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| tradename = many<ref>{{cite web|title=Artemether - Drugs.com|url=https://www.drugs.com/international/artemether.html|website=www.drugs.com|accessdate=7 December 2016}}</ref>
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| Drugs.com = {{drugs.com|international|artemether}}
| Drugs.com = {{drugs.com|international|artemether}}
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| legal_status =
| routes_of_administration = by mouth
| routes_of_administration = intramuscular<ref name=Es2014/>


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'''Artemether''' is a medication used for the treatment of [[malaria]]. Specifically it is given for multiple drug-resistant strains of ''[[Plasmodium falciparum]]''. It is given by [[intramuscular|injection in a muscle]].<ref>{{cite book|last1=Baker|first1=J. R.|last2=Baker|first2=John Robin|last3=Muller|first3=R.|last4=Rollinson|first4=D.|title=Advances in Parasitology|date=2001|publisher=Greenwood Publishing Group|isbn=9780120317509|page=205|url=https://books.google.com/books?id=Iaf--6vvbkwC&pg=PA205|language=en}}</ref>
'''Artemether''' is a medication used for the treatment of [[malaria]].<!-- <ref name=Es2014/> --> Specifically it is used for severe malaria rather than [[quinine]].<!-- <ref name=Es2014/> --> It may not be as effective as [[artesunate]].<!-- <ref name=Es2014/> --> It is given by [[intramuscular|injection in a muscle]].<ref name=Es2014>{{cite journal|last1=Esu|first1=E|last2=Effa|first2=EE|last3=Opie|first3=ON|last4=Uwaoma|first4=A|last5=Meremikwu|first5=MM|title=Artemether for severe malaria.|journal=The Cochrane database of systematic reviews|date=11 September 2014|issue=9|pages=CD010678|pmid=25209020}}</ref>


<!-- Side effects and mechanism -->
<!-- Side effects and mechanism -->
It is in the [[artemisinin]] class of medication.<ref name=Kov2015>{{cite journal|last1=Kovacs|first1=SD|last2=Rijken|first2=MJ|last3=Stergachis|first3=A|title=Treating severe malaria in pregnancy: a review of the evidence.|journal=Drug safety|date=February 2015|volume=38|issue=2|pages=165-81|pmid=25556421}}</ref>
Chemically, it is a [[semisynthesis|semi-synthetic]] [[derivative (chemistry)|derivative]] of [[artemisinin]].


<!-- History, society and culture -->
<!-- History, society and culture -->
It is on the [[World Health Organization's List of Essential Medicines]], the most important medications needed in a basic [[health system]].<ref>{{cite web|title=WHO Model List of EssentialMedicines|url=http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|work=World Health Organization|accessdate=22 April 2014|date=October 2013}}</ref> It is available in combination with [[lumefantrine]], known as [[artemether/lumefantrine]], which is available as a [[generic medication]].
It is on the [[World Health Organization's List of Essential Medicines]], the most important medications needed in a basic [[health system]].<ref>{{cite web|title=WHO Model List of EssentialMedicines|url=http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1|work=World Health Organization|accessdate=22 April 2014|date=October 2013}}</ref> It is available in combination with [[lumefantrine]], known as [[artemether/lumefantrine]], which is available as a [[generic medication]]. The wholesale cost in the [[developing world]] per dose is <ref>{{cite web|title=Name|url=http://erc.msh.org/dmpguide/index.cfm?search_cat=yes&display=yes&module=dmp&language=english&year=2014|website=International Drug Price Indicator Guide|accessdate=January 2016}}</ref>


