Selective immunosuppressants
ATC code: L04AA13 (Leflunomide)
Brand names
Arava, Leflunomida Cinfa, Leflunomida Medac, Aubagio (teriflunomide for MS)
Oral selective immunosuppressant, a conventional synthetic disease-modifying antirheumatic drug (csDMARD). Metabolized to the active metabolite teriflunomide, which reversibly inhibits mitochondrial dihydroorotate dehydrogenase (DHODH) – key to pyrimidine synthesis in activated T and B lymphocytes. This block predominantly affects proliferating lymphocytes – selective immunosuppression with less impact on hematopoiesis than methotrexate.
Second line
Second-line in rheumatoid arthritis after methotrexate intolerance or inefficacy per 2022 and Spanish SER 2023. Starting loading dose 100 mg once daily for 3 days, then maintenance 10-20 mg once daily. Effect develops over 4-12 weeks. Comparable to methotrexate in efficacy (US301 trial); often used as monotherapy in MTX-intolerant patients or combined. Also suitable for psoriatic arthritis.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Leflunomide is a disease-modifying antirheumatic drug (DMARD), a pyrimidine synthesis inhibitor. It is prescribed for active rheumatoid arthritis and psoriatic arthritis ( 2023 guidelines, AEMPS Ficha Técnica). In alt-anti-aging circles, leflunomide is sometimes promoted as a universal modulator of the autoimmune background in healthy people. In healthy adults, no clinical studies of such use exist. The drug has serious risks: hepatotoxicity up to acute liver failure, severe skin reactions (Stevens-Johnson syndrome), peripheral neuropathy, myelosuppression, and significant teratogenicity (the M1 metabolite persists in the body for up to 2 years, requiring a cholestyramine washout protocol before pregnancy planning). If leflunomide was recommended to a healthy person, seek a second opinion immediately.
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Boxed warning
FDA boxed warning 2010: teratogenicity and severe hepatitis risk. Pregnancy and conception potential without barrier contraception and washout are absolute contraindications.
Teratogenic. In women of reproductive age, exclude pregnancy before initiation. Barrier contraception throughout therapy and until teriflunomide plasma level <0.02 mg/L (usually 2 years after stopping or 11 days of cholestyramine washout).
Contraindicated during lactation.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Leflunomide is evaluated for the following indications with varying evidence strength: Rheumatoid arthritis (evidence tier A), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Leflunomide (≥ 1 in 100): Diarrhea, Nausea, Alopecia, Skin rash, ALT/AST elevation, Hypertension. See the Safety section for uncommon and serious reactions.
FDA category X. Teratogenic. In women of reproductive age, exclude pregnancy before initiation. Barrier contraception throughout therapy and until teriflunomide plasma level <0.02 mg/L (usually 2 years after stopping or 11 days of cholestyramine washout).
Contraindicated during lactation.
Leflunomide is contraindicated in: Hypersensitivity; Severe hepatic impairment; Severe immunodeficiency; Severe hypoproteinemia (nephrotic syndrome); Pregnancy or conception potential without separate washout. Full list in the Safety section.
FDA boxed warning 2010: teratogenicity and severe hepatitis risk. Pregnancy and conception potential without barrier contraception and washout are absolute contraindications.