FDA Warns of Serious Side Effects Related to Popular Anemia Drugs. The U.S. Food and Drug Administration (FDA) has issued a new warning about erythropoiesis-stimulating agents (ESAs), which are drugs that are used to treat anemia. The warnings relate to darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). All three of the drugs are made by Amgen Inc., although Procrit is distributed and marketed by a Johnson & Johnson subsidiary.
“Recently completed studies describe an increased risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure when ESAs were given at higher than recommended doses,” the FDA said. “In other studies, more rapid tumor growth occurred in patients with head and neck cancer who received these higher doses.
“In studies where ESAs were given at recommended doses, an increased risk of death was reported in patients with cancer who were not receiving chemotherapy and an increased risk of blood clots was observed in patients following orthopedic surgery.”
This new labeling change marks the fourth time in the past decade that the products’ label warnings were forced to be updated. “The agency is in the process of re-evaluating the safety of Aranesp, Epogen, and Procrit on the basis of the results of recent clinical studies,” said Dr. Steven Galson, director of FDA’s Center for Drug Evaluation and Research. “The new studies provide significant new information for both prescribers and patients, and the new information applies to all ESAs, which share the same mechanism of action. The safety of these products will be discussed when the Oncologic Drugs Advisory Committee (ODAC) meets in May and further revisions to the labeling may occur after that meeting.”
FDA Asking the Drug Makers to Add a Black-Box Warning
The FDA is asking the drug makers to add a black-box warning, the agency’s most serious alert, that “advises physicians to monitor red blood cell levels (hemoglobin) and to adjust the ESA dose to maintain the lowest hemoglobin level needed to avoid the need for blood transfusions.”
According to the FDA, ESAs are “genetically engineered forms of the naturally occurring human protein, erythropoietin.” Erythropoietin is produced by the kidneys and increases red-blood-cell levels. Currently, the FDA has approved these drugs for treating anemia in patients with chronic kidney failure and in patients whose anemia is a result of chemotherapy. Combined domestic sales of the three drugs reached approximately $10 billion last year alone.
In January, Amgen sent a letter to medical professionals warning them of an elevated risk of fatalities associated with the use of Aranesp in cancer patients. Amgen conducted a clinical trial to test the safety and efficacy of Aranesp on patients whose anemia was caused by the cancer itself, not by chemotherapy. While the drug is not currently approved for this usage, corporate estimates say that approximately 10 to 12 percent of all Aranesp sales are for that exact off-label (unapproved) usage.
The safety of Epogen has also been questioned by the medical community. Last November, two studies in the New England Journal of Medicine cited the overuse of anemia drugs in the treatment of kidney patients. Scientists have found that anemic kidney patients are susceptible to heart problems or death when aggressively treated with these drugs. Epogen has also been under attack by Congress because of the strain it places on Medicare. Anemia drugs are currently Medicare’s largest drug expenditure.