Brand names: Epogen, Procrit, Retacrit
Drug class: Hematopoietic Agents
- Erythropoietic Agents
- Growth Factors
- CSFs
- Colony-stimulating Factors
VA class: BL400
Chemical name: 1-165-Erythropoietin (human clone λHEPOFL13 protein moiety)
Molecular formula: C₈₀₉H₁₃₀₁N₂₂₉O₂₄₀S₅
CAS number: 113427-24-0

Medically reviewed by Drugs.com on Nov 27, 2023. Written by ASHP.

Introduction

Epoetin alfa, a biosynthetic form of the glycoprotein hormone erythropoietin, is a hematopoietic agent that principally affects erythropoiesis.

Epoetin alfa-epbx is biosimilar to epoetin alfa (Epogen; Procrit). A biosimilar is a biological that is highly similar to an FDA-licensed reference biological with the exception of minor differences in clinically inactive components and for which there are no clinically meaningful differences in safety, purity, or potency. Biosimilars are approved through an abbreviated licensure pathway that establishes biosimilarity between a proposed biological and reference biological but does not independently establish safety and effectiveness of the proposed biological. In order to be considered an interchangeable biosimilar, a biological product must meet additional requirements beyond demonstrating biosimilarity to its reference product. The currently available epoetin alfa biosimilar does not have interchangeable data at this time.

Uses for Epoetin Alfa

Epoetin alfa and epoetin alfa-epbx have not been shown to improve quality of life, fatigue, or patient well-being.

Anemia of Chronic Kidney Disease

Epoetin alfa and epoetin alfa-epbx are used for the treatment of anemia associated with chronic kidney disease (CKD), including that in patients who are dialysis-dependent and in those who do not yet require maintenance dialysis (predialysis patients), to reduce the need for RBC transfusions.

Epoetin alfa has been designated an orphan drug by the US Food and Drug Administration (FDA) for anemia associated with end-stage renal disease (ESRD).

Epoetin alfa products are not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.

The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends addressing all correctable causes of anemia prior to starting erythropoietin stimulating agent (ESA) therapy and weighing the potential benefits and risks of ESAs for each patient where therapy is considered. Individualization of therapy when using ESAs is stressed throughout this guideline, as individual patient responses to treatment may differ. The guideline does not specify a preferred ESA and suggests that ‘copy’ versions of ESAs should only be those which have been designated a true biosimilar. The Kidney Disease Outcomes Quality Initiative (KDOQI) US Commentary on the 2012 KDIGO guideline states that for maintenance therapy, KDOQI supports a lower limit of goal hemoglobin of 11 g/dL.

Anemia in Patients with HIV infection Treated with Zidovudine

Epoetin alfa and epoetin alfa-epbx are used for the treatment of anemia associated with zidovudine therapy in patients with HIV infection; the drug is indicated in such patients with endogenous serum erythropoietin concentrations of ≤500 milliunits/mL who are receiving zidovudine therapy in dosages ≤4.2 grams per week.

Epoetin alfa products are not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.

Epoetin alfa has been designated an orphan drug by the FDA for anemia associated with HIV infection or HIV treatment.

Older nucleoside reverse transcriptase inhibitors (NRTIs), including zidovudine, stavudine, and didanosine, are no longer recommended in routine clinical practice in the United States, and thus have reduced the need for epoetin alfa products in this setting. Zidovudine does still have a role in the prevention of perinatal transmission of HIV and is also recommended as an alternative agent in pediatric HIV infection.

Anemia Due to Chemotherapy in Patients with Nonmyeloid Malignancies

Epoetin alfa and epoetin alfa-epbx are used for the treatment of chemotherapy-induced anemia in patients with nonmyeloid malignancies in whom chemotherapy is planned for at least 2 additional months.

Therapy with epoetin alfa products or other ESAs should be initiated only when the hemoglobin concentration is <10 g/dL and should be discontinued after completion of a course of myelosuppressive chemotherapy.

Epoetin alfa products are not indicated for use in patients with cancer receiving: hormonal agents, biologic products, or radiation therapy unless they are also receiving concomitant myelosuppressive chemotherapy; myelosuppressive chemotherapy when the anticipated outcome is cure; myelosuppressive chemotherapy in whom the anemia can be managed by transfusion.

Epoetin alfa products are not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.

