Ask the Experts - Adverse Effects of Leflunomide
Ask the Experts - Adverse Effects of Leflunomide
How safe is leflunomide? What are we to make of recent data on its effects on the liver?
Monique Camerlain, MD
Most adverse effects of leflunomide are minor, such as gastrointestinal symptoms, skin rash, alopecia, dyspepsia, hypertension, and elevated transaminases. The drug is immunosuppressive and thus can increase the risk of infection. Leflunomide is contraindicated in pregnancy, and patients who wish to become pregnant are generally treated with cholestyramine to enhance elimination of the drug. Pancytopenia has been reported as a rare occurrence associated with leflunomide. Unexplained weight loss in association with leflunomide treatment of rheumatoid arthritis was recently reported to be more common than previously thought and is believed to be due to the effects of leflunomide on mitochondrial adenosine triphosphate (ATP) generation.
Substantial recent attention has been focused on the possibility that serious liver toxicity can occur in leflunomide-treated patients. Fortunately, such toxicity appears to be uncommon. However, regular monitoring of liver function during leflunomide therapy remains an important guideline, and transaminase elevations or depression of serum albumin should be taken seriously. It is not clear from the current literature whether serious hepatotoxicity associated with leflunomide is mediated by potentiation of hepatotoxicity induced by concurrently used agents (including methotrexate) or via direct actions of leflunomide on the liver.
How safe is leflunomide? What are we to make of recent data on its effects on the liver?
Monique Camerlain, MD
Most adverse effects of leflunomide are minor, such as gastrointestinal symptoms, skin rash, alopecia, dyspepsia, hypertension, and elevated transaminases. The drug is immunosuppressive and thus can increase the risk of infection. Leflunomide is contraindicated in pregnancy, and patients who wish to become pregnant are generally treated with cholestyramine to enhance elimination of the drug. Pancytopenia has been reported as a rare occurrence associated with leflunomide. Unexplained weight loss in association with leflunomide treatment of rheumatoid arthritis was recently reported to be more common than previously thought and is believed to be due to the effects of leflunomide on mitochondrial adenosine triphosphate (ATP) generation.
Substantial recent attention has been focused on the possibility that serious liver toxicity can occur in leflunomide-treated patients. Fortunately, such toxicity appears to be uncommon. However, regular monitoring of liver function during leflunomide therapy remains an important guideline, and transaminase elevations or depression of serum albumin should be taken seriously. It is not clear from the current literature whether serious hepatotoxicity associated with leflunomide is mediated by potentiation of hepatotoxicity induced by concurrently used agents (including methotrexate) or via direct actions of leflunomide on the liver.
