The anti-malarial drug tafenoquine (Krintafel, GlaxoSmithKline) reduces relapse risk in patients with Plasmodium vivax, but declines in hemoglobin were noted in some patients, according to data from two phase 3, double-blind, randomized controlled trials. Both studies were published online in the New England Journal of Medicine. Data from the two studies led to FDA approval of the drug last year.

The first study, the Dose and Efficacy Trial Evaluating Chloroquine and Tafenoquine in Vivax Elimination, enrolled 522 patients from Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. All patients had confirmed P vivax infection and received a 3-day course of chloroquine plus study medication. Marcus V.G. Lacerda and colleagues randomly assigned patients in a 2:1:1 manner to receive a single dose of tafenoquine, primaquine, or placebo. Matched placebos were administered as needed to ensure blinding and patients were followed for 6 months.

People with normal G6PD activity were included

Due to the risk associated with both tafenoquine and primaquine for drug-induced hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, only those with normal G6PD activity were included in the study. In the intention-to-treat population, the researchers found that 62.4% of patients in the tafenoquine group were recurrence-free at 6 months compared with 69.6% in the primaquine group and 27.7% in the placebo group.

With respect to safety, the researchers found the greatest decline in hemoglobin among patients in the tafenoquine group, with 14 of 260 patients experiencing a decline of >3 g/dL or ≥ 30% of baseline. This was noted in only 2 of 133 patients in the placebo group and 2 of 129 patients in the primaquine group. No symptoms of anemia were reported, and no clinical intervention was required for any patient.

The study compared tafenoquine to primaquine

The second study, the Global Assessment of Tafenoquine Hemolytic Risk, also compared tafenoquine to primaquine for prevention of P vivaxrelapse. In this trial, Alejandro Llanos?Cuentas, MD, from the Universidad Peruana Cayetano Heredia in Peru, and colleagues enrolled 251 patients with confirmed P vivax parasitemia from seven hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand. An effort was made to recruit female patients with moderate G6PD levels; however, only one person met the inclusion criteria. All other recruited patients had normal G6PD enzyme activity.

In an accompanying editorial, Nicholas J. White writes: "The two current studies showed that with appropriate G6PD testing, tafenoquine can be given safely" and "solves the potentially important problem of poor adherence to daily primaquine by providing a radical cure in a single dose." However, White continues, "the requirement for accurate quantitative G6PD assessments and the current prescribing restrictions will limit the potential deployment of tafenoquine, at least in the immediate future."

This sentiment is echoed by authors of the DETECTIVE trial. "The qualitative [G6PD] test evaluated here failed to identify 16 patients most at risk for hemolysis. If tafenoquine use is expanded, adoption of reliable quantitative point-of-care G6PD tests will be needed; such tests are not currently available but are in development," they conclude.