Teriflunomide
Multiple sclerosis disease-modifying therapies
Multiple sclerosis disease-modifying therapiesPregnancy: contraindicated
Contraindicated: teratogenic and embryolethal in animals. Women who wish to become pregnant stop it and undergo accelerated elimination first.
An oral DHODH inhibitor for relapsing multiple sclerosis; it can injure the liver and harm a fetus, and stays in the body for months.
Quick facts
- Group
- Multiple sclerosis disease-modifying therapies
- Target
- Dihydroorotate dehydrogenase (DHODH)
- Used for
- Relapsing forms of multiple sclerosis
- Key effects
- Headache · Diarrhoea and nausea · Hair thinning
- Monitor
- Transaminases · Pregnancy test before starting
- ATC
- L04AK02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows teriflunomide (named A77 1726 in the crystal) bound to human dihydroorotate dehydrogenase, next to its FMN cofactor and orotate.
Teriflunomide reversibly inhibits dihydroorotate dehydrogenase, the mitochondrial enzyme of de novo pyrimidine synthesis. The proliferation of activated T and B lymphocytes, which need new pyrimidines to divide, falls. The exact way this helps multiple sclerosis is not known but may involve fewer activated lymphocytes in the CNS.
- Teriflunomide inhibits DHODH in mitochondria
- De novo pyrimidine synthesis slows
- Activated lymphocytes proliferate less
- Fewer relapses in relapsing MS
Indications
- Relapsing forms of multiple sclerosis Multiple sclerosis →
Adverse effects
Common
- Headache
- Diarrhoea and nausea
- Hair thinning (alopecia)
- Raised ALT
Contraindications
- Pregnancy, and women who could become pregnant without effective contraception
- Severe liver impairment
- Current leflunomide treatment; hypersensitivity to teriflunomide or leflunomide
Key interactions
- Leflunomide
- Contraindicated together
- Warfarin
- Peak INR may fall; INR is monitored closely
- Rosuvastatin and other BCRP or OATP1B1/1B3 substrates
- Higher exposure of those drugs; their doses are limited
- Oral contraceptives (ethinylestradiol, levonorgestrel)
- Higher hormone exposure; the contraceptive is chosen with care
- Other hepatotoxic drugs
- Higher risk of severe liver injury
- Live vaccines
- Not recommended
What is monitored
- Transaminases and bilirubin within 6 months before starting; ALT at least monthly for the first 6 months
- Recent complete blood count before starting
- Pregnancy test before starting in women who could become pregnant
- Screening for latent tuberculosis
- Blood pressure at the start and during treatment
Administration and safety
- Accelerated elimination with cholestyramine or activated charcoal is used for liver injury, severe reactions, planned pregnancy or when stopping in women who could become pregnant
- Not started during an active infection
Pregnancy and breastfeeding
Contraindicated: teratogenic and embryolethal in animals. Women who wish to become pregnant stop it and undergo accelerated elimination first.
Nursing care
- Confirm a negative pregnancy test and effective contraception
- Teach signs of liver injury: nausea, vomiting, abdominal pain, tiredness, loss of appetite, jaundice
- Report fever, infections, rash or numbness of hands and feet
- Explain that hair thinning is common
Pharmacokinetics
- Absorption
- Oral, once daily
- Elimination
- Very slow: on average 8 months (up to 2 years) to reach very low levels unless cholestyramine or activated charcoal is given for 11 days
- Half-life
- Median about 18 to 19 days
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme does teriflunomide inhibit?
Dihydroorotate dehydrogenase, in de novo pyrimidine synthesis.
What are teriflunomide's two boxed warnings?
Hepatotoxicity and embryofetal toxicity.
How is teriflunomide removed quickly from the body?
An accelerated elimination procedure with cholestyramine or activated charcoal.
Which drug must not be combined with teriflunomide?
Leflunomide.
Connections
← Back to the class: Multiple sclerosis disease-modifying therapies
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - TERIFLUNOMIDE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Teriflunomide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 1D3H: HUMAN DIHYDROOROTATE DEHYDROGENASE COMPLEXED WITH ANTIPROLIFERATIVE AGENT A771726 (RCSB Protein Data Bank, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.