The American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH) published a joint guideline that provides recommendations for use of ESAs in patients with cancer. Per ASCO/ASH, ESAs and their biosimilars may be offered to patients with chemotherapy-induced anemia whose cancer treatment is not curative in intent and whose hemoglobin is <10 g/dL. The guideline’s Expert Panel considers epoetin alfa and beta, darbepoetin, and biosimilar epoetin alfa to be equivalent with respect to effectiveness and safety. In patients with nonmyeloid hematologic malignancies who are receiving concurrent myelosuppressive chemotherapy, hematologic response to cancer treatment should be observed before considering therapy with ESAs; particular caution should be exercised in the use of ESAs in patients with an increased risk of thromboembolic complications.

Reduction of Red Blood Cell Transfusion Requirements in Anemic Surgery Patients

Epoetin alfa and epoetin alfa-epbx are used perioperatively to reduce the need for allogeneic RBC transfusions in adults with perioperative hemoglobin concentrations >10 to ≤13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery.

Epoetin alfa products are not indicated in those who are willing to donate autologous blood prior to surgery or undergoing cardiac or vascular surgery.

Epoetin alfa products are not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.

The American Society of Anesthesiologists Task Force on Perioperative Blood Management published a guideline on the use of perioperative blood transfusion and adjuvant therapies. Per the Task Force, erythropoietin with or without iron may be administered to reduce the need for transfusions in select patient populations (e.g., renal insufficiency, anemia of chronic disease, refusal of transfusion).

Other Uses

Therapy with ESAs may be beneficial prior to elective surgery to increase the volume of blood available for autologous donation, particularly for procedures in which the potential for substantial blood loss exists (e.g., hip or knee replacement)^{† [off-label]}. The manufacturers state that epoetin alfa products are not indicated in anemic patients who are willing to donate autologous blood prior to surgery.

Therapy with ESAs (epoetin alfa or darbepoetin alfa) has been evaluated in the treatment of anemia of prematurity, a condition in premature neonates that is due to impaired production of erythropoietin after birth, which is more pronounced in preterm infants who are already born with lower hematocrit compared to term infants^{† [off-label]}.

Therapy with ESAs may be useful for delayed hemolytic transfusion reaction (DHTR) in patients with sickle cell disease^{† [off-label]}. The 2020 ASH guidelines recommend ESAs with or without IV iron as supportive care for all patients with DHTR. A 2014 Expert Panel Report from the Department of Health and Human Services acknowledges data supporting ESAs for DHTR. Neither guideline gives preference to a specific ESA product.

Therapy with ESAs may be useful for patients with myelodysplastic syndrome^{† [off-label]}. ASCO and ASH published a joint guideline that provides recommendations for use of ESAs in patients with cancer. Patients with nonchemotherapy-associated anemia should generally not be offered ESAs, with the exception of patients with lower risk myelodysplastic syndromes and a serum erythropoietin level ≤500 units/L. The guideline does not give preference to a specific ESA product for this use.

Therapy with ESAs (epoetin alfa or darbepoetin alfa) may be useful for infants with hypoxic-ischemic encephalopathy (HIE)^{† [off-label]}.

Therapy with ESAs may be useful to improve the efficiency and production of RBCs and limit blood loss in patients who refuse or are unable to receive allogeneic blood or blood products^†.

Epoetin Alfa Dosage and Administration

General

• Give a copy of the medication guide and instruct patients to read the guide prior to initiating therapy with epoetin alfa products and each time the drug is dispensed.

• Instruct patients who self-administer epoetin alfa products regarding proper, safe use of the drugs, including information on aseptic technique, on storage and disposal of the drugs and administration equipment, and on recognition and management of sensitivity reactions.

• Discontinue therapy with epoetin alfa products when cancer chemotherapy is completed.

Pretreatment Screening

• Assess iron status (i.e., transferrin saturation, serum ferritin concentration) prior to starting therapy.

• Correct or exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding) prior to stating therapy.

• Initiate supplemental iron therapy if serum ferritin concentration is <100 mcg/L or transferrin saturation is <20%. The manufacturer states that the majority of patients with CKD will require supplemental iron during the course of ESA therapy.

• Control hypertension prior to starting therapy.

Patient Monitoring

• Monitor iron status (i.e., transferrin saturation, serum ferritin concentration) throughout therapy.

• Monitor hemoglobin weekly after initiation of therapy and following each dose adjustment until stable and sufficient to minimize the need for RBC transfusion; monitor hemoglobin at least monthly thereafter.

