Popular Anemia Drugs Have Increased Risk Of Death, Blood Clots, Strokes, And Heart Attacks, Especially In Context Of Off-label Prescribing And Use
(Posted by Tom Lamb at DrugInjuryWatch.com)
On March 9, 2007 the FDA announced that Amgen Inc. and Johnson & Johnson (J&J) would add strong new warnings to their anemia drugs Procrit, Epogen, and Aranesp after several recent studies showed a higher risk of death and life-threatening side effects in some patients. The timing of this announcement by the FDA surprised some observers -- and not just because the FDA issued this drug safety alert late on a Friday afternoon -- given that this new "black box" warning for Procrit, Epogen, and Aranesp comes just two months before an advisory committee of outside experts is scheduled to meet and discuss the serious cardiovascular risks that have been associated with these popular anemia drugs.
In fact, in its March 9 FDA News release entitled "FDA Strengthens Safety Information for Erythropoiesis-Stimulating Agents (ESAs)", the agency hinted that there may be more revisions to the label, or package insert, for Procrit, Epogen, and Aranesp:
"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 Steven Galson, MD, MPH, 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."
According to a March 9, 2007 Reuters article by Lisa Richwine, Amgen as well as J&J will be sending out so-called "Dear Doctor" letters to notify healthcare providers about the new warnings being added to labels, or package inserts, for Procrit, Epogen, and Aranesp:
- "Amgen, in a statement, said it was informing doctors about the new warnings."
- "Johnson & Johnson also said it was contacting doctors about the warnings."
Usually these types of letters provide explanation and guidance as regards significant changes to a drug's label, such as the addition of a black-box warning, which can be helpful to doctors and patients, both
As of March 12, 2007, however, there was no link on the FDA's web site to any such "Dear Doctor" from either drug company.
Given the current absence of that further explanation and guidance from Amgen and J&J, we draw this information for patients from the March 9, 2007 FDA Public Health Advisory, "Erythropoiesis-Stimulating Agents (ESAs)":
Patients currently using or considering the use of an ESA should know the following:
- A higher chance of death and an increased rate of tumor growth were reported in patients with advanced head and neck cancer receiving radiation therapy and in patients with metastatic breast cancer receiving chemotherapy, when ESAs were given to maintain hemoglobin levels of more than 12 g/dL.
- A higher chance of death was reported and no fewer blood transfusions were received when ESAs were given to patients with cancer and anemia not receiving chemotherapy.
- A higher chance of death was reported and an increased number of blood clots, strokes, heart failure, and heart attacks was reported in patients with chronic kidney failure when ESAs were given to maintain hemoglobin levels of more than 12 g/dL.
- A higher chance of blood clots was reported in patients who were scheduled for major surgery and given ESAs.
- ESAs are not approved for treatment of the symptoms of anemia, such as fatigue in patients with cancer, surgical patients and patients with HIV.
- If you have any questions you should talk with your health care provider.
A March 10, 2007 article in The Wall Street Journal derived what is, perhaps, the essence of the new black-box warnings being put on Procrit, Epogen, and Aranesp -- namely, that off-label prescribing of these anemia drugs is in large part the problem:
FDA officials said the black box was sparked by recent studies that have pointed to risks tied to the drugs, particularly when doctors used them for very aggressive treatments. Karen Weiss, deputy director of the agency's office of oncology drug products, said the "bulk of the data that has raised concerns" came when patients were given higher-than-recommended doses, whether they were suffering from anemia tied to kidney problems or cancer treatment. The evidence is that "this type of strategy is not beneficial and in fact has some evidence of harm," she said....
The FDA's alert advises doctors treating anemia in patients with kidney disease or cancer not to push hemoglobin levels in the blood over 12 grams per deciliter of blood. Tests for the level of hemoglobin -- the protein in red blood cells that binds with oxygen -- measure the oxygen-carrying capacity of the blood.
Pushing hemoglobin to levels as high as 13, 14, or 15 -- done by physicians acting on their own against label recommendations or by researchers testing benefits of more intense treatment -- carries a heightened increased risk of death, or serious cardiovascular events....
If not before, we will bring you further developments about the safety of Procrit, Epogen, and Aranesp after the scheduled May 2007 advisory committee meeting.