Arthritis Self-Management

Risk of Liver Damage With Leflunomide

by David W. Golann

The US Food and Drug Administration (FDA) has issued a warning about the risk of severe liver damage in people taking the arthritis drug leflunomide. The drug, which is available both under its brand name Arava and as a generic, is approved to treat rheumatoid arthritis (RA).

The new FDA warning follows reports of 49 cases of severe liver damage in people taking leflunomide, leading to 36 hospitalizations and 14 deaths, between August 2002 and May 2009. This is not the first time the risks of leflunomide have been brought to the FDA’s attention. A 2002 report from consumer watchdog group Public Citizen found 130 cases of severe liver damage in people taking leflunomide, prompting the FDA to issue an initial warning about the drug in 2003.

The expanded warning, which will appear in a prominent box on the leflunomide label, stipulates the following:

• People who have liver diseases, such as hepatitis, should not take leflunomide.
• People who have levels of alanine transaminase (ALT) liver enzymes more than two times the normal upper limit should not take leflunomide.
• People who start taking leflunomide should have their liver function monitored every month for the first three months and then every three months thereafter. If their liver enzymes are found to be more than twice the upper limit, they should stop taking leflunomide and take a short course of the drug cholestyramine, which “washes out” the leflunomide.

The new warning also notes that doctors should be especially cautious when prescribing leflunomide to people who are already taking a drug that can harm the liver. Among these drugs is the pain reliever acetaminophen, which is the active ingredient in Tylenol and is also found in many other prescription and over-the-counter drugs. Nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil) and naproxen sodium (Aleve) — frequent treatments for arthritis — also pose a risk to the liver, as do drugs in the statin class. (Statins are used to lower cholesterol; examples include atorvastatin [Lipitor] and rosuvastatin [Crestor].) In the FDA’s analysis of the liver damage reports that prompted the warning, the agency found the greatest risk of liver damage was in people taking other drugs that can harm the liver.

In addition, people taking leflunomide should be on the lookout for signs of liver damage, which can include itching, yellow eyes or skin, dark urine, loss of appetite, or light-colored stools.

Leflunomide is in a class of drugs known as disease-modifying antirheumatic drugs (DMARDs). By interfering with the disease process of inflammatory types of arthritis, DMARDs can slow or halt the joint and organ damage caused by these conditions. The most commonly used DMARD in people with inflammatory arthritis is methotrexate (Rheumatrex, Trexall). Like leflunomide, methotrexate carries risks for the liver, and it is recommended that people taking methotrexate have their liver function monitored every one to two months.

Last Reviewed on July 21, 2010

David W. Golann is the Associate Editor of Arthritis Self-Management.

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