Contraindications and Drug Interactions

Leflunomide is teratogenic in animal models; it is absolutely contraindicated in pregnancy, in women who may become pregnant, and in breast-feeding women. Because of its long half-life, the M1 metabolite of leflunomide may remain in the body for up to 2 years; therefore, a drug elimination procedure using choles-tyramine should be used before any attempt at pregnancy. This drug is not recommended for use in children. Caution should be used when administering this drug to individuals with renal or hepatic disease, heavy alcohol use, or immunosuppression.

The long half-life of leflunomide must be taken into account to prevent drug interactions. Hepatotoxicity is possible if leflunomide is given in conjunction with a he-patotoxic agent such as methotrexate or certain NSAIDs. Leflunomide inhibits CYP2C9, the enzyme responsible for the metabolism of numerous drugs. Rifampin induces the P450 enzyme responsible for converting leflunomide to its Ml metabolite. Cholestyramine enhances the clearance of leflunomide and its Ml metabolite.

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