==Medical uses==
==Medical uses==

Revision as of 14:01, 7 December 2016

Artemether
Clinical data
Trade namesmany[1]
AHFS/Drugs.comInternational Drug Names
Routes of
administration		intramuscular[2]
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
Identifiers
  • (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-methoxy-3,6,9-trimethyldecahydro-12H-3,12-epoxy[1,2]dioxepino[4,3-i]-2-benzopyran
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.189.847 Edit this at Wikidata
Chemical and physical data
FormulaC16H26O5
Molar mass298.374 g/mol g·mol−1
3D model (JSmol)
  • C[C@@H]1CC[C@@H]3C42OO[C@](C)(CC[C@@H]12)O[C@H]4O[C@H](OC)[C@@H]3C
  • InChI=1S/C16H26O5/c1-9-5-6-12-10(2)13(17-4)18-14-16(12)11(9)7-8-15(3,19-14)20-21-16/h9-14H,5-8H2,1-4H3/t9-,10-,11+,12+,13+,14-,15-,16-/m1/s1 checkY
  • Key:SXYIRMFQILZOAM-HVNFFKDJSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Artemether is a medication used for the treatment of malaria. Specifically it is used for severe malaria rather than quinine. It may not be as effective as artesunate. It is given by injection in a muscle.[2]

It is in the artemisinin class of medication.[3]

It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[4] It is available in combination with lumefantrine, known as artemether/lumefantrine, which is available as a generic medication. The wholesale cost in the developing world per dose is [5]

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.[6] Artemether can also be used to treat severe malaria.[7]

The World Health Organization recommends the treatment of uncomplicated P. falciparum with artemisinin-based combination therapy.[8] 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.[9]

Artemether can also be used in treating and preventing trematode infections of schistosomiasis when used in combination with praziquantel.[10]

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.[11][12]

Side effects

Possible side effects include cardiac effects such as bradycardia and QT interval prolongation.[13] Also, possible central nervous system toxicity has been shown in animal studies.[14][15]

Drug interactions

Plasma artemether level was found to be lower when the combination product was used with lopinavir/ritonavir.[15] There is also decreased drug exposure associated with concurrent use with efavirenz or nevirapine.[16][17]

Artemether/lumefantrine should not be used with drugs that inhibit CYP3A4.[18]

Hormonal contraceptives may not be as efficacious when used with artemether/lumefantrine.[18]

Pharmacology

Mechanism of action

Artemether is an artemisinin derivative and the mechanism of action for artemisinins is unknown.[19][20]

One of the proposed mechanisms is that through inhibiting anti-oxidant and metabolic enzymes, artemistinin 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.[19]

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.[20]

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.[21]

Artemether is metabolized in the human body to the active metabolite, dihydroartemisinin, primarily by hepatic enzymes CYP3A4/5.[21] Both the parent drug and active metabolite are eliminated with a half-life of about 2 hours.[21]

Chemistry

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,[22] which acts by creating reactive free radicals in addition to affecting the membrane transport system of the plasmodium organism.[13]

