DMARD (pyrimidine synthesis inhibitor) Pregnancy: Contraindicated in pregnancy and in women of childbearing potential not using reliable contraception. The active metabolite A771726 is suspected to cause serious birth defects. Women of childbearing potential must use effective contraception during treatment and for up to 2 years afterwards (waiting period) or up to 11 days after treatment if the washout procedure is used. Before a planned pregnancy, A771726 plasma concentration must be confirmed below 0.02 mg/l on 2 separate tests at least 14 days apart, with a waiting period of one-and-a-half months between the first concentration below 0.02 mg/l and fertilisation. Any delay in onset of menses or suspicion of pregnancy must be reported to the physician immediately. Contraindicated in breast-feeding women.

Leflunomide

Brand names: Arava

Leflunomide is a disease-modifying antirheumatic drug (DMARD) used in rheumatoid and psoriatic arthritis.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Rheumatoid arthritis: loading dose 100 mg once daily for 3 days, then maintenance 10 mg to 20 mg once daily depending on the severity (activity) of the disease

Route: Oral — tablets swallowed whole with sufficient liquid; absorption is not affected by food

Frequency: Once daily

Source: UK SPC (eMC) §4.2 for Leflunomide 10 mg Film-coated Tablets (https://www.medicines.org.uk/emc/product/4944/smpc). VERBATIM: 'In rheumatoid arthritis: leflunomide therapy is usually started with a loading dose of 100 mg once daily for 3 days... The recommended maintenance dose is leflunomide 10 mg to 20 mg once daily depending on the severity (activity) of the disease.' The SPC adds: 'Omission of the loading dose may decrease the risk of adverse events.' ONSET: the therapeutic effect usually starts after 4 to 6 weeks and may further improve up to 4 to 6 months. INITIATION: treatment should be initiated and supervised by specialists experienced in the treatment of rheumatoid arthritis. MANDATORY MONITORING: ALT (SGPT) and a complete blood cell count including differential white cell count and platelet count must be checked simultaneously and with the same frequency — before initiation, every two weeks during the first six months of treatment, and every 8 weeks thereafter. DOSE REDUCTION FOR LIVER ENZYMES (§4.4): for ALT elevations between 2- and 3-fold the upper limit of normal, dose reduction from 20 mg to 10 mg may be considered with weekly monitoring; if ALT elevations of more than 2-fold ULN persist, or elevations of more than 3-fold ULN are present, leflunomide must be discontinued and washout procedures initiated. WASHOUT PROCEDURE (§4.4/§4.6, active metabolite A771726 half-life usually 1 to 4 weeks): colestyramine 8 g three times daily for 11 days, or alternatively 50 g of activated powdered charcoal four times daily for 11 days; may be repeated as clinically necessary. Avoid alcohol during treatment because of potential additive hepatotoxicity. ELDERLY: no dosage adjustment is required in patients above 65 years of age. PAEDIATRIC: 'Leflunomide is not recommended for use in patients below 18 years since efficacy and safety in juvenile rheumatoid arthritis (JRA) have not been established' — no paediatric dose is stated, so paedDose is null; verify any under-18 use against a children's formulary. No maximum dose beyond the 20 mg once-daily maintenance range is stated in §4.2. §4.5 was not retrieved in this bundle (§4.4 truncated at the source-fetch limit) — interactions below come from the §4.4 DMARD statement and the US label §7; verify against the full UK §4.5.

Dose adjustments

Renal

No dose adjustment is recommended in patients with mild renal insufficiency. Contraindicated in patients with moderate to severe renal insufficiency because insufficient clinical experience is available in this group.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

US labelling (FDA)

Reference — US labelling, may differ from UK

Loading dosage for patients at low risk for leflunomide -associated hepatotoxicity and leflunomide -associated myelosuppression: 100 mg daily for 3 days. ( 2.1 ) Maintenance dosage: 20 mg daily. ( 2.1 ) Maximum recommended daily dosage: 20 mg once daily. ( 2.1 ) If 20 mg once daily is not tolerated, may decrease dosage to 10 mg once daily. ( 2.1 ) Screen patients for active and latent tuberculosis, pregnancy test (females), blood pressure, and laboratory tests before starting leflunomide tablets.( 2.2 ) 2.1 Recommended Dosage The recommended dosage of Leflunomide is 20 mg once daily. Treatment may be initiated with or without a loading dose, depending upon the patient's risk of leflunomide …

Source: US FDA prescribing information (openFDA / DailyMed), label dated 2025-12-17. Accessed 2026-06-12. US dosing and indications can differ from UK practice — use UK sources for prescribing decisions.

