Artesunate

Artesunate is a water-soluble artemisinin derivative given intravenously or intramuscularly for severe falciparum malaria, rectally as a pre-referral dose for children, and orally within combination therapy. It clears parasites faster than quinine and lowers mortality in severe malaria. Delayed haemolysis can occur 1 to 3 weeks after treatment.

Class. Antimalarial; artemisinin derivative.

Mechanism. Converted to dihydroartemisinin, which generates free radicals from the endoperoxide bridge after activation by haem iron and damages parasite proteins across all blood stages.

Pharmacokinetics. Rapidly hydrolysed to dihydroartemisinin. Half life of artesunate under 1 hour and of dihydroartemisinin about 1 hour. Eliminated by glucuronidation.

Severe falciparum malaria (adults and children 20 kg or more). 2.4 mg/kg intravenously or intramuscularly at 0, 12 and 24 hours, then once daily until the patient can take oral treatment.

Children under 20 kg. 3 mg/kg in each dose at the same times.

Minimum parenteral treatment. 24 hours (at least 3 doses), then a full 3-day course of an oral artemisinin combination.

Pre-referral (rectal) treatment. Single dose of 10 mg/kg rectally for children under 6 years with suspected severe malaria who cannot take oral treatment, using weight-banded suppositories, then immediate transfer.

Oral artesunate (within combinations). 4 mg/kg once daily for 3 days, for example with amodiaquine, mefloquine or sulfadoxine pyrimethamine.

Loading dose, maintenance dose and titration. Doses are given at 0, 12 and 24 hours. Maximum: 3 mg/kg in each parenteral dose.

Main alternative. Intravenous quinine when artesunate is unavailable.

Contraindications. Hypersensitivity to artesunate or artemisinins.

Serious adverse effects. Post-artesunate delayed haemolysis (haemoglobin fall at 1 to 3 weeks, mostly in hyperparasitaemia), hypersensitivity, neutropenia, raised liver enzymes, and QT prolongation (uncommon).

Common adverse effects. Dizziness, nausea, vomiting, abdominal pain and injection-site pain.

Interactions. Few. Efavirenz and rifampicin lower dihydroartemisinin levels modestly.

Common prescribing errors. Stopping after the parenteral phase without a full oral course, not repeating the haemoglobin check, and giving oral artesunate alone.

Special groups. - Pregnancy: preferred in all trimesters for severe malaria. - Breastfeeding: compatible. - Children: weight-based; 3 mg/kg in each dose under 20 kg. - Older adults: usual dose. - Kidney impairment: no adjustment. - Liver impairment: no adjustment.

Regional points. Severe malaria in children is common in East Africa, and a rectal pre-referral dose can be lifesaving where transfer takes hours; parenteral artesunate is the first-line drug for severe malaria in national policy.

Formulations. Powder for injection 60 mg vial with ampoules of sodium bicarbonate 5% and 0.9% sodium chloride; rectal capsules 50 mg and 200 mg; oral tablets 50 mg (in combinations).

Administration. Dissolve 60 mg in 1 mL of sodium bicarbonate, shake, then add 5 mL of 0.9% sodium chloride for intravenous use (10 mg/mL, give by slow injection over 1 to 2 minutes) or 2 mL for intramuscular use (20 mg/mL, give into the anterior thigh). Use within 1 hour of preparation.

Baseline. Rapid test or microscopy with parasite count, haemoglobin, glucose, creatinine, lactate where available, pregnancy test.

Monitoring. Glucose every 4 to 6 hours; parasite count at 24 and 48 hours; haemoglobin weekly for 4 weeks after discharge.

Stopping thresholds. Stop for anaphylaxis or severe hypersensitivity; switch to oral treatment once the patient can swallow and has had at least 3 parenteral doses.

Referral and escalation. Admission for all severe malaria, and early review for anaemia, acute kidney injury and hyperparasitaemia over 10%.