Leflunomide
Prescription ·Exploratory record · not publication-reviewed ·Updated July 13, 2026
A pyrimidine synthesis inhibitor DMARD used for the treatment of active rheumatoid arthritis and psoriatic arthritis. Leflunomide is an alternative to methotrexate for patients who cannot tolerate it, or may be used in combination under specialist supervision. It has a very long active metabolite half-life requiring cholestyramine washout if rapid elimination is needed.
Exploratory record, not a reviewed medical publication.
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This generated database record has not completed a claim-level review by a qualified human medical reviewer. Bibliography links and evidence labels are not approval. The page remains available for reference and is excluded from search indexing.
What the research says.
A quick, data-only summary. The full evidence, dosing, and sources are below.
A pyrimidine synthesis inhibitor DMARD used for the treatment of active rheumatoid arthritis and psoriatic arthritis. NutriStack rates the supporting evidence as strong. Common adult dosing is Loading dose: 100 mg daily for 3 days (optional, often omitted to improve tolerability); Maintenance: 20 mg daily (10 mg if not tolerated) (as prescribed by your physician), though a prescriber sets the actual dose. This profile indexes 10 sources.
- Diarrhea (most common)
- Nausea
- Elevated liver enzymes (hepatotoxicity)
- Pregnancy (Pregnancy Category X) and women of childbearing potential not using reliable contraception
- Severe hepatic impairment or pre-existing liver disease
The bottom line
Evidence rating strong. Most-documented uses: disease modification in rheumatoid arthritis, reduction of joint swelling, pain, and structural damage, treatment of psoriatic arthritis. 10 sources indexed (2000–2019), with 0 interaction records on file.
How it works, mechanistically.
Core mechanism
Rapidly converted to its active metabolite teriflunomide, which inhibits dihydroorotate dehydrogenase (DHODH), a mitochondrial enzyme essential for de novo pyrimidine synthesis. Activated lymphocytes depend on de novo pyrimidine synthesis for clonal expansion, so DHODH inhibition selectively suppresses proliferating T and B lymphocytes, reducing autoimmune-mediated joint inflammation. Also inhibits tyrosine kinase activity.
Dosing & protocol.
Can be taken with or without food; the active metabolite has an extremely long half-life (~2 weeks) due to enterohepatic recirculation; cholestyramine washout procedure required if rapid elimination is needed (e.g., before pregnancy)
Full safety detail.
Side effects
- Diarrhea (most common)
- Nausea
- Elevated liver enzymes (hepatotoxicity)
- Alopecia (hair thinning)
- Skin rash
- Hypertension
- Peripheral neuropathy
- Increased infection risk (immunosuppression)
Sources, by evidence tier.
Numbered references. Citations throughout the page link here.
Meta-analyses & systematic reviews
5- 1Efficacy and safety of leflunomide in IgA nephropathy: a systematic review and meta-analysisPMIDYi J, He Z, Xu S et al. · International urology and nephrology · 2019
Yi J, He Z, Xu S et al.. Efficacy and safety of leflunomide in IgA nephropathy: a systematic review and meta-analysis. International urology and nephrology. 2019
- 2Efficacy and safety of leflunomide in psoriatic arthritis treatment: A single-arm meta-analysisPMIDDai Q, Xu L, Yu X · International journal of rheumatic diseases · 2019
Dai Q, Xu L, Yu X. Efficacy and safety of leflunomide in psoriatic arthritis treatment: A single-arm meta-analysis. International journal of rheumatic diseases. 2019
- 3Leflunomide-induced interstitial lung disease (a systematic review)PMIDRaj R, Nugent K · Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2013
Raj R, Nugent K. Leflunomide-induced interstitial lung disease (a systematic review). Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG. 2013
- 4Leflunomide in monotherapy of rheumatoid arthritis: meta-analysis of randomized trialsPMIDGolicki D, Newada M, Lis J et al. · Polskie Archiwum Medycyny Wewnetrznej · 2012
Golicki D, Newada M, Lis J et al.. Leflunomide in monotherapy of rheumatoid arthritis: meta-analysis of randomized trials. Polskie Archiwum Medycyny Wewnetrznej. 2012
- 5Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implicationsPMIDHewitson PJ, Debroe S, McBride A et al. · Journal of clinical pharmacy and therapeutics · 2000
Hewitson PJ, Debroe S, McBride A et al.. Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implications. Journal of clinical pharmacy and therapeutics. 2000
Reference material
5- 6Fraenkel L et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2021.Source linkedPMID
- 7Smolen JS et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020.Source linkedPMID
- 8Osiri M et al. Leflunomide for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2003.Source linkedPMID
- 9Alfaro-Lara R, Espinosa-Ortega HF, Arce-Salinas CA et al.. Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis. Reumatologia clinica. 2019Source linkedPMID
- 10Padda IS, Goyal A. Leflunomide. 2026Source linkedPMID
Common questions.
Quick answers about Leflunomide, drawn from the data on this page.
What is Leflunomide?
A pyrimidine synthesis inhibitor DMARD used for the treatment of active rheumatoid arthritis and psoriatic arthritis. Leflunomide is an alternative to methotrexate for patients who cannot tolerate it, or may be used in combination under specialist supervision. It has a very long active metabolite half-life requiring cholestyramine washout if rapid elimination is needed.
What is Leflunomide used for?
Commonly cited benefits of Leflunomide include: Disease modification in rheumatoid arthritis; Reduction of joint swelling, pain, and structural damage; Treatment of psoriatic arthritis; Alternative to methotrexate when MTX is not tolerated; Improved physical function. NutriStack rates the overall evidence as strong.
What is a typical dose of Leflunomide?
A typical adult dose of Leflunomide is Loading dose: 100 mg daily for 3 days (optional, often omitted to improve tolerability); Maintenance: 20 mg daily (10 mg if not tolerated) (as prescribed by your physician). The commonly recommended form is Tablet. These are general ranges, not personalized advice; confirm the right dose with a clinician.
What are the side effects of Leflunomide?
Reported side effects include diarrhea (most common), nausea, elevated liver enzymes (hepatotoxicity), alopecia (hair thinning), skin rash, hypertension. This is educational information; check with a healthcare professional before use.
How strong is the evidence for Leflunomide?
NutriStack rates this as Strong, meaning multiple high-quality meta-analyses or systematic reviews converge on the same finding. Full tier criteria are at https://nutristackapp.com/methodology/evidence-tiers.
Use this with your stack
Leflunomide in NutriStack.
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