Artemether/lumefantrine

Artemether/lumefantrine

Combination of
Artemether	Antimalarial
Lumefantrine	Antimalarial
Clinical data
Trade names	Coartem, Riamet, Falcynate-LF
AHFS/Drugs.com	monograph
MedlinePlus	a609024
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Oral
Identifiers
ATC code	P01BF01 (WHO)
ChemSpider	21106282
(verify)

Artemether/lumefantrine, sold under the trade name Coartem among others, is a combination of the two medications artemether and lumefantrine.^[1] It is used to treat malaria caused by Plasmodium falciparum that is not treatable with chloroquine. It is not typically used to prevent malaria. It is taken by mouth.^[1]

Common side effects include muscle and joint pains, fever, loss of appetite, and headache. Serious side effects include prolonged QT syndrome. While not well studied it appears to be okay in pregnancy. The dose does not need changing in those with mild or moderate kidney or liver problems.^[1]

The combination came into medical use in 1992.^[2] They were both developed in China.^[2][3] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.^[4] The wholesale cost is between 0.10 and 1.2 USD per day as of 2014.^[5] It is not available as a generic medication and a course of treatment costs between 100 and 200 USD in the United States.^[6]

Medical uses

The combination is an effective and well-tolerated malaria treatment, providing high cure rates even in areas of multi-drug resistance.^[7][8]

Side effects

Coartem can cause anaphylactic reactions. The drug frequently causes headache, dizziness and 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.^[9]

Interactions

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 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.^[9]

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.^[10][11] 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. 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 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".^[12]

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)^[13] becoming the first ACT approved in the United States.

Dispersible

In January 2009, Novartis and Medicines for Malaria Venture (MMV) launched Coartem Dispersible, a 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.^[14] The sweet-tasting Coartem Dispersible tablets disperse quickly in small amounts of water, easing administration and ensuring effective dosing.

Artemether/lumefantrine tablets are available in Pakistan under trade name Malagon AL by Chas.A.Mendoza and Artelum by W. Woodwards Pakistan.

References

1. "Artemether and Lumefantrine". The American Society of Health-System Pharmacists. Retrieved Dec 2, 2015.
2. Ravina, Enrique (2011). The evolution of drug discovery : from traditional medicines to modern drugs (1. Aufl. ed.). Weinheim: Wiley-VCH. p. 139. ISBN 9783527326693.
3. Nightingale, Charles H. (2007). Antimicrobial pharmacodynamics in theory and clinical practice (2nd ed.). New York: Informa Healthcare. p. 380. ISBN 9781420017137.
4. "WHO Model Lists of Essential Medicines". World Health Organization. Retrieved 2015-11-05.
5. "Artemether + Lumefantrine". International Drug Price Indicator Guide. Retrieved 4 December 2015.
6. Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 45. ISBN 9781284057560.
7. Makanga et al, Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated plasmodium falciparummalaria: a pooled analysis of individual patient data; Am. J. Trop. Med. Hyg., 74(6), 2006, pp. 991–998
8. Mueller et al, 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; Acta Tropica 100 (2006) 41–53
9. Drugs.com: Coartem
10. WHO Prequalification Programme: Priority Essential Medicines. Access to Artemesinin-based antimalarial medicinal products of acceptable quality. Available at http://healthtech.whoz.int/pq/lists/ mal_suppliers.pdf Accessed May 2008.
11. WHO Health Systems and Services: Prequalification Programme. Available at http://healthtech.who.int/pq/ Accessed May 2008.
12. Make Trade Fair: Patients before Profits.
13. http://www.fda.gov/bbs/topics/NEWS/2009/NEW01989.html
14. 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, H. P.; Andriano, K.; Cousin, M.; Lefèvre, G.; Ubben, D.; Premji, Z. (2008). "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". The Lancet 372 (9652): 1819–1827. doi:10.1016/S0140-6736(08)61492-0. PMID 18926569.