pharmacology and toxicology of leflunomide

leflunomide (lef), used for rheumatoid arthritis, inhibits dihydro-orotate dehydrogenase (dhodh) and tyrosine kinase (tk) enzymes and has anti-inflammatory, lymphocyte proliferation regulatory, immunosuppression and chondroprotective effects. the most common adverse effects are gastrointestinal disorders, weight loss, hypertension, skin infection, and neurological and hematological toxicity. it also produces hepatotoxicity and teratogenic effects on long term therapy. the food and drug administration (fda) categorized it as black box warning drug since 2010. therefore, it is necessary to give toxicological informations to scientific communities. this review article is elaborately describes the toxicity of this drug during its long and short term therapies.