 and as late as day 8 of primaquine dosing 6
• The risk of serious adverse events is higher with higher doses (1 mg/kg/day for 7 days showed increased serious adverse events compared to 0.5 mg/kg/day for 14 days) 3

Clinical Pearls

• Primaquine is the only available antimalarial drug that kills dormant liver stages (hypnozoites) of P. vivax and P. ovale 4, 7
• The 7.5 mg weekly dose represents half of the standard 15 mg daily dose, administered once weekly instead of daily
• Despite its importance in preventing relapse and reducing transmission, primaquine remains underused due to concerns about G6PD deficiency 4
• The mortality risk from primaquine is estimated at one in 621,428 treated individuals, with almost all deaths following multiple dosing for vivax malaria relapse prevention 8

By following this dosing algorithm and monitoring protocol, clinicians can safely administer primaquine to prevent relapse in malaria while minimizing the risk of hemolytic complications in G6PD deficient patients.