The clinical efficacy of artemether/lumefantrine (Coartem)

Michael Makanga, Srivicha Krudsood, Michael Makanga, Srivicha Krudsood

Abstract

Current World Health Organization (WHO) guidelines for the treatment of uncomplicated falciparum malaria recommend the use of artemisinin-based combination therapy (ACT). Artemether/lumefantrine is an ACT prequalified by the WHO for efficacy, safety and quality, approved by Swissmedic in December 2008 and recently approved by the USA FDA. Coartem is a fixed-dose combination of artemether and lumefantrine. Its two components have different modes of action that provide synergistic anti-malarial activity. It is indicated for the treatment of infants, children and adults with acute, uncomplicated infection due to Plasmodium falciparum or mixed infections including P. falciparum. A formulation with improved palatability has been developed especially for children (Coartem Dispersible), which rapidly disperses in a small amount of water for ease of administration. The efficacy of the six-dose regimen of artemether/lumefantrine has been confirmed in many different patient populations around the world, consistently achieving 28-day PCR (polymerase chain reaction)-corrected cure rates of >95% in the evaluable population, rapidly clearing parasitaemia and fever, and demonstrating a significant gametocidal effect, even in areas of widespread parasite resistance to other antimalarials.

Figures

Figure 1
Figure 1
28-day PCR-corrected cure rate for artemether/lumefantrine in Studies A025,A026 and A028 [10-12].
Figure 2
Figure 2
Efficacy of dispersible AL formulation across body weight groups [14].
Figure 3
Figure 3
Median time to (A) parasite clearance and (B) fever clearance for dispersible artemether/lumefantrine formulation and crushed tablets [14].
Figure 4
Figure 4
28-day PCR-corrected cure rate for AL in Study A2401 [15].

