PRIMAQUINE PHOSPHATE
Clinical safety rating
avoidOther drugs that cause hemolysis or depress myeloid function can have additive effects Can cause hemolytic anemia in patients with G6PD deficiency.
Primaquine is a 8-aminoquinoline antimalarial agent that disrupts the mitochondrial function of malarial parasites. It is active against hypnozoites of Plasmodium vivax and P. ovale, and gametocytes of P. falciparum. The exact mechanism is thought to involve the generation of reactive oxygen species through redox cycling, leading to parasite death.
| Metabolism | Primaquine is extensively metabolized in the liver, primarily via CYP2C8 and CYP2D6. Major metabolites include carboxyprimaquine and other oxidative products. |
| Excretion | Renal: approximately 1% unchanged; major metabolites (e.g., carboxyprimaquine) are excreted renally. Fecal/biliary: minor route (less than 5%). Total renal elimination of parent drug and metabolites accounts for about 60-70% of a dose. |
| Half-life | Terminal elimination half-life ranges from 4 to 6 hours in healthy adults; may be prolonged in renal impairment. Clinical context: due to short half-life, daily dosing is required; accumulation of active metabolites may contribute to efficacy. |
| Protein binding | Approximately 70% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 2.5-3.5 L/kg; extensive distribution into tissues including liver, lungs, and erythrocytes. |
| Bioavailability | Oral: approximately 75-80% (first-pass metabolism reduces systemic availability; food decreases rate but not extent). |
| Onset of Action | Oral: antimalarial effect begins within 24-48 hours (radical cure of P. vivax/P. ovale hypnozoites requires 14-day course). |
| Duration of Action | Single dose: therapeutic effect lasts approximately 24-48 hours; full course (14 days) needed to eradicate liver hypnozoites. |
| Molecular Weight | 455.34 |
Adults: 30 mg (base) orally once daily for 14 days for radical cure of Plasmodium vivax and P. ovale; 15 mg (base) orally once daily for 14 days for prevention of relapse in mild cases. For prophylaxis: 30 mg (base) orally once daily beginning 1 day before travel, continued daily during travel, and for 7 days after leaving endemic area (alternative to chloroquine). Administer with food.
| Dosage form | TABLET |
| Renal impairment | No specific guidelines; use with caution in renal impairment. For severe renal impairment (CrCl <30 mL/min), consider alternative therapy due to lack of data. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution and monitor for adverse effects; dose adjustment not well defined, but consider reducing dose to 15 mg (base) daily and monitoring G6PD status. |
| Pediatric use | Children: For radical cure of P. vivax or P. ovale: 0.5 mg/kg (base) orally once daily for 14 days (maximum 30 mg). For prophylaxis: 0.5 mg/kg (base) orally once daily (maximum 30 mg) starting 1 day before travel, daily during travel, and 7 days after leaving endemic area. Must test for G6PD deficiency before use. |
| Geriatric use | No specific dose adjustments; use with caution due to age-related decline in hepatic and renal function. Monitor for hemolytic anemia and gastrointestinal effects. Consider lower starting dose (15 mg base daily) and adjust based on tolerability. |
| 1st trimester | Avoid use; potential for hemolytic anemia in G6PD-deficient fetuses. |
| 2nd trimester | Avoid use; risk outweighs benefits unless treating life-threatening malaria. |
| 3rd trimester | Avoid use; near term risk of hemolysis in neonate with G6PD deficiency. |
Clinical note
Other drugs that cause hemolysis or depress myeloid function can have additive effects Can cause hemolytic anemia in patients with G6PD deficiency.
| FDA category | Contraindicated |
| Placental transfer | Primaquine crosses the placenta; extent not well quantified but sufficient to cause fetal hemolysis in G6PD deficiency. |
| Breastfeeding | Primaquine is excreted into breast milk in small amounts. Risk of hemolysis in G6PD-deficient infants; breastfeeding not recommended unless infant G6PD status confirmed normal. |
| Lactation Rating | L4 |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: animal studies show embryotoxicity, but human data limited; avoid unless benefit justifies risk. Second/third trimesters: potential risk of hemolytic anemia in G6PD-deficient fetuses; use only if clearly needed. |
| Fetal Monitoring | Monitor complete blood count (CBC), especially hemoglobin and reticulocyte count. Assess G6PD status before therapy. Monitor for signs of hemolysis, methemoglobinemia (pulse oximetry, co-oximetry if needed). In pregnancy, periodic ultrasound for fetal growth assessment. |
| Fertility Effects | No known adverse effects on fertility in humans based on limited data. Animal studies show no significant reproductive impairment. |
■ FDA Black Box Warning
Primaquine phosphate can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency must be ruled out before starting treatment. Severe hemolysis may occur and can lead to death.
| Common Effects | GI upset |
| Serious Effects |
G6PD deficiencyPregnancyBreastfeeding (unless infant G6PD normal)Concurrent use with quinacrineKnown hypersensitivity to primaquine
| Precautions | Hemolytic anemia in G6PD-deficient patients: Screen for G6PD deficiency prior to use and avoid in such patients unless benefit outweighs risk, Methemoglobinemia: Can occur, especially in patients with NADH-methemoglobin reductase deficiency or other predisposing conditions, Hematologic toxicity: Monitor blood counts; caution in patients with anemia or other blood disorders, Hepatic impairment: Use with caution; may need dose adjustment, Psychiatric effects: Rarely associated with anxiety, confusion, or psychosis |
| Food/Dietary | Grapefruit juice may increase plasma concentrations of primaquine, raising risk of toxicity. Take with food to reduce gastrointestinal irritation. No other significant food interactions known. |
| Clinical Pearls | Primaquine is the only 8-aminoquinoline used for radical cure of Plasmodium vivax and P. ovale hypnozoites. Screen for G6PD deficiency before initiation to prevent hemolytic anemia. Administer with food to reduce gastrointestinal upset. Watch for methemoglobinemia; discontinue if cyanosis or oxygen saturation drops. Avoid in pregnancy and lactation unless benefit outweighs risk. |
| Patient Advice | Take with food or milk to prevent stomach upset. · Complete the full course even if you feel better. · Report dark urine, yellowing of skin/eyes, or unusual tiredness immediately. · Avoid grapefruit juice as it may increase side effects. · Do not use during pregnancy or breastfeeding without consulting your doctor. · Keep out of reach of children and store at room temperature. |
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