Pharmacology · Conventional disease-modifying antirheumatic drugs (DMARDs)
Leflunomide !
A rheumatoid arthritis tablet that stops activated lymphocytes making pyrimidines. It stays in the body for months and is very harmful in pregnancy.
Updated 2026-11-01
The figure shows teriflunomide (A771726), the active metabolite of leflunomide, bound to human DHODH next to its flavin cofactor.
Mechanism of action
Leflunomide is converted to teriflunomide, which inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme of de novo pyrimidine synthesis. Activated lymphocytes need a fast supply of pyrimidines to divide, so their proliferation is slowed and inflammation in the joints falls.
- Converted to teriflunomide, the active form
- Teriflunomide inhibits DHODH in mitochondria
- De novo pyrimidine synthesis falls
- Activated lymphocytes cannot proliferate
Pharmacokinetics
- Absorption
- Taken by mouth and converted to teriflunomide
- Elimination
- Very slow; an accelerated elimination procedure with cholestyramine or activated charcoal can remove it
- Half-life
- Teriflunomide about 18 to 19 days
Indications
- Active rheumatoid arthritis in adults Rheumatoid arthritis →
Adverse effects
Common
- Diarrhoea
- Raised liver enzymes
- Hair loss
- Rash
- Hypertension
Contraindications
- Pregnancy
- Severe liver impairment
- Hypersensitivity to leflunomide
Key interactions
- Methotrexate and other hepatotoxic or immunosuppressive drugs
- More liver and bone marrow toxicity.
- Warfarin
- Teriflunomide can lower the INR; monitored closely.
- Cholestyramine or activated charcoal
- Speed elimination of teriflunomide; used on purpose to wash it out.
- Rifampicin
- Raises teriflunomide levels.
- Live vaccines
- Not recommended during treatment and while levels remain.
What is monitored
- ALT before starting and regularly
- Blood counts
- Blood pressure
- Pregnancy test before starting
- Tuberculosis screening before starting
Administration and safety
- Oral tablet once a day.
- After stopping, its active metabolite stays in the blood for a long time unless an accelerated elimination procedure is used.
Nursing care
- Confirm tuberculosis screening, a negative pregnancy test and baseline liver tests and blood counts before the first dose.
- Teach reliable contraception and that the drug persists for months; a washout procedure is used before a planned pregnancy.
- Measure blood pressure at visits.
- Teach the signs of liver injury, infection, new cough or breathlessness, and numbness in hands or feet.
Pregnancy and breastfeeding
Contraindicated: it can cause birth defects; if pregnancy occurs, the drug is stopped and an accelerated elimination procedure is started.
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme does teriflunomide inhibit?
Dihydroorotate dehydrogenase, a mitochondrial enzyme of de novo pyrimidine synthesis.
A woman on leflunomide wants to become pregnant. What is done first?
Leflunomide is stopped and an accelerated elimination procedure with cholestyramine or activated charcoal is used until teriflunomide levels are very low.
Which screening is done before starting leflunomide?
Active and latent tuberculosis, pregnancy test, blood pressure, liver tests and blood counts.
Related drugs
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Leflunomide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2024); DailyMed - LEFLUNOMIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); HUMAN DIHYDROOROTATE DEHYDROGENASE COMPLEXED WITH ANTIPROLIFERATIVE AGENT A771726 (RCSB Protein Data Bank, 2000).
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Representative model, for educational purposes only.