References

    1. WHO guidelines for the treatment of malaria 2006
    1. White NJ, van Vugt M, Ezzet F. Clinical pharmacokinetics and pharmacodynamics of artemether/lumefantrine. Clin Pharmacokinet. 1999;37:105–125. doi: 10.2165/00003088-199937020-00002.
    1. World Health Organization The WHO prequalification project
    1. Olliaro P, Wells TNC. The global portfolio of new antimalarial medicines under development. Clin Pharmacol & Therapeutics. 2009;85:584–595. doi: 10.1038/clpt.2009.51.
    1. Cousin M, Kummerer S, Lefèvre G, Marrast AC, Stein D, Weaver M, Advisory Committee Briefing Book. Coartem® (artemether/lumefantrine) Tablets for the treatment of malaria in patients with acute, uncomplicated infections due to Plasmodium falciparum or mixed infections including P. falciparum. NDA 22-268. 2008.
    1. WHO World Malaria Report 2008: Chapter 4 - Interventions to control malaria
    1. Novartis Drug Regulatory Affairs Coartem®/Riamet® Basic Prescribing Information. 2007.
    1. WHO Model List of Essential Medicines
    1. WHO Model List of Essential Medicines for Children
    1. van Vugt M, Wilairatana P, Gemperli B, Gathmann I, Phaipun L, Brockman A, Luxemburger C, White NJ, Nosten F, Looareesuwan S. Efficacy of six doses of artemether/lumefantrine (benflumetol) in multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg. 1999;60:936–942.
    1. van Vugt M, Looareesuwan S, Wilairatana P, McGready R, Villegas L, Gathmann I, Mull R, Brockman A, White NJ, Nosten F. Artemether/lumefantrine for the treatment of multi-drug resistant falciparum malaria. Trans R Soc Trop Med Hyg. 2000;94:545–548. doi: 10.1016/S0035-9203(00)90082-8.
    1. Lefèvre G, Looareesuwan S, Treeprasertsuk S, Krudsood S, Silachamroon U, Gathmann I, Mull R, Bakshi R. A clinical and pharmacokinetic trial of six doses of artemether/lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg. 2001;64:247–256.
    1. Falade C, Makanga M, Premji Z, Ortmann CE, Stockmeyer M, de Palacios PI. Efficacy and safety of artemether/lumefantrine (Coartem®) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg. 2005;99:459–467. doi: 10.1016/j.trstmh.2004.09.013.
    1. 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. 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. Lancet. 2008;372:1819–1827. doi: 10.1016/S0140-6736(08)61492-0.
    1. Hatz C, Soto J, Nothdurft HD, Zoller T, Weitzel T, Loutan L, Bricaire F, Gay F, Burchard GD, Andriano K, Lefèvre G, De Palacios PI, Genton B. Treatment of acute uncomplicated falciparum malaria with artemether/lumefantrine in non-immune populations: a safety, efficacy and pharmacokinetic study. Am J Trop Med Hyg. 2008;78:241–247.
    1. Bukirwa H, Yeka A, Kamya MR, Talisuna A, Banek K, Bakyaita N, Rwakimari JB, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, Staedke SG. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clin Trials. 2006;1:e7. doi: 10.1371/journal.pctr.0010007.
    1. Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ. Combination therapy for uncomplicated falciparum malaria in Ugandan children. JAMA. 2007;297:2210–2219. doi: 10.1001/jama.297.20.2210.
    1. Gürkov R, Eshetu T, Miranda IB, Berens-Riha N, Mamo Y, Girma T, Krause E, Schmidt M, Hempel JM, Löscher T. Ototoxicity of artemether/lumefantrine in the treatment of falciparum malaria: a randomized trial. Malar J. 2008;7:179. doi: 10.1186/1475-2875-7-179.
    1. Kabanywanyi AM, Mwita A, Sumari D, Mandike R, Mugittu K, Abdulla S. Efficacy and safety of artemisinin-based antimalarial in the treatment of uncomplicated malaria in children in southern Tanzania. Malar J. 2007;6:146. doi: 10.1186/1475-2875-6-146.
    1. Kamya MR, Yeka A, Bukirwa H, Lugemwa M, Rwakimari JB, Staedke SG, Talisuna AO, Greenhouse B, Nosten F, Rosenthal PJ, Wabwire-Mangen F, Dorsey G. Artemether/lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial. PLoS Clin Trials. 2007;2:e20. doi: 10.1371/journal.pctr.0020020.
    1. Mårtensson A, Strömberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Björkman A. Efficacy of artesunate plus amodiaquine versus that of artemether/lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis. 2005;41:1079–1087. doi: 10.1086/444460.
    1. Mårtensson A, Ngasala B, Ursing J, Isabel Veiga M, Wiklund L, Membi C, Montgomery SM, Premji Z, Farnert A, Bjorkman A. Influence of consecutive-day blood sampling on polymerase chain reaction-adjusted parasitological cure rates in an antimalarial-drug trial conducted in Tanzania. J Infect Dis. 2007;195:597–601. doi: 10.1086/510910.
    1. Mohamed AO, Eltaib EH, Ahmed OA, Elamin SB, Malik EM. The efficacies of artesunate-sulfadoxine-pyrimethamine and artemether/lumefantrine in the treatment of uncomplicated, Plasmodium falciparum malaria, in an area of low transmission in central Sudan. Ann Trop Med Parasitol. 2006;100:5–10. doi: 10.1179/136485906X86239.
