artemether/lumefantrine
antimalarial combination· Brands: Coartem, Riamet, LonartPO
Mechanism of action
Artemether is a lipid-soluble artemisinin derivative that is rapidly absorbed and converted to the active metabolite dihydroartemisinin. It acts by generating free radicals that damage parasite proteins, leading to parasite death. Lumefantrine is a synthetic antimalarial that interferes with the parasite's heme detoxification process, causing toxic accumulation. The two drugs have synergistic activity against the erythrocytic stages of Plasmodium falciparum, with artemether providing rapid clearance of parasites and lumefantrine providing prolonged action to prevent recrudescence.
Pharmacokinetics
Artemether is rapidly absorbed, reaching peak plasma concentrations within 2 to 3 hours, and is extensively metabolized by CYP3A4 to the active metabolite dihydroartemisinin. It has a short elimination half-life of about 1 to 2 hours. Lumefantrine is slowly absorbed, with peak levels at 4 to 8 hours, and its absorption is significantly enhanced by fatty food. It is highly protein bound (>99%), metabolized by CYP3A4, and has a long terminal half-life of approximately 2 to 3 days, allowing twice-daily dosing and a 3-day regimen. Both drugs are eliminated mainly via bile and faeces.
Indications & dosing
Treatment of acute uncomplicated Plasmodium falciparum malaria
For weight ≥35 kg. Each tablet contains artemether 20 mg and lumefantrine 120 mg. Take with food or drink to enhance absorption.
- adult · PO: 4 tablet 0,8,24,36,48,60h · For weight ≥35 kg. Each tablet contains artemether 20 mg and lumefantrine 120 mg. Take with food or drink to enhance absorption.
Treatment of acute uncomplicated Plasmodium falciparum malaria
For children weighing 5 to <15 kg. Each tablet contains artemether 20 mg and lumefantrine 120 mg. Tablets can be crushed and mixed with food.
- pediatric · PO: 1 tablet 0,8,24,36,48,60h · For children weighing 5 to <15 kg. Each tablet contains artemether 20 mg and lumefantrine 120 mg. Tablets can be crushed and mixed with food.
Treatment of acute uncomplicated Plasmodium falciparum malaria
For children weighing 15 to <25 kg. Each tablet contains artemether 20 mg and lumefantrine 120 mg.
- pediatric · PO: 2 tablet 0,8,24,36,48,60h · For children weighing 15 to <25 kg. Each tablet contains artemether 20 mg and lumefantrine 120 mg.
Treatment of acute uncomplicated Plasmodium falciparum malaria
For children weighing 25 to <35 kg. Each tablet contains artemether 20 mg and lumefantrine 120 mg.
- pediatric · PO: 3 tablet 0,8,24,36,48,60h · For children weighing 25 to <35 kg. Each tablet contains artemether 20 mg and lumefantrine 120 mg.
Contraindications & precautions
- Hypersensitivity to artemether, lumefantrine, or any excipient of the formulation · Rare but possible.
- Severe malaria (e.g., cerebral malaria) · Requires parenteral artesunate or alternative, not oral therapy.
- Pregnancy (first trimester) · Use only if benefit outweighs risk; consider quinine.
- Known QT interval prolongation or use of other drugs that prolong QT interval · Lumefantrine can prolong QT; avoid with halofantrine, etc.
- Take with a fatty meal or milk to improve absorption of lumefantrine.
- Correct electrolyte disturbances (hypokalaemia, hypomagnesaemia) before starting therapy.
- Caution in patients with hepatic impairment, as artemether and lumefantrine are metabolised via CYP3A4.
- Avoid concurrent use of drugs that induce or inhibit CYP3A4, as they may affect plasma concentrations.
- Use with caution in patients with a history of serious adverse drug reactions to antimalarials.
- If a dose is vomited within 30 minutes, the dose should be repeated.
Adverse effects
- Headache
- Dizziness
- Nausea
- Vomiting
- Diarrhoea
- QT interval prolongationserious
- Severe cutaneous reactions (e.g., Stevens-Johnson syndrome)serious
Renal & hepatic adjustment
- Hepatic impairment (mild): No dose adjustment required.
- Hepatic impairment (moderate): No dose adjustment required, but monitor for adverse effects.
- Hepatic impairment (severe): Use with caution; limited data. Consider alternative antimalarial if feasible.
Monitoring, pregnancy & toxicity
- Parasite clearance · Monitor parasite density and clinical response at 24, 48 and 72 hours
- ECG · Baseline ECG if at risk of QT prolongation; monitor QTc during treatment
- Full blood count · At baseline and if signs of haematological toxicity
- Liver function tests · At baseline and if hepatic toxicity is suspected
- Pregnancy: Recommended for the treatment of uncomplicated P. falciparum malaria in the second and third trimesters. In the first trimester, use only if quinine plus clindamycin is not available or contraindicated.
- Toxicity: QT interval prolongation and risk of ventricular arrhythmias · Monitor ECG, correct electrolyte imbalances, discontinue if QTc > 500 ms or significant prolongation occurs.
- Toxicity: Gastrointestinal disturbances (nausea, vomiting, diarrhoea) · Supportive care, ensure hydration, consider antiemetic if severe.
- Toxicity: Hypersensitivity reactions (skin rash, pruritus, angioedema) · Discontinue treatment, use antihistamines and corticosteroids as appropriate.
- Toxicity: Neurological symptoms (headache, dizziness, ataxia) · Symptomatic treatment; if severe, discontinue and evaluate.
Clinical notes
Indicated for the treatment of uncomplicated Plasmodium falciparum malaria. Administer orally with a fatty meal, as this increases lumefantrine absorption. The standard adult regimen is 4 tablets at 0, 8, 24, 36, 48, and 60 hours. Not recommended for severe malaria or in children weighing less than 5 kg. Avoid in pregnancy, especially the first trimester, unless no alternative is available. Caution in QT prolongation, cardiac disease, and with drugs that affect CYP3A4. Common adverse effects include headache, dizziness, nausea, and abdominal pain. Always follow national treatment guidelines and local resistance patterns.
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BNF; WHO malaria treatment guidelines; local formulary