Artemether-lumefantrine

Artemether-lumefantrine

• artemether (an artemisinin derivative) is an antimalarial agent used in combination with lumefantrine for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum
  • is administered in combination with lumefantrine for improved efficacy
    
    
  • artemisinin-based combination therapies are highly effective first-line malaria treatments (1)
    • artemether-lumefantrine is the most widely used and the current WHO guidelines, which recommend weight-based dosing regimens for children, were extrapolated from adult clinical studies
      
      
  • artemisinin derivatives allow more parasite clearance than any other anti-malarial drug (parasite numbers can be reduced by a factor of 10^5 per asexual cycle, compared with 10^2-10^3 with other anti-malarial drugs) (2)
    
    
  • combination therapy exerts its effects against the erythrocytic stages of Plasmodium spp. and may be used to treat infections caused by P. falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas
    • artemether works against the erythrocytic stages of P. falciparum via inhibition of nucleic acid and protein synthesis
      • has a rapid onset of action and is rapidly cleared from the body
      • provides rapid symptomatic relief by reducing the number of malarial parasites
      • is administered in combination with lumefantrine for improved efficacy
      • when combined with efficacious anti-malarials with slower elimination rates, such as lumefantrine, shorter courses of treatment (three days) become effective (2)
      • in comparison to artemether, lumefantrine has a much longer half life and is believed to clear residual parasites
        • lumefantrine exposure is crucial to prevent malaria recrudescence, and the day 7 concentration is a significant factor in determining therapeutic response

Reference:

1. Simeon S et al. Optimizing Lumefantrine Dosing for Young Children in High-Malaria-Burden Countries Using Pharmacokinetic-Pharmacodynamic Simulations. Open Forum Infect Dis. 2024 Oct 17;11(11):ofae627.
2. Makanga M, Krudsood S. The clinical efficacy of artemether/lumefantrine (Coartem). Malar J. 2009 Oct 12;8 Suppl 1(Suppl 1):S5. doi: 10.1186/1475-2875-8-S1-S5.