• Monitor blood pressure throughout therapy and initiate antihypertensive medications as needed. Reduce or withhold epoetin alfa products if blood pressure becomes difficult to control.

  Monitor patients for seizures and premonitory neurologic symptoms during the first several months of therapy. Epoetin alfa products increase the risk of seizure in patients with CKD.

• Monitor for severe anemia and low reticulocyte count during treatment, which could indicate presence of neutralizing antibodies.

• Monitor for serious blistering and skin exfoliation reactions as well as serious allergic reactions; discontinue therapy immediately if these reactions occur.

Premedication and Prophylaxis

• Administer deep vein thrombosis prophylaxis to surgical patients receiving therapy for the reduction of allogeneic RBC transfusions.

Other General Considerations

• Adjustments to concomitant dialysis medications may be required after initiating epoetin alfa products.

• Only use single-dose vials (i.e., the benzyl-alcohol free formulation) in women who are pregnant or breastfeeding, neonates, and infants; do not admix epoetin alfa products from single-dose vials with bacteriostatic saline containing benzyl alcohol for these populations.

• Because of the ergogenic effects of therapy with ESAs (i.e., increases in erythrocyte count, hematocrit and hemoglobin concentration, and oxygen-carrying capacity of blood), the potential exists for abuse of these drugs by athletes, especially those participating in high-aerobic demand, endurance-type events. Effects of ESAs would be expected to be similar to those of homologous or autologous RBC transfusions (“blood doping”), which have been used by athletes to increase cardiac output, oxygen uptake capacity of blood, and aerobic exercise endurance by increasing arterial blood oxygen content. These effects may be particularly evident in individuals with greater initial aerobic fitness. Erythropoietins and agents affecting erythropoiesis are included on the World Anti-Doping Code International Standard Prohibited List of substances in- and out-of-competition.

Administration

Administer epoetin alfa products by IV or sub-Q injection.

IV or Sub-Q

In patients undergoing hemodialysis, the manufacturers recommend that epoetin alfa products be given IV rather than sub-Q because of reports of pure red cell aplasia (PRCA) associated with the latter administration route.

Do not shake or freeze vials of epoetin alfa product, and discard the vials if subjected to these conditions.

Visually inspect the contents of vials of epoetin alfa product for discoloration and/or particulate matter prior to administration whenever solution and container permit; if either is present, discard the solution.

Withdraw the appropriate dose of the epoetin alfa product from the vial into the syringe for administration; once the dose has been withdrawn from the vial, administer promptly.

Do not generally mix epoetin alfa products with other drug solutions. However, the manufacturers of Epogen and Procrit state that the preservative-free formulation from single-use vials may be admixed in equal parts (in a 1:1 ratio) in a syringe with bacteriostatic 0.9% sodium chloride injection (preserved with benzyl alcohol) at the time of administration.

Discard unused portions of epoetin alfa product from single-dose preservative-free vials. Any unused portion of epoetin alfa product from multi-dose vials can be stored, protected from light, between 2–8°C for 21 days after initial entry. Because of the risks associated with benzyl alcohol, do not use epoetin alfa product that has been admixed with injection solutions containing benzyl alcohol in neonates, infants, pregnant women, and nursing women.

Dosage

Pediatric Patients

Anemia of Chronic Kidney Disease

IV or Sub-Q

Children and infants ≥1 month of age: Initially, 50 units/kg 3 times weekly; IV administration recommended in patients undergoing hemodialysis.

Initiate therapy when hemoglobin concentration <10 g/dL. Reduce or interrupt therapy if hemoglobin approaches or exceeds 12 g/dL.

Dosage Modifications

Adjust dosage based on hemoglobin concentrations. Consider rate of hemoglobin increase or decrease, ESA responsiveness, and hemoglobin variability when determining whether adjustments are needed; a single hemoglobin excursion may not require a dosage change.

If hemoglobin concentration increases by >1 g/dL in any 2-week period, reduce dosage by 25% or more as necessary to reduce risk of a rapid response.

If hemoglobin has not increased by >1 g/dL after 4 weeks of therapy, increase dosage by 25%.

Do not increase dosage more frequently than once every 4 weeks. If an adequate response not obtained within 12 weeks, evaluate for other causes of anemia. Further dosage increase not likely to improve patient response and may increase risks of therapy; use lowest dosage sufficient to reduce need for RBC transfusions and discontinue drug if responsiveness does not improve.

