Artemether and Lumefantrine

Mechanism of action
In the United States, these drugs are not marketed individually,
but only together as a combination product for treatment
of acute, uncomplicated malaria infections caused by Plasmodium falciparum. Both
drugs are active against erythrocytic
stages of the infection. Artemether and its major metabolite
are rapid schizonticides (selectively destroying the
schizont of a sporozoan parasite), with activity attributed to
the endoperoxide component common to each substance.
Artemether inhibits an essential calcium adenosine triphosphatase.
The exact mechanism of lumefantrine is unknown,
but it may inhibit b-hematin formation by complexing with
hemin. Both artemether and lumefantrine inhibit nucleic acid
and protein synthesis.
Pharmacokinetics
Food, especially a high-fat meal, increases absorption of both
drugs considerably. Taking the drugs with meals is therefore
important to achieving adequate antimalarial efficacy. When
the drugs are used soon after mefloquine, plasma levels of
lumefantrine are decreased; this is thought to be secondary
to reduced absorption resulting from a mefloquine-induced
decrease in bile production. In this situation, consumption
of food with artemether/lumefantrine becomes even more
important.
Adverse effects
The most important concern with artemether/lumefantrine is
prolongation of the QT interval on electrocardiograms. Both
drugs are metabolized primarily by CYP3A4; therefore the
malarial treatment must be used with caution in individuals
taking CYP3A4 inducers or inhibitors simultaneously