FDA Approves ARAKODA (Tafenoquine) for the Prophylaxis of Malaria in Patients Aged 18 Years and Older

On August 8, 2018, the U.S. Food and Drug Administration (FDA) 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 anemia, 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 (MOA) and Pharmacokinetics (PK)

  • MOA: Tafenoquine is an 8-aminoquinoline antimalarial drug that is active against all the stages of Plasmodium species including the hypnozoite (dormant stage) in the liver. The molecular target of tafenoquine is not known.
  • General PK: AUC and Cmax increased proportionally over the dose range from 100 mg to 400 mg (0.5 to 2 times the approved recommended dose) following a single tafenoquine dose under fasted conditions in healthy adult subjects. The mean plasma accumulation ratio of tafenoquine was approximately 4.4 when healthy adult subjects were administered tafenoquine 200 mg once weekly for 10 weeks without a loading dose under fasted conditions. The mean (%CV) tafenoquine Cmax was 147 ng/mL (20.7%) and AUC was 70 hr*mcg/mL (24.6%) following single ARAKODA 200 mg doses to healthy adult subjects under fed conditions with a high-calorie, high-fat meal (approximately 1000 calories with 19% protein, 31% carbohydrate, and 50% fat).
  • Absorption: Although no dedicated food effect study was conducted with ARAKODA, the majority of clinical trials were conducted under fed conditions.
  • Distribution: Protein binding of tafenoquine is greater than 99.5%. The apparent volume of distribution of tafenoquine in healthy adult subjects is 2470 L [inter-individual variability (IIV): 24.1%].
  • Elimination: The apparent oral clearance of tafenoquine is approximately 4.2 L/hr (IIV: 23.6%) and mean terminal half-life is approximately 16.5 days (range: 10.8 days to 27.3 days) in healthy adult subjects.
  • Metabolism: Negligible metabolism of tafenoquine was observed in vitro in human liver microsomes and hepatocytes. Unchanged tafenoquine represented the only notable drug-related component in plasma approximately 3 days following tafenoquine once daily oral doses to healthy adult subjects.
  • Excretion: The full excretion profile of tafenoquine in humans is unknown.

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 coadministered 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, diarrhea, nausea, vomiting, increased ALT, motion sickness, insomnia, depression, abnormal dreams, and anxiety.

Full prescribing information is available at https://go.usa.gov/xUtQR.

Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval.

A non-comprehensive list of examples of clinical substrates, inhibitors and inducers for metabolic and transporter system related interactions may be found at https://go.usa.gov/xXY9C.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.