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Epoetin Alfa

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
Brands: Epogen, Procrit

Medically reviewed by Drugs.com on Oct 13, 2020. Written by ASHP.

Warning

    Risk of Increased Mortality and Serious Adverse Events
  • Increased risk of death, serious cardiovascular events, and stroke reported in patients with chronic kidney disease (CKD) receiving therapy with epoetin alfa or other erythropoiesis-stimulating agents (ESAs) targeted to hemoglobin concentrations >11 g/dL in controlled clinical studies. (See Increased Mortality and Cardiovascular and Thromboembolic Events under Cautions.)

  • No trial has identified a hemoglobin target, ESA dosage, or dosing strategy that does not increase these risks.

  • Use lowest ESA dosage sufficient to reduce need for RBC transfusion in patients with CKD.

  • ESA therapy shortened overall survival and increased risk of tumor progression or recurrence in some studies in patients with breast, non-small cell lung, head and neck, lymphoid, or cervical cancers. (See Increased Mortality and/or Tumor Progression under Cautions.)

  • To decrease these risks and risk of serious cardiovascular and thromboembolic events in anemic patients with cancer, use lowest ESA dosage sufficient to avoid RBC transfusion.

  • Use ESAs in cancer patients only for treatment of anemia caused by concomitant myelosuppressive chemotherapy.

  • ESAs not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.

  • Discontinue ESAs following completion of a course of chemotherapy.

  • Due to increased risk of DVT, DVT prophylaxis recommended in surgical patients receiving epoetin alfa perioperatively.

Introduction

Biosynthetic (recombinant DNA origin) form of the glycoprotein hormone erythropoietin, a hematopoietic agent that principally affects erythropoiesis.

Uses for Epoetin Alfa

Anemia of Chronic Kidney Disease

Treatment of anemia associated with chronic kidney disease (CKD) to reduce need for RBC transfusions; designated an orphan drug by FDA for this use.

First-line therapy for appropriately selected patients with anemia of CKD.

Used to increase and/or maintain hemoglobin concentrations and hematocrit and decrease the need for RBC transfusions.

Used in CKD patients who currently are undergoing dialysis therapy, as well as predialysis patients with CKD and severe symptoms of anemia who do not yet require maintenance dialysis. Manufacturers and some authorities recommend use in patients with end-stage kidney disease who currently are undergoing hemodialysis or peritoneal dialysis therapy and also in predialysis patients with CKD who have a hematocrit <30% or hemoglobin concentration <10 g/dL.

Some evidence suggests once-weekly darbepoetin alfa has similar safety and efficacy as equivalent doses of epoetin alfa given 2 or 3 times weekly in patients with CKD undergoing hemodialysis or peritoneal dialysis.

ESAs, including epoetin alfa, may increase risk for death, stroke, and serious cardiovascular events when targeted to hemoglobin concentrations >11 g/dL in patients with CKD. (See Boxed Warning.) FDA has issued public health advisories regarding these risks. Weigh potential benefits of ESAs in reducing RBC transfusions against risk of serious cardiovascular events in patients with CKD. Individualize therapy and use lowest possible dosage that will reduce need for RBC transfusion.

Not intended for patients with CKD who require acute correction of severe anemia; do not use as a substitute for emergency transfusion.

Not established that ESAs improve quality of life, fatigue, or patient well-being.

Zidovudine-induced Anemia in HIV-infected Patients

Treatment of anemia associated with zidovudine therapy in patients with HIV infection; indicated in patients with endogenous serum erythropoietin concentrations ≤500 milliunits/mL and who are receiving zidovudine dosages of ≤4.2 g per week (designated an orphan drug by FDA for this use).

Used to increase and/or maintain hemoglobin concentrations and hematocrit and decrease the need for transfusions.

Has been used to treat anemia associated with HIV infection in patients not receiving zidovudine.

Not intended for patients who require acute correction of severe anemia; do not use as a substitute for emergency transfusion.

Not established that ESAs improve quality of life, fatigue, or patient well-being.

Chemotherapy-induced Anemia in Patients with Nonmyeloid Malignancies

Treatment of chemotherapy-induced anemia in patients with nonmyeloid malignancies in whom chemotherapy is planned for at least 2 additional months; used to decrease the need for blood transfusions in such patients.

ESAs not indicated in patients with chemotherapy-induced anemia when the anticipated outcome is cure of the underlying malignancy. ESAs do not improve outcomes of cancer chemotherapy (e.g., in terms of greater tumor shrinkage, delayed tumor progression, increased survival). Not established that ESAs improve quality of life, fatigue, or patient well-being.

