Artemether/lumefantrine

Artemether/lumefantrine

Combination of
Artemether	Antimalarial
Lumefantrine	Antimalarial
Clinical data
MedlinePlus	a609024
Pregnancy cat.	C(US)
Legal status	?
Routes	Oral
Identifiers
ATC code	P01BF01
ChemSpider	21106282 Y
Y(what is this?)  (verify)

The combination artemether/lumefantrine (trade names Coartem and Riamet) is an artemisinin-based combination therapy (ACT) indicated for the treatment of acute uncomplicated plasmodium falciparum malaria. Coartem is produced by the Swiss pharmaceutical company, Novartis.

Artemether is a derivative of artemisinin, and lumefantrine (or benflumetol) is an antimalarial drug. Coartem is an effective and well-tolerated malaria treatment, providing cure rates of up to^{[weasel words]} 97%, even in areas of multi-drug resistance.^[1][2][3]

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.^[4][5]

In 2002, artemether/lumefantrine tablets were added to the WHO's Essential Medicines list,^[1][6] 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).

Since 2001, Novartis has supplied 250 million treatments of Coartem without profit for public sector use in Africa, saving an estimated 630,000 lives.^{[citation needed]}

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.^[7]

Interactions

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.^[7]

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".^[8]

Coartem Dispersible

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 amount 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.^[9]

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.^{[citation needed]}

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)^[10] becoming the first ACT approved in the United States. Millions of Americans travel to malaria-endemic regions on business or pleasure, and cases of travelers’ malaria continue to be a problem. In addition, many of the US military are stationed in malaria-endemic countries. US patients now have access to ACTs, the standard of care and treatment for malaria.

Coartem is now available in the United States through major wholesalers. This distribution model will allow patients in need to have access to the drug within 24 hours through retail pharmacies across the country. Novartis will sell the entire 24-tablet adult course of Coartem therapy for $69.60, on par with other currently available branded antimalarial treatments. The amount one pays at the pharmacy will depend upon insurance coverage and what the pharmacy charges for the medication.

Coartem was granted priority review by the FDA, a treatment typically granted to address urgent, unmet medical needs. Along with FDA approval, Novartis was awarded a one-time priority review voucher to be used for a future new drug application. Artemether/lumefantrine tablets are available in Pakistan under trade name Artelum by W. Woodwards Pakistan.

References

1. ^ ^{a b} Data on File, Coartem Product Monograph, Novartis AG. 5th Edition. November 2005.
2. ^ 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
3. ^ 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
4. ^ 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.
5. ^ WHO Health Systems and Services: Prequalification Programme. Available at http://healthtech.who.int/pq/ Accessed May 2008.
6. ^ 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)
7. ^ ^{a b} Drugs.com: Coartem
8. ^ Make Trade Fair: Patients before Profits.
9. ^ Abdulla, S.; Sagara, I.; Borrmann, S.; Dalessandro, U.; Gonzalez, R.; Hamel, M.; Ogutu, B.; Martensson, A. et al. (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. doi:10.1016/S0140-6736(08)61492-0. PMID 18926569.  edit
10. ^ http://www.fda.gov/bbs/topics/NEWS/2009/NEW01989.html