Leflunomide (Arava), an immunomodulatory agent used in the treatment of rheumatoid arthritis, has a new black box warning stating that it can cause severe liver injury. Although the leflunomide label had carried a boldface warning statement about the risk of severe liver injury since 2003, the Food and Drug Administration (FDA) felt that a stronger and more prominent warning was justified. Nurses should closely monitor patients taking leflunomide for signs of liver damage.
The black box warning lists several specific points related to the use of this drug to minimize the risk of liver damage:
* Patients with preexisting liver disease shouldn't receive leflunomide.
* Patients with an elevated liver enzyme level (an alanine aminotransferase [ALT] value greater than two times the upper limit of normal) shouldn't receive leflunomide.
* Caution should be used in patients who are also taking other drugs that can cause liver injury.
* Liver enzymes should be monitored at least monthly for three months after a patient starts taking leflunomide and at least quarterly thereafter.
* If the ALT level rises to more than two times the upper limit of normal while the patient is taking leflunomide, the drug should be stopped, a cholestyramine washout should be started to speed the removal of leflunomide from the body, and follow-up liver-function tests should be conducted at least weekly until the ALT value is within the normal range.
Between August 2002 and May 2009, the FDA received 49 reports of cases of severe liver injury, 36 requiring hospitalization. Among those reports were 14 deaths, five liver transplantations, and nine life-threatening events. Almost all (46 of 49) of the patients had also received other hepatotoxic drugs, and 14 had either preexisting liver disease or a history of alcohol abuse (or both).
Nurses prescribing or caring for patients taking leflunomide should confirm that they're appropriate candidates for the drug. Patients taking leflunomide should be monitored for signs of liver disease (jaundice, itching, light colored stools, a loss of appetite, and dark colored urine). Nurses should teach patients the symptoms of liver disease and instruct them to contact their provider if they experience them. For more information, read the FDA Drug Safety Communication at http://bit.ly/aYU0yN.