By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved a single-dose treatment for radical cure (prevention of relapse) of Plasmodium vivax malaria. It is the first new treatment for P. vivax in more than 60 years. Tafenoquine, which is chemically similar to primaquine, received priority review as well as orphan and breakthrough therapy designations. It is marketed as Krintafel.

INDICATIONS

Tafenoquine is indicated for the radical cure of P. vivax malaria in patients ≥ 16 years of age who have received appropriate antimalarial therapy for acute P. vivax infection.1

DOSAGE

The recommended measurement is a single dose of 300 mg (2 × 150 mg). It is coadministered on the first or second day of the appropriate antimalarial therapy (e.g., chloroquine) for acute P. vivax malaria.

POTENTIAL ADVANTAGES

Tafenoquine is the first single-dose radical cure for P. vivax because of its long elimination half-life (approximately 15 days). Tafenoquine showed similar recurrence-free efficacy to primaquine for 14 days.2

POTENTIAL DISADVANTAGES

There is risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.1 G6PD testing must be performed before prescribing. Tafenoquine is contraindicated in patients with G6PD deficiency or unknown G6PD status. Use in pregnancy is not recommended, as the G6PD status of the fetus is unknown. Infant G6PD status should be determined before breastfeeding. The long elimination half-life of tafenoquine would be problematic if given inadvertently to a patient with G6PD deficiency. Other adverse reactions include methemoglobinemia, psychiatric effects, and hypersensitivity reactions.

COMMENTS

The efficacy of tafenoquine was established in a double-blind trial that included 522 adult subjects who were positive for P. vivax.1,2 Subjects were randomized to tafenoquine (2 × 150 mg on either day 1 or 2; n = 260), active control (primaquine 15 mg once daily on days 2-15; n = 129), or placebo (n = 133). All subjects received chloroquine 600 mg on days 1 and 2 and 300 mg on day 3. The primary efficacy endpoint was freedom from recurrence at six months. This was defined as initial clearance of P. vivax, took no antimalarial drugs, and were confirmed parasite-free at the six-month assessment. Recurrence-free efficacy rates at six months were 60% for tafenoquine, 64% for primaquine, and 26% for placebo.

CLINICAL IMPLICATIONS

According to the World Health Organization’s latest World Malaria Report, there were 216 million cases of malaria in 2016.3 The two species that pose the greatest threat are Plasmodium falciparum and P. vivax, with the former prevalent in Africa and the latter dominant in Asia, Latin America, and in some parts of Africa.3 The life cycle of the malaria parasite involves the mosquito and human hosts.4 During a blood meal, sporozoites of P. vivax are inoculated into the human host. These infect the liver cells, mature, and reenter the bloodstream, infecting healthy erythrocytes. For P. vivax, a dormant stage (hypnozoites) persists in the liver and is the source of relapse. Tafenoquine is active against the liver stage, including hypnozoites, as well as other stages in the life cycle in humans.1

The limitation of tafenoquine is the risk of hemolytic anemia in G6PD-deficient individuals. The estimated G6PD deficiency prevalence is 7-15%.5 In areas where the frequency of G6PD deficiency allele is > 10%, an estimated 15% of males and 25% of females will be unable to receive tafenoquine.5 In these patients, the World Health Organization recommends primaquine at 0.75 mg base/kg body weight once a week for eight weeks with close medical supervision.6 The cost for tafenoquine was not available at the time of this review.

REFERENCES

  1. Krintafel Prescribing Information. GlaxoSmithKline, July 2018. Available at: https://bit.ly/2wjVJhR. Accessed Aug. 27, 2018.
  2. ClinicalTrials.gov. Ph 2B/3 tafenoquine (TFQ) study in prevention of vivax relapse. Available at: https://bit.ly/2PFw8bj. Accessed Aug. 27, 2018.
  3. World Health Organization. Malaria fact sheet. Available at: https://bit.ly/2Auedkc. Accessed Aug. 27, 2018.
  4. Centers for Disease Control and Prevention, DPDx - Laboratory Identification of Parasites of Public Health Concern. Malaria. Available at: https://bit.ly/2odGl1Z. Accessed Aug. 27, 2018.
  5. Watson J, Taylor WRJ, Bancone G, et al. Implications of current therapeutic restrictions for primaquine and tafenoquine in the radical cure of vivax malaria. PLoS Negl Trop Dis 2018; Apr 20;12(4):e0006440. doi: 10.1371/journal.pntd.0006440. eCollection 2018 Apr.
  6. World Health Organization. Testing for G6PD deficiency for safe use of primaquine in radical cure of P. vivax and P. ovale malaria. Available to view online at: https://bit.ly/2oc1idM. Accessed Aug. 27, 2018.