FDA Safety Announcement on Erythropoiesis-Stimulating Agents (ESAs)

2010-02-16

The American Society of Hematology (ASH) wanted to alert you to this important safety announcement from the Food and Drug Administration (FDA). 

The FDA is requiring all drugs called erythropoiesis-stimulating agents (ESAs) to be prescribed and used under a risk management program, known as a risk evaluation and mitigation strategy (REMS), to ensure the safe use of these drugs. The ESAs that are part of the REMS are marketed under the names Epogen®, Procrit®, and Aranesp®. FDA required Amgen, the manufacturer of these products, to develop a risk management program because studies show that ESAs can increase the risk of tumor growth and shorten survival in patients with cancer who use these products. Studies also show that ESAs can increase the risk of heart attack, heart failure, stroke, or blood clots in patients who use these drugs for other conditions.

As part of the REMS, a Medication Guide explaining the risks and benefits of ESAs must be provided to all patients receiving ESAs. In addition to the Medication Guide, Amgen was required to develop the ESA Assisting Providers and Cancer Patients With Risk Information for the Safe Use of ESAs (APPRISE) Oncology Program for health-care professionals who prescribe ESAs to patients with cancer. 

Under the ESA APPRISE Oncology Program, Amgen will ensure that only those hospitals and health-care professionals who have enrolled and completed training in the program will prescribe and dispense ESAs to patients with cancer. Amgen is also required to oversee and monitor the program to ensure that hospitals and health-care professionals are fully compliant with all aspects of the program.

The goals of the REMS for the ESAs are: 

  • To support informed decisions between patients and their health-care professionals who are considering treatment with an ESA by educating them on the risks of ESAs
  • To mitigate the risk of decreased survival and/or poorer tumor outcomes in patients with cancer by implementing the part of the REMS called the ESA APPRISE Oncology Program

Additional Information for Health-Care Professionals and Hospitals: ESA Use in Cancer 

The ESA APPRISE Oncology Program requires that all health-care professionals who prescribe ESAs for patients with cancer do the following:

  • Complete a training module that covers the use of ESAs. Completion of the training module is required for enrollment in the ESA APPRISE Oncology Program.
  • Sign the patient/health-care professional acknowledgement form prior to the patient receiving an ESA. The acknowledgment form attests that the health-care professional and patient have discussed the risks of using an ESA.
  • Re-enroll in the ESA APPRISE Oncology Program every three years.

Health-care professionals not enrolled in the ESA APPRISE Oncology Program will not be able to prescribe ESAs for use in patients with cancer.

As part of the enrollment in the ESA APPRISE Oncology Program, health-care professionals must attest to their understanding of the following:

  • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
  • To decrease the risks of ESAs, the lowest dose needed should be used to avoid red blood cell transfusion.
  • ESAs should be discontinued following completion of a chemotherapy course of treatment.
  • Aranesp is indicated for the treatment of anemia due to the effect of concomitantly administered chemotherapy, based on studies that have shown a reduction in the need for red blood cell transfusions in patients with metastatic, non-myeloid malignancies.
  • Epogen/Procrit is indicated for the treatment of anemia due to the effect of concomitantly administered chemotherapy, based on studies that have shown a reduction in the need for red blood cell transfusions in patients with metastatic, non-myeloid malignancies receiving chemotherapy for a minimum of two months.
  • ESAs are not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy.
  • ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.
  • ESA use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.

Additional Information for Health-Care Professionals: Non-Cancer Use of ESAs

  • Health-care professionals who prescribe ESAs for anemia not caused by cancer chemotherapy are required to provide a copy of the Medication Guide to each patient or their representative when an ESA is dispensed.
  • Health-care professionals who use ESAs only for non-cancer uses are not required to enroll in the ESA APPRISE Oncology Program.

Evaluation and Monitoring of the APPRISE Oncology Program

Amgen will be responsible for ensuring compliance with the program:

  • Amgen will conduct real-time monitoring of prescribing and purchases in private-practice settings and clinic audits.
  • Hospitals in the program will be audited to ensure compliance with the ESA APPRISE Oncology Program.
  • Failure to comply will result in a suspension of access to ESAs.

Next Steps/Additional Information

ASH was informed that Amgen will be distributing additional information to health-care professionals within 45 days of today’s announcement (March 24, 2010).  In the meantime, health-care professionals should begin to receive mailings from Amgen on how to register, enroll in the APPRISE program, and obtain copies of the Medication Guide.

If you have any questions about the ESA APPRISE Oncology Program:

  • Visit the FDA Web site.
  • Contact your local Amgen or Centocor Ortho Biotech Products Field Representative.
  • Call the ESA APPRISE Oncology Program Call Center at 866-284-8089.

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