What precautions and monitoring are required in patients taking leflunomide?
Before starting leflunomide, a CBC with platelets, hepatitis B and C serologies, AST, ALT, albumin, and creatinine (CrCl) should be obtained. Monitor with a CBC, creatinine, and liver transaminases every 2 to 4 weeks for the first 3 months, then every 8 to12 weeks for the next 3 to 6 months, and then every 12 weeks.
Leflunomide should not be used in patients with hepatic impairment or positive viral hepatitis serology and is also contraindicated in pregnancy. Caution should be used in patients with renal impairment because there are currently no clinical data available in this group of patients. However, leflunomide has been used successfully in patients on hemodialysis without need for dose adjustment.
Leflunomide has an extremely long half-life due to enterohepatic recirculation; in some cases, it may take up to 2 years to reach undetectable plasma concentrations. Because of this, an enhanced drug elimination procedure has been developed in cases of overdose, toxicity, or desire for pregnancy (both males and females). Cholestyramine 8 g three times daily for 11 days (does not have to be consecutive days) will rapidly reduce plasma concentrations in these situations. In patients desiring to become pregnant, the active metabolite plasma level must be documented to be <0.02 μg/mL on two occasions 14 days apart.
Rifampin increases serum level of active metabolite of leflunomide, which can increase toxicity. Warfarin therapy may be potentiated by leflunomide.