The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific

Tafenoquine is being developed for radical cure and post-exposure prophylaxis of Plasmodium vivax malaria. In an open-label study, 1512 Australian Defence Force personnel received one of three tafenoquine 3 d regimens [400 mg once daily (od), 200 mg twice daily (bid), 200 mg od] or daily primaquine (22.5 mg) plus doxycycline (100 mg) over 14 d in Bougainville and in Timor-Leste for post-exposure prophylaxis. The relapse rate of subjects treated in Bougainville with tafenoquine (n = 173) was 1.2% (200 mg bid × 3 d) and 2.3% (400 mg od × 3 d), while primaquine plus doxycycline (n = 175) was 3.4%. For subjects treated in Timor-Leste with tafenoquine (n = 636), the relapse rate was 4.9% (200 mg od × 3 d), 5.3% (200 mg bid × 3 d) and 11.0% (400 mg od × 3d), while primaquine plus doxycycline (n = 289) was 10.0%. The most frequent adverse events reported across all groups were nausea, abdominal distress and diarrhoea. There was a dose-dependent reduction in adverse events with a reduced dose of tafenoquine, with the lowest dose (total 600 mg over 3 d) producing rates of adverse events equivalent to that of primaquine plus doxycycline. The much shorter dosing regimen of tafenoquine should increase compliance, which is often suboptimal with primaquine after leaving an endemic area. [Australian New Zealand Clinical Trials Registry Number 12607000588493]