Pharmacokinetic Interactions between Tafenoquine and Dihydroartemisinin-piperaquine or Artemether-lumefantrine in Healthy Adult Subjects

03 Oct 2016

Justin A. Greena, Khadeeja Mohamed, Navin Goyal, Samia Bouhired, Azra Hussaini, Siôn W. Jones, Gavin C. K. W. Koh, Ivan Kostov, Maxine Taylor, Allen Wolstenholm and Stephan Duparc

Antimicrobial Agents and Chemotherapy

Photo: Pichit/


Tafenoquine is in development as a single-dose treatment for relapse prevention in Plasmodium vivax malaria. Tafenoquine must be co-administered with a blood schizonticide; either chloroquine or artemisinin-based combination therapy (ACT). This open-label, randomized, parallel-group study evaluated potential drug interactions between tafenoquine and two ACTs: dihydroartemisinin-piperaquine or artemether-lumefantrine. Healthy volunteers of either sex, aged 18–65 years, without glucose-6-phosphate dehydrogenase deficiency, were randomized into five cohorts (n=24 per cohort) to receive tafenoquine on day 1 (300 mg) plus: once daily dihydroartemisinin-piperaquine on days 1, 2 and 3 (120:960 mg for 36–<75 kg bodyweight; 160:1280 mg for ≥75–100 kg bodyweight); or artemether-lumefantrine (80:480 mg) two doses 8 h apart on day 1, then twice daily on days 2 and 3; or each drug given alone. The pharmacokinetic parameters of tafenoquine, piperaquine, lumefantrine, artemether, and dihydroartemisinin were determined using non-compartmental methods. Point estimates and 90% confidence intervals were calculated for AUC and Cmax comparisons of tafenoquine plus ACT versus tafenoquine or ACT. All subjects receiving dihydroartemisinin-piperaquine experienced QTc prolongation (a known risk for this drug), but tafenoquine co-administration had no clinically relevant additional effect. Tafenoquine co-administration had no clinically relevant effects on dihydroartemisinin, piperaquine, artemether or lumefantrine pharmacokinetics. Dihydroartemisinin-piperaquine co-administration increased tafenoquine Cmax by 38% (90% confidence interval: 25 to 52%), AUC0–∞ by 12% (1 to 26%) and t1/2 by 29% (19 to 40%); with no effect on AUC0–last. Artemether-lumefantrine co-administration had no effect on tafenoquine pharmacokinetics. Tafenoquine can be co-administered with dihydroartemisinin-piperaquine or artemether-lumefantrine without dose adjustment for any of these compounds. (This clinical trial is registered at with the study identifier NCT02184637).

View the full article on the Antimicrobial Agents and Chemotherapy website.