Tafenoquine is an 8-aminoquinoline anti-malarial drug recently approved as a single-dose (300 mg) therapy for Plasmodium vivax relapse prevention, when co-administered with 3-days of chloroquine or other blood schizonticide. Tafenoquine 200 mg weekly after a loading dose is also approved as travellers’ prophylaxis. The development of tafenoquine has been conducted over many years, using various dosing regimens in diverse populations.
There is a pressing need for compounds with broad-spectrum activity against malaria parasites at different life cycle stages to achieve malaria elimination. However, this goal cannot be accomplished without targeting the tenacious dormant liver stage hypnozoite that causes multiple relapses after the first episode of illness. In search for the magic bullet to radically cure Plasmodium vivax malaria, tafenoquine outperformed other candidate drugs and was approved by the US Food and Drug Administration in 2018. Tafenoquine is an 8-aminoquinoline that inhibits multiple life stages of different Plasmodium species.
The cure of patients with Plasmodium vivax malaria requires killing both the asexual stages of the parasites in the blood as well as the dormant liver stages (hypnozoites) — together known as radical cure. Until recently, primaquine was the only available hypnozoiticidal agent. However, in 2018, the Therapeutic Goods Administration in Australia and the Food and Drug Administration in the United States granted licences for tafenoquine for the radical cure of P. vivax malaria and for malaria chemoprophylaxis.
Plasmodium vivax is a frequent cause of recurring malaria in endemic areas as in its latent stage it resides in liver, and is responsible for relapse.
Treatment with 8 aminoquinoline Primaquine is given for 14 days, however studies have shown dismal results with adherence to therapy. A new long acting 8 aminoquinoline, Tafenoquine was introduced that showed efficacy and safety almost similar to Primaquine in a single dose regimen, hence giving hopes for improved compliance and help in eradicating malaria.
This report summarizes the published efficacy and safety evidence for the recommended doses for both indications and provides guidance for the use of tafenoquine in the United States. A more comprehensive review of the literature on tafenoquine along with the biologic rationale for its use has been published elsewhere (10).
Primaquine administration results in H 2O 2 accumulation in bone marrow, where gametocytes and asexual parasites are therefore killed. This finding, by Camarda et al. , supports the theory that the nonperipheral blood origin of recurrent Plasmodium vivax malaria is both hypnozoites (relapse source) and merozoites (recrudescence source), not hypnozoites only.