Antimalarial (artemisinin-based combination, ACT)
Artemether + lumefantrine is a combined antimalarial medicine (ACT), used to treat uncomplicated Plasmodium falciparum malaria. It is effective and fast, but must be taken with food and is not used in severe malaria.
Also known as: Coartem
Carbamazepine (a CYP3A4 inducer) lowers Artemether and Lumefantrine levels — risk of malaria treatment failure.
Carbamazepine is a potent inducer of CYP3A4, the pathway that metabolises artemether and lumefantrine; coadministration can substantially reduce antimalarial concentrations and compromise malaria cure. In epileptic patients with malaria, prefer an antimalarial less dependent on CYP3A4 (e.g. atovaquone+proguanil) and, if the combination is unavoidable, monitor the clinical and parasitological response closely.
Carbamazepine + artemether+lumefantrine: carbamazepine induces CYP3A4 and lowers antimalarial levels, with risk of therapeutic failure. Avoid the combination.
Enzymatic induction of CYP3A4: faster metabolism of both components with lower systemic exposure.
Clinical and parasitological response to treatment (fever, parasitaemia).
Persistent or recurrent fever, no improvement after 48–72 h.
Consider an alternative antimalarial regimen or dose adjustment and confirm parasitological cure.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Clarithromycin prolongs QT and inhibits CYP3A4, raising Lumefantrine exposure — increased risk of arrhythmias.
Clarithromycin inhibits CYP3A4, the pathway that metabolises artemether and lumefantrine, potentially raising antimalarial concentrations; both drugs prolong the QT interval, so the torsades de pointes risk increases additively. In patients treated for malaria with artemether+lumefantrine, prefer an antibiotic without QT effects (e.g. beta-lactams) if a bacterial infection coexists; if the combination is unavoidable, monitor the ECG and electrolytes.
Artemether+lumefantrine + clarithromycin: clarithromycin raises lumefantrine levels (CYP3A4 inhibition) and both prolong the QT. Monitor ECG or prefer another antibiotic.
CYP3A4 inhibition of Artemether/Lumefantrine metabolism (Clarithromycin) + additive QT prolongation.
ECG (QTc), potassium and clinical signs of arrhythmia.
Palpitations, syncope, chest pain.
Avoid when possible; monitor ECG and signs of toxicity; consider an alternative antibiotic if indicated.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Two QT-prolonging drugs combined — risk of ventricular arrhythmias, higher in at-risk patients.
Both the artemether+lumefantrine combination and ciprofloxacin can prolong the QT interval, and the combination adds up the risk of ventricular arrhythmias, including torsade de pointes. The risk is higher in patients with congenital long QT, hypokalaemia, bradycardia, cardiac disease or taking other QT-prolonging drugs. Whenever possible, avoid the combination; if unavoidable (malaria in a patient needing an antibiotic), monitor the ECG and electrolytes, correct hypokalaemia/hypomagnesaemia and use the shortest possible ciprofloxacin course.
Artemether+lumefantrine + ciprofloxacin: both prolong the QT interval. Avoid or monitor the ECG in at-risk patients.
Additive effect on cardiac repolarisation (potassium channel blockade).
ECG (QTc) and electrolytes if risk factors.
Palpitations, syncope.
Caution in at-risk patients; ECG if vulnerability factors or symptoms.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14c3bc33-201d-492e-9aee-a4d84c813a3d
Increased risk of QT prolongation and neuropsychiatric effects when combined.
Both drugs are antimalarials associated with QT prolongation: the artemether-lumefantrine label states that "some antimalarials (e.g. quinine, quinidine), including artemether-lumefantrine, have been associated with prolongation of the QT interval on the ECG" and recommends using other QT-prolonging drugs with caution; the mefloquine label documents QTc prolongation and advises against drugs that alter cardiac conduction (quinine and quinidine are contraindicated, and halofantrine and ketoconazole because of the potentially fatal QT risk). Combining these antimalarials is not used in practice (they are alternatives to each other), but overlap can occur in patients with therapeutic failure. If combined, monitor the ECG, electrolytes (correct hypokalaemia/hypomagnesaemia) and signs of arrhythmia.
Artemether-lumefantrine + mefloquine: additive QT (antimalarials). Avoid the combination; ECG and electrolytes if unavoidable.
Additive QT prolongation; Mefloquine also adds CNS effects.
ECG and neurological status; watch for neuropsychiatric symptoms.
Anxiety, insomnia, psychosis, seizures, palpitations.
Avoid the association; choose a single antimalarial regimen.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Rifampin (a potent CYP3A4 inducer) markedly reduces Artemether and Lumefantrine levels — high risk of malaria treatment failure.
Artemether and lumefantrine are metabolised by CYP3A4; rifampicin is a potent inducer of this isoenzyme and can reduce lumefantrine exposure by more than 90% (AUC), with loss of antimalarial efficacy and risk of relapse or treatment failure. The approved artemether-lumefantrine label contraindicates co-administration with rifampicin. Whenever possible, another antimalarial or an adjusted therapeutic strategy should be chosen; if the combination is unavoidable, monitor clinical response and parasitaemia closely.
Rifampicin (potent CYP3A4 inducer) drastically reduces artemether and lumefantrine levels — risk of malaria treatment failure. Avoid the combination; if unavoidable, consider an alternative antimalarial.