    1. Mukhtar EA, Gadalla NB, El-zaki S-EG, Mukhtar I, Mansour FA, Babiker A, El-Sayed BB. A comparative study on the efficacy of artesunate plus sulphadoxine/pyrimethamine versus artemether/lumefantrine in eastern Sudan. Malar J. 2007;6:92. doi: 10.1186/1475-2875-6-92.
    1. Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C, Greenwood BM, Whitty CJ. Amodiaquine alone, amodiaquine + sulfadoxine-pyrimethamine, amodiaquine + artesunate, and artemether/lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial. Lancet. 2005;365:1474–1480. doi: 10.1016/S0140-6736(05)66417-3.
    1. Yeka A, Dorsey G, Kamya MR, Talisuna A, Lugemwa M, Rwakimari JB, Staedke SG, Rosenthal PJ, Wabwire-Mangen F, Bukirwa H. Artemether/lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS ONE. 2008;3:e2390. doi: 10.1371/journal.pone.0002390.
    1. Mulenga M, Van geertruyden J-P, Mwananyanda L, Chalwe V, Moerman F, Chilengi R, Van Overmeir C, Dujardin JC, D'Alessandro U. Safety and efficacy of lumefantrine-artemether (Coartem®) for the treatment of uncomplicated Plasmodium falciparum malaria in Zambian adults. Malar J. 2006;5:73. doi: 10.1186/1475-2875-5-73.
    1. Toovey S. Effectiveness of co-artemether in an unsupervised outpatient setting for the treatment of falciparum malaria. Travel Med Infect Dis. 2008;6:29–31. doi: 10.1016/j.tmaid.2007.08.007.
    1. Adjei GO, Kurtzhals JA, Rodrigues OP, Alifrangis M, Hoegberg LC, Kitcher ED, Badoe EV, Lamptey R, Goka BQ. Amodiaquine-artesunate vs artemether/lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up. Malar J. 2008;7:127. doi: 10.1186/1475-2875-7-127.
    1. Falade CO, Ogundele AO, Yusuf BO, Ademowo OG, Ladipo SM. High efficacy of two artemisinin-based combinations (artemether/lumefantrine and artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria. Trop Med Int Health. 2008;13:635–643.
    1. Faye B, Ndiaye JL, Ndiaye D, Dieng Y, Faye O, Gaye O. Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal. Malar J. 2007;6:80. doi: 10.1186/1475-2875-6-80.
    1. Koram KA, Abuaku B, Duah N, Quashie N. Comparative efficacy of antimalarial drugs including ACTs in the treatment of uncomplicated malaria among children under 5 years in Ghana. Acta Trop. 2005;95:194–203. doi: 10.1016/j.actatropica.2005.06.018.
    1. Meremikwu M, Alaribe A, Ejemot R, OyoIta A, Ekenjoku J, Nwachukwu C, Ordu D, Ezedinachi E. Artemether/lumefantrine versus artesunate plus amodiaquine for treating uncomplicated childhood malaria in Nigeria: randomized controlled trial. Malar J. 2006;5:43. doi: 10.1186/1475-2875-5-43.
    1. Owusu-Agyei S, Asante KP, Owusu R, Adjuik M, Amenga-Etego S, Dosoo DK, Gyapong J, Greenwood B, Chandramohan D. An open label, randomised trial of artesunate+amodiaquine, artesunate+chlorproguanil-dapsone and artemether/lumefantrine for the treatment of uncomplicated malaria. PLoS ONE. 2008;3:e2530. doi: 10.1371/journal.pone.0002530.
    1. Sagara I, Dicko A, Djimde A, Guindo O, Kone M, Tolo Y, Thera MA, Sogoba M, Fofana M, Ouattara A, Sissoko M, Jansen HF, Doumbo OK. A randomized trial of artesunate-sulfamethoxypyrazine-pyrimethamine versus artemether/lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali. Am J Trop Med Hyg. 2006;75:630–636.
    1. Sowunmi A, Gbotosho GO, Happi CT, Adedeji AA, Fehintola FA, Folarin OA, Tambo E, Fateye BA. Therapeutic efficacy and effects of artemether/lumefantrine and amodiaquine-sulfalene-pyrimethamine on gametocyte carriage in children with uncomplicated Plasmodium falciparum malaria in southwestern Nigeria. Am J Trop Med Hyg. 2007;77:235–241.
    1. Sutherland CJ, Ord R, Dunyo S, Jawara M, Drakeley CJ, Alexander N, Coleman R, Pinder M, Walraven G, Targett GA. Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether. PLoS Med. 2005;2:e92. doi: 10.1371/journal.pmed.0020092.
    1. Zongo I, Dorsey G, Rouamba N, Tinto H, Dokomajilar C, Guiguemde RT, Rosenthal PJ, Ouedraogo JB. Artemether/lumefantrine versus amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Burkina Faso: a randomized non-inferiority trial. Lancet. 2007;369:491–498. doi: 10.1016/S0140-6736(07)60236-0.
    1. Zongo I, Dorsey G, Rouamba N, Dokomajilar C, Séré Y, Rosenthal PJ, Ouédraogo JB. Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether/lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso. Clin Infect Dis. 2007;45:1453–1461. doi: 10.1086/522985.
    1. Fanello CI, Karema C, van Doren W, Van Overmeir C, Ngamije D, D'Alessandro U. A randomised trial to assess the safety and efficacy of artemether/lumefantrine (Coartem®) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwanda. Trans R Soc Trop Med Hyg. 2007;101:344–350. doi: 10.1016/j.trstmh.2006.06.010.
