Identification

Name
Teriflunomide
Accession Number
DB08880
Description

Teriflunomide is the active metabolite of leflunomide, and it acts as an immunomodulatory agent by inhibiting pyrimidine synthesis. It is marketed under the name Aubagio® and is indicated for the treatment of multiple sclerosis, specifically relapsing forms. The FDA label states an important warning about the risk of hepatoxicity and teratogenicity for patients using teriflunomide.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 270.2073
Monoisotopic: 270.061612157
Chemical Formula
C12H9F3N2O2
Synonyms
  • (Z)-2-cyano-alpha,alpha,alpha-trifluoro-3-hydroxy-p-crotonotoluidide
  • Teriflunomida
  • Tériflunomide
  • Teriflunomide
  • Teriflunomidum
External IDs
  • A 77-1726
  • A 771726
  • A-771726
  • A77 1726
  • A771726
  • HMR 1726
  • HMR-1726
  • HMR1726

Pharmacology

Indication

Used in the treatment of relapsing forms of multiple sclerosis (MS).

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Teriflunomide is an immunomodulatory agent that decreases the amount of activated CNS lymphocytes, which results in anti-inflammatory and antiproliferative effects.

Mechanism of action

The exact mechanism by which teriflunomide acts in MS is not known. What is known is that teriflunomide prevents pyrimidine synthesis by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase, and this may be involved in its immunomodulatory effect in MS.

TargetActionsOrganism
UDihydroorotate dehydrogenase (quinone), mitochondrial
inhibitor
Humans
Absorption

After oral administration of teriflunomide, maximum plasma concentrations are reached, on average, in 1-4 hours.

Volume of distribution

After a single intravenous dose, the volume of distribution is 11 L.

Protein binding

Teriflunomide is extensively plasma protein bound(>99%).

Metabolism

Teriflunomide mainly undergoes hydrolyis to minor metabolites. Other minor metabolic pathways include oxidation, N-acetylation and sulfate conjugation. Teriflunomide is not metabolized by CYP450 or flavin monoamine oxidase.

Route of elimination

Teriflunomide is eliminated unchanged and mainly through bile. Specifically 37.5% is eliminated in the feces and 22.6% in urine.

Half-life

The median half-life is 18 to 19 days.

Clearance

After a single IV dose, teriflunomide has a total body clearance of 30.5 mL/h.

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Teriflunomide is contraindicated in pregnant women or women of childbearing age due to the risk of teratogenicity. Teriflunomide is also contraindicated in severe hepatic impairment due to reports of hepatotoxicity, hepatic failure, and death.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Teriflunomide.
AbemaciclibTeriflunomide may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
AcenocoumarolThe serum concentration of Acenocoumarol can be decreased when it is combined with Teriflunomide.
AcetaminophenThe serum concentration of Acetaminophen can be decreased when it is combined with Teriflunomide.
Activated charcoalActivated charcoal can cause a decrease in the absorption of Teriflunomide resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcyclovirThe serum concentration of Acyclovir can be decreased when it is combined with Teriflunomide.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Teriflunomide.
Adenovirus type 7 vaccine liveThe risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Teriflunomide.
AfatinibTeriflunomide may decrease the excretion rate of Afatinib which could result in a higher serum level.
AgomelatineThe serum concentration of Agomelatine can be decreased when it is combined with Teriflunomide.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AubagioTablet14 mgOralSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2013-11-15Not applicableCanada flag
AubagioTablet, film coated14 mgOralSanofi Aventis Groupe2013-08-26Not applicableEU flag
AubagioTablet, film coated14 mgOralSanofi Aventis Groupe2013-08-26Not applicableEU flag
AubagioTablet, film coated14 mgOralSanofi Aventis Groupe2013-08-26Not applicableEU flag
AubagioTablet, film coated14 mg/1OralGenzyme Corporation2013-05-01Not applicableUS flag
AubagioTablet, film coated14 mgOralSanofi Aventis Groupe2013-08-26Not applicableEU flag
AubagioTablet, film coated14 mgOralSanofi Aventis Groupe2013-08-26Not applicableEU flag
AubagioTablet, film coated7 mg/1OralGenzyme Corporation2013-05-01Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
TeriflunomideTablet, film coated14 mg/1OralMsn Laboratories Private Limited2019-04-24Not applicableUS flag
TeriflunomideTablet, film coated7 mg/1OralAmneal Pharmaceuticals NY LLC2018-10-01Not applicableUS flag
TeriflunomideTablet, film coated14 mg/1OralGlenmark Pharmaceuticals Inc., USA2020-05-01Not applicableUS flag
TeriflunomideTablet, film coated14 mg/1OralAmneal Pharmaceuticals of New York Llc2020-06-17Not applicableUS flag
TeriflunomideTablet, film coated7 mg/1OralMsn Laboratories Private Limited2019-04-24Not applicableUS flag
TeriflunomideTablet, film coated7 mg/1OralGlenmark Pharmaceuticals Inc., USA2020-05-01Not applicableUS flag
TeriflunomideTablet, film coated14 mg/1OralAmneal Pharmaceuticals NY LLC2018-10-01Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L04AA31 — Teriflunomide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as trifluoromethylbenzenes. These are organofluorine compounds that contain a benzene ring substituted with one or more trifluoromethyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Trifluoromethylbenzenes
Direct Parent
Trifluoromethylbenzenes
Alternative Parents
Anilides / N-arylamides / Vinylogous acids / Secondary carboxylic acid amides / Nitriles / Enols / Organopnictogen compounds / Organofluorides / Organic oxides / Hydrocarbon derivatives
show 2 more
Substituents
Alkyl fluoride / Alkyl halide / Anilide / Aromatic homomonocyclic compound / Carbonitrile / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Enol / Hydrocarbon derivative
show 13 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
nitrile, enamide, aromatic amide, enol, (trifluoromethyl)benzenes (CHEBI:68540)

