Erythropoietin drugs: What to know about anemia-fighting medications

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Erythropoietin drugs: What to know about anemia-fighting medications

Understand the risks of erythropoietin used to treat anemia related to dialysis or chemotherapy.

Photo of Amy Williams, M.D.
Amy Williams, M.D.

If you're undergoing hemodialysis for kidney disease or chemotherapy for cancer, you may be familiar with erythropoietin drugs that treat anemia — low red blood cell count. These medications are called erythropoiesis-stimulating agents, or ESAs. ESAs are genetically engineered forms of the human protein erythropoietin (uh-rith-ro-POI-uh-tin), which is important in the production of red blood cells.

The Food and Drug Administration (FDA) has issued warnings to doctors to exercise caution when prescribing ESAs. Included in the warnings are darbepoetin alfa (Aranesp) and epoetin alfa (Epogen, Procrit).

Here to answer some questions about erythropoietin and ESAs is Amy Williams, M.D., a consultant in the Division of Nephrology and Hypertension at Mayo Clinic, Rochester, Minn.

First, what is erythropoietin and why is it especially important to people undergoing dialysis or chemotherapy?

Erythropoietin is a hormone produced by your kidneys that stimulates bone marrow to make healthy red blood cells, which carry oxygen. The hematocrit level in your blood is a measure of the level of healthy oxygen-carrying red blood cells in your body. Anemia occurs when your hematocrit falls below the normal range. Usually, that's prevented by the kidneys making extra erythropoietin and prompting your bone marrow to produce more red blood cells. 

One consequence of kidney disease is decreased production of erythropoietin. Chemotherapy also can cause decreased erythropoietin production and may decrease erythropoietin's effectiveness. In both of these instances, giving erythropoietin can increase red blood cell production, eliminating the need for blood transfusions and improving your well-being.

How are ESAs potentially helpful to people with anemia caused by kidney problems or chemotherapy?

Anemia may decrease your quality of life. Symptoms of anemia include fatigue, decreased exercise tolerance, weakness, shortness of breath, and difficulty with concentration, attention span and memory. Cold intolerance, sexual dysfunction and anorexia may also occur. Correcting anemia in chronic diseases such as kidney disease can prevent these symptoms and improve overall well-being. The studies looking at the use of ESAs in people receiving chemotherapy generally show no improvement in symptoms, unless the anemia is very severe.

What are the concerns with these medications?

There are few concerns with this class of medications if used correctly to reverse anemia. However, when used to build healthy red blood cell concentrations to excessively high levels they may lead to increased risks of cardiovascular problems.

Clinical studies have reported that hemoglobin levels above 12 grams per deciliter (g/dL) in people on erythropoietin increase the risk of serious cardiovascular events such as congestive heart failure, heart attacks, blood clots and stroke.

Increased chance of cancer recurrence or decreased response of cancer to chemotherapy and radiation therapy also have been reported. The FDA has issued a warning that restricts the use of ESAs in people with certain forms of cancer. The warning is based on studies that found shortened survival and more rapid tumor growth in people with breast, non-small cell lung, head and neck, lymphoid and cervical cancers when given doses to increase hemoglobin levels to or above 12 g/dL.

Another FDA warning calls for using the lowest dose of ESAs — only enough to avoid the need for blood transfusion. Explain why higher levels might cause problems.

The side effects identified could arise from abnormally high levels of hemoglobin or from the medication itself. Erythropoietin has been shown to increase the constriction of small arteries, which could explain the vascular side effects observed. Extremely high hemoglobin levels can increase the viscosity of the blood, leading to heart problems and blood clots.

Why erythropoietin should cause an increased risk of cancer to recur or a decreased response to cancer therapy is uncertain, and more research is needed to understand this problem. It's also unclear why these agents should cause an increased chance of death in people with cancer who are not receiving chemotherapy or radiation therapy.

What do you tell people who've been taking these drugs or who've been asking for them?

When a person has anemia due to chronic kidney disease, we discuss the side effects and risks of anemia. We also discuss the options for treatment, which, for many, is limited to either erythropoietin or blood transfusions. Erythropoietin is well tolerated if started at an individualized starting dose and carefully monitored for the degree of hemoglobin increase. As the hemoglobin reaches the goal of 11 to12 g/dL, the dose is reduced to prevent further increase in hemoglobin. It's important for someone who is considering erythropoietin therapy to understand the benefits of preventing symptomatic anemia and the need for careful monitoring to prevent excessive hemoglobin levels.

People with cancer who are currently being treated with chemotherapy or radiation need to understand that no study has demonstrated less fatigue with use of these agents, in spite of what the commercials say. In people with cancer who are not undergoing active therapy, these agents have never been shown to significantly improve anemia.

Last Updated: 04/23/2008
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