Chloroquine

Chloroquine is an oral 4-aminoquinoline for blood-stage treatment of P. vivax, P. ovale, P. malariae and P. knowlesi where parasites remain sensitive, and for weekly prophylaxis in chloroquine-sensitive areas. Falciparum resistance is now so widespread, including in East Africa, that it is no longer used for falciparum malaria there. It is dangerous in overdose, particularly in children.

Class. Antimalarial; 4-aminoquinoline.

Mechanism. Accumulates in the parasite food vacuole and blocks detoxification of haem into haemozoin, killing the parasite.

Pharmacokinetics. Well absorbed orally. Half life 20 to 60 days. Large volume of distribution. Metabolised by CYP2D6 and CYP3A4; excreted in urine and tissues.

Chloroquine-sensitive P. vivax, P. ovale, P. malariae (adults and children). 10 mg base/kg on day 1, 10 mg base/kg on day 2, and 5 mg base/kg on day 3 (total 25 mg base/kg), orally.

Adult weight-banded alternative. 600 mg base on day 1, 600 mg base on day 2, and 300 mg base on day 3.

Prophylaxis (sensitive areas). 5 mg base/kg once weekly (adult 300 mg base), starting 1 week before travel and continuing 4 weeks after return.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 600 mg base in a single dose.

Main alternative. Artemisinin combination therapy.

Contraindications. Hypersensitivity to 4-aminoquinolines; retinal or visual field disease; porphyria; myasthenia gravis.

Serious adverse effects. Cardiac arrhythmia, QT prolongation and cardiotoxicity in overdose, hypoglycaemia, irreversible retinopathy after long use, seizures, neuropsychiatric effects, and bone marrow suppression (rare).

Common adverse effects. Pruritus (common in people with dark skin), nausea, headache, dizziness and blurred vision.

Interactions. - Antacids and kaolin reduce absorption; separate by at least 4 hours. - Ciclosporin and digoxin levels rise. - Mefloquine and QT-prolonging drugs add risk. - Reduces the effect of some vaccines.

Common prescribing errors. Using it for falciparum malaria in resistant areas, giving it to a child as a dose in tablets rather than by weight, and leaving tablets within reach of children.

Special groups. - Pregnancy: safe for sensitive vivax and for prophylaxis. - Breastfeeding: compatible. - Children: weight-based; fatal in small overdoses. - Older adults: usual dose. - Kidney impairment: reduce the dose in severe impairment. - Liver impairment: caution.

Regional points. Falciparum resistance is widespread in East Africa, so chloroquine is not used for falciparum malaria; for P. vivax in Ethiopia, Eritrea and Sudan, resistance has been reported in some areas.

Formulations. Tablets 150 mg base (250 mg phosphate); syrup 50 mg base/5 mL.

Administration. After food to reduce nausea.

Baseline. Malaria species, weight, pregnancy status, visual symptoms, G6PD if primaquine is planned.

Monitoring. Symptoms and parasite clearance on day 3 and day 28; vision in long-term users.

Stopping thresholds. Stop for arrhythmia, visual field change or severe skin reaction.

Referral and escalation. Admission for overdose, arrhythmia or suspected resistance.