The Quinism Foundation Calls on GSK to Take Action to Better Emphasize Limitations of Use for Krintafel® (Tafenoquine)

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Despite Published CDC Recommendations, Krintafel® is Not Indicated by the FDA for Use in Presumptive Anti-Relapse Therapy

The U.S. Army celebrates the U.S. approval of tafenoquine (photo courtesy of the U.S. Army Medical Research and Materiel Command)

GSK must take appropriate action to better emphasize that approved use of Krintafel® is limited to those receiving appropriate antimalarial therapy for acute P. vivax infection and that the drug is NOT indicated for presumptive anti-relapse therapy

The Quinism Foundation has sent correspondence to Evan Berland, at GlaxoSmithKline (GSK) Global Public Health, calling on GSK to take appropriate action to protect the health of asymptomatic U.S. travelers, including proposing further changes to the "Limitation of Use" section of the U.S. Prescribing Information for Krintafel®, to better emphasize that the drug is not indicated by the U.S. Food and Drug Administration (FDA) for presumptive anti-relapse therapy [1].

“Since the 2018 U.S. approval of Krintafel® for prevention of relapse of P. vivax infection in those receiving appropriate antimalarial therapy for acute P. vivax infection," wrote Remington Nevin, MD, MPH, DrPH, executive director of The Quinism Foundation, "the drug has been widely recommended for off-label use in presumptive anti-relapse therapy among asymptomatic U.S. travelers, including in published recommendations by the U.S. Centers for Disease Control and Prevention (CDC)."

"Although the prevention of relapse of P. vivax malaria infection and presumptive anti-relapse therapy of asymptomatic travelers are clearly separate and distinct indications," Dr. Nevin noted, "CDC recommendations nonetheless confuse these terms, and even state erroneously use of Krintafel® in asymptomatic U.S. travelers for presumptive anti-relapse therapy 'is consistent with FDA labeling'."

In his correspondence, Dr. Nevin noted that in a "Dear Health Care Provider" letter, dated February 6, 2020 [2], GSK released data from a recent clinical trial that demonstrates that tafenoquine lacks efficacy in preventing P. vivax relapse when used with antimalarial drugs other than chloroquine. Dr. Nevin noted that the proposed change in the indication for Krintafel® as described by GSK in its "Dear Health Care Provider Letter", which would limit the use of the drug to co-administration with chloroquine only, has critical safety implications for use of the drug by asymptomatic U.S. travelers.

"CDC recommendations for Krintafel® to be co-administered with other drugs, such as atovaquone-proguanil and doxycycline that are commonly used by asymptomatic U.S. travelers for the prophylaxis of malaria," [3] Dr. Nevin wrote, would be "clearly at odds with the proposed change in indication for Krintafel®, which would limit the use of the drug to co-administration with chloroquine only, and presumably only at appropriate doses for treatment of acute P. vivax infection."

"Given that tafenoquine has been demonstrated to lack efficacy in preventing P. vivax relapse when used with antimalarial drugs other than chloroquine," Dr. Nevin noted, "current CDC recommendations for use of Krintafel® with other drugs in presumptive anti-relapse therapy may endanger asymptomatic U.S. travelers by placing them at risk of acute malaria from failed elimination of dormant hypnozoites. Consequently, GSK must take appropriate action to better emphasize that approved use of Krintafel® is limited to those receiving appropriate antimalarial therapy for acute P. vivax infection and that the drug is NOT indicated for presumptive anti-relapse therapy."

Dr. Nevin concluded his letter by recommending removal of the ambiguous term 'radical cure' from the U.S. Prescribing Information to reduce the risk of confusion between prevention of relapse and presumptive anti-relapse therapy.

"Tafenoquine, originally developed by the U.S. Army, is a member of a class of antimalarial drug known as 8-aminoquinolines found during World War II-era studies to be uniformly neurotoxic,” said Dr. Nevin. “A leading researcher involved in testing of this class of drug in rhesus monkeys has noted ‘all of nearly one hundred and forty 8-aminoquinolines examined… produce rather remarkable and highly specific lesions in the central nervous system [CNS].’” [4] “Publicly-available data support a conclusion that tafenoquine shares the liability to CNS neurotoxicity of related 8-aminoquinolines,” said Dr. Nevin.

About The Quinism Foundation

The Quinism Foundation, founded in January 2018, in White River Junction, Vermont, promotes and supports education and research on quinism, the family of medical disorders caused by exposure to quinoline drugs, including mefloquine and tafenoquine.

Dr. Nevin is a board-certified occupational medicine and preventive medicine physician and former U.S. Army medical officer and epidemiologist. He is author of more than 30 scientific publications on malaria and the quinoline antimalarials.

1. GSK. Krintafel® (Tafenoquine) U.S. Prescribing Information. July 2018.
2. GSK. Dear Health Care Provider Letter. February 6, 2020.
3. CDC. Guidance for Using Tafenoquine for Prevention and Antirelapse Therapy for Malaria – United States, 2019. MMWR. 2019;68(46):1062-1068.
4. Schmidt IG, Schmidt LH. Neurotoxicity of the 8-aminoquinolines. III. The effects of pentaquine,isopentaquine, primaquine, and pamaquine on the central nervous system of the rhesus monkey. Journal of neuropathology and experimental neurology. 1951;10(3):231-254.

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