Artemether/lumefantrine: Difference between revisions

{{Short description|Combination drug}}

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 457619723

| type = combo

| component1 = Artemether

| class1 = [[Antimalarial]]

| component2 = Lumefantrine

| class2 = [[Antimalarial]]

| tradename = Coartem, Riamet, Falcynate-LF

| Drugs.com = {{drugs.com|monograph|artemether-and-lumefantrine}}

| MedlinePlus = a609024

| pregnancy_AU = D

| pregnancy_US = C

| pregnancy_category =

| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->

| legal_US = Rx-only

| legal_status =

| routes_of_administration = By mouth

| CAS_number = 141204-94-6

| ATC_prefix = P01

| ATC_suffix = BF01

| ChemSpiderID = 21106282

<!-- Definition and medical uses -->

'''Artemether/lumefantrine''', sold under the trade name '''Coartem''' among others, is a combination of the two medications [[artemether]] and [[lumefantrine]].<ref name=AHFS2015>{{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=Dec 2, 2015|url-status=live|archive-url=https://web.archive.org/web/20151208162852/http://www.drugs.com/monograph/artemether-and-lumefantrine.html|archive-date=2015-12-08}}</ref> It is used to treat [[malaria]] caused by ''[[Plasmodium falciparum]]'' that is not treatable with [[chloroquine]].<ref name=AHFS2015/> It is not typically used to prevent malaria.<ref name=AHFS2015/> It is taken by mouth.<ref name=AHFS2015/>

<!-- Side effects and mechanism -->

Common side effects include muscle and joint pains, fever, loss of appetite, and headache.<ref name=AHFS2015/> Serious side effects include [[Long QT syndrome|prolongation of the QT interval]].<ref name=AHFS2015/> While not well studied, it appears to be safe for use in pregnancy.<ref name=AHFS2015/> The dose does not need changing in those with mild or moderate kidney or liver problems.<ref name=AHFS2015/>

<!-- History, society, and culture -->

This combination came into medical use in 1992<ref name=Enr2011>{{cite book|last1=Ravina|first1=Enrique|title=The evolution of drug discovery : from traditional medicines to modern drugs|date=2011|publisher=Wiley-VCH|location=Weinheim|isbn=9783527326693|page=139|edition=1. Aufl.|url=https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA139|url-status=live|archive-url=https://web.archive.org/web/20151208072054/https://books.google.ca/books?id=iDNy0XxGqT8C&pg=PA139|archive-date=2015-12-08}}</ref> and was developed in China.<ref name=Enr2011/><ref>{{cite book|last1=Nightingale|first1=Charles H.|title=Antimicrobial pharmacodynamics in theory and clinical practice|date=2007|publisher=Informa Healthcare|location=New York|isbn=9781420017137|page=380|edition=2nd|url=https://books.google.com/books?id=sXf42EROuhEC&pg=PA380|url-status=live|archive-url=https://web.archive.org/web/20151208050646/https://books.google.ca/books?id=sXf42EROuhEC&pg=PA380|archive-date=2015-12-08}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | 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> It is not available as a [[generic medication]].<ref name=Ric2015>{{cite book|last1=Hamilton|first1=Richart|title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=45}}</ref>

==Medical uses==

The combination is an effective and well-tolerated malaria treatment, providing high cure rates even in areas of multi-drug resistance.<ref>{{cite journal |display-authors=6 |vauthors=Makanga M, Premji Z, Falade C, Karbwang J, Mueller EA, Andriano K, Hunt P, De Palacios PI |title=Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: a pooled analysis of individual patient data |journal=Am. J. Trop. Med. Hyg. |volume=74 |issue=6 |pages=991–8 |date=June 2006 |pmid=16760509 |doi= 10.4269/ajtmh.2006.74.991|doi-access=free }}</ref><ref>{{cite journal |vauthors=Mueller EA, van Vugt M, Kirch W, Andriano K, Hunt P, de Palacios PI |title=Efficacy and safety of the six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in adolescents and adults: a pooled analysis of individual patient data from randomized clinical trials |journal=Acta Trop. |volume=100 |issue=1–2 |pages=41–53 |date=November 2006 |pmid=17045558 |doi=10.1016/j.actatropica.2006.09.007 }}</ref>

Coartem can cause [[anaphylactic reaction]]s. The drug frequently causes headache, dizziness and [[Anorexia (symptom)|anorexia]], although mild forms in most cases. Other fairly common side effects (more than 3% of patients) include sleep disorder, [[tinnitus]], [[tremor]], [[palpitation]], as well as unspecific reactions like [[vertigo]], gastrointestinal disorders, itch and [[nasopharyngitis]].<ref name="Drugs.com">[https://www.drugs.com/coartem.html Drugs.com: Coartem] {{webarchive |url=https://web.archive.org/web/20160521122932/http://www.drugs.com/coartem.html |date=May 21, 2016 }}</ref>

Food, in particular fat, enhances the absorption of both artemether and lumefantrine, and patients are advised to take the tablets with food as soon as a meal can be tolerated. Coartem has a potential to [[QT prolongation|prolong the QT interval]], so combinations with other drugs having that property can cause irregular heartbeat, potentially leading to lethal [[ventricular fibrillation]]. The combination with [[halofantrine]], another antimalarial, can cause a life-threatening QT prolongation. Drugs and other substances influencing the activity of the liver enzyme [[CYP3A4]], including grapefruit juice, can either increase or lower blood levels of artemether/lumefantrine, depending on the sort of substance. This can either lead to more severe side effects or to reduced efficiency.<ref name="Drugs.com" />

