Dosing and uses of Coartem (artemether-lumefantrine)
Adult dosage forms and strengths
artemether/lumefantrine
tablet
- 20mg/120mg
Malaria
35 kg or greater: Administer 24 tablets over 3 days; use a 3-day treatment schedule with total of 6 doses
Day 1: 4 tablets initially and 4 tablets again after 8 hours
Days 2 & 3: 4 tablets BID (morning & evening)
Administration
Take with food
If patient vomits out dose within 1-2 hours, give another dose
Pediatric dosage forms and strengths
artemether/lumefantrine
tablet
- 20mg/120mg
Malaria
5 to <15 kg: Administer 6 tablets over 3 days; 1 tablet initially and again after 8 hours on first day; follow by 1 tablet BID (morning & evening) for the next 2 days
15 to <25 kg: Administer 12 tablets over 3 days; 2 tablets initially and again after 8 hours on first day; follow by 2 tablets BID (morning & evening) for the next 2 days
25 to <35 kg: Administer 18 tablets over 3 days; 3 tablets initially and again after 8 hr on 1st day; follow by 3 tablets BID (morning & evening) for the next 2 days
35 kg or greater: As in adults; administer 24 tablets over 3 days; 4 tablets initially and again after 8 hr on 1st day; follow by 4 tablets BID (morning & evening) for the next 2 days
Administration
Take with food
May crush tablets & mix with small amount of water; follow dose with food or drink
If patient vomits out dose within 1-2 hours, give another dose
Coartem (artemether-lumefantrine) adverse (side) effects
>10%
Abdominal pain (17%)
Anorexia (40%)
Arthralgia (34%)
Asthenia (38%)
Chills (23%)
Dizziness (39%)
Fatigue (17%)
Headache (56%)
Myalgia (32%)
Nausea (26%)
Palpitations (18%)
Pyrexia (25%)
Sleep disorder (22%)
Vomiting (17%)
1-10%
Anemia (4%)
Cough (6%)
Diarrhea (7%)
Hepatomegaly (9%)
Malaise (3%)
Nasopharyngitis (3%)
Pruritus (4%)
Rash (3%)
Splenomegaly (9%)
Vertigo (3%)
Postmarketing Reports
Anaphylaxis
Urticaria
Angioedema
Skin reactions (bullous eruption)
Warnings
Contraindications
Hypersensitivity
Coadministration with strong CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, St. John’s wort) can result in decreased artemether and/or lumefantrine serum concentrations and loss of antimalarial efficacy
Cautions
Not approved for severe/complicated P. falciparum infections
Not approved for prevention
Concurrent CYP3A4 or CYP2D6 inhibitors / inducers
May render hormonal contraceptives ineffective
If patient vomits out drug repeatedly, use alternative treatment
Avoid with conditions that prolong Qt
- Long QT syndrome, history of symptomatic cardiac disease, clinically relevant bradycardia, or severe cardiac disease
- Family history of congenital QT prolongation or sudden death
- Electrolyte imbalance (eg, hypokalemia, hypomagnesemia)
- Coadministration with other drugs that prolong QT interval (eg, class IA antiarrhythmics [quinidine, procainamide, disopyramide], or class III antiarrhythmics [amiodarone, sotalol] antiarrhythmic agents, antipsychotics [pimozide, ziprasidone], antidepressants; certain antibiotics [macrolide, fluoroquinolones], antiretrovirals [eg, ritonavir], cisapride
- CYP3A4 and CYP2D6 inhibitors may increase serum levels by inhibiting metabolism, and therefore risk for QT prolongation
- QT prolongation with other antimalarials; duplicate antimalarials should not be given concomitantly, unless there is no other treatment option, due to limited safety data
- Not for concomitant administration with halofantrine within one month of each other due to potential additive effects on QT interval
- Cautiously use quinine and quinidine for malaria following Coartem due to long half-life of Coartem and potential additive QT prolongation
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if either component enters breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Coartem (artemether-lumefantrine)
Protein Bound: artemether: 95.4% & lumefantrine: 99.7%
Peak Plasma Time: artemether 2 hr; lumefantrine 6-8 hr
Half-Life, Elimination: artemether 2 hr; lumefantrine 3-6 d
Metabolism: by CYP3A4
Metabolites: artemether: dihydroartemisinin (DHA) (active); lumefantrine: desbutyl-lumefantrine
Enzymes Inhibited: lumefantrine: CYP2D6
Enzymes Induced: artemether: CYP3A4
Excretion: urine (animal studies)
Mechanism of action
Artemether and active metabolite (DHA): via endoperoxide
Lumefantrine: unknown; possibly inhibits beta-hematin formation
Both artemether and lumentantrine inhibit nucleic acid and protein synthesis
