Interactions between tafenoquine and artemisinin-combination therapy partner drug in asexual and sexual stage Plasmodium falciparum

•Interactions of tafenoquine with other antimalarials are studied in P. falciparum.•Synergistic interactions occur with most drugs in asexual erythrocytic stages.•Tafenoquine will likely increase the potency of other drugs against asexual stages.•Synergism is found with naphthoquine, pyronaridine and piperaquine in gametocytes.•Tafenoquine may interfere with other drugs against P. falciparum gametocytes.

The 8-aminoquinoline tafenoquine (TFQ), a primaquine derivative, is currently in late-stage clinical development for the radical cure of P. vivax. Here drug interactions between TFQ and chloroquine and six artemisinin-combination therapy (ACT) partner drugs in P. falciparum asexual stages and gametocytes were investigated. TFQ was mostly synergistic with the ACT-partner drugs in asexual parasites regardless of genetic backgrounds. However, at fixed ratios of 1:3, 1:1 and 3:1, TFQ only interacted synergistically with naphthoquine, pyronaridine and piperaquine in gametocytes. This study indicated that TFQ and ACT-partner drugs will likely have increased potency against asexual stages of the malaria parasites, whereas some drugs may interfere with each other against the P. falciparum gametocytes.

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