    1. Guthmann J-P, Cohuet S, Rigutto C, Fortes F, Saraiva N, Kiguli J, Kyomuhendo J, Francis M, Noël F, Mulemba M, Balkan S. High efficacy of two artemisinin-based combinations (artesunate + amodiaquine and artemether + lumefantrine) in Caala, Central Angola. Am J Trop Med Hyg. 2006;75:143–145.
    1. Ndayiragije A, Niyungeko D, Karenzo J, Niyungeko E, Barutwanayo M, Ciza A, Bosman A, Moyou-Somo R, Nahimana A, Nyarushatsi JP, Barihuta T, Mizero L, Ndaruhutse J, Delacollette C, Ringwald P, Kamana J. Efficacité de combinaisons thérapeutiques avec des dérivés de l'artémisinine dans le traitement de l'accès palustre non-complique au Burundi. Trop Med Int Health. 2004;9:673–679. doi: 10.1111/j.1365-3156.2004.01255.x.
    1. Broek I van den, Kitz C, Al Attas S, Libama F, Balasegaram M, Guthmann JP. Efficacy of three artemisinin combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in the Republic of Congo. Malar J. 2006;5:113. doi: 10.1186/1475-2875-5-113.
    1. Piola P, Fogg C, Bajunirwe F, Biraro S, Grandesso F, Ruzagira E, Babigumira J, Kigozi I, Kiguli J, Kyomuhendo J, Ferradini L, Taylor W, Checchi F, Guthmann JP. Supervised versus unsupervised intake of six-dose artemether/lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet. 2005;365:1467–1473. doi: 10.1016/S0140-6736(05)66416-1.
    1. Krudsood S, Chalermrut K, Pengruksa C, Srivilairit S, Silachamroon U, Treeprasertsuk S, Kano S, Brittenham GM, Looareesuwan S. Comparative clinical trial of two-fixed combinations dihydroartemisinin-napthoquine-trimethoprim (DNP®) and artemether/lumefantrine (Coartem®/Riamet®) in the treatment of acute uncomplicated falciparum malaria in Thailand. Southeast Asian J Trop Med Public Health. 2003;34:316–321.
    1. Rojanawatsirivej C, Vijaykadga S, Amklad I, Wilairatna P, Looareesuwan S. Monitoring the therapeutic efficacy of antimalarials against uncomplicated falciparum malaria in Thailand. Southeast Asian J Trop Med Public Health. 2003;34:536–541.
    1. Stohrer JM, Dittrich S, Thongpaseuth V, Vanisaveth V, Phetsouvanh R, Phompida S, Monti F, Christophel EM, Lindegardh N, Annerberg A, Jelinek T. Therapeutic efficacy of artemether/lumefantrine and artesunate-mefloquine for treatment of uncomplicated Plasmodium falciparum malaria in Luang Namtha Province, Lao People's Democratic Republic. Trop Med Int Health. 2004;9:1175–1183. doi: 10.1111/j.1365-3156.2004.01320.x.
    1. Mayxay M, Khanthavong M, Lindegårdh N, Keola S, Barends M, Pongvongsa T, Yapom R, Annerberg A, Phompida S, Phetsouvanh R, White NJ, Newton PN. Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether/lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic. Clin Infect Dis. 2004;39:1139–1147. doi: 10.1086/424512.
    1. Ratcliff A, Siswantoro H, Kenangalem E, Maristela R, Wuwung RM, Laihad F, Ebsworth EP, Anstey NM, Tjitra E, Price RN. Two fixed-dose artemisinin combinations for drug-resistant falciparum and vivax malaria in Papua, Indonesia: an open-label randomised comparison. Lancet. 2007;369:757–765. doi: 10.1016/S0140-6736(07)60160-3.
    1. Hutagalung R, Paiphun L, Ashley EA, McGready R, Brockman A, Thwai KL, Singhasivanon P, Jelinek T, White NJ, Nosten FH. A randomized trial of artemether/lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand. Malar J. 2005;4:46. doi: 10.1186/1475-2875-4-46.
    1. Broek IV van den, Maung UA, Peters A, Liem L, Kamal M, Rahman M, Rahman MR, Bangali AM, Das S, Barends M, Faiz AM. Efficacy of chloroquine + sulfadoxine-pyrimethamine, mefloquine + artesunate and artemether + lumefantrine combination therapies to treat Plasmodium falciparum malaria in the Chittagong Hill Tracts, Bangladesh. Trans R Soc Trop Med Hyg. 2005;99:727–735. doi: 10.1016/j.trstmh.2005.02.007.
    1. Haque R, Thriemer K, Wang Z, Sato K, Wagatsuma Y, Salam MA, Akther S, Akter J, Fukuda M, Miller RS, Noedl H. Therapeutic efficacy of artemether/lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Bangladesh. Am J Trop Med Hyg. 2007;76:39–41.
    1. Thapa S, Hollander J, Linehan M, Cox-Singh J, Bista MB, Thakur GD, Davis WA, Davis TM. Comparison of artemether/lumefantrine with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in Eastern Nepal. Am J Trop Med Hyg. 2007;77:423–430.
    1. Jansen FH, Lesaffre E, Penali LK, Zattera MJ, Die-Kakou H, Bissagnene E. Assessment of the relative advantage of various artesunate-based combination therapies by a multi-treatment Bayesian random-effects meta-analysis. Am J Trop Med Hyg. 2007;77:1005–1009.
    1. Falade C, Manyando C. Safety profile of Coartem® - the evidence base. Malar J. 2009;8:S8.

Source: PubMed

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