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INDICATIONS

• Not currently FDA approved.

• Falciparum malaria, uncomplicated disease in geographic areas of known chloroquine, quinine, or multidrug resistance.
• No data in complicated falciparum malaria
• Vivax malaria: Limited efficacy observed in one Thai study: rapid parasite clearance observed with 4-dose regimen, relapse was common, suggesting minimal activity against the hypnozoite stage of P. vivax (Karbwang et al, 2000).

USUAL ADULT DOSING

• Fixed-dose 20mg artemether/120mg lumefantrine tablet formulation: 4-dose regimen over 48 hours is now considered inferior; 6-dose regimen over 3 or 5 days is superior and recommended (van Vugt et al, 1999).
• Uncomplicated Falciparum malaria; adults (>35 kg): 6-dose regimen over 3 days (4 tablets/dose at 0, 8, 24, 36, 48, and 60 hours)
• Uncomplicated Falciparum malaria; Adults (>35 kg): 6-dose regimen over 5 days (4 tablets/dose at 0, 8, 24, 48, 72, and 96 hours)
• Weight-based dosing: artemether-lumefantrine 1 tab stat, then 8 hours later, followed by 1 tab bid x 2 days (total course=6 tabs for 10kg to <15kg); Artemether-lumefantrine 2 tab stat, then 8 hours later, followed by 2 tab bid x 2 days (total course=12 tabs for 15 kg to <25kg); Artemether-lumefantrine 3 tab stat, then 8 hours later, followed by 3 tab bid x 2 days (total course=18 tabs for 25 kg to <35kg); Artemether-lumefantrine 4 tab stat, then 8 hours later, followed by 4 tab bid x 2 days (total course=24 tabs for 35kg to <65kg); >65kg limited experience, but consider Artemether-lumefantrine 4 tab stat, then 8 hours later, followed by 4 tab bid x 2 days with close monitoring
• Should be administered with food containing at least 1.3 g of fat.

RENAL DOSING

ADVERSE DRUG REACTIONS

• Generally well tolerated.

• Rash, pruritis
• Nausea and vomiting (generally within 1 hour of 1st dose), abdominal pain, anorexia, and diarrhea
•  Anemia 
• Myalgias
• Dizziness, headache, asthenia, insomnia
• Cough

• Hemolytic anemia
• Increased QTc interval, modest ST-elevations
• Nystagmus, abnormal gait, paresthesias, tremor

DRUG INTERACTIONS

• Aurothioglucose: Increased risk of blood dyscrasias. Avoid aurothioglucose co-administration.
• Droperidol: may increase risk of QTc prolongation. Avoid droperidol co-administration.
• Manufacturer recommends against the co-administration of artemether/lumefantrine with the following drugs: grapefruit juice; antiarrhythmics, such as amiodarone, disopyramide, flecainide, procainamide and quinidine; antibacterials, such as macrolides and quinolones; all antidepressants; antifungals such as imidazoles and triazoles; terfenadine; other antimalarials; all antipsychotic drugs; and beta blockers, such as metoprolol and sotalol. However, there is no evidence that co-administration with these drugs would be harmful. (WHO guidelines for the treatment of malaria. 2006.)
• Rifampicin, EFV, and NVP may decrease artemether and lumefantrine serum concentrations. Monitor closely for anti-malarial activity with co-administration.
• HIV-protease inhibitors may increase artemether and lumefantrine serum concentrations. Consider EKG monitoring for QTc prolongation.

SPECTRUM

• Plasmodium falciparum (Chloroquine-resistant)

PHARMACOLOGY

Pharmacology

COMMENTS

• Artemisinin-based combination therapy (ACT) is currently the WHO recommended treatment of choice for the treatment of uncomplicated falciparum malaria: based on the level of resistance, in Africa, artemether-lumefantrine and artesunate + amodiaquine are the ACTs of choice; Amodiaquine + sulfadoxine-pyrimethamine may be considered as an interim option in situations where ACTs cannot be made available. Fixed artemether/lumefantrine is not indicated in the treatment of complicated falciparum malaria or Plasmodium vivax malaria.

REFERENCES