Leflunomide
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Dosing and administration[3]
Oral once daily, swallowed whole. The active metabolite (A771726) has a long half-life; a cholestyramine or activated-charcoal washout is used for toxicity, before pregnancy, or when switching to another DMARD.
| Indication | Starting dose | Titration and maximum |
|---|---|---|
| Rheumatoid arthritis and psoriatic arthritis | 20 mg once daily. An optional loading dose of 100 mg once daily for 3 days may be used in patients at low risk of hepatotoxicity and myelosuppression to reach steady state faster, but is often omitted for tolerability. | If 20 mg daily is not tolerated, reduce to 10 mg daily; observe carefully after any reduction given the long metabolite half-life. |
Onset. Onset over about 4 to 6 weeks or more.
Renal adjustment. Use with caution in renal impairment; the active metabolite is not appreciably removed by dialysis.
Hepatic. Contraindicated in severe hepatic impairment and if ALT is above twice the upper limit of normal before starting; interrupt and consider washout if ALT rises above 3 times the upper limit of normal.
Monitoring
- ALT and CBC at baseline, then at least monthly for the first 6 months, then every 6 to 8 weeks.
- Interrupt therapy and start a washout if ALT exceeds 3 times the upper limit of normal.
- Monitor blood pressure (leflunomide can raise it).
Contraindications
- Pregnancy and breast-feeding; effective contraception and a completed washout are required before conception.
- Pre-existing acute or chronic liver disease, or ALT above twice the upper limit of normal.
- Severe immunodeficiency, significant bone marrow impairment, or serious active infection.
- Concurrent teriflunomide; age under 18 years.
Key interactions
- Other hepatotoxic drugs and methotrexate: additive hepatotoxicity, monitor closely.
- Rifampin can raise metabolite levels.
- Warfarin: monitor INR.
- Avoid live vaccines.
Clinical notes
Common side effects
Diarrhoea, nausea, reversible alopecia, hypertension, and transaminitis are recognised. Not sourced on this draft.
Tests and monitoring
Baseline complete blood count, liver transaminases, and serum creatinine before starting, with hepatitis B and C screening where risk factors are present. On treatment, check CBC, transaminases, and creatinine every 2 to 4 weeks for the first 3 months, every 8 to 12 weeks from 3 to 6 months, and every 12 weeks beyond 6 months, testing more often after a dose increase. This is the ACR conventional-DMARD monitoring schedule, defined for rheumatoid arthritis. Monitor blood pressure as well, given the risk of hypertension.[1, 2]
Important cautions
Long half-life via enterohepatic recirculation; a cholestyramine washout is used when rapid elimination is needed and before conception. Contraindicated in pregnancy; reproductive-health guidance is on the pregnancy record. Hepatotoxicity risk; limit alcohol. To confirm from primary sources.
References
- Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762-784. doi:10.1002/art.23721 https://doi.org/10.1002/art.23721
- Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2016;68(1):1-25. doi:10.1002/acr.22783 (published simultaneously in Arthritis & Rheumatology) https://doi.org/10.1002/acr.22783
- ARAVA / leflunomide tablets Product Monograph. Health Canada authorized product monograph. https://pdf.hres.ca/dpd_pm/00022354.PDF