What is the recommended dose of primaquine (Antimalarial medication) in the Artemisinin-based Combination Therapy-Sulfadoxine-Pyrimethamine (ACT-SP) regimen?

Primaquine Dosage in ACT-SP Regimen

The recommended dose of primaquine in the Artemisinin-based Combination Therapy-Sulfadoxine-Pyrimethamine (ACT-SP) regimen is 0.25 mg/kg as a single dose, which does not require G6PD testing prior to administration.

Primaquine Dosing Guidelines

Standard Dosing for Different Scenarios:

1. For P. falciparum (transmission blocking):

   • Single dose of 0.25 mg/kg (typically 15 mg in adults) 1, 2
   • Administered together with the first dose of ACT
   • No G6PD testing required at this dose

2. For P. vivax/P. ovale (radical cure/anti-relapse):

   • Adults: 30 mg base per day for 14 days 1
   • Children: 0.3 mg/kg/day for 14 days 1
   • G6PD testing recommended before administering this regimen

Safety Considerations

G6PD Deficiency:

• The single low dose (0.25 mg/kg) for P. falciparum is clinically well-tolerated even in G6PD-deficient individuals 2
• Mean fractional hemoglobin changes after single-dose primaquine in G6PD deficient subjects (-5.0%) were greater than in G6PD normal subjects (0.3%) but were clinically insignificant 2
• For the higher 14-day dosing regimen used for P. vivax/P. ovale, G6PD testing is strongly recommended 1

Monitoring:

• When using the higher dose regimens for radical cure, monitor for signs of hemolysis, especially in the first 7 days 1
• Baseline and follow-up hemoglobin measurements are recommended for the 14-day regimen but not necessary for the single low dose 1

Special Populations

Pregnancy and Lactation:

• Primaquine is contraindicated during pregnancy 3
• Small amounts are secreted in breast milk, but insufficient to cause harm 3

Children:

• Children can receive weight-based dosing:
  • 0.25 mg/kg for transmission blocking (P. falciparum)
  • 0.3 mg/kg/day for 14 days for radical cure (P. vivax/P. ovale) 1

Alternative Regimens

For patients who cannot tolerate the standard 14-day course for P. vivax/P. ovale:

• Weekly dosing: 0.75 mg/kg once weekly for 8 weeks 1, 4
• Shorter high-dose regimen: 0.5 mg/kg/day for 7 days 4, 5

Common Pitfalls and Caveats

1. Failure to distinguish between transmission-blocking and radical cure doses:

   • Single low dose (0.25 mg/kg) is for P. falciparum gametocyte clearance
   • Higher dose 14-day regimen is for P. vivax/P. ovale hypnozoite elimination

2. Unnecessary withholding of single-dose primaquine:

   • The 0.25 mg/kg single dose is safe even without G6PD testing 2, 6
   • Withholding this dose may contribute to ongoing malaria transmission

3. Inadequate monitoring for the 14-day regimen:

   • Higher doses require monitoring for hemolysis, especially in areas with severe G6PD deficiency variants 1

4. Confusion about concurrent medications:

   • Primaquine can be safely administered with ACT-SP regimens
   • No significant drug interactions exist between primaquine and components of ACT-SP that would affect efficacy or increase toxicity 3

In conclusion, when using primaquine as part of an ACT-SP regimen for P. falciparum malaria, the single 0.25 mg/kg dose is safe, effective for blocking transmission, and does not require G6PD testing. For radical cure of P. vivax or P. ovale, higher doses over 14 days are needed with appropriate G6PD screening.