Boxed Warning Added to Rheumatoid Arthritis Drug Label

The FDA has added information on severe liver injury to the boxed warning for Arava (leflunomide, Sanofiaventis)—a drug used to treat rheumatoid arthritis—to highlight the risk for severe liver injury in patients using this drug and how this risk might be reduced. The FDA previously required a boxed warning stating that leflunomide was contraindicated in pregnant women or women of childbearing potential who were not using reliable contraception.

Although a bolded warning statement on severe liver injury was added to the leflunomide drug label in 2003, the FDA determined that information on severe liver injury should be included in the boxed warning to highlight the importance of appropriate patient selection before starting treatment, and monitoring once treatment has begun.

The decision to add information on severe liver injury to the boxed warning was based on the FDA’s 2010 review of adverse event reports that identified 49 cases of severe liver injury, including 14 cases of fatal liver failure, between August 2002 and May 2009. In this review, the greatest risk for liver injury was seen in patients taking other drugs known to cause liver injury and patients with pre-existing liver disease.