Anemia in Patients with HIV infection Treated with Zidovudine

IV or Sub-Q

Children 8 months to 17 years of age have received dosages of 50–400 units/kg 2 or 3 times weekly.

Anemia Due to Chemotherapy in Patients with Nonmyeloid Malignancies

IV

Pediatric patients 5–18 years of age: Initially, 600 units/kg once weekly. Initiate only if hemoglobin concentration <10 g/dL and at least 2 additional months of chemotherapy is planned.

Discontinue epoetin alfa therapy following completion of a chemotherapy course. Use the lowest possible dosage to avoid RBC transfusions.

Dosage Modifications

If the hemoglobin increases by <1 g/dL within 4 weeks and remains <10 g/dL, increase weekly dosage to 900 units/kg (maximum 60,000 units weekly).

If hemoglobin increases by >1 g/dL in any 2-week period or reaches a concentration sufficient to avoid RBC transfusion, reduce dosage by 25%.

If hemoglobin exceeds a level needed to avoid RBC transfusion, withhold therapy until the hemoglobin falls to a level where RBC transfusion may be required, then resume at a dosage 25% less than the previous dosage.

Discontinue epoetin alfa therapy after 8 weeks if no response based on hemoglobin concentrations or if RBC transfusions are still required.

Adults

Anemia of Chronic Kidney Disease

IV or Sub-Q

Patients on dialysis: Initially, 50–100 units/kg 3 times weekly; IV administration recommended in patients undergoing hemodialysis. Initiate therapy when hemoglobin concentration <10 g/dL. Reduce or interrupt therapy if hemoglobin approaches or exceeds 11 g/dL.

Patients not on dialysis: Initially, 50–100 units/kg 3 times weekly. Consider initiating therapy when hemoglobin <10 g/dL and the following 2 conditions apply: rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and a goal of therapy is to reduce risk of alloimmunization and/or other risks associated with RBC transfusions. Reduce or interrupt therapy if hemoglobin >10 g/dL.

Dosage Modifications

Adjust dosage based on hemoglobin concentrations. Consider rate of hemoglobin increase or decrease, ESA responsiveness, and hemoglobin variability when determining whether adjustments are needed; a single hemoglobin excursion may not require a dosage change.

If hemoglobin increases by >1 g/dL in any 2-week period, reduce dosage by 25% or more as necessary to reduce risk of a rapid response.

If hemoglobin has not increased by >1 g/dL after 4 weeks of therapy, increase dosage by 25%.

Do not increase more frequently than once every 4 weeks. If an adequate response not obtained within 12 weeks, evaluate for other causes of anemia. Further dosage increases are not likely to improve patient response and may increase risks of therapy; use lowest dosage sufficient to reduce need for RBC transfusions and discontinue drug if responsiveness does not improve.

Anemia in Patients with HIV Infection Treated with Zidovudine

IV or Sub-Q

Initially, 100 units/kg 3 times weekly in patients with endogenous serum erythropoietin concentrations ≤500 milliunits/mL receiving ≤4.2 g/week of zidovudine.

Dosage Modifications

If hemoglobin does not increase after 8 weeks, increase the 3-times-weekly dose by 50–100 units/kg at 4- to 8-week intervals until an adequate hemoglobin concentration or a dosage of 300 units/kg 3 times weekly is reached. Discontinue therapy if hemoglobin does not increase after 8 weeks of treatment with 300 units/kg 3 times weekly.

If hemoglobin >12 g/dL, withhold therapy until hemoglobin decreases to <11 g/dL. Reduce dosage by 25% upon reinitiation.

Anemia Due to Chemotherapy in Patients with Nonmyeloid Malignancies

Sub-Q

Initiate only if hemoglobin concentration <10 g/dL and at least 2 additional months of chemotherapy is planned. Discontinue following completion of a chemotherapy course.

3-times-weekly regimen: Initially, 150 units/kg 3 times weekly.

Once-weekly regimen: Initially, 40,000 units weekly.

Dosage Modifications

3-times-weekly regimen: If hemoglobin concentration has not increased by ≥1 g/dL within 4 weeks and remains <10 g/dL, increase dosage to 300 units/kg 3 times weekly.

Once-weekly regimen: If hemoglobin has not increased by ≥1 g/dL within 4 weeks and remains <10 g/dL, increase dosage to 60,000 units weekly.

