primaquine
Antimalarial· Brands: Malirid, NiguaPO
Mechanism of action
Primaquine is a prodrug that is metabolised to an active metabolite which acts on hypnozoites of Plasmodium vivax and P. ovale, preventing relapse. It also has activity against gametocytes of P. falciparum, reducing transmission. The exact mechanism is not fully understood, but it may involve generation of reactive oxygen species causing damage to parasite membranes and mitochondria.
Pharmacokinetics
Primaquine is well absorbed from the gastrointestinal tract after oral administration. It is rapidly metabolised in the liver, with an elimination half-life of about 3 to 6 hours. It is widely distributed into tissues, but only small amounts cross the blood-brain barrier. It is poorly protein bound and is excreted mainly as metabolites in urine.
Indications & dosing
Radical cure (prevention of relapse) of uncomplicated malaria caused by Plasmodium vivax or P. ovale
Give after a schizonticide such as chloroquine. Check G6PD status first. Take with food.
- adult · PO: 15 mg daily · Give after a schizonticide such as chloroquine. Check G6PD status first. Take with food.
Radical cure (prevention of relapse) of malaria caused by Plasmodium vivax or P. ovale
Weight-based dose, maximum 15 mg daily. Check G6PD status before use.
- pediatric · PO: 0.3 mg/kg daily · Weight-based dose, maximum 15 mg daily. Check G6PD status before use.
Treatment of Pneumocystis jirovecii pneumonia (in combination with clindamycin)off-label
Off-label use. Used for mild to moderate PJP in patients who cannot tolerate or fail first-line therapy. Usually given for 21 days with clindamycin. Check G6PD status.
- adult · PO: 30 mg daily · Off-label use. Used for mild to moderate PJP in patients who cannot tolerate or fail first-line therapy. Usually given for 21 days with clindamycin. Check G6PD status.
Contraindications & precautions
- Known hypersensitivity to primaquine
- G6PD deficiency · Risk of severe haemolytic anaemia
- Pregnancy · Potential haemolysis in the fetus; generally avoided
- Severe hepatic impairment · Use with caution; risk of increased exposure
- Concurrent use of drugs that cause haemolysis or methaemoglobinaemia · Additive risk
- Screen for G6PD deficiency before starting treatment
- Monitor for methaemoglobinaemia, especially with higher doses or prolonged use
- Use with caution in patients with renal or hepatic impairment
- Avoid concurrent use of other drugs associated with haemolysis or methaemoglobinaemia
- Advise patients to report symptoms such as dark urine, jaundice, or breathlessness
Adverse effects
- Haemolytic anaemia (risk increased in G6PD deficiency)serious
- Methaemoglobinaemiaserious
- Nausea
- Vomiting
- Abdominal cramps
- Headache
- Leucopeniaserious
- Rash
- Pruritus
Monitoring, pregnancy & toxicity
- G6PD enzyme status · Before treatment initiation
- Complete blood count (haemoglobin, haematocrit) · At baseline and periodically during treatment
- Methaemoglobin levels · If signs or symptoms of methaemoglobinaemia develop
- Signs of haemolysis (dark urine, jaundice, anaemia) · During treatment; especially in G6PD deficiency or high doses
- Pregnancy: Contraindicated in pregnancy: primaquine can cause haemolysis in the fetus due to G6PD deficiency, and risk outweighs benefit. If treatment is essential, alternative antimalarials should be used. Consider deferring treatment until after delivery.
- Toxicity: Haemolytic anaemia (especially in G6PD deficiency) · Discontinue primaquine immediately; provide supportive care with fluids, blood transfusion if severe; monitor haemoglobin and renal function.
- Toxicity: Methaemoglobinaemia · Discontinue; consider methylene blue (1-2 mg/kg IV) if methaemoglobin > 20% or severe symptoms; monitor pulse oximetry.
- Toxicity: Gastrointestinal effects (nausea, abdominal pain) · Administer with food; consider dose reduction if severe; manage symptomatically.
Clinical notes
Primaquine is used for radical cure of P. vivax and P. ovale malaria, usually in combination with a schizonticide. It is also used for gametocyte killing in P. falciparum malaria. It should be given with food to reduce gastrointestinal side effects. It is contraindicated in patients with G6PD deficiency due to risk of haemolysis, and in pregnancy and lactation. Doses must be adjusted in mild G6PD deficiency, but it is generally avoided. Caution is needed in liver or renal disease.
Log in to read the full primaquine monograph
A free account unlocks the complete drug reference, the interaction checker, prescription practice and every other learning tool.
BNF; local formulary