Safety evaluation of fixed combination piperaquine plus dihydroartemisinin (Artekin®) in Cambodian children and adults with malaria

Aims  To assess the haemodynamic, electrocardiographic and glycaemic effects of piperaquine-dihydroartemisinin (Artekin®) fixed combination therapy in uncomplicated malaria.Methods  Sixty-two Cambodians (32 children and 30 adults) with falciparum or vivax malaria were given Artekin® given as four age-based oral doses over 32 h. Supine and erect blood pressure, the electrocardiographic QT interval and plasma glucose were measured before treatment and then at regular intervals during a 4-day admission period as part of efficacy and safety monitoring. QT intervals were rate-corrected (QTc) using Bazett's formula.Results  Artekin® therapy was well tolerated and all patients responded to treatment. Average parasite and fever clearance times were 19 and 12 h, respectively. The pretreatment mean fall in systolic blood pressure on standing was 8 ± 6 mmHg and 6-hourly measurements over 72 h showed no significant change (P = 0.48). There was a significant lengthening of the mean QTc to a maximum of 11 ms0.5 (95% confidence interval 4–18 ms0.5) relative to baseline at 24 h (P = 0.003). The maximal QTc prolongation observed in any patient was 53 ms0.5. There was a mean 0.4 mmol l−1 reduction in the post-absorptive plasma glucose during the first 48 h but no episodes of hypoglycaemia (plasma glucose