Can we give primaquine (an antimalarial medication) together with Riamet (lumefantrine/artemether) for a patient with malaria, specifically Plasmodium vivax or Plasmodium falciparum?

Primaquine and Riamet (Artemether-Lumefantrine) Can Be Given Together

Yes, primaquine should be administered concurrently with Riamet (artemether-lumefantrine) for P. vivax malaria to achieve both blood-stage clearance and radical cure of liver hypnozoites. 1, 2

Treatment Approach by Species

For P. vivax Malaria

• Administer Riamet for blood-stage parasites alongside primaquine 15 mg base daily for 14 days to prevent relapse from dormant liver stages 1
• The FDA label explicitly states primaquine should be given "concurrently" with blood schizontocidal drugs (like Riamet) to eradicate exoerythrocytic parasites 2
• While artemisinin-based combinations like Riamet are registered only for P. falciparum in Europe, they are recommended for P. vivax from chloroquine-resistant areas (Papua New Guinea, Indonesia, Sabah) 1
• Among artemisinin combinations, dihydroartemisinin-piperaquine is preferred over artemether-lumefantrine for P. vivax due to piperaquine's longer half-life, though both are effective 1

For P. falciparum Malaria

• Primaquine is NOT needed with Riamet for uncomplicated P. falciparum unless the goal is transmission blocking 2, 3
• Primaquine's role in falciparum malaria is limited to gametocytocidal activity (preventing transmission), not radical cure 2
• A single low dose (0.25 mg/kg) can be added to block transmission in elimination settings, but this is optional 3

Critical Safety Requirements Before Primaquine

G6PD Testing is Mandatory

• Test for G6PD deficiency before any primaquine administration to prevent life-threatening hemolysis 1, 4
• Patients with G6PD activity ≥70% can safely receive standard primaquine doses (0.25-0.5 mg/kg/day for 14 days) 5
• Those with intermediate G6PD deficiency (30-70% activity, non-Mediterranean variant) require modified dosing: 0.75 mg base/kg weekly for 8 weeks with close hemolysis monitoring 1, 4
• Mediterranean G6PD variant (B-) carries very high risk of severe hemolysis and primaquine should be avoided or limited to maximum 5 days 4, 6

Contraindications

• Never give primaquine to pregnant or breastfeeding women 1
• Severe G6PD deficiency (<30% activity) is an absolute contraindication 4

Dosing Regimens

Standard Primaquine Protocol

• 15 mg base daily for 14 days remains the WHO-recommended regimen for radical cure 1, 7
• This provides 210 mg total adult dose and reduces relapse risk by 80% compared to no primaquine 1
• Seven-day regimens at 0.5 mg/kg/day (same total dose) show similar efficacy but less evidence 8

Alternative for G6PD-Intermediate Patients

• Weekly primaquine 0.75 mg base/kg (maximum 45 mg) for 8 weeks with weekly monitoring for hemolysis and methemoglobinemia 4
• Tafenoquine 300 mg single dose is an alternative (requires G6PD >70%), but only available in US/Australia 4

Monitoring During Concurrent Therapy

Hematological Surveillance

• Check hemoglobin at baseline, days 2-3, days 5-7, and day 14 5
• Monitor for hemoglobin reduction >25% to <7 g/dL, which occurred in only 0.3-0.5% of patients with normal G6PD receiving standard doses 5
• Weekly methemoglobin monitoring if using modified primaquine regimens 4

Parasitological Follow-up

• Thick blood smear every 12 hours until parasitemia <1%, then every 24 hours until negative 1
• Relapse rates at 6 months: 4-9% without primaquine versus <2% with 14-day primaquine 1, 7

Common Pitfalls to Avoid

• Do not withhold primaquine from G6PD-normal patients due to unfounded safety concerns - the mortality risk is approximately 1 in 621,428 exposures, with most deaths occurring in unscreened G6PD-deficient patients 9
• Do not use shorter primaquine courses (<7 days at standard dose) - five-day regimens show 10-fold higher relapse rates 7
• Do not delay primaquine - it should start concurrently with or immediately after blood-stage treatment, not weeks later 6, 2
• If methemoglobinemia develops, stop primaquine immediately but continue Riamet to complete blood-stage treatment, then consider weekly primaquine once resolved 4