Leflunomide

• Not used in pregnancy — pre-pregnancy RA/PsA maintenance only

Inhibits dihydro-orotate dehydrogenase → blocks de novo pyrimidine synthesis → halts rapidly dividing lymphocytes. Active metabolite (teriflunomide) has a very long half-life (~2 weeks) with extensive enterohepatic recycling.

• Stopping is NOT enough — active metabolite persists for up to 2 years
• Needs cholestyramine (or activated charcoal) washout before conception
• Confirm level <0.02 mg/L on 2 tests ≥14 days apart before trying to conceive

Washout

Cholestyramine 8g PO TDS × 11 days (or activated charcoal 50g q12h × 11 days)

Confirm cleared

Plasma level <0.02 mg/L on 2 occasions ≥14 days apart

• AbsolutePregnancy (teratogenic in animal studies; human data limited but manufacturer maintains contraindication)
• AbsoluteBreastfeeding — insufficient data

• Hepatotoxicity
• Diarrhoea
• Hypertension
• Alopecia

• • If pregnancy occurs while on leflunomide (or within 2 years of stopping without washout): start washout immediately + detailed fetal ultrasound.
• • Human case data have not shown a clear malformation pattern, but teratogenicity in humans remains undetermined — do not use this to reassure over active washout.

• Methotrexate

  Avoid

  Additive hepatotoxicity

• Warfarin

  Caution

  ↑ INR

• 💡 Unlike methotrexate (3-month washout), leflunomide's active metabolite needs an active elimination protocol — simply stopping and waiting is not considered adequate.
• 💡 Men planning conception should also complete washout — manufacturer advises 3.5 months to 2 years, or cholestyramine washout, before their partner conceives.