Teriflunomide

Products

Teriflunomide is commercially available in the form of film-coated tablets (Aubagio). It was approved in many countries in 2013. Teriflunomide can be taken perorally, unlike earlier MS medications, and does not need to be injected.

Structure and properties

Teriflunomide (C12H9F3N2O2, Mr = 270.2 g/mol) is the active metabolite of the prodrug leflunomide (Arava), which is approved for arthritis treatment. It exists as a white powder that is practically insoluble in water.

Effects

Teriflunomide (ATC L04AA31) has antiproliferative, immunomodulatory, and anti-inflammatory properties. It inhibits the new synthesis of pyrimidine in mitochondria. The effects are due to reversible inhibition of the enzyme dihydroorotate dehydrogenase. Neosynthesis is particularly significant for rapidly dividing cells such as lymphocytes. In multiple sclerosis, the number of activated B and T lymphocytes in the central nervous system is reduced. Teriflunomide reduces the relative risk of new relapses by about 30%, thereby mitigating disease progression. Teriflunomide has a very long half-life of up to 19 days.

Indications

For the treatment of relapsing-remitting multiple sclerosis.

Dosage

According to the SmPC. The drug is taken once daily and independently of meals.

Contraindications

  • Hypersensitivity
  • Pregnancy
  • Severe liver disease
  • Combination with leflunomide (Arava, generics)

Teriflunomide has fruit-damaging and liver-toxic properties. Full precautions can be found in the drug label.

Interactions

Teriflunomide is a substrate and inhibitor of BCRP, inhibits CYP2C8, OATP1B1, and OAT3, and induces CYP1A2. Interactions are possible with vitamin K antagonists and ethinyl estradiol, among others.

Adverse effects

The most common potential adverse effects include elevated liver enzymes (ALT), hair loss, diarrhea, influenza, nausea, and sensory disturbances. Teriflunomide has a potential for rare serious adverse reactions such as hepatotoxicity, renal disease, hyperkalemia, and severe skin reactions.