Normal Dose of Primaquine for Treating Hypnozoites in Vivax Malaria
The standard dose of primaquine for radical cure of P. vivax hypnozoites is 30 mg base (equivalent to 15 mg base tablet, two tablets) daily for 14 days in G6PD-normal adults, which must be administered following blood schizontocidal treatment to prevent relapses. 1, 2, 3
Standard Dosing Regimen
For G6PD-Normal Patients
- Adults: 30 mg base per day (0.5 mg/kg/day) for 14 days is the high-standard dose recommended by the CDC and WHO 2
- Alternative standard dose: 15 mg base daily (0.25 mg/kg/day) for 14 days, though this lower dose may be insufficient for Southeast Asian strains 1
- Children: 0.3 mg/kg/day for 14 days 1
The FDA-approved regimen specifies 1 tablet (15 mg base) daily for 14 days, administered concurrently with chloroquine 3. However, recent evidence suggests the higher dose of 30 mg base daily (0.5 mg/kg/day) is more effective, particularly for tropical strains.
Critical Pre-Treatment Requirement
- G6PD testing is mandatory before primaquine administration to prevent life-threatening hemolysis 1, 2
- Primaquine should never be given to patients with severe G6PD deficiency without appropriate dose modification 1
Modified Dosing for G6PD Deficiency
For Mild to Moderate G6PD Deficiency (30-70% activity)
- 45 mg base once weekly for 8 weeks can be used as an alternative regimen 1
- This weekly dosing reduces the risk of hemolysis while maintaining anti-hypnozoite efficacy 1
Contraindications
- Absolute contraindications: Pregnancy, breastfeeding women, infants less than 6 months old, and severe G6PD deficiency 1, 4
- Among Asian populations with high rates of severe G6PD deficiency, primaquine should not be administered for longer than 5 days without G6PD testing 1
Evidence for Dosing Recommendations
Efficacy Comparison
Recent high-quality evidence from Cambodia demonstrates that the 7.0 mg/kg total dose (0.5 mg/kg/day for 14 days) is significantly more effective than the 3.5 mg/kg total dose (0.25 mg/kg/day for 14 days) for Southeast Asian P. vivax strains 5. The higher dose reduced recurrence risk by 5.9-fold compared to the lower dose (4.7% vs 24.4% recurrence at 90 days, p=0.0141) 5.
A Cochrane systematic review found that the 5-day primaquine regimen has no value as anti-relapse therapy and should be abandoned 6. The standard 14-day course remains essential for radical cure 7, 6.
Geographic Considerations
- Chloroquine-resistant areas (Papua New Guinea, Indonesia, Sabah): Consider artemisinin-based combination therapy plus primaquine 1
- Southeast Asian strains: The higher dose (0.5 mg/kg/day for 14 days) is strongly recommended due to higher relapse rates with standard dosing 5
Clinical Implementation
Timing and Co-Administration
- Primaquine should be started concurrently with blood schizontocidal treatment (chloroquine or ACT) 1, 3
- Co-administration with chloroquine boosts primaquine blood levels, enhancing efficacy 1
Monitoring Requirements
- Monitor for hemolysis signs: dark urine, jaundice, fatigue, particularly in the first week of treatment 2
- Clinical improvement should occur within 48 hours of starting treatment 2
- Follow-up blood smears confirm parasite clearance 2
Safety Profile
Both the standard (0.25 mg/kg/day) and high-standard (0.5 mg/kg/day) 14-day regimens are well-tolerated in G6PD-normal individuals with comparable safety profiles 5. A retrospective study showed an 80% risk reduction of relapse in patients prescribed primaquine for P. vivax malaria 1.
Common Pitfalls to Avoid
- Do not use 5-day regimens: Despite historical use in some national programs, 5-day primaquine courses are ineffective and should be abandoned 6
- Do not omit G6PD testing: Administering primaquine without G6PD status assessment risks severe hemolytic anemia 1, 2
- Do not underdose in endemic areas: The lower 3.5 mg/kg total dose may be insufficient for tropical strains, particularly in Southeast Asia 5
- Do not forget pregnancy screening: Primaquine is contraindicated in pregnancy and must be deferred until after delivery 1, 4