artesunate
Antimalarial· Brands: Artesun, ArsumaxIMIVPO
Mechanism of action
Artesunate is an artemisinin derivative that acts as a prodrug, rapidly hydrolysed to the active metabolite dihydroartemisinin. The endoperoxide bridge in dihydroartemisinin is cleaved by iron in the parasite, generating free radicals that damage parasite proteins and membranes, leading to parasite death. It is active against the erythrocytic stages of Plasmodium species, including chloroquine-resistant strains.
Pharmacokinetics
Artesunate is rapidly hydrolysed to dihydroartemisinin, the principal active metabolite. Dihydroartemisinin is extensively metabolised via glucuronidation and has a short half-life of about 1 to 2 hours. Artesunate is given intravenously or intramuscularly for severe malaria; oral bioavailability is poor and unpredictable. The drug is highly bound to plasma proteins and is eliminated mainly in the urine, primarily as metabolites.
Indications & dosing
Severe malaria
Give on admission, at 12 hours and at 24 hours, then once daily until oral therapy is tolerated. IM is an alternative if IV access is unavailable.
- adult · IV: 2.4 mg/kg 0,12,24h then daily · Give on admission, at 12 hours and at 24 hours, then once daily until oral therapy is tolerated. IM is an alternative if IV access is unavailable.
Severe malaria
Same regimen as adults; use weight-based dosing. IM is an alternative if IV access is unavailable.
- pediatric · IV: 2.4 mg/kg 0,12,24h then daily · Same regimen as adults; use weight-based dosing. IM is an alternative if IV access is unavailable.
Uncomplicated P. falciparum malaria (in combination therapy)
Give once daily for 3 days, together with a partner drug such as mefloquine to prevent resistance.
- adult · PO: 4 mg/kg once daily · Give once daily for 3 days, together with a partner drug such as mefloquine to prevent resistance.
Contraindications & precautions
- Hypersensitivity to artesunate or other artemisinin derivatives · Do not use in patients with a known allergy to artemisinins.
- First trimester of pregnancy · Use only when severe malaria is present and the benefit outweighs the potential risk to the fetus. Alternatives may be considered in some regions.
- Severe G6PD deficiency · Risk of haemolysis is increased; however, in life-threatening malaria, the drug may still be indicated with close monitoring.
- Monitor for signs of hypersensitivity reactions, including anaphylaxis, during the intravenous infusion.
- Screen for G6PD deficiency prior to treatment where possible; monitor for haemolysis if deficiency is present.
- Perform a baseline and follow-up ECG in patients with risk factors for QT prolongation.
- Complete a full course of an artemisinin-based combination therapy (ACT) after parenteral artesunate to prevent recrudescence.
- Monitor for delayed haemolysis at approximately 2 weeks post-treatment, including full blood count and LDH.
- Do not use artesunate for uncomplicated malaria; use an oral ACT instead.
Adverse effects
- Nausea
- Vomiting
- Headache
- Dizziness
- Injection site pain
- Delayed haemolysis (occurring 1-2 weeks after treatment)serious
- Anaphylaxisserious
- QT interval prolongationserious
Monitoring, pregnancy & toxicity
- Parasite density (blood smear) · Every 12 hours until negative
- Haemoglobin/haematocrit · At baseline and weekly for 4 weeks to detect delayed haemolysis
- Blood glucose · Every 6 hours, especially in pregnant women
- ECG · Baseline and after treatment if clinically indicated
- Pregnancy: Artesunate is the first-line treatment for severe malaria in pregnancy, including in the first trimester. The risk of untreated severe malaria outweighs any potential drug risk.
- Toxicity: Delayed haemolytic anaemia · Monitor haemoglobin weekly for 4 weeks after treatment; blood transfusion if severe.
- Toxicity: Transient QT interval prolongation · Monitor ECG; avoid other QT-prolonging drugs where possible.
- Toxicity: Hypersensitivity reactions (anaphylaxis) · Discontinue and treat with adrenaline if required.
Clinical notes
Artesunate is first-line treatment for severe Plasmodium falciparum malaria, generally given intravenously or intramuscularly. A typical adult dose is 2.4 mg/kg at presentation, repeated at 12 hours and 24 hours, then daily if needed. Once the patient can swallow, oral artemisinin-based combination therapy is used to complete treatment. Artesunate has been shown to be more effective than quinine in reducing mortality. Availability and licensing vary by country, so local and national guidelines should be followed.
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BNF; WHO guidelines; local protocol