, Volume 78, Issue 14, pp 1517–1523 | Cite as

Tafenoquine: First Global Approval

  • James E. FramptonEmail author
AdisInsight Report


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.


Compliance with Ethical Standards


The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. James Frampton is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.


  1. 1.
    Crockett M, Kain KC. Tafenoquine: a promising new antimalarial agent. Expert Opin Investig Drugs. 2007;16(5):705–15.CrossRefGoogle Scholar
  2. 2.
    Campo B, Vandal O, Wesche DL, et al. Killing the hypnozoite—drug discovery approaches to prevent relapse in Plasmodium vivax. Pathog Glob Health. 2015;109(3):107–22.CrossRefGoogle Scholar
  3. 3.
    Ebstie YA, Abay SM, Tadesse WT, et al. Tafenoquine and its potential in the treatment and relapse prevention of Plasmodium vivax malaria: the evidence to date. Drug Des Dev Ther. 2016;10:2387–99.CrossRefGoogle Scholar
  4. 4.
    Adis Insight. Drug profile: tafenoquine; 2018.Google Scholar
  5. 5.
    GlaxoSmithKline. KRINTAFEL (tafenoquine) tablets, for oral use: US prescribing information. 2018. Accessed 9 Aug 2018.
  6. 6.
    Food and Drug Administration. NDA210795, NDA approval letter dated 07/20/2018. Accessed 9 Aug 2018.
  7. 7.
    Medicines for Malaria Venture, GlaxoSmithKline. US FDA approves Krintafel (tafenoquine) for the radical cure of P. vivax malaria [media release]. 20 Jul 2018.
  8. 8.
    60 Degrees Pharmaceuticals. US Food and Drug Administration approves ARAKODA™ (tafenoquine) tablets for oral use; first preventative antimalarial approved in almost two decades [media release]. 9 Aug 2018.
  9. 9.
    60 Degrees Pharmaceuticals LLC. ARAKODA™ (tafenoquine) tablets, for oral use: US prescribing information. 2018. Accessed 9 Aug 2018.
  10. 10.
    GlaxoSmithKline. GSK submits regulatory application for single-dose tafenoquine for the treatment of Plasmodium vivax malaria to Australia’s Therapeutic Goods Administration [media release]. 15 Dec 2017.
  11. 11.
    60 Degrees Pharmaceuticals (60P) media center (Press). 28 Apr 2015.
  12. 12.
    Knight. Knight takes right angle with 60 Degrees Pharmaceuticals LLC [media release]. 11 Dec 2015.
  13. 13.
    Dow G, Smith B. The blood schizonticidal activity of tafenoquine makes an essential contribution to its prophylactic efficacy in nonimmune subjects at the intended dose (200 mg). Malar J. 2017;16(1):209.CrossRefGoogle Scholar
  14. 14.
    Fukuda MM, Krudsood S, Mohamed K, et al. A randomized, double-blind, active-control trial to evaluate the efficacy and safety of a three day course of tafenoquine monotherapy for the treatment of Plasmodium vivax malaria. PLoS One. 2017;12(11):e0187376.CrossRefGoogle Scholar
  15. 15.
    Green JA, Mohamed K, Goyal N, et al. Pharmacokinetic interactions between tafenoquine and dihydroartemisinin–piperaquine or artemether–lumefantrine in healthy adult subjects. Antimicrob Agents Chemother. 2016;60(12):7321–32.PubMedPubMedCentralGoogle Scholar
  16. 16.
    FDA. FDA briefing document: tafenoquine tablet, 150 mg_Meeting of the Antimicrobial Drugs Advisory Committee (AMDAC). 2018. Accessed 9 Aug 2018.
  17. 17.
    Lanners HN. Effect of the 8-aminoquinoline primaquine on culture-derived gametocytes of the malaria parasite Plasmodium falciparum. Parasitol Res. 1991;77(6):478–81.CrossRefGoogle Scholar
  18. 18.
    Carvalho L, Luque-Ortega JR, Manzano JI, et al. Tafenoquine, an antiplasmodial 8-aminoquinoline, targets leishmania respiratory complex III and induces apoptosis. Antimicrob Agents Chemother. 2010;54(12):5344–51.CrossRefGoogle Scholar
  19. 19.
    Carvalho L, Martinez-Garcia M, Perez-Victoria I, et al. The oral antimalarial drug tafenoquine shows activity against Trypanosoma brucei. Antimicrob Agents Chemother. 2015;59(10):6151–60.CrossRefGoogle Scholar
