Antimalarial (artemisinin-based combination, ACT)
Artesunate + amodiaquine is a combination medicine used to treat uncomplicated Plasmodium falciparum malaria. It is taken orally for 3 days, with doses adjusted by weight. Completing the full course is essential to cure the infection and prevent resistance.
Also known as: Coarsucam
Clarithromycin prolongs QT and inhibits CYP3A4 (involved in Amodiaquine metabolism) — risk of arrhythmias and toxicity.
Amodiaquine is partly metabolised by CYP3A4; clarithromycin inhibits this enzyme and can raise its concentrations, increasing the risk of hepatotoxicity and QT prolongation (both drugs prolong the QT interval). Prefer an alternative antibiotic during artesunate+amodiaquine antimalarial treatment and, if the combination is unavoidable, monitor the ECG, transaminases and electrolytes.
Artesunate+amodiaquine + clarithromycin: clarithromycin raises amodiaquine levels (CYP3A4 inhibition) and both prolong the QT. Avoid if possible.
Additive QT prolongation + enzymatic inhibition that may raise Amodiaquine levels.
ECG (QTc) and signs of toxicity.
Palpitations, jaundice (amodiaquine hepatotoxicity).
Avoid when possible; monitor ECG; consider an alternative antibiotic.
WHO — WHO Guidelines for malaria: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria ; DailyMed/FDA (NIH/NLM) — approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Carbamazepine (a CYP2C8/3A4 inducer) accelerates Amodiaquine metabolism — risk of subtherapeutic levels and treatment failure.
Carbamazepine induces the monooxygenases (including CYP3A4) involved in the metabolism of artesunate (and its active metabolite dihydroartemisinin) and amodiaquine; antimalarial levels can fall below the therapeutic threshold and compromise response. Prefer an alternative antimalarial in patients on carbamazepine and, if the combination is unavoidable, monitor the clinical and parasitological response.
Carbamazepine + artesunate+amodiaquine: carbamazepine induces antimalarial metabolism, with risk of subtherapeutic levels and failure. Avoid if possible.
Enzymatic induction reducing exposure to Amodiaquine (the ACT component).
Clinical and parasitological response to treatment.
Persistent or recurrent fever, no improvement after 48–72 h.
Consider an alternative ACT and confirm parasitological cure.
WHO — WHO Guidelines for malaria: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria ; DailyMed/FDA (NIH/NLM) — approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Amiodarone adds to Amodiaquine's QT-prolonging effect — risk of ventricular arrhythmias.
Amodiaquine blocks the IKr channel and prolongs the QT interval; combined with amiodarone (which also prolongs QT and inhibits CYP3A4, potentially raising amodiaquine levels), the risk of ventricular arrhythmias, including torsades de pointes, increases additively. In patients on chronic amiodarone, prefer an antimalarial without QT effects. If the combination is unavoidable, monitor the ECG and electrolytes and correct hypokalaemia.
Artesunate+amodiaquine + amiodarone: additive QT prolongation (amodiaquine). Avoid, or monitor ECG if unavoidable.
Additive prolongation of cardiac repolarisation.
ECG (QTc), potassium and magnesium.
Palpitations, syncope.
Prefer to avoid; if unavoidable, monitor ECG and electrolytes.
WHO — WHO Guidelines for malaria: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria ; DailyMed/FDA (NIH/NLM) — approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Alcohol may worsen amodiaquine gastrointestinal effects and hepatotoxicity; limit intake.
Limit or avoid alcohol intake during treatment.
WHO — Malaria guidelines (artesunate + amodiaquine, Coarsucam): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
Taking with food may reduce amodiaquine-related nausea; absorption is not relevantly affected.
Take with food if nausea occurs.
WHO — Malaria guidelines (artesunate + amodiaquine, Coarsucam): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
Amodiaquine is hepatotoxic (including severe hepatitis); use with caution in patients with liver disease.
Monitor liver function; stop with hepatitis symptoms.
WHO — Malaria guidelines (artesunate + amodiaquine, Coarsucam): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
Amodiaquine prolongs the QT interval; the risk increases in patients with QT prolongation or with QT-prolonging drugs.
Monitor ECG in at-risk patients; avoid with QT-prolonging drugs.
WHO — Malaria guidelines (artesunate + amodiaquine, Coarsucam): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
WHO does not recommend artesunate + amodiaquine in the 1st trimester; in the 2nd and 3rd trimesters it may be used if the benefit justifies it.
Avoid in the 1st trimester; consider only if no alternative exists.
Excreted into breast milk in small amounts; compatible with breastfeeding under supervision.
No specific additional contraception.
WHO — Malaria guidelines (artesunate + amodiaquine, Coarsucam): https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Fixed-dose artemisinin-based combination therapy (ACT) with dual antimalarial action: artesunate (prodrug) rapidly clears P. falciparum parasitaemia, and amodiaquine, with longer action, clears the remaining parasites. Efficacy in uncomplicated malaria is established in clinical trials; most adverse reactions resemble the symptoms of the malaria attack itself.
Artesunate is a prodrug rapidly converted to dihydroartemisinin (DHA), which contains the endoperoxide ring responsible for activity: peroxide cleavage by iron ions from parasite haem generates free radicals that damage parasite proteins and membranes. Amodiaquine (4-aminoquinoline) accumulates in the parasite digestive vacuole and inhibits haemozoin (malaria pigment) polymerisation, like chloroquine, with activity against chloroquine-resistant strains.
Artesunate is rapidly absorbed (Tmax ~0.38 hours; Cmax ~185 ng/mL after a single combined dose) and absorption is rapid for both drugs. A high-fat meal decreases artesunate Cmax and AUC (66% and 13%) but increases those of amodiaquine (23% and 58%). Amodiaquine has unknown absolute bioavailability; desethylamodiaquine concentrates 4–6 times more in whole blood than in plasma. Artesunate is minimally protein bound.
Artesunate is extensively hydrolysed by plasma esterases (and possibly CYP2A6) to DHA, which is then further metabolised by glucuronidation before excretion. Amodiaquine is extensively metabolised in the liver by CYP2C8 to desethylamodiaquine, the main active metabolite, with a very long half-life; only ~2% is excreted unchanged in urine.
Artesunate has a very short half-life (~3–29 minutes; DHA ~40–95 minutes). Desethylamodiaquine, the active metabolite of amodiaquine, is eliminated with a terminal half-life of 9–18 days, providing the prolonged action of the combination therapy; amodiaquine volume of distribution is 20–40 L/kg.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
