Abstract:
Background: The World Health Organization recommends artemisinin-based combination (ACT) for the treatment
of uncomplicated malaria. Post-licensure safety data on newly registered ACT is critical for evaluating their risk/
benefit profile in malaria endemic countries. The clinical safety of the newly registered combination, Eurartesim®,
following its introduction into the public health system in four African countries was assessed.
Methods: This was a prospective, observational, open-label, non-comparative, longitudinal, multi-centre study
using cohort event monitoring. Patients with confirmed malaria had their first dose observed and instructed on
how to take the second and the third doses at home. Patients were contacted on day 5 ± 2 to assess adherence
and adverse events (AEs). Spontaneous reporting of AEs was continued till day 28. A nested cohort who completed full
treatment course had repeated electrocardiogram (ECG) measurements to assess effect on QTc interval.
Results: A total of 10,925 uncomplicated malaria patients were treated with Eurartesim®. Most patients,95% (10,359/
10,925), did not report any adverse event following at least one dose of Eurartesim®. A total of 797 adverse events were
reported. The most frequently reported, by system organ classification, were infections and infestations (3. 24%) and
gastrointestinal disorders (1. 37%). In the nested cohort, no patient had QTcF > 500 ms prior to day 3 pre-dose 3. Three
patients had QTcF > 500 ms (509 ms, 501 ms, 538 ms) three to four hours after intake of the last dose. All the QTcF
values in the three patients had returned to <500 ms at the next scheduled ECG on day 7 (470 ms, 442 ms, 411
ms). On day 3 pre- and post-dose 3, 70 and 89 patients, respectively, had a QTcF increase of ≥ 60 ms compared
to their baseline, but returned to nearly baseline values on day 7.
Conclusion: Eurartesim® single course treatment for uncomplicated falciparum malaria is well-tolerated. QT interval
prolongation above 500 ms may occur at a rate of three per 1,002 patients after the third dose with no association of
any clinical symptoms. QT interval prolongation above 60 ms was detected in less than 10% of the patients without
any clinical abnormalities.
