Tafenoquine

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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
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
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] The mechanism of action 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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Malaria is a mosquito-borne infectious disease that affects vertebrates and Anopheles mosquitoes. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria. The mosquito vector is itself harmed by Plasmodium infections, causing reduced lifespan.

<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.

Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young children and pregnant women. As of 2018, modern treatments, including for severe malaria, continued to depend on therapies deriving historically from quinine and artesunate, both parenteral (injectable) drugs, expanding from there into the many classes of available modern drugs. Incidence and distribution of the disease is expected to remain high, globally, for many years to come; moreover, known antimalarial drugs have repeatedly been observed to elicit resistance in the malaria parasite—including for combination therapies featuring artemisinin, a drug of last resort, where resistance has now been observed in Southeast Asia. As such, the needs for new antimalarial agents and new strategies of treatment remain important priorities in tropical medicine. As well, despite very positive outcomes from many modern treatments, serious side effects can impact some individuals taking standard doses.

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

Glucose-6-phosphate dehydrogenase deficiency (G6PDD), also known as favism, is the most common enzyme deficiency anemia worldwide. It is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. Following a specific trigger, symptoms such as yellowish skin, dark urine, shortness of breath, and feeling tired may develop. Complications can include anemia and newborn jaundice. Some people never have symptoms.

<span class="mw-page-title-main">Artemether</span> Chemical compound

Artemether is a medication used for the treatment of malaria. The injectable form is specifically used for severe malaria rather than quinine. In adults, it may not be as effective as artesunate. It is given by injection in a muscle. It is also available by mouth in combination with lumefantrine, known as artemether/lumefantrine.

<span class="mw-page-title-main">Artesunate</span> Chemical compound

Artesunate (AS) is a medication used to treat malaria. The intravenous form is preferred to quinine for severe malaria. Often it is used as part of combination therapy, such as artesunate plus mefloquine. It is not used for the prevention of malaria. Artesunate can be given by injection into a vein, injection into a muscle, by mouth, and by rectum.

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

Chloroquine is an antiparasitic medication that treats malaria. It works by increasing the levels of haeme in the blood, a substance toxic to the malarial parasite. This kills the parasite and stops the infection from spreading. 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 the NIH does not recommend its use for this purpose. It is taken by mouth.

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

Primaquine is a medication used to treat and prevent malaria and to treat Pneumocystis pneumonia. Specifically it is used for malaria due to Plasmodium vivax and Plasmodium ovale along with other medications and for prevention if other options cannot be used. It is an alternative treatment for Pneumocystis pneumonia together with clindamycin. It is taken by mouth.

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

Plasmodium vivax is a protozoal parasite and a human pathogen. This parasite is the most frequent and widely distributed cause of recurring malaria. Although it is less virulent than Plasmodium falciparum, the deadliest of the five human malaria parasites, P. vivax malaria infections can lead to severe disease and death, often due to splenomegaly. P. vivax is carried by the female Anopheles mosquito; the males do not bite.

<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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<span class="mw-page-title-main">8-Aminoquinoline</span> Antimalarial drug precursor

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<span class="mw-page-title-main">Pamaquine</span> A drug (of the 8-aminoquinoline class) formerly used to treat malaria

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References

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  2. Use During Pregnancy and Breastfeeding
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