If hemoglobin reaches a concentration sufficient to avoid the need for RBC transfusion or increases by >1 g/dL in any 2-week period, reduce dosage by 25%.

If the hemoglobin exceeds a concentration needed to avoid RBC transfusion, temporarily withhold therapy until the hemoglobin falls to a concentration where RBC transfusion may be required, then resume at a dosage 25% less than the previous dosage.

Discontinue therapy after 8 weeks if no response based on hemoglobin concentrations or if RBC transfusions are still required.

Reduction of Red Blood Cell Transfusion Requirements in Anemic Surgery Patients

Sub-Q

Prior to therapy, obtain hemoglobin to ensure concentration >10 but ≤13 g/dL.

300 units/kg once daily for 10 days prior to surgery, on the day of surgery, and for 4 days after surgery.

Alternatively, 600 units/kg once weekly for 3 weeks prior to surgery (i.e., days 21, 14, and 7 before surgery), with an additional dose given on the day of surgery.

Prophylaxis for deep vein thrombosis is strongly recommended during therapy.

Special Populations

Hepatic Impairment

No special dosage recommendations.

Renal Impairment

No special dosage recommendations.

Geriatric Patients

Individualized dosing is recommended for treatment of anemia due to CKD.

No special dosage recommendations for treatment of patients with zidovudine-induced anemia, chemotherapy-induced anemia, or for patients undergoing elective surgery.

Cautions for Epoetin Alfa

Contraindications

• Uncontrolled hypertension.

• Pure red cell aplasia (PRCA) following treatment with epoetin alfa products or other erythropoietin proteins.

• History of a serious allergic reaction to epoetin alfa products.

• Use of epoetin alfa products from multi-dose vials containing benzyl alcohol in women who are pregnant or breastfeeding, neonates, and infants.

Warnings/Precautions

Warnings

Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism

Increased risk of death and serious and life-threatening cardiovascular events (e.g., myocardial infarction (MI), stroke, congestive heart failure, hemodialysis vascular access thrombosis) when targeting hemoglobin concentrations exceeding 11 g/dL in patients with CKD.

Targeting a hemoglobin concentration exceeding 11 g/dL does not provide additional benefit.

Use with caution in patients with concurrent cardiovascular disease and stroke.

Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at greater risk for cardiovascular events and mortality; an increase in hemoglobin concentration exceeding 1 g/dL in a 2-week period may contribute to these risks.

Increased risk of serious adverse cardiovascular events (MI and stroke) and/or death in patients with cancer.

Increased risk of death in patients undergoing coronary artery bypass graft surgery (CABG).

Increased risk of deep vein thrombosis in patients undergoing orthopedic surgery has also been observed. Antithrombotic prophylaxis is strongly recommended for surgical patients.

Increased Mortality and Tumor Progression

Increased mortality and risk of tumor progression or recurrence in patients with cancer.

Shortened progression-free survival (PFS) and/or overall survival (OS) observed in patients receiving chemotherapy for breast, cervical, and lymphoid cancer; in patients receiving radiation therapy with advanced head and neck cancer; and in patients with non-small cell lung cancer and other cancers who were not receiving chemotherapy or radiation therapy.

Therapy should only be initiated in patients with cancer receiving chemotherapy if the hemoglobin is less than 10 g/dL, and if there is a minimum of 2 additional months of planned chemotherapy.

Not approved for use in patients with cancer who are: not receiving concomitant myelosuppressive chemotherapy; receiving myelosuppressive chemotherapy when the anticipated outcome is cure; receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion.

Other Warnings and Precautions

Hypertension

May cause new onset or an exacerbation of hypertension during therapy, particularly during the early phase of therapy when hematocrit is rising.

Hypertensive encephalopathy and seizures have been reported in patients with CKD.

Monitor blood pressure prior to initiation and throughout therapy and initiate antihypertensive medications as needed.

Management of persistently high blood pressure may require initiation or increased dosage of antihypertensive therapy. A decrease in the dosage of epoetin alfa product or temporary discontinuation of therapy may be necessary if blood pressure becomes too difficult to control.

Advise patients to maintain compliance with concomitant antihypertensive therapy and dietary restrictions.

Seizures

Risk of seizures in patients with CKD.

Monitor patients for seizures and premonitory neurologic symptoms during the first several months of therapy.

