FDA: Modified dosing recommendations for Erythropoiesis-Stimulating Agents

Chronic Kidney Disease patients need more conservative dosing

/ Author:  / Reviewed by: Joseph V. Madia, MD

The U.S. Food and Drug Administration (FDA) is informing healthcare professionals of modified recommendations for more conservative dosing of erythropoiesis-stimulating agents (ESAs) in patients with chronic kidney disease (CKD) to improve the safe use of these drugs.

The FDA has made these recommendations because of data showing increased risks of cardiovascular events with ESAs in this patient population. The manufacturer has revised the Boxed Warning, Warnings and Precautions, and Dosage and Administration sections of the labels for the ESAs to include this new information.

More than 20 million people aged 20 years or older in the United States have CKD. Patients with CKD lose the ability to make red blood cells and become anemic. The ESAs treat certain types of anemia by stimulating the bone marrow to produce red blood cells and by decreasing the need for blood transfusions. Drugs in the ESA class are epoetin alfa (marketed as Epogen and Procrit) and darbepoetin alfa (marketed as Aranesp).

The ESA labels now warn:

  • In controlled trials with CKD patients, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a hemoglobin level of greater than 11 g/dL.
  • No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.

ESA labels now recommend:

  • For patients with CKD, consider starting ESA treatment when the hemoglobin level is less than 10 g/dL. This advice does not define how far below 10 g/dL is appropriate for an individual to initiate. This advice also does not recommend that the goal is to achieve a hemoglobin of 10 g/dL or a hemoglobin above 10 g/dL. Individualize dosing and use the lowest dose of ESA sufficient to reduce the need for red blood cell transfusions. Adjust dosing as appropriate.

The drug label previously recommended that ESAs should be dosed to achieve and maintain hemoglobin levels within the target range of 10 to 12 g/dL in CKD patients. This target concept has been removed from the label. 

Healthcare professionals should weigh the possible benefits of using ESAs to decrease the need for red blood cell transfusions in CKD patients against the increased risks for serious cardiovascular events, and should inform their patients of the current understanding of potential risks and benefits. Therapy should be individualized to the patient and the lowest possible ESA dose given to reduce the need for transfusions.

Treatment with ESAs in CKD has also been discussed at FDA Advisory Committee meetings in September 2007 and October 2010.

FDA is continuing to evaluate the safety of ESAs and is requiring the manufacturer to conduct additional trials. FDA will update the public when more information is available.

Additional Information for Patients with CKD

  • The use of ESAs can increase the risk for stroke, heart attack, heart failure, blood clots, and death.
  • The ESA Medication Guide (Epogen/Procrit or Aranesp) contains information on the benefits and risks of using these drugs.
  • Patients should have blood tests while using ESAs. The test results may help guide treatment and lower the risks of using these drugs. A healthcare professional will indicate how often to have blood tests.
  • Questions or concerns about ESAs should be discussed with a healthcare professional.
Reviewed by: 
Review Date: 
July 8, 2011