Artemether is a medication used for the treatment of

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or deat ...

. The injectable form is specifically used for severe malaria rather than

quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to '' Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal l ...

. In adults, it may not be as effective as

artesunate Artesunate (AS) is a medication used to treat malaria. The intravenous form is preferred to quinine for severe malaria. Often it is used as part of combination therapy, such as artesunate plus mefloquine. It is not used for the prevention of ma ...

. It is given by injection in a muscle. It is also available by mouth in combination with lumefantrine, known as artemether/lumefantrine. Artemether causes relatively few side effects. An

irregular heartbeat Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

may rarely occur. While there is evidence that use during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

may be harmful in animals, there is no evidence of concern in humans. The

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...

(WHO) therefore recommends its use during pregnancy. It is in the

artemisinin Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to ''Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for her di ...

class of medication. Artemether has been studied since at least 1981, and been in medical use since 1987. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Medical uses

Artemether is an antimalarial drug for uncomplicated malaria caused by '' P. falciparum'' (and chloroquine-resistant '' P. falciparum'') or chloroquine-resistant '' P. vivax'' parasites. Artemether can also be used to treat severe malaria. The

(WHO) recommends the treatment of uncomplicated '' P. falciparum'' with

artemisinin-based combination therapy Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...

. Given in combination with lumefantrine, it may be followed by a 14-day regimen of

primaquine Primaquine is a medication used to treat and prevent malaria and to treat ''Pneumocystis'' pneumonia. Specifically it is used for malaria due to '' Plasmodium vivax'' and '' Plasmodium ovale'' along with other medications and for prevention if o ...

to prevent relapse of ''P. vivax'' or ''P. ovale'' malarial parasites and provide a complete cure. Artemether can also be used in treating and preventing trematode infections of

schistosomiasis Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloo ...

when used in combination with

praziquantel Praziquantel (PZQ), sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections in mammals, birds, amphibians, reptiles, and fish. In humans specifically, it is used to treat sc ...

. 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.

Side effects

Possible side effects include cardiac effects such as bradycardia and

QT interval The QT interval is a measurement made on an electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the Q wave to the end of the T wave, and approximates to the time taken ...

prolongation. Also, possible central nervous system toxicity has been shown in animal studies.

Drug interactions

Plasma artemether level was found to be lower when the combination product was used with lopinavir/ritonavir. There is also decreased drug exposure associated with concurrent use with efavirenz or nevirapine. Artemether/lumefantrine should not be used with drugs that inhibit

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

. Hormonal contraceptives may not be as efficacious when used with artemether/lumefantrine.

Pharmacology

Mechanism of action

Artemether is an

derivative and the mechanism of action for artemisinins is. Artemether interact with ferriprotoporphyrin IX (heme) or ferrous ions in the acidic parasite food vacuole, and generates cytotoxic radical species The accepted mode of action of the peroxide containing drug involve its interaction with heme (byproduct of hemoglobin degradation), derived from proteolysis of haemoglobin. This interaction results in the formation of toxic oxygen and carbon centered radicals. One of the proposed mechanisms is that through inhibiting anti-oxidant and metabolic enzymes, artemisinin derivatives inflict oxidative and metabolic stress on the cell. Some pathways affected may concern glutathione and glucose metabolism. As a consequence, lesions and reduced growth of the parasite may result. Another possible mechanism of action suggests that arteristinin drugs exert their cidal action through 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.

Pharmacokinetics

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. Artemether is metabolized in the human body to the active metabolite, dihydroartemisinin, primarily by hepatic enzymes CYP3A4/5. Both the parent drug and active metabolite are eliminated with a half-life of about 2 hours.

Chemistry

Artemether is a

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ...

ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again b ...

derivative of

, which is a peroxide-containing

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the c ...

isolated from the antimalarial plant ''

Artemisia annua ''Artemisia annua'', also known as sweet wormwood, sweet annie, sweet sagewort, annual mugwort or annual wormwood (), is a common type of wormwood native to temperate Asia, but naturalized in many countries including scattered parts of North Am ...

''. 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, which acts by creating reactive free radicals in addition to affecting the membrane transport system of the plasmodium organism.

References

{{portal bar, Medicine Antimalarial agents Organic peroxides Sesquiterpenes Trioxanes Chinese discoveries World Health Organization essential medicines Wikipedia medicine articles ready to translate Heterocyclic compounds with 4 rings Methoxy compounds