Relapse Prevention in G6PD-Deficient Patients with P. vivax/P. ovale Malaria
For G6PD-deficient patients with P. vivax or P. ovale malaria, use weekly primaquine at 0.75 mg base/kg (maximum 45 mg) for 8 weeks with close monitoring, or consider tafenoquine 300 mg as a single dose if G6PD activity is >70%, though in many cases the safest approach is to forgo radical cure and treat relapses as they occur. 1
Primary Treatment Options
Weekly Primaquine Regimen (Preferred for Most G6PD-Deficient Patients)
- Administer primaquine 0.75 mg base/kg weekly for 8 weeks once methemoglobin levels normalize after acute treatment 1
- This regimen is specifically recommended for patients with intermediate G6PD deficiency and can be applied to those with primaquine sensitivity 1
- Requires weekly methemoglobin monitoring throughout the 8-week course 1
- Must retest for G6PD deficiency if not previously confirmed, as G6PD deficiency increases risk of both hemolysis and methemoglobinemia 1
Tafenoquine (Alternative Single-Dose Option)
- A single 300 mg dose of tafenoquine may be considered if quantitative G6PD testing confirms >70% enzyme activity 1, 2
- Available only in the United States and Australia, not in Europe 1
- Contraindicated in G6PD deficiency or unknown G6PD status per FDA labeling 2
- Offers the advantage of single-dose administration, improving adherence compared to multi-day regimens 2
No Radical Cure (Conservative Approach)
- Forgoing radical cure and treating relapses as they occur may be the safest approach in many G6PD-deficient patients 1
- This is a reasonable strategy in non-endemic settings where reinfection risk is absent 1
- Particularly appropriate for patients with severe G6PD deficiency (<30% activity) or Mediterranean G6PD variant (B-) 1
Critical Safety Considerations
G6PD Testing Requirements
- All patients must undergo G6PD testing before any primaquine or tafenoquine administration to prevent life-threatening hemolysis 3, 2
- Quantitative testing is required for tafenoquine (must document >70% activity) 2
- The Mediterranean G6PD variant (B-) carries very high risk of severe complications with primaquine and should avoid these medications 1
Absolute Contraindications
- Severe G6PD deficiency (<30% activity) is an absolute contraindication to standard primaquine dosing 3
- Never give primaquine to pregnant or breastfeeding women 3
- G6PD-deficient infants may be at risk from exposure through breast milk; advise women not to breastfeed a G6PD-deficient infant for 3 months after tafenoquine 2
Monitoring Requirements
- Monitor for clinical signs of hemolysis including dark urine, jaundice, fatigue, and declining hemoglobin 1
- Weekly methemoglobin monitoring is required if attempting the modified weekly primaquine regimen 1
- If methemoglobinemia develops, stop primaquine immediately; the patient can still achieve radical cure later with alternative strategies 1
Concurrent Blood-Stage Treatment
- Continue chloroquine or alternative blood-stage antimalarial to complete treatment of acute infection 1
- Standard chloroquine dosing: 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
- Tafenoquine should be coadministered on the first or second day of chloroquine therapy 2
Important Caveats
Population-Specific Risks
- Asian populations may have higher rates of severe G6PD deficiency 1
- In populations where severe G6PD deficiency is common, primaquine should not be administered for greater than 5 days to avoid life-threatening hemolysis 1
Drug Interactions with Tafenoquine
- Avoid coadministration with drugs that are substrates of organic cation transporter-2 (OCT2) or multidrug and toxin extrusion (MATE) transporters 2
- Use with antimalarials other than chloroquine is not recommended due to risk of P. vivax malaria recurrence 2