Chemical Identifiers

UNII
1C058IKG3B
CAS number
163451-81-8
InChI Key
UTNUDOFZCWSZMS-YFHOEESVSA-N
InChI
InChI=1S/C12H9F3N2O2/c1-7(18)10(6-16)11(19)17-9-4-2-8(3-5-9)12(13,14)15/h2-5,18H,1H3,(H,17,19)/b10-7-
IUPAC Name
(2Z)-2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]but-2-enamide
SMILES
C\C(O)=C(/C#N)C(=O)NC1=CC=C(C=C1)C(F)(F)F

References

Synthesis Reference

Keshav Deo, Samir Patel, Snehal Dhol, Sunil Sanghani, Vishal Ray, " PROCESS FOR PREPARING TERIFLUNOMIDE." U.S. Patent US20110092727, issued April 21, 2011.

US20110092727
General References
  1. O'Connor PW, Li D, Freedman MS, Bar-Or A, Rice GP, Confavreux C, Paty DW, Stewart JA, Scheyer R: A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology. 2006 Mar 28;66(6):894-900. [PubMed:16567708]
  2. Tallantyre E, Evangelou N, Constantinescu CS: Spotlight on teriflunomide. Int MS J. 2008 Jun;15(2):62-8. [PubMed:18782502]
KEGG Drug
D10172
PubChem Compound
54684141
PubChem Substance
347827807
ChemSpider
16737143
BindingDB
50018011
RxNav
1310520
ChEBI
68540
ChEMBL
CHEMBL973
ZINC
ZINC000013512456
PDBe Ligand
A26
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Teriflunomide
AHFS Codes
  • 92:20.00 — Immunomodulatory Agents
PDB Entries
1d3h / 1tv5
FDA label
Download (527 KB)
MSDS
Download (124 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentDisseminated Sclerosis1
4RecruitingTreatmentDisseminated Sclerosis2
4RecruitingTreatmentMultiple Sclerosis, Pharmacokinetics1
4RecruitingTreatmentRelapsing Multiple Sclerosis (RMS)1
4RecruitingTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
3Active Not RecruitingTreatmentDisseminated Sclerosis2
3Active Not RecruitingTreatmentRelapsing Multiple Scelrosis1
3Active Not RecruitingTreatmentRelapsing Multiple Sclerosis (RMS)2
3CompletedTreatmentDisseminated Sclerosis7
3CompletedTreatmentRelapsing Multiple Sclerosis (RMS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral14 mg
Tablet, coatedOral14 mg
Tablet, film coatedOral14 mg
Tablet, coated14 mg
Tablet
Tablet, film coatedOral14 mg/1
Tablet, film coatedOral7 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6794410No2004-09-212022-04-15US flag
US9186346No2015-11-172034-02-04US flag
US8802735No2014-08-122030-09-14US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySoluble in DMSO (practically insoluble in water).From FDA label.
Predicted Properties
PropertyValueSource
Water Solubility0.0124 mg/mLALOGPS
logP2.3ALOGPS
logP2.14ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)5.48ChemAxon
pKa (Strongest Basic)-3.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area73.12 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity64.39 m3·mol-1ChemAxon
Polarizability23.15 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Ubiquinone binding
Specific Function
Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
Gene Name
DHODH
Uniprot ID
Q02127
Uniprot Name
Dihydroorotate dehydrogenase (quinone), mitochondrial
Molecular Weight
42866.93 Da
References
  1. Palmer AM: Teriflunomide, an inhibitor of dihydroorotate dehydrogenase for the potential oral treatment of multiple sclerosis. Curr Opin Investig Drugs. 2010 Nov;11(11):1313-23. [PubMed:21157651]
  2. Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA: The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase. Biochemistry. 1996 Jan 30;35(4):1270-3. [PubMed:8573583]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Chan A, de Seze J, Comabella M: Teriflunomide in Patients with Relapsing-Remitting Forms of Multiple Sclerosis. CNS Drugs. 2016 Jan;30(1):41-51. doi: 10.1007/s40263-015-0299-y. [PubMed:26758290]
  2. FDA label, Teriflunomide [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Kis E, Nagy T, Jani M, Molnar E, Janossy J, Ujhellyi O, Nemet K, Heredi-Szabo K, Krajcsi P: Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: implications for drug resistance. Ann Rheum Dis. 2009 Jul;68(7):1201-7. doi: 10.1136/ard.2007.086264. Epub 2008 Apr 8. [PubMed:18397960]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da

Drug created on May 19, 2013 20:55 / Updated on October 27, 2020 11:13

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