An integrated assessment of the clinical safety of artemether-lumefantrine: a new oral fixed-dose combination antimalarial drug

Artemether-lumefantrine (A-L), a new fixed-dose oral antimalarial drug, com bines the fast onset of action of artemether (an artemisinin derivative) in terms of parasite clearance with the high cure rate of lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria. The extens ive clinical trial database of A-L has allowed a comprehensive evaluation o f its tolerability and safety in a total of 1869 patients (including 243 ch ildren aged 5-12 years and 368 children aged <5 years). The most commonly r eported and possibly related adverse effects following A-L therapy involved the gastro-intestinal (abdominal pain, anorexia, nausea, vomiting, diarrho ea) and central nervous (headache, dizziness) systems. Pruritus and rash we re reported by <2% of patients. More than 90% of the reported adverse event s, many of which overlapped considerably with the clinical symptomatology o r evolution of acute malaria, were rated mild to moderate in intensity. Com pared to A-L, significantly higher incidences of vomiting and pruritus were observed with chloroquine, dizziness, nausea and vomiting with mefloquine, somnolence with Pyrimethamine + sulfadoxine, and vomiting and dizziness wi th quinine. There were no serious or persistent neurological side-effects r elated to A-L administration. A-L did not lead to any clinically relevant a lterations of the laboratory parameters. Serial electrocardiographic data w ere available for 713 patients. The frequency of QT interval prolongations was similar to or lower than that observed with chloroquine, mefloquine, or artesunate + mefloquine; these changes were considerably less frequent tha n with quinine or halofantrine. All patients with QT prolongation remained asymptomatic and no adverse clinical cardiac events were reported. Artemeth er-lumefantrine can thus be expected to show, both in children and in adult s, a favourable safety profile for the treatment of acute, uncomplicated, P . falciparum malaria; it could as well be a reserve treatment option for tr avellers to endemic countries.