Primaquine

Primaquine is an oral 8-aminoquinoline antimalarial that kills the dormant liver stages of Plasmodium vivax and ovale (radical cure) and the gametocytes of Plasmodium falciparum (reducing transmission). It causes dose-related haemolysis in G6PD deficiency, which is common in East Africa. It is contraindicated in pregnancy.

Class. Antimalarial; 8-aminoquinoline.

Mechanism. Metabolites generate oxidative stress within parasite mitochondria; the liver-stage and gametocytocidal action is unique to this class.

Pharmacokinetics. Well absorbed orally. Half life 4 to 9 hours. Metabolised by CYP2D6 to active metabolites. Reduced CYP2D6 activity can lower efficacy.

Radical cure of P. vivax or P. ovale (adults and children). 0.25 mg/kg daily for 14 days (0.5 mg/kg daily for 14 days in East Asia and Oceania), started with or after blood-stage treatment, after G6PD status is known.

Transmission blocking in falciparum malaria. Single low dose of 0.25 mg/kg (adults 15 mg) with an artemisinin combination, in areas aiming to reduce transmission; not for children under 6 months.

G6PD intermediate or mildly deficient. 0.75 mg/kg once weekly for 8 weeks (specialist care), where tested.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 30 mg daily.

Main alternative. Tafenoquine for P. vivax (single dose, G6PD tested).

Contraindications. Hypersensitivity; pregnancy; infants under 6 months; severe G6PD deficiency; breastfeeding unless the infant is known to have normal G6PD; concurrent use of other haemolytic drugs.

Serious adverse effects. Acute haemolytic anaemia and haemoglobinuria in G6PD deficiency, methaemoglobinaemia, neutropenia (rare), and QT prolongation (rare).

Common adverse effects. Abdominal pain, nausea, vomiting and cyanosis from low-level methaemoglobinaemia.

Interactions. Mepacrine and other haemolytic drugs add risk; CYP2D6 inhibitors may lower activity; avoid dapsone and nitrofurantoin during treatment.

Common prescribing errors. Giving without G6PD status, prescribing in pregnancy, giving to infants under 6 months, and stopping early.

Special groups. - Pregnancy: contraindicated. - Breastfeeding: avoid unless the infant’s G6PD status is normal. - Children: weight-based dosing from 6 months. - Older adults: usual dose. - Kidney impairment: no adjustment. - Liver impairment: caution.

Regional points. G6PD deficiency (A- variant) affects up to 1 in 5 men in parts of East Africa, and quantitative G6PD testing is rarely available, so primaquine for transmission blocking is limited to the single low dose; P. vivax is uncommon except in parts of Ethiopia, Eritrea and Sudan.

Formulations. Tablets 7.5 mg and 15 mg (base).

Administration. With food, once daily at the same time each day.

Baseline. G6PD status, haemoglobin, pregnancy test, drug history.

Monitoring. Haemoglobin and urine colour in the first week; counsel to report dark urine at once.

Stopping thresholds. Stop for dark urine, haemoglobin fall of more than 25 g/L, or haemolytic features.

Referral and escalation. Admission for suspected haemolysis; specialist review for recurrent vivax malaria.