Artemether
Template:Short description Template:Drugbox Artemether is a medication used for the treatment of malaria.<ref name=drugs/><ref name=Esu2019>Template:Cite journal</ref> The injectable form is specifically used for severe malaria rather than quinine.<ref name=Esu2019 /> In adults, it may not be as effective as artesunate.<ref name=Esu2019 /> It is given by injection in a muscle.<ref name=Esu2019 /> It is also available by mouth in combination with lumefantrine, known as artemether/lumefantrine.<ref name=drugs/><ref name="Coartem FDA label" />
Artemether causes relatively few side effects.<ref name=Kov2015/> An irregular heartbeat may rarely occur.<ref name=Kov2015/> While there is evidence that use during pregnancy may be harmful in animals, there is no evidence of concern in humans.<ref name=Kov2015/> The World Health Organization (WHO) therefore recommends its use during pregnancy.<ref name=Kov2015/> It is in the artemisinin class of medication.<ref name=Kov2015>Template:Cite journal</ref>
Artemether has been studied since at least 1981, and has been in medical use since 1987.<ref>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref>
Medical usesEdit
Artemether is an antimalarial drug for uncomplicated malaria caused by P. falciparum (and chloroquine-resistant P. falciparum) or chloroquine-resistant P. vivax parasites.<ref name=drugs/><ref>Template:Cite journal</ref> Artemether can also be used to treat severe malaria.<ref name=Esu2019 />
The World Health Organization (WHO) recommends the treatment of uncomplicated P. falciparum with artemisinin-based combination therapy.<ref>Template:Cite book</ref> Given in combination with lumefantrine, it may be followed by a 14-day regimen of primaquine to prevent relapse of P. vivax or P. ovale malarial parasites and provide a complete cure.<ref>Template:Cite book</ref>
Artemether can also be used in treating and preventing trematode infections of schistosomiasis when used in combination with praziquantel.<ref>Template:Cite journal</ref>
Artemether is rated category C by the FDA based on animal studies where artemisinin derivatives have shown an association with fetal loss and deformity. Some studies, however, do not show evidence of harm.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Side effectsEdit
Possible side effects include cardiac effects such as bradycardia and QT interval prolongation.<ref name=drugs/><ref name="Artemether">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Also, possible central nervous system toxicity has been shown in animal studies.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=Askling2012>Template:Cite journal</ref>
Drug interactionsEdit
Plasma artemether level was found to be lower when the combination product was used with lopinavir/ritonavir.<ref name=Askling2012/> There is also decreased drug exposure associated with concurrent use with efavirenz or nevirapine.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Artemether/lumefantrine should not be used with drugs that inhibit CYP3A4.<ref name=drugs/><ref name=Stover2012>Template:Cite journal</ref>
Hormonal contraceptives may not be as efficacious when used with artemether/lumefantrine.<ref name=Stover2012/>
PharmacologyEdit
Mechanism of actionEdit
A possible mechanism of action is that artemisinin drugs exert their cidal action by inhibiting PfATP6. Since PfATP6 is an enzyme regulating cellular calcium concentration, its malfunctioning will lead to intracellular calcium accumulation, which in turns causes cell death.<ref name=Guo2016>Template:Cite journal</ref>
PharmacokineticsEdit
Absorption of artemether is improved 2- to 3-fold with food. It is highly bound to protein (95.4%). Peak concentrations of artemether are seen 2 hours after administration.<ref name="Coartem FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Artemether is metabolized in the human body to the active metabolite, dihydroartemisinin, primarily by hepatic enzymes CYP3A4/5.<ref name="Coartem FDA label"/> Both the parent drug and active metabolite are eliminated with a half-life of about 2 hours.<ref name="Coartem FDA label"/>
ChemistryEdit
Artemether is a methyl ether derivative of artemisinin, which is a peroxide-containing lactone isolated from the antimalarial plant Artemisia annua. It is also known as dihydroartemisinin methyl ether, but its correct chemical nomenclature is (+)-(3-alpha,5a-beta,6-beta,8a-beta, 9-alpha,12-beta,12aR)-decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin. It is a relatively lipophilic and unstable drug,<ref>Template:Cite journal</ref> which acts by creating reactive free radicals in addition to affecting the membrane transport system of the plasmodium organism.<ref name="Artemether"/>