Tafenoquine

Identification

Summary

Tafenoquine is an antiparasitic agent used for the treatment and prevention of relapse of Vivax malaria.

Brand Names

Arakoda, Krintafel

Generic Name

Tafenoquine

DrugBank Accession Number

DB06608

Background

Tafenoquine is an 8-aminoquinoline analogue of primaquine which varies only on the presence of a 5-phenoxy group.^1,3 It was discovered by the scientists at the Walter Reed Army Institute of Research in 1978 as a substitute for primaquine that would be more effective against relapsing vivax malaria.³ Tafenoquine was further developed collaboratively between GlaxoSmithKline and Medicines for Malaria Venture.² It was FDA approved on July 20, 2018.⁶

Type

Small Molecule

Groups

Approved, Investigational

Structure

3D

Download

MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Tafenoquine (DB06608)

×

Close

Weight

Average: 463.501
Monoisotopic: 463.208276263

Chemical Formula

C₂₄H₂₈F₃N₃O₃

Synonyms

• Tafenoquine

External IDs

• SB 252263
• SB-252263-AAB

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

Pharmacology

Indication

Tafenoquine is used for the treatment and prevention of relapse of Vivax malaria in patients 16 years and older. Tafenoquine is not indicated to treat acute vivax malaria.¹

Malaria is a disease that remains to occur in many tropical countries. Vivax malaria, caused by Plasmodium vivax, is known to be less virulent and seldom causes death. However, it causes a substantive illness-related burden in endemic areas and it is known to present dormant forms in the hepatocytes named hypnozoites which can remain dormant for weeks or even months. This dormant form produces ongoing relapses.¹

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Vivax malaria		••••••••••••		••• •••••

Create Account

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

In vitro studies have shown that tafenoquine presents an average 50% inhibitory concentration of 0.436 mcg against blood stages of seven strains of P. falciparum. In chloroquine-resistant P. falciparum strains the IC50 of tafenoquine was greater when compared with primaquine and it ranged from 0.5 to 33.1 mcg. In studies evaluating the transmission-blocking activity of tafenoquine against the sporogonic stage of P. vivax, it was showed a reduced transmission at doses higher than 25 mg/kg.²

In clinical trials, it was reported a tafenoquine-induced relapse prevention of 91.9% in cases of vivax malaria when pretreated with chloroquine. In prophylactic studies, tafenoquine showed an efficacy range from 84 to 87% against falciparum malaria and 99.1% against vivax malaria.²

Mechanism of action

The mechanism of action of tafenoquine is not well established but studies have reported a longer and more effective action when compared to primaquine.¹ The active moiety of tafenoquine, 5,6 ortho quinone tafenoquine, seems to be redox cycled by P. falciparum which are upregulated in gametocytes and liver stages. Once inside, the oxidated metabolite produces hydrogen peroxide and hydroxyl radicals. It is thought that these radicals produce leads to the parasite death.²

On the other hand, tafenoquine inhibits heme polymerase in blood stage of parasites which explains the activity against blood stages of parasites.²

Absorption

The first-in-human pharmacokinetic study showed a tmax of 13.8 hours and this study suggested that the prolonged absorption from the gut can be due to absorption in the distal gastrointestinal tract combined with a slow clearance. The AUC and Cmax demonstrated an intersubject variability. The bioavailability of tafenoquine is increased in the presence of a high-fat meal by modifying the amount of drug absorbed rather than the rate of absorption. Once absorbed, the concentration of tafenoquine in the whole body is two-fold higher than the corresponding concentration in plasma and it seems to be highly distributed in the liver showing an AUC of approximately 80 times more than what is found in the plasma.²

Volume of distribution

Tafenoquine presents a high volume of distribution of approximately 2 560 L.²

Protein binding

The plasma protein binding of tafenoquine in humans is very high and it represents about 99.5%.⁵

Metabolism

The activation of tafenoquine needs the activity of CYP 2D6 liver microsomal enzyme. This activation step produces the metabolite 5,6 ortho quinone tafenoquine. This metabolite is internalized by the parasite and reduced to radicals by ferredoxin-NADP+ reductase and diflavin reductase enzymes.² In the human, tafenoquine is metabolized by several metabolic pathways including O-demethylation, N-dealkylation, N-oxidation and oxidative deamination as well as C-hydroxylation of the 8-aminoalkylamino side chain.⁵

Hover over products below to view reaction partners

• Tafenoquine
  • 5,6-ortho-quinone

Route of elimination

After degradation by different metabolic pathways, tafenoquine is slowly excreted from the body primarily in the feces and renal elimination of the unchanged form is very low.⁵

Half-life

Tafenoquine presents a long half-life of approximately 14 days.⁴

Clearance

Tafenoquine presents a low clearance of approximately 6 L/h.²

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

Toxicity

Tafenoquine can cause hemolysis in people with glucose-6-phosphate dehydrogenase deficiency.¹ In preclinical studies, renal cell adenomas and carcinomas are increased in male rats with an overdose administration. However, this drug does not seem to be carcinogenic in humans and it was shown to lack mutagenic potential. In fertility studies, tafenoquine resulted in a reduced number of viable fetuses, implantation sites and corpora lutea.^Label

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Integrate drug-drug interactions in your software
Abatacept	The metabolism of Tafenoquine can be increased when combined with Abatacept.
Abemaciclib	The excretion of Abemaciclib can be decreased when combined with Tafenoquine.
Abiraterone	The metabolism of Tafenoquine can be decreased when combined with Abiraterone.
Acebutolol	The metabolism of Tafenoquine can be decreased when combined with Acebutolol.
Acetaminophen	The metabolism of Tafenoquine can be decreased when combined with Acetaminophen.

