Primaquine
Antimalarials
AntimalarialsPregnancy: contraindicated
Not given in pregnancy because it crosses the placenta and can cause haemolysis in a G6PD-deficient fetus; weekly chloroquine prevents relapses until delivery and breastfeeding…
8-aminoquinoline that kills dormant liver forms of P. vivax and P. ovale (radical cure) and blocks transmission; it can cause haemolysis in G6PD deficiency.
Quick facts
- Group
- Antimalarials
- Target
- Not fully known: reactive metabolites act on liver hypnozoites and gametocytes
- Used for
- Radical cure of P · Single low dose with an ACT for P
- Key effects
- Nausea · Rash and itching · Mild anaemia
- Monitor
- G6PD status before a full course · Haemoglobin
- ATC
- P01BA03
No doses: the clinician sets them by the current guideline.
Mechanism of action
An 8-aminoquinoline whose exact target is unknown. Liver enzymes (CYP2D6 above all) turn it into reactive, oxidising intermediates that kill the dormant liver forms (hypnozoites) of P. vivax and P. ovale and sterilise gametocytes of all species, including P. falciparum. It has little effect on the blood stages that cause fever, so it is always paired with a blood schizonticide. The same oxidant metabolites damage red cells that lack G6PD.
- CYP2D6 turns it into reactive oxidant metabolites
- They kill liver hypnozoites of P. vivax and P. ovale
- They sterilise gametocytes, blocking transmission
- Red cells without G6PD suffer oxidant haemolysis
Indications
- Radical cure of P. vivax and P. ovale malaria (14-day course) together with chloroquine or an ACT Malaria →
- Single low dose with an ACT for P. falciparum to reduce transmission (no G6PD test needed for that single dose) Malaria →
- Terminal prophylaxis after long exposure to P. vivax or P. ovale Malaria →
- Pneumocystis pneumonia (alternative use) Pneumocystis pneumonia (PCP) →
Adverse effects
Common
- Nausea, vomiting, heartburn and abdominal cramps (better with food)
- Rash and itching
- Mild anaemia
- Cyanosis from methaemoglobinaemia
Contraindications
- Severe G6PD deficiency (full courses)
- Pregnancy (the fetus may be G6PD deficient)
- Breastfeeding, unless the infant's G6PD status is known to be normal; infants under 6 months
- Severe NADH methaemoglobin reductase deficiency
- Diseases with a tendency to granulocytopenia (active rheumatoid arthritis, lupus) and drugs that cause haemolysis or marrow suppression
Key interactions
- Dihydroartemisinin-piperaquine, artesunate-pyronaridine and chloroquine
- Raise primaquine and carboxyprimaquine levels
- Strong CYP2D6 inhibitors
- Expected to reduce its activation and efficacy (people with poor CYP2D6 metabolism relapse more often)
- Marrow-suppressing drugs
- Additive blood toxicity
- Dapsone and chloroquine
- May add to methaemoglobinaemia
What is monitored
- G6PD status before a full course (WHO recommends it; Colombia's guideline notes it is not ordered routinely there)
- Urine colour and signs of anaemia during treatment
- Haemoglobin, especially with intermediate G6PD activity
- Pregnancy test in women of childbearing age
Administration and safety
- Oral, once daily for the full course, with food to reduce stomach upset.
- Given together with the blood-stage drug (chloroquine or ACT), not instead of it.
- Low-strength tablets exist for children; check the strength dispensed.
- People with G6PD deficiency may receive a weekly regimen under close medical supervision.
Pregnancy and breastfeeding
Not given in pregnancy because it crosses the placenta and can cause haemolysis in a G6PD-deficient fetus; weekly chloroquine prevents relapses until delivery and breastfeeding end.
Nursing care
- Before: check G6PD result if available, pregnancy and breastfeeding status, and history of dark urine with fava beans or other drugs.
- Teach the patient to stop and seek care at once for red, brown or black urine, pallor, shortness of breath or yellow eyes.
- Watch for blue-grey lips (methaemoglobinaemia).
- Explain why the long course matters: without it vivax malaria comes back weeks or months later.
Pharmacokinetics
- Absorption
- Rapid and nearly complete oral absorption; peak within a few hours
- Distribution
- Wide; concentrates in red cells; crosses the placenta
- Metabolism
- Monoamine oxidase to inactive carboxyprimaquine; CYP2D6 (also CYP2C19, CYP3A4) to the active, haemolytic intermediates
- Elimination
- Mainly biliary, also some unchanged in urine
- Half-life
- Short, about 7 hours on average
Test yourself
Think of the answer, then tap the question to see it.
Why is primaquine added to chloroquine in P. vivax malaria?
Chloroquine clears only blood stages; primaquine kills the dormant liver hypnozoites and prevents relapses (radical cure).
What is the most important adverse effect of primaquine?
Acute haemolysis in G6PD deficiency, shown by dark urine, pallor and jaundice; its severity depends on dose and the G6PD variant.
Why is a single low dose given with an ACT in P. falciparum malaria?
It sterilises gametocytes and lowers transmission to mosquitoes; at that dose G6PD testing is not required.
Why can primaquine fail in some patients even when taken correctly?
It needs CYP2D6 to form active metabolites; people with low CYP2D6 activity activate it poorly and relapse more often.
Connections
← Back to the class: Antimalarials
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Primaquine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); Adopción Parcial de Guía de Práctica Clínica Diagnóstico y tratamiento de la malaria, OMS 2022. Guía para Colombia, GPC #67-2022 (Ministerio de Salud y Protección Social (Colombia), 2022); Treatment of Uncomplicated Malaria (Centers for Disease Control and Prevention (CDC), 2026).
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Representative model, for educational purposes only.