PRIMAQUINE
Clinical safety rating: avoid
Contraindicated (not allowed)
Antimalarial agent that eliminates exoerythrocytic forms (hypnozoites) of Plasmodium vivax and P. ovale; also active against gametocytes. Mechanism involves generation of reactive oxygen species via redox cycling, disrupting parasite mitochondrial function.
| Metabolism | Primaquine is metabolized primarily by CYP1A2 and CYP3A4; also undergoes monoamine oxidase (MAO) metabolism. Metabolites include primaquine carboxy metabolite. |
| Excretion | Primarily renal (60-65% as unchanged drug and metabolites); small amounts in feces (<5%) |
| Half-life | Terminal elimination half-life of approximately 4-7 hours; in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, half-life may be prolonged due to accumulation in erythrocytes |
| Protein binding | Approximately 90-95% bound to plasma proteins, primarily to albumin |
| Volume of Distribution | Apparent volume of distribution (Vd) approximately 2.5-3.5 L/kg, indicating extensive tissue distribution, including high concentrations in erythrocytes and liver, which is relevant for anti-relapse activity |
| Bioavailability | Oral bioavailability is approximately 96%, with peak plasma concentrations reached within 1-3 hours |
| Onset of Action | Oral administration: onset of antimalarial activity within 1-2 hours; for radical cure of Plasmodium vivax, clinical effects seen within 24-48 hours |
| Duration of Action | Antimalarial effect persists for 1-2 days after single dose; for radical cure, multiple doses over 14 days are required to eliminate hepatic hypnozoites |
15 mg (base) orally once daily for 14 days for radical cure of P. vivax and P. ovale; 30 mg (base) orally once daily for 7 days for terminal prophylaxis.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended for renal impairment; use with caution in severe renal impairment due to potential accumulation. |
| Liver impairment | Contraindicated in severe hepatic impairment; use with caution in mild-to-moderate impairment, reduce dose by 50% in Child-Pugh B, avoid in Child-Pugh C. |
| Pediatric use | 0.3 mg/kg (base) orally once daily for 14 days; maximum 15 mg/day. |
| Geriatric use | No specific dose adjustment, but monitor for hemolytic effects due to age-related decline in G6PD activity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other drugs that cause hemolysis or depress myeloid function can have additive effects Can cause hemolytic anemia in patients with G6PD deficiency.
| Breastfeeding | Primaquine is excreted into breast milk in small amounts. M/P ratio not established. Risk of hemolysis in G6PD-deficient infants. Avoid breastfeeding in women with infant G6PD deficiency; use caution. |
| Teratogenic Risk | Primaquine crosses the placenta. In the first trimester, fetal G6PD deficiency increases risk of hemolytic anemia. Second and third trimesters: potential for fetal methemoglobinemia. Risk of hemolysis in G6PD-deficient fetuses; contraindicated in pregnancy except for severe malaria treatment when no alternatives exist. |
■ FDA Black Box Warning
Primaquine can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Screen all patients for G6PD deficiency before prescribing.
| Common Effects | GI upset |
| Serious Effects |
["G6PD deficiency (absolute)","Concurrent use of quinacrine (due to increased toxicity)","Pregnancy (safe alternative not established; risk of hemolysis in G6PD-deficient fetus)","Lactation if infant is G6PD deficient"]
| Precautions | ["Hemolytic anemia in G6PD deficiency – screen and monitor","Methemoglobinemia – monitor for signs especially in infants and G6PD-deficient patients","QT interval prolongation – use with caution with other QT-prolonging drugs","Hematologic toxicity – monitor CBC in prolonged therapy"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal G6PD status before initiation. During therapy: complete blood count, reticulocyte count, methemoglobin levels; fetal monitoring for signs of hemolysis or methemoglobinemia (ultrasound, Doppler). |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment. |