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|Trade names||Coartem, Riamet, Falcynate-LF|
|Pregnancy cat.||C (US)|
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The combination artemether/lumefantrine (trade names Coartem and Riamet, Falcynate-LF) is a fixed-dose combination artemisinin-based combination therapy (ACT) indicated for the treatment of acute uncomplicated Plasmodium falciparum malaria.
The individual drugs were both initially developed in China. Artemether is one of the semi-synthetic derivatives of artemisinin, and lumefantrine (also known as benflumetol and CGP 56695 during development) is purely synthetic. The combination is an effective and well-tolerated malaria treatment, providing high cure rates even in areas of multi-drug resistance.
In 2001, Coartem became the first fixed dose artemisinin-based combination therapy to meet the World Health Organization's (WHO) pre-qualification criteria for efficacy, safety and quality. In 2002, artemether/lumefantrine tablets were added to the WHO's Essential Medicines list, an index of essential drugs which help guide the purchasing decisions of Member States and UN agencies. Coartem 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).
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.
Effect of food and interactions
Food 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.
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".
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) becoming the first ACT approved in the United States.
In January 2009, Novartis and Medicines for Malaria Venture (MMV) launched Coartem Dispersible, the first artemisinin-based combination therapy developed specifically for children suffering from malaria. Coartem Dispersible contains the same ratio of artemether and lumefantrine as Coartem. A phase III study published in The Lancet showed that Coartem Dispersible provides a high cure rate of 97.8% for uncomplicated Plasmodium falciparum malaria, which is comparable to that of Coartem (98.5%). Investigators also reported that it had a good safety profile. The sweet-tasting Coartem Dispersible tablets disperse quickly in small amounts of water, easing administration and ensuring effective dosing.
Novartis and MMV provide malaria case management educational programs, which include hands-on training for local healthcare workers, customized training manuals, and user-friendly packaging to ensure that Coartem Dispersible is properly used and to improve patient compliance. Like Coartem, Coartem Dispersible is provided to the public sector without profit.
Artemether/lumefantrine tablets are available in Pakistan under trade name Malagon AL by Chas.A.Mendoza and Artelum by W. Woodwards Pakistan.
- Data on File, Coartem Product Monograph, Novartis AG. 5th Edition. November 2005.
- 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
- 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
- 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.
- WHO Health Systems and Services: Prequalification Programme. Available at http://healthtech.who.int/pq/ Accessed May 2008.
- Essential Medicines: WHO Model List. 14th Edition. March 2005. Available at: http://whqlibdoc.who.int/hq/2005/a87017_eng.pdf. Accessed November 8, 2005 (from Coartem Fact-Sheet)
- Drugs.com: Coartem
- Make Trade Fair: Patients before Profits.
- 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.