Anemia Drugs Change Black Box Warning

The FDA today approved revisions to a “black box” warning and other safety-related label changes for the anemia drugs Procrit, Aranesp, and Epogen.

Those drugs are erythropoiesis-stimulating agents (ESAs). They boost production of red blood cells.

The revisions expand labeling changes made in March 2007, which emphasize using the lowest possible dose of the drugs to avoid the need for a blood transfusion.

Highlights in the revised warning include:

  * Risks for certain cancer patients
  * Risks for patients with chronic kidney failure
  * A statement that ESAs haven’t been shown to improve symptoms of anemia, fatigue, and quality of life in cancer patients.

“FDA strongly recommends that prescribers talk to their patients about the risks that ESAs might cause cancers to grow more quickly or shorten survival before they prescribe these drugs or continue ESA therapy. These risks should be weighed against the potential for red cell blood transfusion and their associated risks,” the FDA’s Richard Pazdur, MD, said in a news conference.

Pazdur directs the FDA’s Office of Oncology Drug Products.
Procrit, Aranesp, and Epogen

ESAs are approved for treating certain cases of anemia, including in some cancer patients and people with chronic kidney failure.

Epogen and Procrit are also approved for use in certain anemia patients who are scheduled to undergo major surgery to reduce blood transfusions during or shortly after surgery and for the treatment of anemia caused by zidovudine (AZT) therapy in people with HIV, the virus that causes AIDS.

For cancer patients, the new boxed warnings emphasize that ESAs caused tumor growth and shortened survival in patients with advanced breast, head and neck, lymphoid, and non-small-cell lung cancer when they received a dose that attempted to achieve a hemoglobin level of 12 grams per deciliter (g/dL) or greater.

The boxed warnings also emphasize that no clinical data are available to determine whether there is a similar risk of shortened survival or increased tumor growth for cancer patients who receive an ESA dose that attempts to achieve a hemoglobin level of less than 12 g/dL. This is the hemoglobin level commonly achieved in clinical practice.

Health care providers determine whether a patient is anemic and decide on ESA dosing by measuring how much of the protein known as hemoglobin is present in a patient’s red blood cells.

An earlier boxed warning, approved in March, described the results of six studies demonstrating that survival was shorter and tumors progressed faster when ESAs were used to achieve hemoglobin levels of 12 g/dL or greater in cancer patients.

Today’s new boxed warning also clarifies that ESAs should only be used in patients with cancer when treating anemia specifically caused by chemotherapy and not for other causes of anemia.

Moreover, the revised warning states that ESAs should be discontinued once the patient’s chemotherapy course has been completed.
ESAs and Chronic Kidney Failure

For patients with chronic kidney failure, the new boxed warning states that ESAs should be used to maintain a hemoglobin level between 10 g/dL and 12 g/dL.

Maintaining higher hemoglobin levels in patients with chronic kidney failure increases the risk of death and serious cardiovascular reactions such as stroke, heart attack, or heart failure, according to the FDA.

In addition to the boxed warning, the new labeling provides specific instructions for dosage adjustments and hemoglobin monitoring for chronic kidney failure patients who don’t respond to ESA treatment with an adequate increase in their hemoglobin levels.

The new labeling also emphasizes that there are no data from controlled trials demonstrating that ESAs improve symptoms of anemia, quality of life, fatigue, or patient well-being for patients with cancer or for patients with HIV undergoing AZT therapy.

Procrit, Aranesp, and Epogen are made by Amgen. Procrit is sold by Ortho Biotech, a subsidiary of Johnson & Johnson.