General Information

Krintafel (tafenoquine) is an 8-aminoquinoline derivative with activity against all stages of the P. vivax lifecycle, including hypnozoites.

Krintafel is specifically indicated for the radical cure (prevention of relapse) of Plasmodium vivax malaria in patients aged 16 years and older who are receiving appropriate antimalarial therapy for acute P. vivax infection.

Krintafel is supplied as a tablet for oral administration. The recommended dose in patients aged 16 years and older is a single dose of 300 mg administered as two 150-mg tablets taken together. Co-administer Krintafel on the first or second day of the appropriate antimalarial therapy (e.g. chloroquine) for acute P. vivax malaria. Administer Krintafel with food to increase systemic absorption. Swallow tablets whole. Do not break, crush, or chew the tablets. In the event of vomiting within 1 hour after dosing, a repeat dose should be given. Re-dosing should not be attempted more than once.

Mechanism of Action

Krintafel (tafenoquine), an 8-aminoquinoline antimalarial, is active against the liver stages including the hypnozoite (dormant stage) of P. vivax. In addition to its effect on the parasite, tafenoquine causes red blood cell shrinkage in vitro. Tafenoquine is active against pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of P. vivax. The activity of tafenoquine against the pre-erythrocytic liver stages of the parasite prevents the development of the erythrocytic forms of the parasite, which are responsible for relapses in P. vivax malaria.

Clinical Trial Results

The FDA approval of Krintafel was based on two trials.

Trial 1: a double-blind, controlled clinical trial of 522 adults positive for P. vivax across 3 regions (Asia, Africa, and Latin America). All patients received chloroquine phosphate (600-mg free base on Days 1 and 2 with 300-mg free base on Day 3) to treat the acute infection in addition to either a one-time dose of KRINTAFEL (two 150-mg tablets) on Day 1 or Day 2 (n = 260), an active control (n = 129), or placebo (n = 133). Patients were considered recurrence-free at 6 months if they demonstrated initial parasite clearance, took no anti-malarial medications and were confirmed parasite-free at the 6-month final assessment (i.e., absence of relapse or new infection). The risk of recurrence for Krintafel plus chloroquine was reduced by 76% compared with placebo plus chloroquine.

Trial 2: this was a dose-ranging trial with a study design similar to Trial 1, 57 and 54 subjects were randomized to tafenoquine 300-mg single dose plus chloroquine (same dose as in Trial 1) and placebo plus chloroquine groups, respectively. Tafenoquine plus chloroquine demonstrated a statistically significantly higher rate of recurrence-free efficacy at 6 months compared with the placebo plus chloroquine control group (84% versus 39%, with a difference of 45% and 95%).