Enzymatic induction accelerating ACT metabolism, with substantial reductions in Lumefantrine exposure.
Clinical and parasitological response; watch for recurrent malaria.
Persistent or recurrent fever, parasitaemia on smear.
Avoid the combination. If rifampin is essential, use an alternative antimalarial regimen and confirm parasitological cure.
DailyMed/FDA (NIH/NLM) — approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf
Both prolong the QT interval; the combination raises the risk of ventricular arrhythmias (e.g. torsades de pointes), especially with long QT, hypokalaemia or heart disease.
Both amiodarone and lumefantrine prolong the QT interval by blocking potassium channels (IKr). The additive effect increases the risk of torsades de pointes and sudden death, especially in patients with a prolonged baseline QT, hypokalaemia, bradycardia or structural heart disease. Whenever possible, prefer an antimalarial without QT effects (e.g. atovaquone+proguanil). If the combination is unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Artemether+lumefantrine + amiodarone: additive QT prolongation with risk of torsades de pointes. Avoid the combination or monitor the ECG closely.
Additive effect on cardiac repolarisation: Lumefantrine blocks potassium channels (hERG) and Amiodarone prolongs QT and is arrhythmogenic on its own.
ECG with QTc measurement, potassium and magnesium; closer monitoring in patients with risk factors.
Syncope, palpitations, dizziness, seizures.
Avoid whenever possible. If unavoidable, use with caution, correct hypokalaemia/hypomagnesaemia and monitor the ECG.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Additive QT prolongation; the association is usually avoided as it adds no benefit and increases arrhythmic risk.
Both drugs are antimalarials that prolong the QT interval: the artemether-lumefantrine label states that "some antimalarials (e.g. quinine, quinidine), including artemether-lumefantrine, have been associated with prolongation of the QT interval on the ECG" and that "QT prolonging drugs, including quinine and quinidine, should be used cautiously following artemether-lumefantrine"; the quinine label documents consistent, dose-dependent QT prolongation with potentially fatal ventricular arrhythmias, and recommends avoiding other QT-prolonging drugs. In practice, these antimalarial combinations are not used together (quinine is an alternative to artemether-lumefantrine for malaria treatment), but they can overlap in patients with therapeutic failure or severe malaria. If the combination is needed, monitor the ECG, electrolytes (correct hypokalaemia/hypomagnesaemia) and signs of arrhythmia.
Quinine + artemether-lumefantrine: additive QT (both antimalarials prolong the QT). Use cautiously and monitor the ECG if combined.
Both prolong cardiac repolarisation via potassium channel blockade.
ECG (QTc), electrolytes and clinical surveillance for arrhythmia.
Palpitations, syncope, dizziness.
Avoid the combination; preferably use a single regimen (ACT or Quinine, not both).
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0
Alcohol may potentiate central nervous system effects during artemether + lumefantrine treatment.
Limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf
Taking with food (particularly with some fat) increases lumefantrine absorption and is recommended to optimise treatment efficacy.
Take with food, preferably with some fat, to maximise absorption.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf
Artemether and lumefantrine are metabolised in the liver (CYP3A4); in severe liver disease exposure may increase and requires caution.
Use with caution in severe liver disease.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf
Lumefantrine prolongs the QT interval; the arrhythmia risk increases in patients with QT prolongation or with QT-prolonging drugs.
Avoid in known QT prolongation or with QT-prolonging drugs; monitor ECG.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf
Artemether + lumefantrine is recommended by WHO for uncomplicated malaria in pregnancy in the 2nd and 3rd trimesters; in the 1st trimester, use if the benefit justifies it.
Use in the 2nd and 3rd trimesters; in the 1st trimester, consider only if the benefit outweighs the risk.
Excreted into breast milk in small amounts; compatible with breastfeeding under supervision.
Possible CYP3A4 induction by artemisinin derivatives — consider an additional contraceptive method if a hormonal contraceptive is used.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Fixed-dose combination antimalarial (artemether and lumefantrine, 1:6 ratio). Artemether is absorbed with a peak about 2 hours after dosing; lumefantrine, highly lipophilic, has a lag time of up to 2 hours and peaks 6 to 8 hours after. Both are highly bound to serum proteins (95.4% and 99.7%). Associated with concentration-dependent QTcF prolongation for lumefantrine (maximum Δ 7.5 ms).
Artemether is rapidly converted to the active metabolite dihydroartemisinin (DHA); antimalarial activity is attributed to the endoperoxide moiety. Lumefantrine inhibits the formation of β-haematin by complexing with hemin. Both inhibit nucleic acid and protein synthesis.
Artemether: peak about 2 hours after dosing; lumefantrine: onset after a lag time of up to 2 hours and peak 6 to 8 hours. Food increases the relative bioavailability of artemether 2- to 3-fold and of lumefantrine 16-fold — patients should take it with a meal as soon as food can be tolerated.
Artemether is metabolised mainly by CYP3A4/5 to active DHA; lumefantrine is metabolised by CYP3A4 to desbutyl-lumefantrine (exposure below 1%). Lumefantrine inhibits CYP2D6 in vitro. With repeated doses, artemether exposure decreases (induction of the metabolising enzymes), while DHA increases.
Artemether and DHA are cleared with a half-life of about 2 hours; lumefantrine is eliminated more slowly, with a half-life of 3 to 6 days in healthy volunteers and in patients with falciparum malaria.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