References

  1. ^ "Artemether - Drugs.com". www.drugs.com. Retrieved 7 December 2016.
  2. ^ a b Esu, E; Effa, EE; Opie, ON; Uwaoma, A; Meremikwu, MM (11 September 2014). "Artemether for severe malaria". The Cochrane database of systematic reviews (9): CD010678. PMID 25209020.
  3. ^ Kovacs, SD; Rijken, MJ; Stergachis, A (February 2015). "Treating severe malaria in pregnancy: a review of the evidence". Drug safety. 38 (2): 165–81. PMID 25556421.
  4. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
  5. ^ "Name". International Drug Price Indicator Guide. Retrieved January 2016. {{cite web}}: Check date values in: |accessdate= (help)
  6. ^ Makanga, Michael; Krudsood, Srivicha (2009-10-12). "The clinical efficacy of artemether/lumefantrine (Coartem)". Malaria Journal. 8 (Suppl 1): S5. doi:10.1186/1475-2875-8-S1-S5. ISSN 1475-2875. PMC 2760240. PMID 19818172.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  7. ^ Esu, E; Effa, EE; Opie, ON; Uwaoma, A; Meremikwu, MM (Sep 11, 2014). "Artemether for severe malaria". The Cochrane database of systematic reviews. 9: CD010678. doi:10.1002/14651858.CD010678.pub2. PMID 25209020.
  8. ^ Information, National Center for Biotechnology; Pike, U. S. National Library of Medicine 8600 Rockville; MD, Bethesda; Usa, 20894 (2015-01-01). TREATMENT OF UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA. World Health Organization. {{cite book}}: |first4= has numeric name (help)CS1 maint: numeric names: authors list (link)
  9. ^ Information, National Center for Biotechnology; Pike, U. S. National Library of Medicine 8600 Rockville; MD, Bethesda; Usa, 20894 (2015-01-01). TREATMENT OF UNCOMPLICATED MALARIA CAUSED BY P. VIVAX, P. OVALE, P. MALARIAE OR P. KNOWLESI. World Health Organization. {{cite book}}: |first4= has numeric name (help)CS1 maint: numeric names: authors list (link)
  10. ^ Pérez del Villar, Luis; Burguillo, Francisco J.; López-Abán, Julio; Muro, Antonio (2012-01-01). "Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis". PloS One. 7 (9): e45867. doi:10.1371/journal.pone.0045867. ISSN 1932-6203. PMC 3448694. PMID 23029285.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  11. ^ Dellicour S, Hall S, Chandramohan D, Greenwood B (2007). "The safety of artemisinins during pregnancy: a pressing question". Malaria J. 6: 15. doi:10.1186/1475-2875-6-15.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  12. ^ Piola P, Nabasumba C, Turyakira E, et al. (2010). "Efficacy and safety of artemether—lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial". Lancet Infect Dis. 10 (11): 762–769. doi:10.1016/S1473-3099(10)70202-4.
  13. ^ a b "Artemether". www.antimicrobe.org. Retrieved 2016-11-09.
  14. ^ "WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition: Protozoa: Malaria: Artemether". apps.who.int. Retrieved 2016-11-09.
  15. ^ a b Askling, Helena H.; Bruneel, Fabrice; Burchard, Gerd; Castelli, Francesco; Chiodini, Peter L.; Grobusch, Martin P.; Lopez-Vélez, Rogelio; Paul, Margaret; Petersen, Eskild (2012-01-01). "Management of imported malaria in Europe". Malaria Journal. 11: 328. doi:10.1186/1475-2875-11-328. ISSN 1475-2875. PMC 3489857. PMID 22985344.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  16. ^ Van geertruyden, J.-P. "Interactions between malaria and human immunodeficiency virus anno 2014". Clinical Microbiology and Infection. 20 (4): 278–285. doi:10.1111/1469-0691.12597. PMC 4368411. PMID 24528518.
  17. ^ Kiang, Tony K. L.; Wilby, Kyle J.; Ensom, Mary H. H. (2013-10-26). "Clinical Pharmacokinetic Drug Interactions Associated with Artemisinin Derivatives and HIV-Antivirals". Clinical Pharmacokinetics. 53 (2): 141–153. doi:10.1007/s40262-013-0110-5. ISSN 0312-5963.
  18. ^ a b Stover, Kayla R.; King, S. Travis; Robinson, Jessica (2012-04-01). "Artemether-Lumefantrine: An Option for Malaria". Annals of Pharmacotherapy. 46 (4): 567–577. doi:10.1345/aph.1Q539. ISSN 1060-0280. PMID 22496476.
  19. ^ a b Saeed, ME; Krishna, S; Greten, HJ; Kremsner, PG; Efferth, T (August 2016). "Antischistosomal activity of artemisinin derivatives in vivo and in patients". Pharmacological research. 110: 216–26. PMID 26902577.
  20. ^ a b Guo, Zongru (2016-03-01). "Artemisinin anti-malarial drugs in China". Acta Pharmaceutica Sinica B. 6 (2): 115–124. doi:10.1016/j.apsb.2016.01.008. PMC 4788711. PMID 27006895.
  21. ^ a b c "Coartem Label" (PDF). FDA. March 2015.
  22. ^ B.M.J. De Spiegeleer, M. D’Hondt, E. Vangheluwe, K. Vandercruyssen, B.G.I. De Spiegeleer, H. Jansen, I. Koijen, J. Van Gompel. Relative response factor determination of artemether degradants with a dry heat stress approach. Journal of Pharmaceutical and Biomedical Analysis 70 (2012) 111– 116.

See also

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