FDA recommends dosing changes for specific anemia drugs

The Food and Drug Administration is recommending stricter dosing guidelines for Erythropoiesis-Stimulating Agents (ESAs) - a synthetic protein that stimulates bone marrow to produce red blood cells - because they can increase the risk of cardiovascular events like heat attack, stroke, thrombosis, even death.

ESAs are commonly used to treat anemia and help reduce the need for blood transfusions in patients with chronic kidney disease (CKD) or who have had chemotherapy or other major surgeries. The drugs in question are Epogen, Procrit and Aranesp, all made by the California-based biotechnology company Amgen.

The new recommendations will be added to the box warning and sections of the package insert. They will recommend doctors and patients weigh the benefits of using ESAs against the risks and individualize therapy.

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

"The goal is to individualize therapy and use the lowest ESA dose possible to reduce the need for red blood cell transfusions."

Currently ESA labels recommend patients with CKD get treatment that would maintain hemoglobin levels - a protein in the red blood cells that carry oxygen - in the 10-12 grams/deciliter (g/dL) range. The new recommendations are different depending on whether the patient is on dialysis. For patients not on dialysis the advice is to start treatment only when the hemoglobin level drops below 10 g/dL. If the hemoglobin exceeds 10 g/dL the treatment should be reduced or stopped. For patients on dialysis the recommendation is to begin therapy when the blood level is less than 10g/dL and reduce or stop the drug if levels exceed 11 g/dL.

Amgen says they are working with the Agency.

"Amgen supports the modified ESA prescribing information as it informs physicians of important safety information," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "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."

According to the Center for Disease Control and Prevention, 26 million Americans 20 years of age and  older have CKD and most don't know they have it.  The National Kidney Foundation says millions more are at increased risk.  It says the two main causes, diabetes and high blood pressure are responsible for approximately two-thirds of the cases and that heart disease is the major cause of death for these patients.

The FDA says it will continue to monitor the safety of ESAs.