==History==

In 2001, the first fixed dose [[artemisinin]]-based combination therapy to meet the World Health Organization's (WHO) pre-qualification criteria for efficacy, safety and quality was created.<ref>WHO Prequalification Programme: Priority Essential Medicines. Access to Artemesinin-based antimalarial medicinal products of acceptable quality. Available at http://healthtech.whoz.int/pq/lists/{{dead link|date=October 2016 |bot=InternetArchiveBot |fix-attempted=yes }} mal_suppliers.pdf Accessed May 2008.</ref><ref>WHO Health Systems and Services: Prequalification Programme. Available at {{cite web|url=http://healthtech.who.int/pq/ |title=New Page 1 |access-date=2009-05-20 |url-status=dead |archive-url=https://web.archive.org/web/20090513060741/http://healthtech.who.int/pq/ |archive-date=2009-05-13 }} Accessed May 2008.</ref> It is approved in over 80 countries worldwide, including various countries in Africa, as well as [[Swissmedic]], the [[European Medicines Agency]] (EMA) and the [[U.S. Food and Drug Administration]] (FDA).

==Society and culture==

===Access to treatment===

Coartem is provided without profit to developing countries using grants from the [[Global Fund to Fight AIDS, Tuberculosis and Malaria]], US [[President's Malaria Initiative]] along with other donors. Novartis has lowered the price of Coartem by 50% since 2001, increasing access to patients around the world. The first significant price reduction occurred in 2006, when the price of Coartem decreased from an average of US$1.57 to US$1.00. In 2006, due to an improved supply situation for the natural ingredient artemisinin, Novartis was able to undertake the pharmaceutical industry's most aggressive manufacturing scale-up of its kind from 4 million treatments in 2004 to 62 million treatments in 2006.{{citation needed|date=March 2016}} Novartis and its partners invested heavily in expanding production capacity at their facilities in China, and Suffern, New York. This increase in production capacity ensured that supplies of Coartem met demand which enabled Novartis to further decrease the price of Coartem. In April 2008, Novartis further reduced the public sector price of Coartem by approximately 20%, to an average of US$0.80 (or US$0.37 for a child's treatment pack). This price reduction was made possible through production efficiency gains.

Prior to this program, Novartis was criticised for [[Novartis#Challenge to India's patent laws|a court case they launched]] against India, seeking to prohibit the marketing of cheap generic drugs. An Indian court ruled against Novartis, saying that the case was a "threat to people suffering from cancer [...] and other diseases who are too poor to pay for them".<ref>[http://www.maketradefair.com/en/index.php?file=a2m_main.html Make Trade Fair: Patients before Profits.] {{webarchive |url=https://web.archive.org/web/20110515184029/http://www.maketradefair.com/en/index.php?file=a2m_main.html |date=May 15, 2011 }}</ref>

===Approval in the United States===

On April 8, 2009, the U.S. Food and Drug Administration (FDA) announced that Coartem was approved for the treatment of acute, uncomplicated malaria infections in adults and children weighing at least five kilograms (approximately 11 pounds)<ref>{{cite web |url=http://www.fda.gov/bbs/topics/NEWS/2009/NEW01989.html |title=FDA Approves Coartem Tablets to Treat Malaria |website=www.fda.gov |access-date=14 January 2022 |archive-url=https://web.archive.org/web/20090411103034/http://www.fda.gov/bbs/topics/NEWS/2009/NEW01989.html |archive-date=11 April 2009 |url-status=dead}}</ref> becoming the first artemisinin-based combination therapy approved in the United States.

===Dispersible===

In January 2009, Novartis and [[Medicines for Malaria Venture]] (MMV) launched Coartem Dispersible, an [[artemisinin]]-based combination therapy developed specifically for children with malaria. Coartem Dispersible contains the same ratio of artemether and lumefantrine as Coartem. It works as well as other formulations.<ref>{{cite journal |vauthors=Abdulla S, Sagara I, Borrmann S, D'Alessandro U, González R, Hamel M, Ogutu B, Mårtensson A, Lyimo J, Maiga H, Sasi P, Nahum A, Bassat Q, Juma E, Otieno L, Björkman A, Beck HP, Andriano K, Cousin M, Lefèvre G, Ubben D, Premji Z |display-authors=6 |title=Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial |journal=Lancet |volume=372 |issue=9652 |pages=1819–27 |date=November 2008 |pmid=18926569 |doi=10.1016/S0140-6736(08)61492-0 |s2cid=8207921 }}</ref> The sweet-tasting Coartem Dispersible tablets disperse quickly in small amounts of water, easing administration and ensuring effective dosing.

{{reflist}}

{{Portal bar|Medicine}}

{{DEFAULTSORT:Artemether Lumefantrine}}

[[Category:Antimalarial agents]]

[[Category:Combination antiviral drugs]]

[[Category:Chinese inventions]]

[[Category:Drugs developed by Novartis]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:World Health Organization essential medicines]]