DMARD (pyrimidine synthesis inhibitor) Pregnancy: CONTRAINDICATED. Teratogenic. Washout with cholestyramine required before conception.

Leflunomide

Brand names: Arava

Adult dose

Dose: Loading: 100 mg once daily for 3 days; maintenance: 10–20 mg once daily

Route: Oral

Frequency: Once daily

Max: 20 mg/day

Loading dose 100 mg/day for 3 days (accelerates onset — but increases side effect risk; often omitted in routine practice). Maintenance: 20 mg daily (reduce to 10 mg if side effects). Washout with cholestyramine required if stopping due to toxicity or pregnancy planning (active metabolite has long half-life — 2 years without washout).

Paediatric dose

Route: Oral

Frequency: Once daily

Max: 20 mg/day

JIA (≥3 years — specialist use): weight-based: <20 kg: 100 mg loading then 10 mg every other day; 20–40 kg: 100 mg loading then 10 mg daily; >40 kg: adult dose. Not widely used in children.

Dose adjustments

Renal

No specific dose adjustment but caution in severe renal impairment.

Hepatic

Avoid in significant hepatic impairment or elevated LFTs (>2× ULN).

Clinical pearls

Washout protocol essential before pregnancy: cholestyramine 8 g TDS for 11 days — verify levels <0.02 mg/L × 2 (14 days apart)
Active metabolite (A77 1726) has half-life up to 2 years — very long persistence
BSR monitoring: FBC and LFTs monthly for first 6 months then 3-monthly
Hypertension common — monitor BP regularly
Peripheral neuropathy: stop if develops — may not be reversible

Contraindications

Severe immunodeficiency
Significant hepatic impairment
Pregnancy (and up to 2 years after stopping without washout)
Breastfeeding
Severe hypoproteinaemia

Side effects

Diarrhoea (most common)
Nausea and GI upset
Hepatotoxicity (raised LFTs)
Hypertension
Alopecia
Peripheral neuropathy (rare)
Teratogenicity (major — enterohepatic recirculation; very long half-life metabolite)

Interactions

Methotrexate — increased hepatotoxicity (avoid combination unless specialist)
Warfarin — enhanced anticoagulant effect
Cholestyramine — drug washout (adsorbs active metabolite)
Rifampicin — increases active metabolite levels

Monitoring

LFTs (monthly then 3-monthly)
FBC
BP
Serum leflunomide metabolite levels (before pregnancy attempt)

Reference: BNFc; BNF; BSR/BHPR RA Guidelines; NICE NG100. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways