Erythropoiesis-Stimulating Agents (ESAs) used to treat patients with chronic kidney disease have been associated with an increased risk of cardiovascular events including stroke, thrombosis and death. Because of new information regarding this link, the FDA is recommending more conservative dosing guidelines be added to the Boxed Warnings section of ESA drug labels. FDA-approved medications in the ESA class include Epogen, Procrit and Aranesp.
What’s the problem?
June 24, 2011 – Today, the U.S. Food & Drug Administration (FDA) announced that it would be modifying dosing recommendations for erythropoiesis-stimulating agents (ESAs) due to an increased risk for cardiovascular events when used to treat anemia in patients with chronic kidney disease (CKD). According to the Centers for Disease Control and Prevention (CDC), more than 20 million people aged 20 or older have CKD.
The administration made the move to change the guidelines for the drugs – which include epoetin alfa (marketed as Epogen and Procrit) and darbepoetin alfa, which is marketed as Aranesp – because of the increased risk of cardiovascular events such as stroke, thrombosis and death. These risks appear to be highest when ESAs are dosed to achieve a normal blood hemoglobin level in individuals with CKD. Additionally, the FDA reports that neither epoetin alfa nor darbepoetin alfa have been shown to improve a patient’s quality of life, fatigue, or patient well-being. Epogen, Procrit and Aranesp are all marketed and manufactured by Amgen Inc., of Thousand Oaks, California.
In addition to revising the labeling of ESA drugs, FDA is issuing a Drug Safety Communication alerting the medical community about the changes. The administration is also conducting its own independent research and requiring Amgen to conduct additional trials to help determine the relationship between ESAs and cardiovascular events.
Erythropoiesis-stimulating agents are synthetic versions of the protein erythropoietin, which stimulates red blood cell production in bone marrow. Blood hemoglobin is the primary indicator of the number of red blood cells in the blood. Anemia is a condition characterized by an abnormally low hemoglobin value. ESAs like Epoetin and Procrit are prescribed to treat certain types of anemia resulting from CKD, chemotherapy and other conditions.
Until the new information concerning the association between ESAs and cardiac events came to the attention of the FDA, product labels for the medications have recommended dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 grams/deciliter (g/dL) in patients with CKD. The modified warning does not contain the phrase ‘target hemoglobin range.’