Food Interactions

• Take with food.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Tafenoquine succinate	DL5J0B8VSS	106635-81-8	CQBKFGJRAOXYIP-UHFFFAOYSA-N

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Arakoda	Tablet, film coated	100 mg/1	Oral	60 Degrees Pharmaceuticals, LLC	2018-08-20	Not applicable
Krintafel	Tablet, film coated	150 mg/1	Oral	GlaxoSmithKline LLC	2019-01-22	Not applicable

Categories

ATC Codes

P01BA07 — Tafenoquine

• P01BA — Aminoquinolines
• P01B — ANTIMALARIALS
• P01 — ANTIPROTOZOALS
• P — ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS

Drug Categories

• Aminoquinolines
• Anti-Infective Agents
• Antimalarials
• Antiparasitic Agents
• Antiparasitic Products, Insecticides and Repellents
• Antiprotozoals
• Cytochrome P-450 CYP2D6 Substrates
• Cytochrome P-450 Substrates
• Heterocyclic Compounds, Fused-Ring
• MATE 1 Inhibitors
• MATE 2 Inhibitors
• MATE inhibitors
• OCT2 Inhibitors
• Quinolines

Classification

Not classified

Affected organisms

• Plasmodium

Chemical Identifiers

UNII

262P8GS9L9

CAS number

106635-80-7

InChI Key

LBHLFPGPEGDCJG-UHFFFAOYSA-N

InChI

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

IUPAC Name

N4-{2,6-dimethoxy-4-methyl-5-[3-(trifluoromethyl)phenoxy]quinolin-8-yl}pentane-1,4-diamine

SMILES

COC1=CC(C)=C2C(OC3=CC=CC(=C3)C(F)(F)F)=C(OC)C=C(NC(C)CCCN)C2=N1

References

General References

1. Rajapakse S, Rodrigo C, Fernando SD: Tafenoquine for preventing relapse in people with Plasmodium vivax malaria. Cochrane Database Syst Rev. 2015 Apr 29;(4):CD010458. doi: 10.1002/14651858.CD010458.pub2. [Article]
2. Ebstie YA, Abay SM, Tadesse WT, Ejigu DA: Tafenoquine and its potential in the treatment and relapse prevention of Plasmodium vivax malaria: the evidence to date. Drug Des Devel Ther. 2016 Jul 26;10:2387-99. doi: 10.2147/DDDT.S61443. eCollection 2016. [Article]
3. Peters W: The evolution of tafenoquine--antimalarial for a new millennium? J R Soc Med. 1999 Jul;92(7):345-52. [Article]
4. Melariri P, Kalombo L, Nkuna P, Dube A, Hayeshi R, Ogutu B, Gibhard L, deKock C, Smith P, Wiesner L, Swai H: Oral lipid-based nanoformulation of tafenoquine enhanced bioavailability and blood stage antimalarial efficacy and led to a reduction in human red blood cell loss in mice. Int J Nanomedicine. 2015 Feb 20;10:1493-503. doi: 10.2147/IJN.S76317. eCollection 2015. [Article]
5. Grayson L., Cosgrove S., Crowe S., Hope W., McCarthy J., Mills J., Mouton J., Paterson D. (2017). Kucer's the use of antibiotics (7th ed.). CRC Press LLc.
6. FDA approval [Link]

External Links

ChemSpider

103196

RxNav

2054023

ChEBI

141487

ChEMBL

CHEMBL298470

PharmGKB

PA166115580

Wikipedia

Tafenoquine

FDA label

Download (369 KB)

MSDS

Download (182 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Not Yet Recruiting	Prevention	Prophylaxis	1
4	Not Yet Recruiting	Treatment	Healthy Lactating Women	1
4	Not Yet Recruiting	Treatment	Malaria caused by plasmodium vivax	1
4	Recruiting	Treatment	Malaria / Malaria caused by plasmodium vivax	1
3	Completed	Treatment	Malaria caused by plasmodium vivax	2

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet, film coated	Oral	100 mg/1
Tablet, film coated	Oral	150 mg/1
Tablet, coated	Oral	150 mg

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US10342791	No	2019-07-09	2035-12-02
US10888558	No	2021-01-12	2035-12-02
US11744828	No	2015-12-02	2035-12-02

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	Insoluble	Melariri P. et al. (2015). Int J Nanomedicine; 10: 1493-1503
logS	2.04	Marella A. et al. (2013). Saudi Pharm J. Jan; 21 (1): 1-12
pKa	9.5	Marella A. et al. (2013). Saudi Pharm J. Jan; 21 (1): 1-12

Predicted Properties

Property	Value	Source
Water Solubility	0.00137 mg/mL	ALOGPS
logP	5.07	ALOGPS
logP	4.97	Chemaxon
logS	-5.5	ALOGPS
pKa (Strongest Acidic)	17.14	Chemaxon
pKa (Strongest Basic)	10.2	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	5	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	78.63 Å2	Chemaxon
Rotatable Bond Count	10	Chemaxon
Refractivity	122.55 m3·mol-1	Chemaxon
Polarizability	47.38 Å3	Chemaxon
Number of Rings	3	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-01ot-0000900000-ac8ff93bfd5606e28a05
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-01p9-0006900000-6c7c2420af19e7f6ade5
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-002b-0000900000-846d2cad9655986d125c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03di-0102900000-4be344ea3e7cbf998c2a
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-029f-0096500000-59f41bf0102a01440cbf
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03di-0926100000-28c059fa15b8cb946178
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Not Available

×

Identify potential medication risks

Easily compare up to 40 drugs with our drug interaction checker.

Get severity rating, description, and management advice.

Learn more

Drug created at March 19, 2008 16:40 / Updated at October 09, 2021 02:48