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.
Alternative to methotrexate when MTX is not tolerated9
Improved physical function
What to watch for
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 1 interaction record on file.
The science
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.
Class
Disease-Modifying Antirheumatic Drug (DMARD)
Dosing
Dosing & protocol.
Common range
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)
Recommended form
Tablet
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)
Safety
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)
Contraindications
Pregnancy (Pregnancy Category X) and women of childbearing potential not using reliable contraception
Severe hepatic impairment or pre-existing liver disease
Leflunomide can cause clinically significant liver injury, including rare severe drug-induced liver injury. Alcohol adds hepatic stress and can make liver enzyme elevations harder to interpret, especially with regular or heavy use. The concern is highest with preexisting liver disease, elevated baseline liver tests, obesity, viral hepatitis, or other hepatotoxic medicines.
Recommendation: Avoid heavy alcohol use while taking leflunomide. If you drink at all, keep intake low and consistent, tell your prescriber, and do not miss scheduled liver blood tests. Stop alcohol and seek medical advice promptly for jaundice, dark urine, severe fatigue, itching, or right upper abdominal pain.
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
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
Raj R, Nugent K. Leflunomide-induced interstitial lung disease (a systematic review). Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG. 2013
Golicki D, Newada M, Lis J et al.. Leflunomide in monotherapy of rheumatoid arthritis: meta-analysis of randomized trials. Polskie Archiwum Medycyny Wewnetrznej. 2012
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
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Leflunomide in NutriStack.
Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.
NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.
NutriStack