What is the recommended lower dose of primaquine (an antimalarial medication) for eradication therapy in a patient with Plasmodium vivax malaria and a history of G6PD (Glucose-6-phosphate dehydrogenase) deficiency?

Lower Dose Primaquine for Eradication Therapy in G6PD Deficiency

For patients with P. vivax malaria and G6PD deficiency, use weekly primaquine at 0.75 mg base/kg (maximum 45 mg) for 8 weeks with close hematological monitoring, rather than the standard daily regimen. 1

G6PD Testing Requirements

• G6PD testing must be performed before prescribing primaquine to determine the appropriate dosage and prevent life-threatening hemolysis 2, 3
• If G6PD status is unknown and testing unavailable, baseline hematocrit and hemoglobin must be checked before treatment, with close hematological monitoring at days 3 and 8 3
• Retest for G6PD deficiency if not previously done, as G6PD deficiency increases risk of both hemolysis and methemoglobinemia 1

Dosing Regimens Based on G6PD Status

G6PD Normal Patients

• Standard regimen: 30 mg base (15 mg tablet) daily for 14 days 2, 3
• Alternative shorter regimen: 0.5 mg/kg/day for 7 days may be used if adherence concerns exist, with no detected difference in recurrence rates 4, 5

Mild to Moderate G6PD Deficiency

• Weekly primaquine at 0.75 mg base/kg (maximum 45 mg) for 8 weeks with weekly methemoglobin monitoring 1
• This regimen is specifically recommended for patients with intermediate G6PD deficiency but can be applied to those with primaquine sensitivity 1

Severe G6PD Deficiency

• Primaquine is contraindicated in severe G6PD deficiency 3
• The CDC recommends that in populations where severe G6PD deficiency is common, primaquine should not be administered for greater than 5 days as longer administration may result in life-threatening hemolysis 1
• Consider forgoing radical cure and treating relapses as they occur, which may be the safest approach in non-endemic settings where reinfection risk is absent 1

Alternative Treatment Options

• Tafenoquine (single 300 mg dose) may be considered as an alternative, though it is not available in Europe and is only approved in the United States and Australia 1
• Tafenoquine requires quantitative G6PD testing with activity >70% 1

Critical Monitoring Requirements

• Weekly methemoglobin monitoring is required if attempting the modified weekly primaquine regimen 1
• Monitor for signs of hemolysis including darkening of urine, marked fall of hemoglobin or erythrocyte count, jaundice, and fatigue 2, 3
• Discontinue primaquine immediately if signs of hemolytic anemia or methemoglobinemia occur 3
• Adequate medical support to manage hemolytic risk must be available 3

Important Population-Specific Caveats

• The Mediterranean G6PD variant (B-) carries very high risk of severe complications with primaquine 1
• Asian populations may have higher rates of severe G6PD deficiency 1
• Areas of high G6PD deficiency prevalence include Africa, Southern Europe, Mediterranean region, Middle East, South-East Asia, and Oceania 3
• Primaquine is absolutely contraindicated in pregnancy, even if the woman is G6PD normal, as the fetus may be G6PD deficient 3

Blood-Stage Treatment Continuation

• Continue chloroquine (or alternative blood-stage antimalarial) to complete treatment of the acute infection 1
• Chloroquine remains first-line for P. vivax at 1000 mg salt initially, then 500 mg at 6,24, and 48 hours 1
• Alternative blood-stage treatments include artemether-lumefantrine or dihydroartemisinin-piperaquine if chloroquine resistance is suspected 1