THOUSAND OAKS, Calif.—Amgen has modified the labeling of its erythropoiesis-stimulating agents (ESAs)—Aranesp and Epogen—to include information about the increased risk of cardiovascular reactions and updated prescribing information in patients with chronic kidney disease (CKD), according to a June 24 news release.
The modified language, which was approved by the U.S. Food and Drug Administration (FDA), includes changes to the Boxed Warning and provides new information for the treatment of patients with CKD who are on dialysis, as well as those not on dialysis. The new language informs prescribers and patients of safety risks that have been identified in clinical trials.
In recognition of the different benefit-risk profiles of ESA therapy in patients on dialysis compared to patients not on dialysis, the modified labeling provides separate treatment guidance for these two CKD populations.
Specifically, for patients on dialysis, the label advises physicians to initiate ESA therapy when the hemoglobin level is less than 10 g/dL and guides physicians to reduce or interrupt the dose when the hemoglobin approaches or exceeds 11 g/dL.
For patients not on dialysis, physicians are asked to consider initiating ESA therapy when the hemoglobin level is below 10 g/dL, when reducing red blood cell transfusion-related risks is a clinical goal and when the rate of hemoglobin decline suggests a transfusion will be likely. Further, for those not on dialysis, physicians should reduce or interrupt the dose when the hemoglobin exceeds 10 g/dL.
This guidance replaces the previous label language specifying a hemoglobin target range of 10-12 g/dL for both populations. The modified prescribing information continues to recognize the benefit of reducing the need for transfusions in CKD patients.
In addition, the Boxed Warning, Warnings and Precautions and Clinical Studies sections have been modified to advise that the use of ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions.
"Amgen supports the modified ESA prescribing information as it informs physicians of important safety information," said Roger M. Perlmutter, MD, PhD, executive vice president of Research and Development at Amgen. "The revised label also provides physicians with more individualized treatment guidance by distinguishing between patients undergoing dialysis as compared with those who are not on dialysis."
The language in the prescribing information was informed by the results from clinical trials, including TREAT (the Trial to Reduce Cardiovascular Events with Aranesp Therapy), which targeted high hemoglobin levels (13 g/dL) in CKD patients who were not on dialysis and found an increased risk of stroke in the patients treated with ESAs compared to those receiving placebo. While TREAT was a study of patients who were not on dialysis, the modified Boxed Warning and other warnings in the label apply to all CKD patients.