Artemether: Difference between revisions

| tradename = manyMany<ref name="drugs">{{cite web|title=Artemether -and Drugs.comLumefantrine (Monograph)|url=https://www.drugs.com/internationalmonograph/artemether-and-lumefantrine.html|websitepublisher=www.drugsDrugs.com|accessdatedate=722 December 2016February 2023|deadurlaccessdate=no|archiveurl=https://web.archive.org/web/20161220222347/https://www.drugs.com/international/artemether.html|archivedate=2017 DecemberFebruary 2016|df=2024}}</ref>

| legal_status = Rx only

| routes_of_administration = intramuscularIntramuscular<ref name=Es2014Esu2019 /> Oral

| CAS_number_Ref = {{cascite|changedcorrect|??CAS}}

| ChEMBL = 1237051

'''Artemether''' is a medication used for the treatment of [[malaria]].<ref name=Es2014drugs/><ref name=Esu2019>{{cite journal | vauthors = Esu EB, Effa EE, Opie ON, Meremikwu MM | title = Artemether for severe malaria | journal = The Cochrane Database of Systematic Reviews | volume = 6 | issue = 6 | pages = CD010678 | date = June 2019 | pmid = 31210357 | pmc = 6580442 | doi = 10.1002/14651858.CD010678.pub3 }}</ref> The injectable form is specifically used for severe malaria rather than [[quinine]].<ref name=Es2014Esu2019 /> ItIn adults, it may not be as effective as [[artesunate]].<ref name=Es2014Esu2019 /> It is given by [[intramuscular|injection in a muscle]].<ref name=Es2014>{{citeEsu2019 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|volume=9|issue=9|pages=CD010678|pmid=25209020|doi=10.1002/14651858.CD010678.pub2|pmc=4455227}}</ref>{{Update inline|reason=Updated version https://www.ncbi.nlm.nih.gov/pubmed/31210357|date = August 2019}} It is also available by mouth in combination with [[lumefantrine]], known as [[artemether/lumefantrine]].<ref name=AHFS2016>{{cite web|title=Artemether and Lumefantrine|url=https://www.drugs.com/monograph/artemether-and-lumefantrine.html|publisher=The><ref American Society of Health-System Pharmacists|accessdatename=28"Coartem NovemberFDA 2016|deadurl=no|archiveurl=https://web.archive.org/web/20161220224045/https://www.drugs.com/monograph/artemether-and-lumefantrine.html|archivedate=20label" December 2016|df=}}</ref>

Artemether causes relatively few side effects.<ref name=Kov2015/> An [[Heart arrhythmia|irregular heartbeat]] may rarely occur.<ref name=Kov2015/> While there is evidence that use during [[pregnancy]] may be harmful in animals models, there is no evidence of concernsconcern in humans.<ref name=Kov2015/> The [[World Health Organization]] (WHO) therefore recommends itits use during pregnancy.<ref name=Kov2015/> It is in the [[artemisinin]] class of medication.<ref name=Kov2015>{{cite journal |last1 vauthors = 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 =165–81 165–181 | date = February 2015 | pmid = 25556421 | pmc = 4328128 | doi = 10.1007/s40264-014-0261-9 }}</ref>

