Anemia of chronic renal failure.

Epoetin alfa can partially reverse anemia associated with CRF, thereby reducing—but not eliminating—the need for transfusions. Benefits accrue to patients on dialysis as well as those who do not yet require dialysis. Initial effects can be seen within 1 to 2 weeks. Hemoglobin reaches maximal acceptable levels (10 to 11 gm/dL) in 2 to 3 months. Unfortunately, although treatment reduces the need for transfusions, it does not improve quality of life, decrease fatigue, or prevent progressive renal deterioration.

For therapy to be effective, iron stores must be adequate. Transferrin saturation should be at least 20%, and ferritin concentration should be at least 100 ng/mL. If pretreatment assessment indicates these values are low, they must be restored with iron supplements.

Chemotherapy-induced anemia.

Epoetin alfa is used to treat chemotherapy-induced anemia in patients with nonmyeloid malignancies, thereby reducing the need for periodic transfusions. Since transfusions require hospitalization, whereas epoetin can be self-administered at home, epoetin therapy can spare patients considerable inconvenience. Because epoetin works slowly (the hematocrit may take 2 to 4 weeks to recover), transfusions are still indicated when rapid replenishment of red blood cells is required. Please note that epoetin is not approved for patients with leukemias and other myeloid malignancies. Why? Because the drug may stimulate proliferation of these cancers. Furthermore, since ESAs can shorten survival time in all cancer patients (see below), epoetin is indicated only when the goal of cancer therapy is palliation. When the goal is cure, ESAs should not be used. (It makes no sense to give a potentially lethal drug to a patient who might be cured.) A new clinical guideline—American Society of Hematology/American Society of Clinical Oncology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients with Cancer—issued in 2010, provides detailed information on using ESAs in patients with cancer.

HIV-infected patients taking zidovudine.

Epoetin alfa is approved for treating anemia caused by therapy with zidovudine (AZT) in patients with AIDS. For these patients, treatment can maintain or elevate erythrocyte counts and reduce the need for transfusions. However, if endogenous levels of erythropoietin are at or above 500 milliunits/mL, raising them further with epoetin is unlikely to help.

Anemia in patients facing surgery.

Epoetin may be given to increase erythrocyte levels in anemic patients scheduled for elective surgery. The drug should be used only when significant blood loss is anticipated—but should not be used prior to cardiac or vascular surgery. For surgical patients, epoetin offers two benefits: (1) it decreases the need for transfusions, and (2) by increasing erythrocyte synthesis, it allows patients to predeposit more blood in anticipation of transfusion needs.

Hypertension.

In patients with CRF, epoetin is frequently associated with an increase in blood pressure. The extent of hypertension is directly related to the rate of rise in the hematocrit. To minimize risk, blood pressure should be monitored and, if necessary, controlled with antihypertensive drugs. If hypertension cannot be controlled, epoetin dosage should be reduced. In patients with pre-existing hypertension (a common complication of CRF), it is imperative that blood pressure be under control prior to epoetin use. About 30% of dialysis patients receiving epoetin require an adjustment in their antihypertensive therapy once the hematocrit has been normalized.

Cardiovascular events.

Epoetin has been associated with an increase in serious cardiovascular events. Among these are cardiac arrest, hypertension, HF, and thrombotic events, including stroke and MI. Risk is greatest when (1) the hemoglobin level exceeds 11 gm/dL or (2) the rate of rise in hemoglobin exceeds 1 gm/dL in any 2-week interval. Accordingly, dosage should be reduced when hemoglobin approaches 11 gm/dL or when the rate of rise exceeds 1 gm/dL in 2 weeks—and, in most patients, dosing should be temporarily stopped if hemoglobin rises to 11 gm/dL or more. To prevent clotting in the artificial kidney, CRF patients on dialysis may need increased anticoagulation with heparin.

Excessive dosage.

To minimize the risk of serious adverse events, the dosage of epoetin alfa and all other ESAs should be the lowest needed to gradually raise hemoglobin content to the lowest level sufficient to reduce the need for RBC transfusions. In most cases, hemoglobin level should not exceed 11 gm/dL. Why? Because when ESAs are administered in doses sufficient to raise hemoglobin above this level, there is an increased risk of serious cardiovascular events and death.

Cancer patients.

Postmarketing reports indicate that ESAs can accelerate tumor progression and shorten life in certain cancer patients—especially when hemoglobin has been driven above 12 gm/dL. In patients with advanced head and neck cancer who are undergoing radiation therapy, ESAs have shortened the time to tumor progression. In patients with metastatic breast cancer who are receiving chemotherapy, ESAs have shortened overall survival and increased deaths from tumor progression. Also, ESAs have increased the risk of death in patients with active malignant disease who are not receiving either radiation or chemotherapy, and hence ESAs are contraindicated for this group.

Renal failure patients.

In patients with anemia of chronic renal failure, ESAs can increase the risk of serious cardiovascular events and death if hemoglobin levels are driven too high. Accordingly, dosage should be individualized to produce hemoglobin levels no higher than 10 to 11 gm/dL.

Preoperative patients.

When given to preoperative patients to reduce the need for RBC transfusion, ESAs have increased the risk of deep vein thrombosis—but only in patients who were not given an anticoagulant. Accordingly, anticoagulant therapy should be considered for all preoperative patients receiving an ESA.

All patients.

Because ESAs can cause serious adverse effects, these drugs must be prescribed and used under a new Risk Evaluation and Mitigation Strategy (REMS), mandated by the Food and Drug Administration in 2010. Under the REMS, all patients must receive a Medication Guide that explains the risks and benefits of ESAs. The goal is to help patients make an informed decision when use of an ESA is under consideration. The guide also informs patients about what they can do to minimize risk.

Cancer patients.

The ESA APPRISE Oncology Program* sets additional requirements for using ESAs in cancer patients. Prescribers must enroll in ESA APPRISE, complete a brief training module, discuss the risks and benefits of ESAs with the patient, and sign a form acknowledging that the discussion took place. Hospitals that dispense ESAs must be enrolled in ESA APPRISE, and must ensure that all ESA prescribers are enrolled as well. Prescribers who use ESAs for patients who do not have cancer are not required to enroll in ESA APPRISE.