Primaquine, an 8-aminoquinoline derivative, is a synthetic antimalarial agent. Its chemical formula is (R,S)-N⁴-(6-Methoxy-8-quinolinyl)-1,4-pentanediamine diphosphate. Its molecular formula is C₁₅H₂₁N₃O.2H₃PO₄.

An 8-aminoquinoline, primaquine is structurally similar to the 4-aminoquinolines but possesses markedly different antimalarial activities.

Primaquine is a tissue schizonticidal agent and is active against the preerythrocytic and exoerythrocytic forms of Plasmodium falciparum, P. malariae, P. ovale and P. vivax. Primaquine is also gametocytocidal against plasmodia, especially the gametocytes of P. falciparum. Although primaquine has some activity against the asexual erythrocytic forms of P. vivax, the drug is generally inactive against the erythrocytic forms of plasmodia. Hence a blood schizonticidal agent, preferably chloroquine, is always given in conjunction with primaquine for the treatment of P. ovale or P. vivax malaria.

The exact mechanism of antimalarial activity of primaquine has not been determined, but the drug appears to interfere with the function of plasmodial DNA.

Primaquine may disrupt the parasite's mitochondria and bind to native DNA. The resulting structural changes create a major disruption in the metabolic process. The gametocyte and exoerythrocyte forms are inhibited. Some gametocytes are destroyed while others are rendered incapable of undergoing maturation division in the mosquito gut. By eliminating tissue (exoerythocyte) infection, primaquine prevents development of blood (erythrocytic) forms responsible for relapses in P. vivax malaria.

Primaquine is well absorbed from the GI tract. After oral administration, peak plasma concentrations of primaquine are reached in 1 to 3 hours. Primaquine as compared to other antimalarials, is found in relatively low concentrations in the tissues. Highest concentrations are in the liver, lungs, brain, heart and skeletal muscle.

Primaquine is rapidly metabolized to a carboxylic acid derivative and then to further metabolites which have varying degrees of activity. Approximately 1% is excreted unchanged in the urine.

Primaquine has a plasma half life of 3.7 - 9.6 hours in healthy adults.

Primaquine is recommended for the radical cure of P. vivax malaria, the prevention of relapse in P. vivax malaria or following the termination of chloroquine phosphate suppressive therapy in an area where P. vivax malaria is endemic.

Because primaquine is not generally active against asexual erythrocytic forms of plasmodia, a blood schizonticidal agent, preferably chloroquine, is always given in conjunction with primaquine.

Concomitant administration of quinacrine and primaquine, the acutely ill suffering from systemic disease manifested by tendency to granulocytopenia (e.g. rheumatoid arthritis and lupus eythematosus), concurrent administration of other potentially hemolytic drugs or bone marrow depressants are contraindications to primaquine.

Hemolytic reactions (moderate to severe): May occur in the following groups of people while receiving primaquine: Glucose-6-phosphate dehydrogenase (G-6-PD) deficient patients; individuals with idiosyncratic reactions (manifested by hemolytic anemia, methemoglobinemia or leukopenia); individuals with nicotinamide adenine dinucleotide (NADH) methemoglobin reductase deficiency; or individuals with a family or personal history of favism.

In such cases, the individual should be monitored closely. Discontinue if marked darkening of the urine or sudden decrease in hemoglobin concentration or leukocyte count occurs.

Monitoring: Anemia, methemoglobinemia and leukopenia have occurred following large doses; do not exceed recommended dose. Perform routine blood examinations (particularly blood cell counts and hemoglobin determinations) during therapy.

Primaquine induced hemolysis in patients with G6PD deficiency can be worsened by liver or renal disease, which may delay elimination of the drug.

Quinacrine: May potentiate the toxicity of antimalarial compounds which are structurally related to primaquine. Do not administer primaquine to patients who have recently received quinacrine.

GI : Nausea, vomiting, epigastric distress, abdominal cramps. Adverse GI effects may be lessened by administering primaquine with meals.

Hematologic : Leukopenia, hemolytic anemia in G-6-PD deficient individuals, methemoglobinemia in NADH methemoglobin reductase deficient individuals.

Other adverse effects : Headache, interference with visual accomodation and pruritus have been reported with primaquine. Hypertension and arrhythmias have also been reported rarely.

Patients suffering from an attack of P. vivax malaria or having parasitized red blood cells should receive a course of chloroquine phosphate, which quickly destroys the erythrocytic parasites and terminates the paroxysm.

Radical treatment
Adults : 0.25mg/Kg or 15mg daily for 14 days following standard chloroquine therapy, or if                    glucose- 6-   phosphate dehydrogenase deficiency is known or suspected, 0.75mg/Kg weekly                    for 8 weeks

Children over 1 year - 0.25mg/Kg daily for 14 days after standard chloroquine therapy

Gametocytocidal therapy

Adults and children - 0.5 - 0.75mg/Kg in a single dose.

Symptoms : Abdominal cramps, vomiting, burning, epigastric distress, CNS and cardiovascular disturbances, cyanosis, methemoglobinemia, moderate leukocytosis or leukopenia, anemia. The most striking symptoms are granulocytopenia and acute hemolytic anemia in sensitive persons. Acute hemolysis occurs, but patients recover completely if dosage is discontinued.

Treatment : Symptomatic

Store in cool dry dark place.

Strip of 10 tablets.