Efficacy and Safety of Dihydroartemisinin‐Piperaquine (Artekin) in Cambodian Children and Adults with Uncomplicated Falciparum Malaria

Abstract

The safety and efficacy of a novel combination of dihydroartemisinin (DHA) and piperaquine, Artekin (Holleykin Pharmaceuticals), were assessed in 106 patients (76 children and 30 adults) with uncomplicated falciparum malaria from 2 remote areas in Cambodia. Age-based doses were given at 0, 8, 24, and 32 h. Mean total DHA and piperaquine doses were 9.1 and 73.9 mg/kg, respectively, for children and 6.6 and 52.9 mg/kg for adults. All patients became aparasitemic within 72 h. Excluding the results for 1 child who died on day 4, there was a 96.9% 28-day cure rate (98.6% in children and 92.3% in adults). Patients who had recrudescent infection received low doses of Artekin. Side effects were reported by 22 patients (21%) but did not necessitate premature cessation of therapy. Although Artekin is a promising and inexpensive option for antimalarial therapy, further efficacy and pharmacokinetic studies are needed, especially for its use in children.

Efficacy and safety of dihydroartemisinin-piperaquine

“…Diarrhoea occurred mainly on days 1-3 after treatment and was mild. The median (range) percentage of patients with post-treatment diarrhoea was 5.2% (4.7-9.9%) overall in these studies (Ashley et al, 2004(Ashley et al, , 2005Denis et al, 2002).…”

“…There were differences between studies in the formulation of the drug given (Table 1), and the dosing schedule, with a four-dose regimen being used in nine studies and a three-dose regimen in five studies (Ashley et al, 2005 compared the three-dose and four-dose regimens). In addition four studies dosed by age rather than weight (Denis et al, 2002;Hien et al, 2004;Hung et al, 2004;. Two Thai studies gave extra DHA or artesunate to some of the patients receiving DHA-PIP to investigate whether the cure rate could be enhanced with more artemisinin derivative.…”

“…In one study on the western border of Thailand, non-severe abdominal pain occurred more frequently in the DHA-PIP group than the MAS3 group; 12.3% (22/179) patients compared to 5% (8/176; P = 0.025) (Ashley et al, 2004). In other studies the median (range) proportion of patients reporting abdominal pain was 6.6% (4.7-11%) (Ashley et al, 2005;Denis et al, 2002;. Diarrhoea within the first 28 days of follow-up was reported by 12% of patients in the four-dose DHA-PIP regimen compared with 5% in the MAS3 group, and 8% in a three-dose DHA-PIP regimen (equivalent total dose DHA-PIP in the two regimens).…”

“…Current formulations contain only DHA 40 mg and PIP 320 mg per tablet. DHA-PIP has been evaluated in large clinical trials in Southeast Asia, China and Rwanda (Ashley et al, 2004(Ashley et al, , 2005Denis et al, 2002;Giao et al, 2004;Hien et al, 2004;Hung et al, 2004;Karema et al, 2006;Karunajeewa et al, 2004;Mayxay et al, 2006;Smithuis et al, 2006;Tangpukdee et al, 2005;Wilairatana et al, 2002;Ying et al, 2003). Further studies in Africa, Asia Oceania and South America have been conducted but not yet reported.…”

Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison

“…Several studies in southeast Asia indicate that this combination is a safe and highly effi cacious treatment for uncomplicated multidrug-resistant falciparum malaria in adults and children. [6][7][8][9] Compared with artesunate-mefl oquine, dihydroartemisinin-piperaquine has several potential advantages. First, it is cheaper (around US$1·50 for an adult treatment), which might improve access to eff ective antimalarial treatment for poor populations.…”