Primaquine

Primaquine is an antimalarial medicine approved to treat vivax malaria at the liver stage — the root cause of relapses. Here is the full set of supported uses from the FDA product evidence:

• Radical cure of vivax malaria: Primaquine Phosphate Tablets eliminate the dormant liver-stage parasites (Plasmodium vivax hypnozoites) that cause the disease to return weeks or months after the initial infection.
• Relapse prevention in vivax malaria: Used concurrently with chloroquine phosphate, which handles the blood-stage infection, while primaquine targets the liver stage.
• After chloroquine suppressive therapy: Primaquine Phosphate Tablets are indicated following the end of chloroquine suppression in people who have been in a vivax-endemic area.

Primaquine is an 8-aminoquinoline — a class of antimalarial drugs that targets parasites hiding in the liver. It is believed to disrupt the energy system (mitochondria) of dormant parasites called hypnozoites and to create reactive molecules that destroy infected liver cells. In humans, its antimalarial action is likely carried out by metabolites formed in the liver by an enzyme called CYP2D6 — which means people with certain genetic variations in CYP2D6 (poor or intermediate metabolizers) may produce fewer active metabolites and could see reduced effectiveness.

Primaquine is also active against gametocytes — the reproductive form of Plasmodium falciparum — though its approved indication in these tablets is specifically for vivax malaria. Resistance to primaquine in Plasmodium species has not been well studied.

Primaquine Phosphate Tablets are taken once daily by mouth for a 14-day course. They can be taken with or without food, but taking them with food may reduce the chance of stomach upset. These tablets are typically given at the same time as a course of chloroquine phosphate, which handles the active blood-stage infection while primaquine targets the hidden liver stage.

• Take every dose at roughly the same time each day.
• Do not stop early, even if you feel better — the full 14 days are needed to clear the liver-stage parasites.
• Follow your prescriber's exact instructions; do not adjust the dose on your own.

The most common side effects of Primaquine Phosphate Tablets involve the stomach and blood:

Hemolytic anemia can be severe or fatal in patients with severe G6PD deficiency. Stop the medication and contact your doctor immediately if you notice dark urine, pale skin, shortness of breath, dizziness, or unusual fatigue.

• Hemolytic anemia risk: The biggest risk with primaquine is red blood cell destruction, especially in people with G6PD deficiency. G6PD testing and a baseline blood count are required before starting. Watch for dark urine, pale skin, fatigue, or shortness of breath — stop the drug and call your doctor right away if these develop.
• Contraindicated in pregnancy: Primaquine can harm a developing baby, including causing life-threatening anemia in a G6PD-deficient fetus. Women of childbearing age need a pregnancy test before starting and must use reliable contraception during treatment and until two menstrual periods have passed after stopping.
• Breastfeeding caution: Do not breastfeed if your infant is G6PD-deficient or their G6PD status is unknown — the infant is at risk for hemolytic anemia from exposure to primaquine in breast milk.
• Heart rhythm effects: Primaquine may interact with other drugs to prolong the QT interval (a change in heart electrical activity that can lead to dangerous arrhythmias). EKG monitoring is recommended if combined with other QT-prolonging medicines.
• Blood monitoring during therapy: Routine blood counts and hemoglobin checks during the 14-day course are strongly advised for all patients — not just those with known G6PD deficiency.

Primaquine Phosphate Tablets interact with several important drug categories — always give your full medication list to your prescriber and pharmacist before starting:

• Quinacrine (mepacrine): Completely contraindicated — greatly increases primaquine's toxicity. Do not take together, and do not start primaquine if you have recently taken quinacrine.
• Hemolytic drugs (medicines that can break down red blood cells): Avoid combining — the combined risk of dangerous anemia is too high.
• Methemoglobinemia-inducing drugs: Avoid combining; if unavoidable, close blood monitoring is required.
• QT-prolonging drugs (heart rhythm medicines and others): Frequent EKG monitoring is needed if these must be used together.
• Strong CYP2D6 inhibitors: These may reduce primaquine's effectiveness by blocking the enzyme that converts it to its active form — consider alternatives or watch closely for signs of relapse.
• MAO-A inhibitors (a class of antidepressants): In people with reduced CYP2D6 activity, combining these raises primaquine blood levels and the risk of side effects — avoid or delay until primaquine treatment is complete.
• CYP1A2 substrate drugs (e.g., duloxetine, theophylline, tizanidine): Primaquine may raise their blood levels; monitor for those drugs' side effects.
• CYP3A4 substrate drugs (e.g., rivaroxaban, calcineurin inhibitors, pimozide): Primaquine may raise their levels; follow specific prescribing guidance for those drugs.
• P-gp substrate drugs (e.g., digoxin, dabigatran): Primaquine may raise their concentrations; close monitoring or dose adjustments for those drugs may be needed.

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• G6PD deficiency: A G6PD test is required before starting. Severe G6PD deficiency is a complete contraindication. Mild to moderate deficiency requires a careful risk-benefit discussion and close monitoring.
• Family or personal history of hemolytic anemia or favism: Tell your doctor — extra caution and monitoring are needed.
• Pregnancy: Primaquine is contraindicated. A pregnancy test is required before starting for all women of reproductive potential.
• Breastfeeding: Do not breastfeed if your infant is G6PD-deficient or if their status is unknown.
• Lupus erythematosus or rheumatoid arthritis: These conditions are a contraindication due to the risk of low white blood cell counts (granulocytopenia).
• Currently taking hemolytic drugs or bone marrow-suppressing drugs: Contraindicated — do not take primaquine alongside these.
• Liver impairment: Moderate liver dysfunction affects how primaquine is processed; no data are available after repeated dosing in patients with liver problems — your prescriber should be aware.
• Kidney impairment: Severe or end-stage kidney disease may increase primaquine peak levels; accumulation of metabolites over repeated dosing is unknown — inform your prescriber.
• Older adults (over 52): There are no pharmacokinetic data in patients over 52 years of age — your prescriber should factor this in.
• Males whose partners may become pregnant: Use a condom during treatment and for 3 months after stopping primaquine.

Taking too much primaquine can cause stomach cramps, vomiting, severe upper-belly pain, headache, insomnia, dangerous changes in heart rhythm (including QT prolongation), bluish skin (from methemoglobinemia — low blood oxygen), and serious red blood cell destruction — especially in people with G6PD deficiency. If you suspect an overdose, seek emergency medical care immediately and consider contacting a poison control center for guidance.

Primaquine targets the dormant liver stages of Plasmodium vivax — called hypnozoites — that persist after the initial infection and are responsible for relapses. By eliminating these liver-stage parasites, as well as blocking the development of the blood-stage forms that cause symptoms, the drug prevents the disease from returning. It is also active against gametocytes of Plasmodium falciparum — the reproductive forms that can be passed to mosquitoes — though this is not the primary approved indication for these tablets.

Primaquine Phosphate Tablets are well absorbed when taken by mouth (bioavailability greater than 70%), with blood levels peaking around 2–3 hours after a dose. Eating a high-fat meal with the tablet modestly increases the amount of drug absorbed. The drug is mostly processed (metabolized) by the liver — primarily through an enzyme called CYP2D6 — and then cleared from the body, with a half-life of about 5–6 hours; about 64% of the drug and its byproducts are eliminated in the urine. People who are CYP2D6 poor or intermediate metabolizers (a genetic variation) break down primaquine more slowly, which can both prolong its half-life and reduce formation of the active metabolites needed for antimalarial effect.

Store at 25° C (77° F); excursions permitted to 15° C – 30° C (59° F – 86° F) Dispense in tight, light-resistant container as defined in the USP/NF.