Leflunomide is an isoxazole immunomodulatory agent which inhibits de novo pyrimidine synthesis and has anti-proliferative activity. Following oral administration, it is rapidly metabolized to A771726, which is active in vitro and is presumed to be the active drug in vivo. Leflunomide has demonstrated prophylactic and therapeutic effects in animal models of autoimmune disease. In addition, leflunomide has exhibited anti-inflammatory and weak analgesic and antipyretic activity. In a model of experimental septicemia, leflunomide did not alter the resistance of mice to bacterial pathogens.
Cholestyramine and activated charcoal may decrease plasma concentration of active metabolite. Concurrent use of methotrexate and other hepatotoxic drugs may increase the risk of hepatotoxicity. Rifampicin increases serum levels of the active metabolite.
Leflunomide is contraindicated in patients with known hypersensitivity to leflunomide or any of the other components of leflunomide, hepatic impairment, severe uncontrolled infections and bone marrow dysplasia.
Adverse reactions associated with the use of leflunomide include diarrhea, nausea, vomiting, abdominal pain, headache, respiratory infection, bronchitis, elevated liver enzymes, aggravation of pre-existing hypertension, alopecia, and rash.
Leflunomide is not recommended for pregnant women. Pregnancy must be avoided during leflunomide treatment or prior to the completion of the drug elimination procedure after leflunomide treatment. Leflunomide should not be used by nursing mothers. It is not known whether leflunomide is excreted in human milk. Many drugs are excreted in human milk and there is a potential for serious adverse reactions in nursing infants from leflunomide. Therefore, a decision should be made whether to proceed with nursing or initiate treatment with leflunomide, taking into account the importance of the drug to the mother.
Caution should be taken for those female with child bearing potential who are not using reliable contraception and for the subject of renal insufficiency. Leflunomide should be stopped before becoming pregnant. Liver function should be monitored before starting treatment.
There is no human experience regarding leflunomide over dosage. In the event of a significant overdose or toxicity, cholestyramine or charcoal administration is recommended to accelerate elimination.
