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

Abstract

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P < 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children.

Efficacy of six-dose regimen of artemether-lumefantrine for the treatment of uncomplicatedfalciparummalaria, three years after its introduction into Ethiopia

“…Study by Lefevre et al (2001) showed a high efficacy and safety of six-dose of AL when administrated as four tablets twice daily for three consecutive days. Moreover, a pooled analysis of individual patient data confirmed higher efficacy of six-dose regimen of AL compared to four-dose regimen in children (Makanga et al, 2006). The present result also indicated the importance of maintaining the sixdose regimen for the treatment of uncomplicated falciparum malaria with regularly monitoring for its effectiveness especially in areas where multi-drug resistance falciparum malaria is common (Hastings et al, 2007).…”

“…Series evidences have shown high efficacy of ACTs against P. falciparum even in multidrug-resistant strains of the parasite (Lefevre et al, 2001;Makanga et al, 2006;Adama et al, 2007;Menard et al, 2008;Kaddouri et al, 2008). Nevertheless, substantial re-assessment of the efficacy of this combination therapy against P. falciparum is crucial to monitor possible emergence of resistance and ensuring a continued coverage of effective treatment.…”

Adherence to artemether/lumefantrine treatment in children under real-life situations in rural Tanzania

“…The limited availability of ALu, combined with its rapid onset of action and rapid clearance of severe clinical symptoms, might tempt caretakers to discontinue treatment prematurely 1 and to keep the remaining medicine for an 'anticipated' next attack. 2 This may accelerate the pace of development of drug resistance, 3 thus making it important to maintain high adherence rates to preserve the efficacy of artemisinin-based combination therapy (ACT) in Africa and elsewhere. 4 Adherence levels as high as 90% have been reported in controlled clinical trials.…”

“…Several factors have been reported to influence adherence to treatment, including: education of caretakers and the use of pre-packaged co-blister packets 12,13 ; drug efficacy and rapid improvement of symptoms 1,3,14 ; local perceptions about the disease 15 ; and caretakers perceiving a child playing after a single dose as a sign of cure. 16 Most of these findings, however, are based on studies performed in Asia or during the time when chloroquine (CQ) and SP were the first-line recommended drugs.…”

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

“…A tablet consists of 20 mg artemether and 120 mg lumefantrine. A 3-day, six-dose regimen of artemether-lumefantrine is effi cacious and safe in both adults and children, 7,8 and is recommended for infants and children weighing 5-35 kg, and adults weighing more than 35 kg. Many countries in sub-Saharan Africa have already adopted artemether-lumefantrine as fi rst-line treatment for uncomplicated malaria, or have initiated the implementation process.…”