Clinical Pharmacology Update: Arakoda by 60 Degrees Pharmaceuticals

Pharmacy Times, May 2019 Skin & Eye Health, Volume 85, Issue 5

The U.S. FDA has approved Arakoda (tafenoquine) tablets, from 60 Degrees Pharmaceuticals, for the prevention of malaria in patients age 18 and older.1 Arakoda is the first new antimalarial agent to receive FDA approval in more than 18 years. Malaria is transmitted via the bite of an infected mosquito and can be life-threatening. In 2015, malaria accounted for approximately 429,000 fatalities and 212 million clinical cases.2

Pharmacology and Pharmacokinetics

Arakoda is an 8-aminoquinoline antimalarial medication. It is believed to inhibit hematin polymerization and induce apoptotic like death of the parasite that is responsible for malaria. Arakoda displays activity against both P. vivax and P. falciparum, the major parasites associated with malaria.1,2

Arakoda reaches maximum plasma concentrations about 14 hours after oral administration and has a mean terminal half-life of about 16.5 days. The pharmacokinetics of Arakoda were not affected by age, body weight, ethnicity or gender.1

Dosage and Administration

Due to the risk of hemolytic anemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency testing must be performed before beginning treatment with Arakoda. A pregnancy test is recommended for women of reproductive potential prior to beginning the medication. Treatment with Arakoda requires a loading regimen, a maintenance regimen, and a terminal prophylaxis regimen. The loading regimen consists of 200 mg orally once each day for the 3 days immediately prior to travel to a malarious area. The maintenance regimen begins 7 days after the final loading dose and consists of 200 mg orally once a week for the duration of the time in the malarious area. The terminal prophylaxis regimen begins once the patient has left the malarious area. It consists of one final 200 mg dose administered 7 days after the last maintenance dose. The medication should be taken with food. Arakoda can be taken continuously for up to 6 months.1

Clinical Trials

The efficacy of Arakoda has been evaluated in 3 controlled, double-blind, randomized trials. Trials 1 and 2 compared Arakoda to placebo in volunteers, some of whom demonstrated semi-immunity prior to the study. The studies showed that Arakoda reduced the incidence of parasitemia relative to placebo. Trial 3 compared Arakoda to mefloquine in healthy, non-immune participants in a malarious region. After 26 weeks, none of the study participants in either group developed malaria. An additional double-blind, placebo-controlled, randomized trial compared Arakoda to placebo in healthy, non-immune patients and found Arakoda to have prophylactic activity against blood-stage P. falciparum parasites.1

Contraindications, Warnings and Precautions

The use of Arakoda is contraindicated in patients with G6PD deficiency or unknown G6PD status, including women who are breastfeeding an infant with G6PD deficiency or unknown G6PD status. It is also contraindicated in patients with current or a history of psychotic disorders and in patients with known hypersensitivity reactions to any component of Arakoda or other 8-aminoquinoline medications.

Patients using Arakoda should be monitored for clinical signs or symptoms of hemolysis and counseled to stop treatment and seek immediate medical attention if signs develop. Arakoda should not be used during pregnancy. Asymptomatic elevations in blood methemoglobin have occurred during treatment with Arakoda. Serious psychotic adverse reactions have been observed in patients with a history of psychosis or schizophrenia when the medication was administered at doses different from the approved dose. If psychotic symptoms (delusion, grossly disorganized thinking or behavior, or hallucinations) develop, discontinuation of treatment may be warranted, and an evaluation by a mental health professional should occur as soon as possible. Serious hypersensitivity reactions have occurred during treatment with Arakoda. Due to the long half-life of Arakoda, hemolytic anemia, hypersensitivity reactions, methemoglobinemia, and psychiatric effects may be delayed in onset and/or duration. Arakoda should not be administered concomitantly with drugs that are substrates of organic cation transporter-2 or multidrug and toxin extrusion transporters.

The most common adverse reactions (incidence ≥1%) are abnormal dreams, anxiety, back pain, depression, diarrhea, dizziness, headache, increased alanine aminotransferase (ALT), insomnia, nausea, motion sickness, and vomiting.1,2

Reference

  • Arakoda [prescribing information]. Washington, DC: 60 Degrees Pharmaceuticals LLC; 2018. https://arakoda.com/?rel=0?rel=0 Accessed February 25, 2019.
  • US Food and Drug Administration Approves Arakoda (tafenoquine) tablets for oral use; First preventative antimalarial approved in almost two decades [press release]. Washington, DC: 60 Degrees Pharmaceuticals; August 9, 2018. https://60degreespharma.com/wp-content/uploads/2018/08/60P-PR-Release_TQ_Approval-8.21.18.pdf?rel=0?rel=0 Accessed February 25, 2019.