Artemether has been studied since at least 1981, and has been in medical use since 1987.<ref>{{cite book|last1 vauthors = Rao|first1=Yi|last2= Y, Zhang|first2=Daqing|last3= D, Li|first3=Runhong R |title=Tu Youyou and the Discovery of Artemisinin: 2015 Nobel Laureate in Physiology or Medicine|date=2016|publisher=World Scientific|isbn=9789813109919|page=162|url=https://books.google.com/books?id=nmZtDQAAQBAJ&pg=PA162|languageurl-status=enlive|deadurl=no|archiveurlarchive-url=https://web.archive.org/web/20170910151644/https://books.google.com/books?id=nmZtDQAAQBAJ&pg=PA162|archivedatearchive-date=2017-09-10|df=}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]], the most effective and safe medicines needed in a [[health system]].<ref name=WHO19th"WHO21st">{{cite webbook | title =WHO ModelWorld ListHealth ofOrganization Essentialmodel Medicineslist of (19thessential List)|url=httpmedicines://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health21st list 2019 Organization|accessdate=8 Decemberyear 2016|date=April 20152019 |deadurl=no|archiveurl=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archivedate=13 Decemberhdl 2016|df=}}< 10665/ref>325771 The| wholesalepublisher cost= inWorld theHealth [[developingOrganization world]]| islocation between= US$0.38Geneva and| US$16.47id per= vial.<ref>{{cite web|title=Artemether|url=http:WHO/MVP/mshpriceguide.orgEMP/enIAU/single-drug-information/?DMFId=65&searchYear=2014|website=International2019.06. DrugLicense: PriceCC IndicatorBY-NC-SA Guide|accessdate=1 January 2016}}</ref> The combination form cost between US$100 and US$200 for a course of treatment in the United States3.<ref0 name=Ric2015>{{citeIGO book|last1=Hamilton|first1=Richart|title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Labhdl-Coat Edition|dateaccess=2015|publisher=Jonesfree & Bartlett Learning|isbn=9781284057560|page=45}}</ref>

Artemether is an antimalarial drug for uncomplicated malaria caused by &nbsp;''[[Plasmodium falciparum|P. falciparum]]'' (and chloroquine-resistant ''[[Plasmodium falciparum|P. falciparum]]'') or chloroquine-resistant ''[[Plasmodium vivax|P. vivax]]'' parasites.<ref name=drugs/><ref>{{Citecite journal |last vauthors = Makanga|first=Michael|last2= M, Krudsood S |first2=Srivicha|date=2009-10-12| title = The clinical efficacy of artemether/lumefantrine (Coartem) | journal = Malaria Journal | volume = 8 | issue = Suppl 1 | pages = S5 | date = October 2009 | pmid = 19818172 | pmc = 2760240 | doi = 10.1186/1475-2875-8-S1-S5 |issn=1475 doi-2875|pmcaccess =2760240|pmid=19818172 free }}</ref> Artemether can also be used to treat severe malaria.<ref>{{cite journal|last1name=Esu|first1=E|last2=Effa|first2=EE|last3=Opie|first3=ON|last4=Uwaoma|first4=A|last5=Meremikwu|first5=MM|title=ArtemetherEsu2019 for severe malaria.|journal=The Cochrane Database of Systematic Reviews|date=Sep 11, 2014|volume=9|pages=CD010678|pmid=25209020|doi=10.1002/14651858.CD010678.pub2|pmc=4455227}}</ref>{{Update inline|reason=Updated version https://www.ncbi.nlm.nih.gov/pubmed/31210357|date = August 2019}}

The [[World Health Organization]] (WHO) recommends the treatment of uncomplicated ''[[Plasmodium falciparum|P. falciparum]]'' with [[artemisinin-based combination therapy]].<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK294441/|title=TREATMENTTreatment OFof UNCOMPLICATEDUncomplicated PLASMODIUMPlasmodium FALCIPARUMfalciparum MALARIA|last=Information|first=National Center for Biotechnology|last2=Pike|first2=U. S. National Library of Medicine 8600 Rockville|last3=MD|first3=Bethesda|last4=Usa|first4=20894Malaria|date=2015-01-01|publisher=World Health Organization|languageurl-status=enlive|deadurl=no|archiveurlarchive-url=https://web.archive.org/web/20170910151644/https://www.ncbi.nlm.nih.gov/books/NBK294441/|archivedatearchive-date=2017-09-10|df=}}</ref> Given in combination with [[lumefantrine]], it may be followed by a 14-day regimen of [[primaquine]] to prevent relapse of ''P. vivax''&nbsp;or&nbsp;''P. ovale'' malarial parasites and provide a complete cure.<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK294428/|title=TREATMENTTreatment OFOf UNCOMPLICATEDUncomplicated MALARIAMalaria CAUSEDCaused BYBy P. VIVAXvivax, P. OVALEovale, P. MALARIAEmalariae ORor P. KNOWLESI|last=Information|first=National Center for Biotechnology|last2=Pike|first2=U. S. National Library of Medicine 8600 Rockville|last3=MD|first3=Bethesda|last4=Usa|first4=20894knowlesi|date=2015-01-01|publisher=World Health Organization|languageurl-status=enlive|deadurl=no|archiveurlarchive-url=https://web.archive.org/web/20170910151644/https://www.ncbi.nlm.nih.gov/books/NBK294428/|archivedatearchive-date=2017-09-10|df=}}</ref>

