Teriflunomide

Synonyms :
(Z)-2-Cyano-alpha,alpha,alpha-trifluoro-3-hydroxy-P-crotonotoluidide, a 77-1726, a 771726, Aubagio, HMR 1726, HMR1726, Teriflunomida, Teriflunomidum

Status : approved

Therapeutic Classification

IMMUNOSUPPRESSANTS

ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS

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.

Used

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

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.

Dosage

Form Route Strength
Tablet oral 14 mg
Tablet, film coated oral 14 mg
Tablet, film coated oral 7 mg

Pharmacodynamics

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

Toxic Effect

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.

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.

Absorption

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

Half Life

The median half-life is 18 to 19 days.

Protein Binding

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

Elimination Route

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

Clearance

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

Volume of Distribution

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

Chemical Classification

Chemical Name

(Z)-2-Cyano-alpha,alpha,alpha-trifluoro-3-hydroxy-P-crotonotoluidide

Brands

name Dosage form Country
Aubagio tablet, film coated US
Aubagio tablet, film coated US
Aubagio tablet Canada

Drug Drug Interactions

  •  Acenocoumarol  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Aminophylline  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Amodiaquine  : CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine.
  •  Asenapine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Atorvastatin  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Avibactam  : May increase the serum concentration of OAT3 Substrates.
  •  Benzylpenicillin  : May increase the serum concentration of OAT3 Substrates.
  •  Betaxolol  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Bosentan  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Butalbital  : May decrease the serum concentration of Caffeine and Caffeine Containing Products.
  •  Caffeine  : May decrease the serum concentration of Caffeine and Caffeine Containing Products.
  •  Cefaclor  : May increase the serum concentration of OAT3 Substrates.
  •  Cholestyramine  : Bile Acid Sequestrants may decrease the serum concentration of Teriflunomide.
  •  Cimetidine  : May increase the serum concentration of OAT3 Substrates.
  •  Ciprofloxacin  : May increase the serum concentration of OAT3 Substrates.
  •  Clomipramine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Clozapine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Colesevelam  : Bile Acid Sequestrants may decrease the serum concentration of Teriflunomide.
  •  Colestipol  : Bile Acid Sequestrants may decrease the serum concentration of Teriflunomide.
  •  Dacarbazine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Denosumab  : May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
  •  Dihydrocodeine  : May decrease the serum concentration of Caffeine and Caffeine Containing Products.
  •  Drospirenone  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Duloxetine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Empagliflozin  : May increase the serum concentration of OAT3 Substrates.
  •  Estradiol  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Estropipate  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Ezetimibe  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Fexofenadine  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Flutamide  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Fluvastatin  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Fluvoxamine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Furosemide  : May increase the serum concentration of OAT3 Substrates.
  •  Gefitinib  : May increase the serum concentration of BCRP/ABCG2 Substrates.
  •  Irinotecan  : May increase the serum concentration of BCRP/ABCG2 Substrates.
  •  Irinotecan  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Isometheptene  : May decrease the serum concentration of Caffeine and Caffeine Containing Products.
  •  Ketoprofen  : May increase the serum concentration of OAT3 Substrates.
  •  Leflunomide  : May enhance the adverse/toxic effect of Teriflunomide. Leflunomide may increase the serum concentration of Teriflunomide.
  •  Lidocaine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Methotrexate  : May increase the serum concentration of OAT3 Substrates.
  •  Methotrexate  : May increase the serum concentration of BCRP/ABCG2 Substrates.
  •  Methotrexate  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Mexiletine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Mirtazapine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Mitoxantrone  : May increase the serum concentration of BCRP/ABCG2 Substrates.
  •  Mycophenolate mofetil  : May increase the serum concentration of OAT3 Substrates.
  •  Mycophenolic acid  : May increase the serum concentration of OAT3 Substrates.
  •  Natalizumab  : Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
  •  Nateglinide  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Norgestimate  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Olanzapine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Olmesartan  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Pazopanib  : BCRP/ABCG2 Inhibitors may increase the serum concentration of Pazopanib.
  •  Pimecrolimus  : May enhance the adverse/toxic effect of Immunosuppressants.
  •  Pimozide  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Piperazine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Pitavastatin  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Pomalidomide  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Pravastatin  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Procaine  : May increase the serum concentration of OAT3 Substrates.
  •  Propranolol  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Rasagiline  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Repaglinide  : Teriflunomide may increase the serum concentration of Repaglinide.
  •  Rifampicin  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Riluzole  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Riociguat  : May increase the serum concentration of BCRP/ABCG2 Substrates.
  •  Roflumilast  : May enhance the immunosuppressive effect of Immunosuppressants.
  •  Ropinirole  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Rosuvastatin  : Teriflunomide may increase the serum concentration of Rosuvastatin.
  •  Simeprevir  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Simvastatin  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Sipuleucel-T  : Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
  •  Stiripentol  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Tasimelteon  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Theophylline  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Thiothixene  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Tofacitinib  : Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
  •  Topotecan  : BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan.
  •  Torasemide  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Trastuzumab  : May enhance the neutropenic effect of Immunosuppressants.
  •  Trifluoperazine  : May decrease the serum concentration of CYP1A2 Substrates.
  •  Valsartan  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Warfarin  : Teriflunomide may decrease the serum concentration of Warfarin.
  •  Zidovudine  : May increase the serum concentration of OAT3 Substrates.

Food Interactions

  • Food does not affect teriflunomide pharmacokinetics, so take with or without food.

Calculated Property

kind Value Source

Affected organism

Humans and other mammals

Target within organism

  • Dihydroorotate dehydrogenase (quinone), mitochondrial : in Human