Artemether: Difference between revisions

| tradename = Many<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|access-date=722 December 2016February 2023|url-status=live|archive-url=https://web.archive.org/web/20161220222347/https://www.drugs.com/international/artemether.html|archive-dateaccessdate=2017 DecemberFebruary 20162024}}</ref>

| legal_status = Rx only

| routes_of_administration = Intramuscular<ref name=Esu2019 /> Oral

'''Artemether''' is a medication used for the treatment of [[malaria]].<ref name=drugs/><ref name=Esu2019>{{Citecite journal |last1 vauthors = Esu|first1=Ekpereonne B.|last2=EB, Effa|first2=Emmanuel E.|last3=EE, Opie|first3=Oko N.|last4=ON, Meremikwu|first4=Martin M.MM |date=18 June 2019|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|issn=1469-493X|pmc=6580442|pmid=31210357 }}</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 [[intramuscular|injection in a muscle]].<ref name=Esu2019 /> 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 American Society of Health-System Pharmacists|access-date=28 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161220224045/https://www.drugs.com/monograph/artemether-and-lumefantrine.html|archive-date=20 December 2016}}</ref><ref name="Coartem FDA label" />

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, 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>{{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|url-status=live|archive-url=https://web.archive.org/web/20170910151644/https://books.google.com/books?id=nmZtDQAAQBAJ&pg=PA162|archive-date=2017-09-10}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</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 |last1 vauthors = Makanga|first1=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 name=Esu2019 />

Artemether can also be used in treating and preventing trematode infections of [[schistosomiasis]] when used in combination with [[praziquantel]].<ref>{{Citecite journal |last1 vauthors = Pérez del Villar|first1=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|pmid=23029285 free | bibcode = 2012PLoSO...745867P|doi-access=free }}</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|hdl-access=free }}</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|url-status=live|archive-url=https://web.archive.org/web/20170223123545/http://www.antimicrobe.org/drugpopup/artemether.htm|archive-date=2017-02-23}}</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|url-status=dead|archive-url=https://web.archive.org/web/20161110043655/http://apps.who.int/medicinedocs/en/d/Jh2922e/2.5.10.html#Jh2922e.2.5.10|archive-date=2016-11-10}}</ref><ref name=Askling2012>{{Citecite journal |last1 vauthors = Askling|first1=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 Van Geertruyden JP |first=J.-P.| 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 |last1 vauthors = Kiang|first1=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 | volume = 53 | issue = 2 | pages = 141–153 | date = February 2014 | pmid = 24158666 | doi = 10.1007/s40262-013-0110-5 |pmid=24158666| s2cid = 1281113|issn=0312-5963 }}</ref>

Artemether/lumefantrine should not be used with drugs that inhibit [[CYP3A4]].<ref name=drugs/><ref name=Stover2012>{{Citecite journal |last1 vauthors = Stover|first1=Kayla R.|last2=KR, King|first2=S. Travis|last3=ST, Robinson J |first3=Jessica|date=2012-04-01| title = Artemether-Lumefantrinelumefantrine: Anan Optionoption for Malariamalaria | journal = The Annals of Pharmacotherapy | volume = 46 | issue = 4 | pages = 567–577 | date = April 2012 | pmid = 22496476 | doi = 10.1345/aph.1Q539 |issn=1060-0280|pmid=22496476| s2cid = 7678606 }}</ref>

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 | pages = 111–116 | date = November 2012 | pmid = 22770733 | doi = 10.1016/j.jpba.2012.06.002 | hdl-access = free | hdl = 1854/LU-2938963|pmid=22770733 | hdl-accessurl = freehttps://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"/>