On February 16, 2010, a Risk Evaluation and Mitigation Strategies (REMS) program to ensure safe use of erythropoiesis-stimulating agents (ESAs) was approved by the US Food and Drug Administration (FDA). The medications included in the REMS program are marketed by Amgen under the trade names Aranesp (darbepoetin alfa) and Epogen (epoetin alfa) and by Centocor Ortho Biotech Products under the name Procrit (epoetin alfa).
The Food and Drug Administration Amendments Act of 2007 (FDAAA), which went into effect on March 25, 2008, reserves the right of the FDA to order REMS for drugs or biologics that have significant toxicity levels and/or demonstrable risk factors. The purpose of these strategies is to ensure that the benefits of specific drugs continue to outweigh risks that they pose for patients. REMS are now being mandated to assess adverse risks associated with specific oncologic drugs, biologics, and supportive care therapies.
Amgen, the manufacturer of Aranesp and Procrit, is required by the FDA to develop the REMS based on studies demonstrating that use of ESAs can increase the risk of tumor growth and shorten survival in patients with cancer. In studies of patients with cancer and patients with renal failure, use of ESAs was shown to increase the risk of myocardial infarction, congestive heart failure, stroke, and thrombotic events.
REMS program have three components, including a medication guide or a patient package insert; a communication plan for healthcare providers; and elements to assure safe use, or ETASU. The specific components used by a REMS program vary based on factors including but not limited to the severity of the risks and the population likely to be exposed. The most common REMS require only the provision of a medication guide.
The REMS program for ESAs requires that all patients receiving ESAs must be provided with a Medication Guide explaining the risks and benefits of ESAs. In addition, Amgen, in collaboration with Centocor Ortho Biotech Products, was required by the FDA to develop the ESA APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe use of ESAs) Oncology program for healthcare professionals who prescribe ESAs to patients with cancer. The ESA APPRISE Oncology program was launched on March 24, 2010.
Under the ESA APPRISE Oncology program, Amgen will ensure that only hospitals and healthcare professionals who have enrolled in the program and completed special training will be able to prescribe and dispense ESAs to patients with cancer. Amgen is also required to monitor the program to ensure that hospitals and healthcare professionals are in full compliance with all aspects of the program.
The ESA APPRISE Oncology program requires that all healthcare professionals who prescribe ESAs in patients with cancer meet the following requirements:
• Complete a training module instructing healthcare professionals about the use of ESAs for patients with cancer. The training module must be completed prior to enrollment of the healthcare professional in the ESA APPRISE Oncology program.
• Obtain a signed patient/healthcare professional acknowledgement form prior to initiating a new course of ESA therapy. The acknowledgement form attests that the healthcare professional and patient have discussed the risks associated with using an ESA.
• Re-enroll in the ESA APPRISE Oncology program every 3 years.
• Healthcare 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, healthcare professionals must attest to understanding 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 cancer.
• Healthcare professionals not enrolled in the ESA APPRISE Oncology program will not be able to prescribe ESAs for use in patients with cancer.
• To decrease the risks of ESAs, the lowest dose of ESAs should be used to avoid red blood cell transfusion.
• Aranesp is indicated for 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, nonmyeloid malignancies receiving chemotherapy.
• 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, nonmyeloid malignancies receiving chemotherapy for a minimum of 2 months.
• ESAs are not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless these patients are receiving comitant 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.
• ESAs should be discontinued following completion of a chemotherapy course of treatment.
Additional information on the ESAs, this REMS, and the ESA APPRISE Oncology Program is available on the FDA website, www.fda.gov. (Search for “Drug Safety Communication: Erythropoiesis-Stimulating Agents [ESAs]: Procrit, Epogen, and Aranesp.”)
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications, is available at www.accessdata.fda.gov/drugsatfda_docs/label/2010/103951s5197lbl.pdf2 and at www.accessdata.fda.gov/drugsatfda_docs/label/2010/103234s5199lbl.pdf3.
A list of FDA-approved REMS is available at www.fda.gov. (Search for “Approved Risk Evaluation and Mitigation Strategies [REMS].”)
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting Program. To do this, an online form can be accessed at at www.fda.gov/medwatch/report.htm4, reports can be faxed to (1-800-FDA-0178), one can mail the postage-paid Form 3500 available at www.fda.gov/medwatch5, or reports can be made by telephone (1-800-FDA-1088).
NCCN.com, the patient/consumer website of the National Comprehensive Cancer Network, provides background information about REMS to patients on their “Living With Cancer” page. Patients who want to learn more about REMS can be referred to “Risk Evaluation and Mitigation Strategies: What Do REMS Mean for You?” available at www.nccn.com/REMS/.
US Food and Drug Administration Approves Risk Evaluation and Mitigation Strategies (REMS) Program to Ensure Safe Use of Erythropoiesis-Stimulating Agents (ESAs)
