leflunomide

Leflunomide is a disease-modifying antirheumatic drug (DMARD) used to treat active rheumatoid arthritis and psoriatic arthritis, including patients who have not responded adequately to other DMARDs. It is sometimes used off-label for other autoimmune conditions, but its approved indications are primarily inflammatory arthritides.

Leflunomide is a prodrug that is converted to its active metabolite teriflunomide. It inhibits dihydroorotate dehydrogenase, a key enzyme in de novo pyrimidine synthesis, leading to reduced proliferation of activated T and B lymphocytes. This immunomodulatory effect underlies its anti-inflammatory action. The drug is absorbed orally and has a long elimination half-life due to enterohepatic recirculation, resulting in sustained exposure even after stopping therapy.

Typical dosing involves a loading regimen of 100 mg daily for 3 days, followed by a maintenance dose of 20 mg once daily; lower doses (for example 10 mg daily) may be used in elderly patients or those with tolerability concerns. Doses are adjusted or avoided in hepatic impairment. Liver function tests and complete blood counts should be monitored regularly because hepatotoxicity and cytopenias are potential adverse effects. Other common side effects include diarrhea, nausea, hypertension, rash, and alopecia. Leflunomide may interact with alcohol and other hepatotoxic drugs, including methotrexate, increasing the risk of liver injury.

Pregnancy is contraindicated due to teratogenic risk. Female patients of childbearing potential and men planning a pregnancy should use effective contraception during treatment and for an extended period after discontinuation. If rapid elimination is required (for pregnancy or severe toxicity), accelerated elimination with cholestyramine or activated charcoal can be used to reduce teriflunomide levels.