Hydroxychloroquine Antimalarial

Hydroxychloroquine is an oral 4-aminoquinoline used mainly in rheumatic disease but also an effective alternative to chloroquine for sensitive P. vivax, P. ovale and P. malariae, and for weekly prophylaxis in chloroquine-sensitive areas. It is not used for falciparum malaria in East Africa because of resistance. It causes less nausea and ocular toxicity than chloroquine in common use, but retinopathy still limits long courses.

Class. Antimalarial; 4-aminoquinoline.

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

Pharmacokinetics. Absorbed well orally. Half life about 40 days. Metabolised by CYP2D6, CYP3A4 and CYP2C8; large volume of distribution.

Treatment of sensitive P. vivax, P. ovale or P. malariae (adults). Hydroxychloroquine sulfate 800 mg (620 mg base) orally, then 400 mg (310 mg base) at 6 hours, 24 hours and 48 hours (total 2000 mg salt).

Children treatment. 13 mg/kg (salt, maximum 800 mg) first dose, then 6.5 mg/kg (maximum 400 mg) at 6, 24 and 48 hours.

Prophylaxis (sensitive areas). Adults 400 mg salt (310 mg base) once weekly; children 5 mg/kg base once weekly (maximum 310 mg base). Start 1 to 2 weeks before travel and continue 4 weeks after return.

Loading dose, maintenance dose and titration. The first dose is followed by three further doses at 6, 24 and 48 hours. Maximum: 800 mg salt in a single dose.

Main alternative. Chloroquine or an artemisinin combination.

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

Serious adverse effects. Retinopathy with long use, QT prolongation and arrhythmia, hypoglycaemia, severe skin reactions, bone marrow suppression, and haemolysis in G6PD deficiency (rare).

Common adverse effects. Nausea, abdominal cramps, headache and rash.

Interactions. Antacids reduce absorption; QT-prolonging drugs (macrolides, fluoroquinolones, ondansetron) add risk; insulin and sulphonylureas may need adjustment.

Common prescribing errors. Using it for falciparum malaria, confusing salt and base doses, and giving long courses without eye screening.

Special groups. - Pregnancy: used for prophylaxis and for sensitive vivax when needed. - Breastfeeding: compatible. - Children: weight-based; keep out of reach. - Older adults: usual dose. - Kidney impairment: caution in severe impairment. - Liver impairment: caution.

Formulations. Tablets 200 mg (155 mg base) and 400 mg.

Administration. With food or milk.

Baseline. Malaria species, weight, visual symptoms, pregnancy test.

Monitoring. Symptoms and parasite clearance; eye screening after 5 years of continuous use.

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

Referral and escalation. Specialist review for long-term use, retinal symptoms and suspected resistance.