Primaquine for Plasmodium vivax and Plasmodium ovale Malaria
For radical cure of P. vivax and P. ovale malaria, administer primaquine 0.5 mg base/kg/day (maximum 30 mg base) orally for 14 days after confirming normal G6PD status. 1
Dosing Regimens
Standard Dosing for Radical Cure
- Adults: 30 mg base (equivalent to 2 tablets of 15 mg base) daily for 14 days 1
- Children: 0.5 mg base/kg/day (maximum 30 mg base) daily for 14 days 1
- Alternative for children: 0.3 mg/kg/day for 14 days in populations where severe G6PD deficiency is less common 1
Alternative Regimens
Seven-day high-dose regimen: 0.5 mg/kg/day for 7 days may be considered when adherence to 14-day therapy is a concern, as there appears to be little or no difference in recurrence rates at 6-7 months compared to the standard 14-day course (RR 0.96,95% CI 0.66 to 1.39) 2, 3. This shorter regimen delivers the same total dose (210 mg adult dose) but may improve completion rates 2.
Weekly dosing for G6PD deficiency: In populations with severe G6PD deficiency (particularly Mediterranean variants), use 0.75 mg base/kg once weekly for 8 weeks 1. This regimen is safer in G6PD-deficient patients, though evidence on efficacy is limited 3.
Critical Safety Considerations
G6PD Testing Requirements
Before administering primaquine, glucose-6-phosphate dehydrogenase (G6PD) status must be verified 1. This is non-negotiable for the standard 14-day regimen, as primaquine causes dose-dependent hemolysis in G6PD-deficient individuals 1.
- If G6PD testing unavailable: Consider the weekly dosing regimen (0.75 mg/kg/week for 8 weeks) in areas where severe G6PD deficiency is common 1
- Asian populations: Exercise particular caution, as severe G6PD deficiency variants are more prevalent; do not administer standard primaquine for more than 5 days without G6PD testing 1
- African (A-) variant: Has milder deficiency and relatively lower risk of severe hemolysis; weekly dosing with close monitoring may be considered 1
Contraindications
- Pregnant women: Absolutely contraindicated 1
- Lactating women: Contraindicated unless infant's G6PD status is confirmed normal 1
- G6PD deficiency: Standard daily regimens contraindicated; use weekly regimen only with close monitoring 1
Timing and Administration
Primaquine is typically administered after initial chloroquine blood-phase therapy, not in combination 1. The FDA label recommends concurrent administration with chloroquine, but clinical practice often sequences them 4.
- Administer with food to minimize gastrointestinal side effects 5
- Complete the full 14-day course to prevent relapse 4
Geographic Considerations
Higher-dose regimens (0.5 mg/kg/day) are particularly important for P. vivax acquired from:
These regions have high-frequency relapsing strains that require the higher dose for adequate radical cure 5.
Standard lower-dose regimens (0.25 mg/kg/day for 14 days) may be considered for P. vivax from areas outside these high-relapse regions, though the higher dose is increasingly preferred globally 1.
Common Pitfalls
- Failing to test for G6PD deficiency: This can result in life-threatening hemolysis 1
- Using inadequate doses in Southeast Asian/Oceanic strains: The standard 0.25 mg/kg/day dose has higher relapse rates in these regions; use 0.5 mg/kg/day 5
- Stopping treatment early: Incomplete courses lead to relapse 4
- Prescribing during pregnancy: Primaquine crosses the placenta and can cause hemolysis in a G6PD-deficient fetus 1
Monitoring
- Baseline hemoglobin/hematocrit before starting therapy 1
- Monitor for signs of hemolysis: dark urine, pallor, fatigue, particularly in first week 1
- Repeat hemoglobin if hemolysis suspected 1
Adverse Effects
Common adverse effects include nausea, vomiting, and abdominal discomfort, which can be minimized by taking with food 1, 5. The most serious adverse effect is hemolytic anemia in G6PD-deficient individuals 1. Methemoglobinemia can also occur but is typically mild 1.