Leflunomide Pharmacology

Leflunomide, branded as Arava, serves as an oral disease-modifying antirheumatic drug (DMARD) primarily for rheumatoid arthritis, though its clinical use has declined in favor of methotrexate and biologics. This prodrug inhibits pyrimidine synthesis to reduce inflammatory responses and requires careful dosing, particularly when utilizing a 100 mg loading dose versus the standard 10 to 20 mg daily maintenance. Safety management is paramount due to two boxed warnings regarding hepatotoxicity and severe teratogenicity, necessitating regular liver function tests and pregnancy screening. Beyond its primary use, leflunomide occasionally treats cytomegalovirus or BK virus in transplant patients off-label. Significant drug interactions include the induction of CYP1A2, which lowers concentrations of drugs like clozapine and duloxetine, and the inhibition of CYP2C8. Clinicians must also monitor for additive immunosuppression when combined with corticosteroids and potential binding issues with bile acid sequestrants.