Tafenoquine: First Global Approval

• Published in: Drugs (New York, N.Y.) N.Y.), 2018-09, Vol.78 (14), p.1517-1523
• Main Author: Frampton, James E.
• Format: Article
• Language: English
• Subjects: Addition polymerization; AdisInsight Report; Aminoquinolines - adverse effects; Aminoquinolines - pharmacokinetics; Aminoquinolines - therapeutic use; Antimalarial agents; Antimalarials - adverse effects; Antimalarials - pharmacokinetics; Antimalarials - therapeutic use; Apoptosis; Collaboration; Dehydrogenases; Drug Approval; Drug dosages; Enzymes; Erythrocytes; Gametocytes; Humans; Internal Medicine; Liver; Malaria; Malaria - drug therapy; Medicine; Medicine & Public Health; Mitochondria; Parasites; Patients; Pharmacology/Toxicology; Pharmacotherapy; Plasmodium; Polymerization; Prevention; Primaquine; Product development; Prophylaxis; R&D; Research & development; Tafenoquine; Treatment Outcome; United States; United States Food and Drug Administration; Vector-borne diseases
• ISSN: 0012-6667; 1179-1950
• DOI: 10.1007/s40265-018-0979-2

Tafenoquine (Krintafel™, Arakoda™), an orally-active 8-aminoquinoline anti-malarial drug, is a long-acting analogue of primaquine with activity against pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of Plasmodium species that include Plasmodium vivax ( P. vivax ) and Plasmodium falciparum . It has been developed by GlaxoSmithKline (formerly SmithKline Beecham) for the radical cure of P. vivax malaria and by 60 Degrees Pharmaceuticals for the prophylaxis of malaria. The exact mechanism(s) of action underlying the anti- Plasmodium activity of tafenoquine are unknown, although it may exert its effect by inhibiting haematin polymerization and, additionally, by inducing mitochondrial dysfunction leading to the apoptotic-like death of the organism. In July 2018, tafenoquine was approved in the USA for the radical cure of P. vivax malaria in patients aged ≥ 16 years who are receiving appropriate antimalarial therapy for acute P. vivax malaria. Subsequently, in August 2018, tafenoquine was approved in the USA for the prophylaxis of malaria in patients aged ≥ 18 years. This article primarily summarizes the milestones in the development of tafenoquine leading to its first global approval for the radical cure of P. vivax malaria.