Artemether can also be used in treating and preventing trematode infections of [[schistosomiasis]] when used in combination with [[praziquantel]].<ref>{{Citecite journal |last vauthors = Pérez del Villar|first=Luis|last2= L, Burguillo|first2=Francisco J.|last3=FJ, López-Abán|first3=Julio|last4= J, Muro A |first4=Antonio|date=2012-01-01| title = Systematic review and meta-analysis of artemisinin based therapies for the treatment and prevention of schistosomiasis | journal = PLOS ONE | volume = 7 | issue = 9 | pages = e45867 | date = 2012-01-01 | pmid = 23029285 | pmc = 3448694 | doi = 10.1371/journal.pone.0045867 |issn=1932 doi-6203|pmcaccess =3448694 free |pmid bibcode =23029285 2012PLoSO...745867P }}</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>{{cite journal | vauthors = Dellicour S, Hall S, Chandramohan D, Greenwood B | title = The safety of artemisinins during pregnancy: a pressing question | journal = Malaria Journal|year= 2007| volume = 6 | pages = 15 | date = February 2007 | pmid = 17300719 | pmc = 1802871 | doi = 10.1186/1475-2875-6-15 |pmid doi-access =17300719|pmc=1802871 free }}</ref><ref>{{cite journal | vauthors = Piola P, Nabasumba C, Turyakira E, Dhorda M, Lindegardh N, Nyehangane D, Snounou G, Ashley EA, McGready R, Nosten F, Guerin PJ | display-authors = 6 | title = Efficacy and safety of artemether—lumefantrineartemether-lumefantrine compared with quinine in pregnant women with uncomplicated Plasmodium falciparum malaria: an open-label, randomised, non-inferiority trial | journal = The Lancet. InfectInfectious Diseases Dis| volume = 10 | issue = 11 | pages =762&ndash;769 762–769 |year date = November 2010 | pmid = 20932805 | doi = 10.1016/S1473-3099(10)70202-4 |display hdl-authorsaccess =etal free | hdl = 10144/116337 }}</ref>

Possible side effects include cardiac effects such as bradycardia and [[QT interval]] prolongation.<ref name=drugs/><ref name="Artemether">{{Cite web|url=http://www.antimicrobe.org/drugpopup/artemether.htm|title=Artemether|website=www.antimicrobe.org|access-date=2016-11-09|deadurlurl-status=nolive|archiveurlarchive-url=https://web.archive.org/web/20170223123545/http://www.antimicrobe.org/drugpopup/artemether.htm|archivedatearchive-date=2017-02-23|df=}}</ref> Also, possible central nervous system toxicity has been shown in animal studies.<ref>{{Cite web|url=http://apps.who.int/medicinedocs/en/d/Jh2922e/2.5.10.html#Jh2922e.2.5.10|title=WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition: Protozoa: Malaria: Artemether|website=apps.who.int|access-date=2016-11-09|deadurlurl-status=nodead|archiveurlarchive-url=https://web.archive.org/web/20161110043655/http://apps.who.int/medicinedocs/en/d/Jh2922e/2.5.10.html#Jh2922e.2.5.10|archivedatearchive-date=2016-11-10|df=}}</ref><ref name=Askling2012>{{Citecite journal |last vauthors = Askling|first=Helena H.|last2=HH, Bruneel|first2=Fabrice|last3= F, Burchard|first3=Gerd|last4= G, Castelli|first4=Francesco|last5= F, Chiodini|first5=Peter L.|last6=PL, Grobusch|first6=Martin P.|last7=MP, Lopez-Vélez|first7=Rogelio|last8= R, Paul|first8=Margaret|last9= M, Petersen E, Popescu C, Ramharter M, Schlagenhauf P |first9 display-authors =Eskild|date=2012-01-01 6 | title = Management of imported malaria in Europe | journal = Malaria Journal | volume = 11 | pages = 328 | date = September 2012 | pmid = 22985344 | pmc = 3489857 | doi = 10.1186/1475-2875-11-328 |issn=1475 doi-2875|pmcaccess =3489857|pmid=22985344 free }}</ref>

