tafenoquine

tafenoquine
IUPAC name	(RS)-2-[(4-[(4-Aminopentyl)(ethyl)amino]pentyl)amino]-6-methoxy-1,3,5-triazin-4(1H)-one
Width	200
Tradename	Krintafel, Arakoda
Drugs.com	Monograph
MedlinePlus	a618052
Licence US	Krintafel
Pregnancy AU	B3
Routes of administration	By mouth
CAS number	106635-80-7
PubChem	115358
ChemSpiderID	103240
UNII	G8GX7P2I3R
KEGG	D10599
ChEBI	134722
ChEMBL	1200749
Chemical formula	C24H28F3N5O3
Molecular weight	491.51 g·mol−1

tafenoquine. It is an 8-aminoquinoline medication used for the radical cure of *Plasmodium vivax* malaria and for prophylaxis against all malaria species. Developed as a successor to primaquine, it offers a single-dose regimen with a significantly longer half-life. Its use is contingent upon testing for glucose-6-phosphate dehydrogenase deficiency due to the risk of hemolytic anemia.

Medical uses

Tafenoquine is indicated for the radical cure of *Plasmodium vivax* malaria in patients aged 16 years and older, in combination with other antimalarials like chloroquine. It targets the dormant hypnozoite stage in the liver, preventing relapse. Additionally, it is approved by the U.S. Food and Drug Administration for chemoprophylaxis against all *Plasmodium* species in adults, with a dosing schedule prior to travel to endemic regions. Its long half-life allows for weekly dosing during exposure and a single post-travel dose, unlike daily regimens required by drugs such as atovaquone/proguanil.

Adverse effects

The most serious adverse effect is dose-related hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase deficiency, necessitating mandatory testing prior to administration. Other common adverse reactions include headache, dizziness, nausea, vomiting, and decreases in hemoglobin. Methemoglobinemia is also a known effect, as with other 8-aminoquinolines. Psychiatric events such as anxiety and insomnia have been reported. Contraindications include pregnancy, breastfeeding, and a history of psychotic disorders.

Pharmacology

Mechanism of action

As an 8-aminoquinoline, its exact mechanism is not fully elucidated but is believed to involve the generation of reactive oxygen species within the parasite, disrupting mitochondrial function and interfering with electron transport. This action is effective against both the blood stage and the hepatic hypnozoite stages of *Plasmodium vivax* and *Plasmodium ovale*.

Pharmacokinetics

Tafenoquine is administered orally and is absorbed in the gastrointestinal tract, with a long terminal half-life of approximately 15 days, enabling prolonged activity. It is extensively metabolized in the liver, primarily via pathways not involving the cytochrome P450 system. Excretion is mainly via the bile and feces.

History

The development of tafenoquine was initiated by the Walter Reed Army Institute of Research in collaboration with GlaxoSmithKline, building upon research into 8-aminoquinolines that began during World War II with pamaquine and later primaquine. Clinical development spanned decades, with pivotal Phase III trials such as the DETECTIVE study conducted across multiple sites in Asia, Africa, and South America. It received its first regulatory approval from the U.S. Food and Drug Administration in 2018, followed by endorsements from the European Medicines Agency and other national bodies.

Society and culture

Tafenoquine is marketed under the trade names Krintafel (for radical cure) and Arakoda (for prophylaxis) by GlaxoSmithKline. Its development and deployment are significant within global malaria eradication efforts, particularly for addressing the challenging hypnozoite reservoir. Access and implementation are influenced by the need for widespread glucose-6-phosphate dehydrogenase deficiency testing infrastructure in endemic countries. The World Health Organization has included it in its Model List of Essential Medicines.

Category:Antimalarial agents Category:8-Aminoquinolines Category:World Health Organization essential medicines