Leflunomide gets new boxed warning

A boxed warning has been added to the label of leflunomide (Arava) highlighting the risk of severe liver injury in patients taking the drug, the FDA announced last week.

The FDA received reports of 49 cases of severe liver injury associated with the rheumatoid arthritis drug, including 14 cases of fatal liver failure, between August 2002 and May 2009. 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, the FDA said. Therefore, the new warning recommends against giving the drug to patients with pre-existing liver disease or elevated liver enzymes (ALT greater than two times the upper limit of normal). Caution should be used in patients who are taking other drugs that can cause liver injury.

Liver enzymes should be monitored at least monthly for three months after starting leflunomide and at least quarterly thereafter. If the ALT rises to greater than two times the upper limit of normal while the patient is on leflunomide, the drug should be stopped and cholestryamine washout begun, the FDA recommended.