Advise patients to contact their healthcare provider for new-onset seizures, premonitory symptoms, or change in seizure frequency.

Lack or Loss of Hemoglobin Response

Evaluate for causative factors in patients who failure to respond or experience a loss of hemoglobin response; inflammation, infection, blood loss, and iron deficiency, may diminish the effects of epoetin alfa products.

Evaluate for PRCA if typical causes of lack or loss of hemoglobin response are excluded. If PRCA is excluded, dose adjustments may be necessary. (See Dosage under Dosage and Administration.)

Pure Red Cell Aplasia

PRCA and severe anemia, with or without other cytopenias, have been associated with neutralizing antibodies in patients receiving ESAs; most cases have been observed in patients treated with sub-Q ESAs for CKD. (See Immunogenicity under Cautions.)

Discontinue epoetin alfa products and evaluate for neutralizing antibodies to erythropoietin if severe anemia and low reticulocyte count develop during treatment. Contact the manufacturer to perform assays for binding and neutralizing antibodies (Procrit: Janssen Biotech at 800-526-7736; Epogen: Amgen at 800-772-6436; Retacrit: Hospira at 800-438-1985).

Permanently discontinue therapy in patients who develop PRCA; do not switch patients to other ESAs.

Serious Allergic Reactions

Severe allergic reactions, including anaphylactic reactions, angioedema, respiratory symptoms, skin rash, and urticaria, may occur in patients receiving therapy with epoetin alfa products.

Discontinue immediately and initiate appropriate therapy if a serious allergic or anaphylactic reaction occurs; do not reinitiate the drug.

Severe Cutaneous Reactions

Risk of serious skin reactions, including blistering, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Discontinue therapy immediately if a severe skin reaction is suspected.

Adverse Reactions Due to Benzyl Alcohol Preservative

Commercially available multidose vials of epoetin alfa products contain benzyl alcohol as a preservative, which has been associated with neurologic and other toxicity in neonates.

Avoid the use of drugs preserved with benzyl alcohol in neonates and infants whenever possible.

Only use single-dose vials (i.e., the benzyl-alcohol free formulation) in women who are pregnant or breastfeeding, neonates, and infants; do not admix epoetin alfa product from single-dose vials with bacteriostatic saline containing benzyl alcohol for these populations.

Risk of Infection Due to Albumin

Remote risk for transmission of human viruses due to albumin content in some forms of epoetin alfa.

Risk in Patients with Phenylketonuria

Each 1 mL single-dose vial of 2,000, 3,000, 4,000, 10,000, and 40,000 units of epoetin alfa-epbx contains 0.5 mg of phenylalanine, which may be harmful to patients with phenylketonuria (PKU).

Consider the combined daily amount of phenylalanine from all sources before prescribing epoetin alfa-epbx to patients with PKU.

Dialysis Management

Adjustments to concomitant dialysis medications may be required.

Increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during dialysis may be required.

Immunogenicity

Risk of immunogenicity and development of antibodies.

Neutralizing antibodies to epoetin alfa products that cross-react with endogenous erythropoietin and other ESAs can result in PRCA or severe anemia (with or without other cytopenias).

Specific Populations

Pregnancy

Use during pregnancy only when potential benefits justify risks to the fetus; if used, use only single-dose formulation without benzyl alcohol.

Lactation

Not known whether epoetin alfa is distributed into human milk; use with caution in nursing women.

When epoetin alfa therapy is needed during nursing, use a benzyl alcohol-free formulation.

If administered, manufacturer states that women not breastfeed for at least 2 weeks after the last dose of epoetin from a multidose vial.

Pediatric Use

Safety and efficacy established in pediatric patients 1 month of age and older with anemia associated with CKD. No difference in safety in pediatric patients with CKD requiring or not requiring dialysis.

Safety and efficacy have not been established in pediatric patients who are younger than 5 years of age with cancer and receiving chemotherapy. Pattern of most adverse events in children at least 5 years of age was similar to that found in adults.

Safety and efficacy have not been established in pediatric patients who are younger than 8 months of age with HIV infection receiving zidovudine.

Commercially available multidose vials of epoetin alfa contain benzyl alcohol as a preservative, which has been associated with neurologic and other toxicity in neonates. Avoid the use of drugs preserved with benzyl alcohol in neonates and infants whenever possible.

Geriatric Use

Patients with anemia associated with CKD or cancer chemotherapy: No overall differences in safety and efficacy relative to younger adults.

