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ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS › IMMUNOSUPPRESSANTS › IMMUNOSUPPRESSANTS › Dihydroorotate dehydrogenase (DHODH) inhibitors
leflunomide
L04AK01
Forms & Strengths
- Oral tablets: 10 mg
- Oral tablets: 20 mg
- Oral tablets: 100 mg
Adult Dosing
- Rheumatoid arthritis: Loading dose of 100 mg once daily for 3 days (optional), followed by a maintenance dose of 20 mg once daily.
- Maintenance dose may be decreased to 10 mg once daily if 20 mg is not well tolerated.
- Psoriatic arthritis: 20 mg once daily (may start with 100 mg daily for 3 days).
Pediatric Dosing
- Safety and efficacy in pediatric patients have not been established.
Indications
- Treatment of active rheumatoid arthritis in adults to reduce signs and symptoms and inhibit structural damage.
- Treatment of active psoriatic arthritis in adults.
Mechanism of Action
- Inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), which is required for de novo pyrimidine synthesis.
- Suppresses proliferation of stimulated lymphocytes (T and B cells) involved in autoimmune inflammation.
Contraindications
- Known hypersensitivity to leflunomide or teriflunomide.
- Pregnancy (category X; must rule out pregnancy prior to treatment and ensure reliable contraception).
- Severe hepatic impairment.
- Pre-existing severe immunodeficiency states (e.g., HIV).
- Active severe infections.
- Significant bone marrow dysplasia or severe anemia, leukopenia, or thrombocytopenia.
Adverse Reactions
- Diarrhea
- Elevated liver enzymes (ALT, AST)
- Alopecia
- Nausea and abdominal pain
- Hypertension
- Rash and pruritus
- Respiratory tract infections
- Leukopenia and thrombocytopenia (rarely severe pancytopenia)
- Peripheral neuropathy
Drug Interactions
- Hepatotoxic drugs: Increased risk of severe hepatotoxicity when coadministered with other hepatotoxic agents (e.g., methotrexate, alcohol).
- CYP2C9 substrates: Leflunomide metabolite (A77 1726) may inhibit CYP2C9 (e.g., warfarin, leading to increased INR).
- Bile acid sequestrants (cholestyramine) and activated charcoal: Significantly accelerate elimination of the active metabolite and are used for rapid drug washout.
- Live vaccines: Avoid administration due to potential for severe infections and decreased vaccine efficacy.
- OATP1B1/B3 substrates: Teriflunomide may increase exposure of substrates such as statins (e.g., rosuvastatin).
Curated Content: Needs Vetting Before Put to Clinical Use