Arava Liver Damage Side Effects Added to Black Box Warning

Federal regulators say they will require Sanofi-Aventis to place a black box warning on the arthritis drug Arava after receiving a number of reports of liver damage on Arava, including at least 14 deaths since 2002. 

The FDA released a drug safety communication on July 13 notifying patients and healthcare professionals that the drug will now carry a boxed warning, the most stringent warning the agency can require a drug to carry. The warning follows an FDA review of adverse events from the side effects of Avara reported between August 2002 and May 2009.

The FDA identified 49 cases of severe liver injury from Arava, including 14 fatalities. The most commonly reported problem was jaundice, but some patients reported encephalopathy and coagulopathy (blood clotting problems) as well. The FDA determined that those patients who had pre-existing liver problems and those taking other drugs that also increased the risk of liver injury were at the most risk.

Arava (leflunomide) is sold by Sanofi-Aventis and was approved by the FDA in 1998 for the treatment of rheumatoid arthritis. It belongs to a family of drugs known as disease-modifying antirheumatic drugs (DMARDs) which have the ability to slow down the progression of rheumatoid arthritis. Other drugs in this family include Rituxan and Cyclosporin A.

The medication already had a bolded warning on the label since 2003 alerting patients and doctors to possible liver injury from Arava. However, the FDA has determined the warning was not strong enough or detailed enough and has now placed it in a black box on the label and has included additional prescribing information.

The FDA is recommending that patients with pre-existing liver disease, or with elevated liver enzymes, not be given Arava. It also suggests that doctors monitor the liver enzymes of patients on Arava monthly for at least three months after they start the drug, and at least quarterly after the first three months. If liver enzymes climb to more than twice the upper limit of what’s considered within the normal range, the patient should be taken off Arava and should be given cholestryamine to speed up the drug’s removal from the body.

Liver damage on Arava is rare but serious, FDA drug reviewers said, and suggested patients be on the lookout for the following symptoms of Arava liver problems:

•  Itching
• Yellow eyes or skin
• Dark urine
• Loss of appetite
• Light-colored stools.

Consumers have been urged to contacted their healthcare provider immediately if they experience any of these symptoms while taking the drug, as it could be indications of Arava liver injury.