Lower Dosages For Anemia Drugs For Patients With Chronic Kidney Disease, FDA

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Main Category: Urology / Nephrology
Also Included In: Blood / Hematology
Article Date: 25 Jun 2011 - 0:00 PDT


In a move to address the risk of cardiovascular events linked to Erythropoiesis-Stimulating Agents (ESAs) used in anemia treatment for patients with chronic kidney disease, the FDA (Food and Drug Administration) is recommending lower dosing guidelines. Cardiovascular events include thrombosis, stroke, and even death.

ESAs are man-made versions of erythropoietin, a protein which make primitive cells in the bone marrow produce erythrocytes (red blood cells) - the oxygen-carrying cells in the blood. Doctors measure hemoglobin levels in order to calculate the number of erythrocytes in the blood. People with anemia have very low hemoglobin values.

ESAs are FDA approved to treat anemia caused by chronic kidney disease, chemotherapy and some other illnesses and conditions. ESA class drugs include Epogen and Procrit (epoetin alfa), and Aranesp (darbepoetin alfa).

The Boxed Warning will have the modified dosing recommendations after the FDA examined clinical trials that demonstrated an increased risk of cardiovascular event risk linked to ESA therapy - specifically, when the therapy is aimed at achieving normal or nearly normal blood hemoglobin levels. The FDA added that according to studies it evaluated, ESAs to not appear to improve fatigue, patient well-being or quality of life.

John Jenkins, M.D., director of the Office of New Drugs in the FDA's Center for Drug Evaluation and Research, said:

"Health care practitioners should carefully consider when to begin treatment with an ESA and actively monitor dosing in patients with chronic kidney disease, keeping in mind the increased risk for serious cardiovascular events, and should talk to their patients about these potential risks.The goal is to individualize therapy and use the lowest ESA dose possible to reduce the need for red blood cell transfusions."

Over 20 million Americans over the age of 20 years have chronic kidney disease, says the CDC (Centers for Disease Control and Prevention). The modified package insert will not include the previous recommended dosing aimed at maintaining hemoglobin levels between 10 and 12 g/dL.

The FDA says that the recommendations will say that:

"Physicians and their patients with chronic kidney disease should weigh the possible benefits of using ESAs to decrease the need for red blood cell transfusions against the increased risks for serious adverse cardiovascular events.

For each patient, individualize dosing and use the lowest dose of ESA sufficient to reduce the need for transfusion.

When treating patients with anemia caused by chronic kidney disease who are not on dialysis, doctors should consider prescribing ESAs only when hemoglobin levels fall below 10 g/dL (plus some other considerations). As soon as hemoglobin levels go over 10 g/dL, treatment should stop, the FDA now recommends.

When treating patients with anemia caused by chronic kidney disease who are on dialysis, ESA treatment should only be prescribed when hemoglobin levels fall below 10 g/dL, and should stop when they exceed 11 g/dL.

The FDA says it decided to announce the new recommendations after analyzing data from various human studies, including the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), which demonstrated that treating patients with ESAs whose hemoglobin levels exceeded 11 g/dL raised the risk of cardiovascular events, and provided patients with no additional benefits.

The Cardiovascular Drugs Advisory Committee and the Drug Safety and Risk management Advisory Committee discussed ESA therapy for the treatment of anemia in patients with chronic kidney disease in September 2007, as did the Cardiovascular and Renal Drugs Advisory Committee which met in October 2010.

Amgen Inc. makes and markets Epogen, Procrit and Aranesp.

Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen, said:

"Amgen supports the modified ESA prescribing information as it informs physicians of important safety information. The revised label also provides physicians with more individualized treatment guidance by distinguishing between patients undergoing dialysis as compared with those who are not on dialysis."

Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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