The U.S. Food and Drug Administration (FDA) has approved ARAKODA (tafenoquine), an antimalarial, indicated for the prophylaxis of malaria in patients aged 18 years and older. The approved recommended dosage of ARAKODA is completion of the full course of therapy including loading, maintenance, and terminal prophylaxis regimens as follows:
- Loading regimen: 200 mg once daily with food for 3 days before travel to a malarious area
- Maintenance regimen: 200 mg once weekly with food 7 days after the last loading dose while in the malarious area
- Terminal prophylaxis regimen: 200 mg one time only with food 7 days after the last maintenance dose in the week following exit from the malarious area
ARAKODA is contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency or unknown G6PD status and when breastfeeding by a lactating woman when the infant is found to be G6PD deficient or if the G6PD status of the infant is unknown, patients with a history of psychotic disorders or current psychotic symptoms (i.e., hallucinations, delusions, and/or grossly disorganized behavior), or patients with known hypersensitivity reactions to tafenoquine, other 8-aminoquinolines, or any component of ARAKODA.
Due to the risk of hemolytic anaemia, test all patients for G6PD deficiency prior to prescribing ARAKODA, and pregnancy testing is recommended for females of reproductive potential prior to initiating treatment. Additional information regarding administration, warnings, and precautions can be found in the full prescribing information linked below.
Mechanism of Action
Tafenoquine, an 8-aminoquinoline antimalarial, is active against all the stages of Plasmodium species that include the hypnozoite (dormant stage) in the liver. Studies in vitro with the erythrocytic forms of Plasmodium falciparum suggest that tafenoquine may exert its effect by inhibiting hematin polymerization and inducing apoptotic-like death of the parasite. In addition to its effect on the parasite, tafenoquine causes red blood cell shrinkage in vitro. The molecular target of tafenoquine is not known.
Antimicrobial activity
Tafenoquine is active against pre-erythrocytic (liver) and erythrocytic (asexual) forms as well as gametocytes of Plasmodium species that include P. falciparum and 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.
Resistance
A potential for development of resistance of Plasmodium species to tafenoquine was not evaluated. Studies with the erythrocytic forms of P. falciparum strains/isolates suggest a potential for cross-resistance with primaquine, an 8-aminoquinoline. Clinical relevance of such findings is not known
Drug Interactions
In vitro observations suggest the potential for increased concentrations of substrates of OCT2 or MATE transporters which may increase the risk of toxicity of these substrates. Avoid coadministration with drugs that are substrates of OCT2 or MATE transporters (e.g., dofetilide, metformin). If coadministration cannot be avoided, monitor for drug-related toxicities and consider dosage reduction, if needed, based on approved product labeling of the co-administered drug.
Use in Specific Populations
The pharmacokinetics of tafenoquine was not significantly impacted by age, sex, ethnicity, or body weight. The effect of renal or hepatic impairment on tafenoquine pharmacokinetics is unknown. If ARAKODA is administered to patients with renal or hepatic impairment, monitor for adverse reactions associated with ARAKODA.
Efficacy and Safety
Efficacy of ARAKODA was demonstrated in three double-blind, randomized, controlled studies. Additional information regarding efficacy trials can be found in the full prescribing information linked below.
The most common adverse reactions (incidence ≥ 1%) were headache, dizziness, back pain, diarrhoea, nausea, vomiting, increased ALT, motion sickness, insomnia, depression, abnormal dreams, and anxiety.
Full prescribing information available at www.accessdata.fda.gov