Zidovudine-treated HIV-infected patients: Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Surgical patients: No overall differences in safety and efficacy relative to younger adults.

Hepatic Impairment

The manufacturer does not make recommendations regarding use in patients with hepatic impairment.

Renal Impairment

Safety and efficacy for the treatment of anemia associated with CKD, regardless of dialysis status, have been established in patients 1 month of age and older.

Common Adverse Effects

Patients with CKD (≥5%): hypertension, arthralgia, muscle spasm, pyrexia, dizziness, medical device malfunction, vascular occlusion, upper respiratory tract infection.

Patients with HIV infection treated with zidovudine (≥5%): pyrexia, cough, rash, injection-site irritation.

Patients with cancer receiving chemotherapy (≥5%): nausea, vomiting, myalgia, arthralgia, stomatitis, cough, weight decrease, leukopenia, bone pain, rash, hyperglycemia, insomnia, headache, depression, dysphagia, hypokalemia, thrombosis.

Surgical patients (≥5%): nausea, vomiting, pruritus, injection-site pain, chills, deep vein thrombosis, cough, hypertension.

Drug Interactions

Interactions between epoetin alfa and other drugs have not been fully evaluated.

Epoetin Alfa Pharmacokinetics

Absorption

C_max achieved 5–24 hours after sub-Q administration.

Little, if any, accumulation at dosages of 50–150 units/kg given IV or sub-Q 3 times weekly or at dosages of 40,000 units weekly given sub-Q.

Distribution

Special Populations

Volume of distribution was 1.5 to 2 times higher in preterm, very low birth-weight infants compared to healthy adults in 1 study.

Elimination

Half-life

4–13 hours.

Special Populations

Half-life is similar in adults older and younger than 65 years of age.

Half-life does not appear to be affected by hemodialysis.

Clearance was 3 times higher in preterm, very low birth-weight infants compared to healthy adults in 1 study.

Stability

Storage

Parenteral

Injection

Unopened vials: 2–8°C. Protect from light; store in original container until use. Use multidose vial up to 21 days after initial entry.

Actions

• Has pharmacologic actions identical to those of endogenous erythropoietin; interacts with progenitor stem cells to increase red cell production.

Advice to Patients

• Provide a copy of the manufacturer's patient information (medication guide) for epoetin alfa products to all patients before starting therapy and when new information about the drug becomes available. Patients who self-administer therapy should read the medication guide prior to initiation and each time the prescription is refilled.

• If applicable, provide the patient or caregiver instructions regarding proper, safe use of the drug for self-administration, including information on aseptic techniques and on storage and disposal of the drug and administration equipment. Advise such patients and caregivers to follow the manufacturer’s “Instructions for Use.”

• Inform patients about the increased risks of death, serious cardiovascular effects, thromboembolic events, and tumor progression in certain populations.

• Inform patients of possible adverse effects, including signs and symptoms of allergic drug reactions. Advise patients to inform their clinician immediately if serious allergic reaction occurs (e.g., whole body rash, shortness of breath, wheezing, decreases in blood pressure, swelling around mouth or eyes, fast pulse, sweating).

• Advise patients to report signs or symptoms of chest pain, pain in the legs with or without swelling, stroke, irregular heartbeats, seizures, confusion, dizziness or loss of consciousness, extreme tiredness, blood clots in hemodialysis vascular access ports, or increases in blood pressure.

• Advise patients to contact a clinician if any new-onset seizures, premonitory symptoms, or changes in seizure frequency occur.

• Advise patients to inform their clinician of redness or pain at the injection site.

• Advise patients to adhere to antihypertensive treatments and dietary restrictions.

• Inform patients of the need to regularly monitor blood pressure and hemoglobin concentration.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed. Epoetin alfa products should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. Inform patients of the risks associated with benzyl alcohol (preservative in some epoetin alfa product formulations) in neonates, infants, and pregnant and nursing women. When therapy is needed during pregnancy or nursing, use of a benzyl alcohol-free formulation is recommended. If an epoetin alfa product from a multidose vial is used in women who are nursing, the manufacturer advises women not to breastfeed for at least 2 weeks after the last dose.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses. Patients should inform clinicians of heart disease, high blood pressure, history of seizures or strokes, and blood disorders (e.g., sickle cell anemia, clotting disorders) prior to treatment initiation.

• Advise patients to inform their clinician of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

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