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>{{Citecite journal |last vauthors = Van geertruyden|first=J.-P.Geertruyden JP | title = Interactions between malaria and human immunodeficiency virus anno 2014 | journal = Clinical Microbiology and Infection | volume = 20 | issue = 4 | pages = 278–285 | date = April 2014 | pmid = 24528518 | pmc = 4368411 | doi = 10.1111/1469-0691.12597|pmc=4368411|pmid=24528518|year=2014 }}</ref><ref>{{Citecite journal |last vauthors = Kiang|first=Tony K.TK, L.|last2=Wilby|first2=Kyle J.|last3=KJ, Ensom|first3=Mary H.MH H.|date=2013-10-26| title = Clinical Pharmacokineticpharmacokinetic Drugdrug Interactionsinteractions Associatedassociated with Artemisininartemisinin Derivativesderivatives and HIV-Antiviralsantivirals | journal = Clinical Pharmacokinetics |language=en| volume = 53 | issue = 2 | pages = 141–153 | date = February 2014 | pmid = 24158666 | doi = 10.1007/s40262-013-0110-5 |pmid s2cid =24158666|issn=0312-5963 1281113 }}</ref>

Artemether/lumefantrine should not be used with drugs that inhibit [[CYP3A4]].<ref name=drugs/><ref name=Stover2012>{{Citecite journal |last vauthors = Stover|first=Kayla R.|last2=KR, King|first2=S. Travis|last3=ST, Robinson J |first3=Jessica|date=2012-04-01| title = Artemether-Lumefantrinelumefantrine: Anan Optionoption for Malaria|url=http://aop.sagepub.com/content/46/4/567malaria | journal = The Annals of Pharmacotherapy |language=en| volume = 46 | issue = 4 | pages = 567–577 | date = April 2012 | pmid = 22496476 | doi = 10.1345/aph.1Q539 |issn s2cid =1060-0280|pmid=22496476 7678606 }}</ref>

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=USlabel2015"Coartem FDA label">{{cite web | title=Coartem- artemether and lumefantrine tablet Label|url website=http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022268s012lbl.pdf|publisher=FDADailyMed | date=March5 August 2019 2015|deadurl=no|archiveurl url=https://web.archive.org/web/20161117151239/http://wwwdailymed.accessdatanlm.fdanih.gov/drugsatfda_docsdailymed/label/2015/022268s012lbldrugInfo.pdf|archivedatecfm?setid=20167866ec19-11dfac-1747d4-a53f-511a12643cbf |df access-date=26 April 2020}}</ref>

Artemether is metabolized in the human body to the active metabolite, dihydroartemisinin, primarily by hepatic enzymes CYP3A4/5.<ref name=USlabel2015"Coartem FDA label"/> Both the parent drug and active metabolite are eliminated with a half-life of about 2 hours.<ref name=USlabel2015"Coartem FDA label"/>

It is a relatively lipophilic and unstable drug,<ref>{{cite journal | last1vauthors = De Spiegeleer | first1 = B.M.J. | last2 =BM, D'Hondt | first2 = M. | last3 =, Vangheluwe | first3 = E. | last4 =, Vandercruyssen | first4 = K. | last5 =, De Spiegeleer | first5 = B.G.I. | last6 =BV, Jansen | first6 = H. | last7 =, Koijen | first7 = I. | last8 =, Van Gompel | first8 = J. | yeardisplay-authors = 20126 | title = Relative response factor determination of β-artemether degradants withby a dry heat stress approach | url = https://biblio.ugent.be/publication/2938963| journal = Journal of Pharmaceutical and Biomedical Analysis | volume = 70 | issuepages = 111–116 | pagesdate = 111–116November 2012 | pmid = 22770733 | doi = 10.1016/j.jpba.2012.06.002 | hdl-access = free | hdl = 1854/LU-2938963 |pmid url =22770733 https://biblio.ugent.be/publication/2938963 }}</ref> which acts by creating reactive free radicals in addition to affecting the membrane transport system of the plasmodium organism.<ref name="Artemether"/>

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