Drug-drug interactions

Evaluation of drug-drug interactions has focused on ivermectin and blood stage active antimalarial drugs, and on antimalarial triple combination therapies (i.e. dihydroartemisinin-piperaquine plus mefloquine). Two clinical trials were completed in healthy volunteers to evaluate these interactions. Co-administration of ivermectin plus dihydroartemisinin-piperaquine led to increased concentrations of ivermectin, which imparted a greater mosquito-lethal effect (Clin Pharmacol Ther. 2020 May; 107(5):1221-1230). For antimalarial triple combinations, results demonstrated a significantly decreased exposure to dihydroartemisinin, when dihydroartemisinin-piperaquine was co-administered with mefloquine (Antimicrob Agents Chemother. 2019 Jul 25; 63(8):e00060-19). All combinations were demonstrated to be safe to be implemented in larger patient populations. In addition to the study in healthy volunteers a non-compartmental analysis of data from the above mentioned TRACII study showed a lower exposure of artemether, its metabolite dihydroartemisinin, and lumefantrine than co-administered with amodiaquine (Lancet. 2020 Apr 25; 395(10233):1345-1360).