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FDA issues advisory on safety of erythropoiesis-stimulating agents
Higher doses of darbepoetin alfa and epoetin alfa associated with increased risks.
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The FDA has issued a public health advisory concerning new safety information about the erythropoiesis-stimulating agents darbepoetin alfa and epoetin alfa.
The new safety information contains revised product labeling that includes updated warnings, a new boxed warning and changes to dosing instructions. The boxed warning advises physicians to monitor hemoglobin levels and adjust the dose of erythropoiesis-stimulating agents to maintain hemoglobin levels needed to avoid blood transfusions.
“This warning should not be construed so as to throw out the baby with the bath water,” Harry S. Jacob, MD, professor of medicine at the University of Minnesota in Minneapolis, and chief medical editor for Hem/Onc Today, said in an interview. “Numerous studies have demonstrated quality-of-life benefits that result from erythropoietin administration. Just don’t overdo this expensive medication, which is true for all therapies.”
Recent studies have found that darbepoetin alfa (Aranesp, Amgen) and epoetin alfa are associated with increased risk for death, thrombosis, stroke and myocardial infarction in patients with chronic kidney failure when given at higher doses than recommended. Other studies found that rapid tumor growth occurred in patients with head and neck cancer who also received higher doses.
Anemia treatments
Erythropoiesis-stimulating agents are genetically engineered forms of erythropoietin, a protein made by the kidney that increases the number of red blood cells. The agents are frequently used to treat anemia.
In studies where the drugs were given at recommended doses, there was an increased risk for death in patients with cancer not receiving chemotherapy. The drug was also associated with an increased risk for blood clots in patients who received orthopedic surgery.
“The FDA is in the process of re-evaluating the safety of [darbepoetin alfa and epoetin alfa] on the basis of the results of recent clinical studies,” Steven Galson, MD, MPH, director of the FDA’s Center for Drug Evaluation and Research, said in a press release. “The new studies provide significant new information for both prescribers and patients. The new information applies to all erythropoiesis-stimulating agents, which share the same mechanism of action.”
It warns of a higher incidence of deep venous thrombosis in patients receiving epoetin alfa. The warning also lists the increased risks when using erythropoiesis-stimulating agents to target a hemoglobin level greater than 12 g/dL.
The safety of the drugs will be discussed at the Oncologic Drugs Advisory Committee meeting in May, and additional label revisions may be made. Previous revisions to product labeling were made in 1997, 2004 and 2005.
Darbepoetin alfa and epoetin alfa are approved to treat anemia in patients with chronic kidney failure and anemia related to chemotherapy. Epoetin alfa is approved for patients undergoing major surgery to reduce chance of blood transfusions. It is also approved to treat anemia due to zidovudine therapy in patients with HIV. – by Emily Shafer