Alerts
Erythropoiesis-Stimulating Agents (Darbepoetin alfa [Aranesp], Erythropoietin alfa [Epogen, Procrit]) – Proposed Changes in Product Labeling
August 7, 2009
The FDA has been evaluating safety data for the erythropoiesis-stimulating agents (ESAs) since May 2004. Because the agents have the same mechanism of action, the FDA believes new safety concerns apply to all agents. A black-box warning was added to the package insert for all ESA products on March 9, 2007 with additional warnings added on November 8, 2007 and March 13, 2008.
The following to the boxed warning for patients with cancer:
- ESA products should not be used to treat anemia associated with chemotherapy if the expected outcome is a cure.
The Dosage and Administration Section of the product labeling was revised as follows:
- For treatment of anemia associated with chemotherapy, therapy should not be started if hemoglobin level is > 10 g/dL. The statement no longer includes an exception for patients with co-morbid conditions unable to tolerate this degree of anemia.
- Darbepoetin alfa dosing for cancer chemotherapy patients:
- Adjust dose to maintain Hgb at the lowest acceptable level to avoid transfusion.
- Withhold dose if Hgb exceeds a level needed to avoid transfusion. Resume at 40% below previous dose when Hgb falls to a level where transfusion may be necessary.
- Erythropoietin Alfa dosing for cancer chemotherapy patients:
- Adjust dose to maintain Hgb at the lowest acceptable level to avoid transfusion.
- Withhold dose if Hgb exceeds a level needed to avoid transfusion. Resume at 25% below previous dose when Hgb falls to a level where transfusion may be necessary.
The FDA recommends healthcare practitioners use ESA products according to their product labeling. Adjust doses to maintain hemoglobin concentrations as low as possible while preventing transfusions. In addition, FDA requires that pharmacists dispense a Medication Guide (MedGuide) to the patient with every prescription for darbepoetin alfa or epoetin alfa.
More information is available at the following links:
- MedWatch Alerts
- March 2007:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm152281.htm - February 2007:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm150817.htm - January 2007:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm150816.htm - Information for Health Care Professionals:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126488.htm - Dear Health Care Professional Letter:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm153899.htm - Questions and Answers on Medication Guides for Erythropoiesis-Stimulating Agents (ESAs)
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109380.htm - Questions and Answers on ESAs:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm110282.htm
The FDA requires the distribution of Medication Guides for drugs determined to be a serious and significant public health concern. With the exception of the ESAs, this requirement applies primarily to medications dispensed in the outpatient setting (refer to Code of Federal Regulations 21CFR208.1) for patient self-administration. When other prescription medications are administered to patients by healthcare professionals (ie, in the hospital, in infusion centers, dialysis centers, clinics, or offices), distributing a Medication Guide is not required, although it may be appropriate to educate patients about the potential hazards of prescription medications, at the clinician’s discretion. When the ESAs are administered to patients by healthcare professionals, a Medication Guide must be distributed when the patient starts therapy, at least once monthly during therapy, and whenever the Medication Guide is substantially updated. The complete list of drugs that require a Medication Guide as part of the FDA-regulated product labeling is available online at: http://www.fda.gov/cder/Offices/ODS/labeling.htm. For more information about the special requirements for ESA Medication Guide, see http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109380.htm.
Updated
August 7, 2009; August 1, 2008; February 20, 2007; January 29, 2007; University of Utah, Drug Information Service. Copyright 2009, Drug Information Service, University of Utah, Salt Lake City, UT.
