Tafenoquine

Tafenoquine is an oral 8-aminoquinoline with a very long half life, given as a single dose for radical cure of P. vivax malaria and as weekly prophylaxis for travellers. It needs a quantitative G6PD test before use because it causes dose-related haemolysis. It is not part of routine East African programmes.

Class. Antimalarial; 8-aminoquinoline.

Mechanism. Active against dormant liver stages and blood stages through oxidative damage to the parasite; the exact mechanism is incompletely understood.

Pharmacokinetics. Absorption increased with food. Half life 15 to 19 days. Cleared mostly by non-renal routes; an OCT2 and MATE substrate.

Radical cure of P. vivax (adults and children 16 years and over, or by weight from 2 years). Single dose of 300 mg with food, given on day 1 or 2 with chloroquine.

Paediatric dose (2 years and over, weight-banded). Single dose: 10 to under 20 kg 100 mg; 20 to under 35 kg 150 mg; 35 to under 45 kg 200 mg; 45 kg or more 300 mg.

Prophylaxis (adults). 200 mg daily for 3 days before travel, then 200 mg weekly during travel, and 200 mg once in the week after return.

Loading dose, maintenance dose and titration. For prophylaxis, 200 mg daily for 3 days before travel. Maximum: 300 mg single dose for treatment.

Main alternative. Primaquine.

Contraindications. G6PD activity under 70% of normal (quantitative test needed); pregnancy; breastfeeding unless the infant has normal G6PD; psychotic disorders or recent psychiatric symptoms; hypersensitivity to 8-aminoquinolines.

Serious adverse effects. Haemolytic anaemia, methaemoglobinaemia, psychiatric events (anxiety, insomnia, psychosis, depression), and, rarely, hypersensitivity.

Common adverse effects. Dizziness, nausea, vomiting, headache, and a small rise in methaemoglobin.

Interactions. Dofetilide: contraindicated; metformin and other OCT2 substrates may rise (monitor); avoid other haemolytic drugs.

Common prescribing errors. Prescribing without quantitative G6PD testing, giving in pregnancy, and giving a prophylaxis course longer than 6 months.

Special groups. - Pregnancy: contraindicated; test before women of childbearing age start. - Breastfeeding: avoid unless infant G6PD is normal. - Children: from 2 years for treatment; prophylaxis from 6 years. - Older adults: usual dose. - Kidney impairment: not studied in severe impairment. - Liver impairment: caution.

Regional points. It is not part of East African programmes, so use is limited to travellers and specialist centres.

Formulations. Tablets 100 mg and 150 mg.

Administration. With food, as a single dose for treatment.

Baseline. Quantitative G6PD test (at least 70% activity), haemoglobin, pregnancy test, psychiatric history.

Monitoring. Haemoglobin at day 7 and day 14; mood and sleep during prophylaxis; methaemoglobin if cyanosis.

Stopping thresholds. Stop for haemolysis, haemoglobin fall of more than 25 g/L, psychiatric symptoms or methaemoglobinaemia with symptoms.

Referral and escalation. Admission for haemolysis or psychosis; specialist review for relapse.