Contraindications

Hypersensitivity (especially previous Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) to leflunomide, to the active metabolite teriflunomide, to peanut or soya, or to any of the excipients
Patients with impairment of liver function
Patients with severe immunodeficiency states, e.g. AIDS
Patients with significantly impaired bone marrow function, or significant anaemia, leucopenia, neutropenia or thrombocytopenia due to causes other than rheumatoid arthritis
Patients with serious infections
Patients with moderate to severe renal insufficiency (insufficient clinical experience)
Patients with severe hypoproteinaemia, e.g. nephrotic syndrome
Pregnant women, or women of childbearing potential not using reliable contraception during treatment and thereafter while plasma levels of the active metabolite exceed 0.02 mg/l; pregnancy must be excluded before starting
Breast-feeding women

Side effects

Mild increase in blood pressure (common; severe increase rare)
Leucopenia (leucocytes >2 G/l, common); anaemia and mild thrombocytopenia (uncommon); pancytopenia and severe leucopenia (rare); agranulocytosis (very rare)
Gastrointestinal: diarrhoea, nausea, vomiting, abdominal pain, oral mucosal disorders (aphthous stomatitis, mouth ulceration), colitis including microscopic colitis (common)
Elevation of liver parameters — transaminases (especially ALT), less often gamma-GT, alkaline phosphatase, bilirubin (common); rare cases of severe liver injury including fatal outcome, mostly within the first 6 months
Paraesthesia, headache, dizziness, peripheral neuropathy (common); increased hair loss, eczema, rash, pruritus, dry skin; CPK increased; anorexia and weight loss; rare severe infections including fatal sepsis and rare interstitial lung disease which may be fatal

Interactions

Concomitant administration of hepatotoxic or haematotoxic DMARDs (e.g. methotrexate) is not advisable (§4.4)
Recent, concomitant or consecutive use of potentially myelotoxic agents may be associated with a higher risk of haematological effects
Other hepatotoxic medicinal products and alcohol — additive hepatotoxicity; alcohol should be avoided during treatment
Rifampin (potent CYP/transporter inducer) — increased teriflunomide plasma concentration by 40%; no dosage adjustment recommended but caution is advised (US label §7)
CYP2C8 substrates (e.g. paclitaxel, pioglitazone, repaglinide, rosiglitazone) — exposure may be increased by teriflunomide, an in vivo CYP2C8 inhibitor; monitor and adjust the concomitant drug dose as required (US label §7)
Note: the UK §4.5 section was not retrieved in this bundle

Clinical monograph

How it works

Its active metabolite inhibits dihydro-orotate dehydrogenase, reducing pyrimidine synthesis and lymphocyte proliferation.

Prescribing in practice

It has a very long half-life — adverse effects can persist for weeks, and an active washout (with colestyramine or activated charcoal) is used for serious toxicity or planned pregnancy.
Hepatotoxicity, hypertension, bone-marrow suppression and diarrhoea/weight loss occur; monitor accordingly.
It is teratogenic — effective contraception and washout before conception are required (for women and relevant advice for men).

Monitoring

Monitor FBC, liver function and blood pressure regularly, especially early in treatment.

Counselling the patient

Report sore throat, fever, bruising, or yellowing of the skin/eyes.
Use effective contraception; a washout is needed before pregnancy.
Your blood pressure and blood tests will be monitored.

Evidence & guidelines

A conventional DMARD for rheumatoid and psoriatic arthritis, with monitoring and a washout procedure for its long half-life.

Reference: BSR/BHPR RA Guidelines; NICE NG100; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways