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U.S. Department of Health and Human Services

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Questions and Answers on Medication Guides for Erythropoiesis-Stimulating Agents (ESAs)

 

 

This information is no longer current. Please see the Drug Safety Communication 2/16/2010.

 

Epoetin alfa (marketed as Procrit, Epogen) Darbepoetin alfa (marketed as Aranesp)

1. Why were Medication Guides for ESAs developed?

The Medication Guides were developed to provide patients with important information about the risks of using ESAs.  The information in the Medication Guides may affect a patient’s decision to take the drug and it gives patients a starting point for discussion with their healthcare provider about the medical decision to prescribe an ESA.

2. What are Erythropoiesis-Stimulating Agents (ESAs)?

ESAs are man-made forms of the protein human erythropoietin.  ESAs are given to patients with low red blood counts due to kidney failure, or due to side effects from other drugs (chemotherapy or zidovudine), or given to patients scheduled for certain types of elective surgery.  ESAs work by stimulating the bone marrow to make more red blood cells so that there is a lower chance that the patient will need red blood cell transfusions.

3. What are these important risks of using ESAs and how can they be managed?

Using ESAs can lead to serious side effects which may result in death.  Some of these side effects are more likely to happen if the patient has cancer or chronic kidney failure.

In patients with all types of cancer for which ESA use is FDA-approved:

  • The tumor may grow faster and the patient may die sooner when ESA treatment is used.  
  • The healthcare provider should prescribe the lowest dose of the ESA that is needed to avoid red blood cell transfusions.   
  • ESAs work by stimulating the bone marrow to make more red blood cells. ESAs have not been shown to improve the symptoms of anemia, quality of life, fatigue, or well-being for patients with cancer.   For that reason, ESAs should be used only to reduce the chance that a patient with low red blood counts (anemia) will get a blood transfusion.
  • Treatment with an ESA should be stopped when chemotherapy treatment is finished.

In all patients taking an ESA:

There is risk of serious heart problems such as heart attack, stroke, heart failure, and a higher chance of death if patients are treated with an ESA to a hemoglobin level above 12 g/dL. 

Patients may get blood clots at any time while taking an ESA.  Patients who are receiving an ESA and scheduled for surgery should talk to their healthcare provider about whether or not to also take a blood thinner to reduce the chance of blood clots during or following surgery.  Clots can form in blood vessels (veins), especially in the leg (deep venous thrombosis or DVT).  Pieces of a blood clot may travel to the lungs and block the blood circulation in the lungs (pulmonary embolus).  The possible symptoms of blood clots are:

  • Chest pain
  • Trouble breathing or shortness of breath
  • Pain in the legs, with or without swelling
  • A cool or pale arm or leg
  • Sudden confusion, or trouble speaking or understanding speech
  • Sudden numbness or weakness of the face, an arm, or leg, especially on one side of the body
  • Sudden trouble seeing
  • Sudden trouble walking, dizziness, loss of balance or coordination
  • Loss of consciousness (fainting)
  • Hemodialysis vascular access stops working.  In patients with chronic kidney failure and a hemodialysis vascular access, blood clots may form in this access.

4. When should the Medication Guide be given to patients? 

The Medication Guide must be given directly to a patient or the patient’s caregiver when the drug is dispensed to the patient. 

5. What is FDA's position on the provision of a Medication Guide when ESAs are administered to patients by a health care provider (e.g. in a physician's office, clinic, hospital inpatient setting, or dialysis center)? (question posted 1/26/2009)

Under FDA's regulations,  when a  Medication Guide is required, it must be dispensed with each new  prescription and with each refill of a prescription.

Because of the nature of ESA treatment, when these particular drugs are administered to patients by a healthcare provider (e.g. in a physician's office, clinic, hospital inpatient setting, or dialysis center), FDA has determined it is not necessary that a patient receive the Medication Guide each time the drug is dispensed. Therefore, for ESA drugs administered in these circumstances,  FDA does  not intend to object if the Medication Guide is dispensed at the initiation of therapy and then at least once a month to each patient or patient caregiver for as long as treatment continues.  If the Medication Guide is materially revised or updated, it should be dispensed at that time, and at least monthly from that time on.

6.  Are the FDA and Amgen considering other actions to improve the safe use of ESAs?

The FDA is working with Amgen on a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of the ESAs outweigh their risks.