• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Drugs

  • Print
  • Share
  • E-mail

FDA Drug Safety Podcast for Healthcare Professionals: Modified dosing recommendations to improve the safe use of Erythropoiesis-Stimulating Agents (ESAs) in chronic kidney disease

Podcast Icon

Welcome, my name is Jennifer Shepherd, a pharmacist in the Division of Drug Information. On June 24, 2011, the Food and Drug Administration issued a Drug Safety Communication informing healthcare professionals of modified recommendations for more conservative dosing of Erythropoiesis-Stimulating Agents (ESAs) in patients with chronic kidney disease, or CKD, to improve the safe use of these drugs. 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).

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.

At this time, FDA recommends that Healthcare Professionals who Treat Patients with CKD be aware that:

  1. Using ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular events and has not been shown to provide additional patient benefit.
  2. No clinical trial to date has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.
  3. The ESA Medication Guide (Epogen/Procrit or Aranesp) should be provided to each patient or their representative when an ESA is dispensed.
  4. The lowest ESA dose sufficient to reduce the need for red blood cell transfusions should be used.
  5. For patients with CKD not on dialysis:
    • Consider initiating ESA treatment only when the hemoglobin level is less than 10 g/dL and the following considerations apply:
      • The rate of hemoglobin decline indicates the likelihood of requiring a red blood cell transfusion; and 
      • Reducing the risk of alloimmunization and/or other red blood cell transfusion-related risks is a goal.
    • If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of ESA and use the lowest dose of ESA sufficient to reduce the need for red blood cell transfusions.
  6. For patients with CKD on dialysis:
    • Initiate ESA treatment when the hemoglobin level is less than 10 g/dL.
    • If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of ESA.
  7. When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly.
  8. For patients who do not respond adequately over a 12-week escalation period, increasing the ESA dose further is unlikely to improve response and may increase risks.
  9. Adverse events involving ESAs should be reported to the FDA MedWatch program at www.fda.gov/medwatch.

Thank you for listening. The FDA is committed to keeping healthcare professionals informed of the latest safety information. Please read the Drug Safety Communication for ESA label changes and other background information detailing this communication. A link to this DSC can be found at www.fda.gov/Drugs/DrugSafety. If you have drug questions, you can reach us at druginfo@fda.hhs.gov.

 

Contact FDA

Toll Free
(855) 543-3784, or
(301) 796-3400
Human Drug Information

Division of Drug Information (CDER)

Office of Communications

Feedback Form

10001 New Hampshire Avenue

Hillandale Building, 4th Floor

Silver Spring, MD 20993