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

Abstract

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 ms(0.5) (95% confidence interval 4-18 ms(0.5)) relative to baseline at 24 h (P = 0.003). The maximal QTc prolongation observed in any patient was 53 ms(0.5). 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 < 3.0 mmol l(-1)) were observed at any time.

Conclusions: Artekin is safe and effective combination therapy for uncomplicated malaria in children and adults. Although piperaquine is a long half-life drug related to other quinoline compounds including chloroquine and quinine, no clinically significant cardiovascular or metabolic effects were observed.

Figure 1

Mean blood pressure and heart rate during and after treatment. The mean supine blood pressure is on the left of each pair of vertical bars and the erect blood pressure on the right; the upper crossbar indicates systolic and the lower diastolic pressure. Mean heart rate is shown as open circles.

Figure 2

Mean ± SD QT_c interval before treatment (0 h) and at 24 and 48 h.

Figure 3

Mean ± SD plasma glucose before treatment (0 h) and at 24 and 48 h.