  20. 20.
    Vennerstrom JL, Nuzum EO, Miller RE, et al. 8-Aminoquinoline derivatives against blood stage Plasmodium falciparum in vitro inhibit hematin polymerization. Antimicrob Agents Chemother. 1999;42:598–602.CrossRefGoogle Scholar
  21. 21.
    Al Mamun Bhuyan A, Bissinger R, Stockinger K, et al. Stimulation of suicidal erythrocyte death by tafenoquine. Cell Physiol Biochem. 2016;39(6):2464–76.CrossRefGoogle Scholar
  22. 22.
    Waters NC, Edstein MD. 8-Aminoquinolines: primaquine and tafenoquine. In: Staines H, Krishna S, editors. Treatment and prevention of malaria: antimalarial drug chemistry, action and use. Basel: Springer; 2012. p. 69–94.Google Scholar
  23. 23.
    Rueangweerayut R, Bancone G, Harrell EJ, et al. Hemolytic potential of tafenoquine in female volunteers heterozygous for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PD Mahidol variant) versus G6PD-normal volunteers. Am J Trop Med Hyg. 2017;97(3):702–11.CrossRefGoogle Scholar
  24. 24.
    Green JA, Patel AK, Patel BR, et al. Tafenoquine at therapeutic concentrations does not prolong Fridericia-corrected QT interval in healthy subjects. J Clin Pharmacol. 2014;54(9):995–1005.CrossRefGoogle Scholar
  25. 25.
    Miller AK, Harrell E, Ye L, et al. Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects. Br J Clin Pharmacol. 2013;76(6):858–67.CrossRefGoogle Scholar
  26. 26.
    Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, et al. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE): a multicentre, double-blind, randomised, phase 2b dose-selection study. Lancet. 2014;383(9922):1049–58.CrossRefGoogle Scholar
  27. 27.
    US National Institutes of Health. identifier NCT01376167. 2018. Accessed 10 Aug 2018.
  28. 28.
    US National Institutes of Health. identifier NCT02216123. 2018. Accessed 10 Aug 2018.
  29. 29.
    GlaxoSmithKline. Krintafel (tafenoquine succinate tablets) FDA Advisory Committee Briefing Document. 2018. Accessed 9 Aug 2018.
  30. 30.
    Tenero D, Green JA, Goyal N. Exposure-response analyses for tafenoquine after administration to patients with Plasmodium vivax malaria. Antimicrob Agents Chemother. 2015;59(10):6188–94.CrossRefGoogle Scholar
  31. 31.
    Walsh DS, Looareesuwan S, Wilairatana P, et al. Randomized dose-ranging study of the safety and efficacy of WR 238605 (tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand. J Infect Dis. 1999;180(4):1282–7.CrossRefGoogle Scholar
  32. 32.
    Walsh DS, Wilairatana P, Tang DB, et al. Randomized trial of 3-dose regimens of tafenoquine (WR238605) versus low-dose primaquine for preventing Plasmodium vivax malaria relapse. Clin Infect Dis. 2004;39(8):1095–103.CrossRefGoogle Scholar
  33. 33.
    Dow GS, Liu J, Lin G, et al. Summary of anti-malarial prophylactic efficacy of tafenoquine from three placebo-controlled studies of residents of malaria-endemic countries. Malar J. 2015;14:473.CrossRefGoogle Scholar
  34. 34.
    Novitt-Moreno A, Ransom J, Dow G, et al. Tafenoquine for malaria prophylaxis in adults: an integrated safety analysis. Travel Med Infect Dis. 2017;17:19–27.CrossRefGoogle Scholar
  35. 35.
    Nasveld PE, Edstein MD, Reid M, et al. Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrob Agents Chemother. 2010;54(2):792–8.CrossRefGoogle Scholar
  36. 36.
    Dow GS, McCarthy WF, Reid M, et al. A retrospective analysis of the protective efficacy of tafenoquine and mefloquine as prophylactic anti-malarials in non-immune individuals during deployment to a malaria-endemic area. Malar J. 2014;13:49.CrossRefGoogle Scholar
  37. 37.
    US National Institutes of Health. identifier NCT02658435. 2018. Accessed 10 Aug 2018.
  38. 38.
    Data on file, GlaxoSmithKline. 2018.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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