Tafenoquine

Last updated

Tafenoquine
(RS)-Tafenoquin Structural Formula V1.svg
Clinical data
Pronunciationta fen' oh kwin
Trade names Krintafel, Arakoda, others
Other namesEtaquine, [1] WR 238605, [1] SB-252263
AHFS/Drugs.com Monograph
MedlinePlus a618050
License data
Pregnancy
category
Routes of
administration
By mouth
Drug class Antimalarial
ATC code
Legal status
Legal status
Identifiers
  • N-[2,6-Dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl]pentane-1,4-diamine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
Chemical and physical data
Formula C24H28F3N3O3
Molar mass 463.501 g·mol−1
3D model (JSmol)
  • FC(F)(F)c3cc(Oc1c(OC)cc(NC(C)CCCN)c2nc(OC)cc(c12)C)ccc3
  • InChI=1S/C24H28F3N3O3/c1-14-11-20(32-4)30-22-18(29-15(2)7-6-10-28)13-19(31-3)23(21(14)22)33-17-9-5-8-16(12-17)24(25,26)27/h5,8-9,11-13,15,29H,6-7,10,28H2,1-4H3 Yes check.svgY
  • Key:LBHLFPGPEGDCJG-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Tafenoquine, sold under the brand name Krintafel among others, is a medication used to prevent and to treat malaria. [3] With respect to acute malaria, it is used together with other medications to prevent relapse by Plasmodium vivax . [3] It may be used to prevent all types of malaria. [3] It is taken by mouth. [4]

Contents

Common side effects include vomiting, headache, and dizziness. [4] Other side effects may include methemoglobinemia, trouble sleeping, and anaphylaxis. [4] In people with G6PD deficiency, red blood cell breakdown may occur. [4] Use in pregnancy is not recommended. [4] Tafenoquine is in the 8-aminoquinoline family of medications. [3] How it works is unclear but it is effective both in the liver and bloodstream. [4] [3] A possible mechanism of action and other novel perspectives have been published. [5]

Tafenoquine was approved for medical use in Australia and in the United States in 2018. [3] [6] Tafenoquine is related to primaquine. [7]

Medical use

Prevention

Tafenoquine may be used to prevent all types of malaria. [3] For this use 200 mg 3 days before travel then 200 mg per week until one week after travel is recommended. [7]

Treatment

Tafenoquine is used for eliminating the hypnozoite stage of Plasmodium vivax and Plasmodium ovale that is responsible for relapse of these malarial infections, even when the blood stages are successfully cleared. Primaquine for 14 days can also be used for this. The advantage of tafenoquine is that it has a long half-life (2–3 weeks) and therefore a single treatment is sufficient. [8] For this use, a single dose of 300 mg is recommended. [7] It is used with another medication, such as chloroquine, that kills the parasites in the bloodstream. [9]

There is a need to determine whether or not tafenoquine kills the numerous, non-circulating asexual P. vivax parasites that are now known to occur in the spleen, bone marrow, and possibly elsewhere in chronic infections. [10] [11]

Chemistry

Tafenoquine contains a stereocenter and consists of two enantiomers. This is a mixture of (R) - and the (S) - Form:

Enantiomers of tafenoquine
(R)-Tafenoquin Structural Formula V1.svg
(R)-Form
(S)-Tafenoquin Structural Formula V1.svg
(S)-Form

History

Tafenoquine was approved for medical use in Australia and in the United States in 2018. [3] [6] Tafenoquine was given an orphan drug designation and was granted breakthrough therapy status in 2013 in the United States. [12] [13]

Society and culture

One version is made by GlaxoSmithKline. [4] While another is made by 60 Degrees Pharmaceutical. [14]

Names

Etaquine was a generic name proposed by WRAIR, and subsequently rejected by CDER.[ citation needed ]

Trade names

Related Research Articles

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<span class="mw-page-title-main">Mefloquine</span> Pharmaceutical drug

Mefloquine, sold under the brand name Lariam among others, is a medication used to prevent or treat malaria. When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure. It can be used to treat mild or moderate malaria but is not recommended for severe malaria. It is taken by mouth.

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<span class="mw-page-title-main">Glucose-6-phosphate dehydrogenase deficiency</span> Medical condition

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<span class="mw-page-title-main">Chloroquine</span> Medication used to treat malaria

Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication. Chloroquine is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus. While it has not been formally studied in pregnancy, it appears safe. It was studied to treat COVID-19 early in the pandemic, but these studies were largely halted in the summer of 2020, and is not recommended for this purpose. It is taken by mouth.

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<i>Plasmodium ovale</i> Species of single-celled organism

Plasmodium ovale is a species of parasitic protozoon that causes tertian malaria in humans. It is one of several species of Plasmodium parasites that infect humans, including Plasmodium falciparum and Plasmodium vivax which are responsible for most cases of malaria in the world. P. ovale is rare compared to these two parasites, and substantially less dangerous than P. falciparum.

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References

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  2. Use During Pregnancy and Breastfeeding
  3. 1 2 3 4 5 6 7 8 Haston JC, Hwang J, Tan KR (November 2019). "Guidance for Using Tafenoquine for Prevention and Antirelapse Therapy for Malaria - United States, 2019". MMWR. Morbidity and Mortality Weekly Report. 68 (46): 1062–1068. doi:10.15585/mmwr.mm6846a4. PMC   6871897 . PMID   31751320.
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  6. 1 2 Hounkpatin AB, Kreidenweiss A, Held J (March 2019). "Clinical utility of tafenoquine in the prevention of relapse of Plasmodium vivax malaria: a review on the mode of action and emerging trial data". Infection and Drug Resistance. 12: 553–570. doi: 10.2147/IDR.S151031 . PMC   6411314 . PMID   30881061.
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  8. Elmes NJ, Nasveld PE, Kitchener SJ, Kocisko DA, Edstein MD (November 2008). "The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific". Transactions of the Royal Society of Tropical Medicine and Hygiene. 102 (11): 1095–1101. doi:10.1016/j.trstmh.2008.04.024. PMID   18541280.
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  11. Markus MB (May 2023). "Putative Contribution of 8-Aminoquinolines to Preventing Recrudescence of Malaria". Tropical Medicine and Infectious Disease. 8 (5): 278. doi: 10.3390/tropicalmed8050278 . PMC   10223033 . PMID   37235326.
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