Not intended for patients who require acute correction of severe anemia; do not use as a substitute for emergency transfusion.

Chronic Anemia Associated with Malignancy

Epoetin alfa and other ESAs not indicated for use in anemic patients with active malignant disease who are not receiving cancer chemotherapy.

Has been used for the treatment and prevention of the normocytic, normochromic anemia associated with malignancy; however, ESAs have been shown to decrease survival in certain cancer patients who are not receiving chemotherapy or radiation therapy.

Reduction of Allogeneic Blood Transfusions in Anemic Surgical Patients

Treatment of anemic patients (hemoglobin >10 to ≤13 g/dL) scheduled to undergo elective, noncardiac, nonvascular surgery; used perioperatively to reduce the need for allogeneic blood transfusions.

Indicated for such patients who are at high risk for perioperative blood loss.

Not intended for patients who require acute correction of severe anemia; do not use as a substitute for emergency transfusion.

Not indicated in patients who are willing to donate autologous blood prior to elective surgery.

Not indicated for reduction of allogeneic RBC transfusions in patients undergoing cardiac or vascular surgery. (See Increased Mortality and Cardiovascular and Thromboembolic Events under Cautions.)

Anemia Associated with Rheumatoid Arthritis and Rheumatic Disease

Has been used for treatment of anemia associated with rheumatoid arthritis and/or rheumatic disease.

Anemia of Prematurity

May be beneficial in the treatment of anemia of prematurity. Optimal patient selection criteria not established.

Myelodysplastic Syndrome

Has been used in patients with myelodysplastic syndromes (designated an orphan drug by FDA for this use). Relatively limited response rates reported; effects of the hormone on nonerythroid cell lines and potential risks of leukemic transformation require elucidation.

Misuse and Abuse

Potential exists for abuse of the drug by athletes, especially those participating in high-aerobic demand, endurance-type events. Effects of epoetin alfa would be expected to be similar to those of homologous or autologous RBC cell transfusions (“blood doping”), which have been used by athletes to increase cardiac output, maximal oxygen uptake capacity of blood, and aerobic exercise endurance by increasing arterial blood oxygen content; effects may be particularly evident in individuals with greater initial aerobic fitness.

Abuse by athletes is difficult to detect; no reliable way to distinguish epoetin alfa from the endogenous hormone using readily available drug-screening methods (e.g., immunoradiometric assay).

Medical and sports experts, including the US and International Olympic Committees and the National Collegiate Athletic Association, consider the use of epoetin alfa to enhance athletic ergogenic potential inappropriate and unacceptable; use by athletes is contrary to the rules and ethical principles of athletic competition.

Epoetin Alfa Dosage and Administration

General

  • In controlled trials of patients with CKD, ESA therapy targeted to hemoglobin concentrations >11 g/dL did not provide additional benefit beyond that achieved with lower hemoglobin targets and was associated with greater risk of death and serious adverse cardiovascular events; no trial to date has identified a target hemoglobin concentration, ESA dosage, or dosing strategy that does not increase these risks. (See Boxed Warning.) Weigh benefits of epoetin alfa against these risks in patients with CKD. Use lowest dosage necessary to reduce the need for RBC transfusion.

  • To decrease risks of shortened survival, tumor progression or recurrence in patients with cancer, use lowest dosage sufficient to reduce the need for RBC transfusion and discontinue following completion of a chemotherapy course.

  • Evaluate iron status (i.e., transferrin saturation, serum ferritin) prior to and during therapy. Administer supplemental iron if serum ferritin <100 mcg/L or transferrin saturation <20%.

  • Exclude or correct other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding) prior to initiating therapy.

Administration

Administer by IV or sub-Q injection. IV injection recommended in patients with CKD undergoing hemodialysis.

Do not dilute or shake prior to use.

Commercially available epoetin alfa injection generally should not be diluted or mixed with other drug solutions except in certain cases of sub-Q administration. (See Sub-Q Administration under Administration.)

IV Administration

Administer by direct IV injection.

In patients undergoing hemodialysis, injection into the venous return line of the dialysis tubing following dialysis eliminates the need for additional venous access.

Sub-Q Administration

At the time of administration, preservative-free epoetin alfa (single-use vial) can be admixed in a syringe with bacteriostatic 0.9% sodium chloride injection (preserved with benzyl alcohol) in a 1:1 ratio; presence of benzyl alcohol may ameliorate injection site discomfort. Because of risks of toxicity, do not admix with benzyl alcohol-preserved solutions in neonates, infants, or pregnant or nursing women.

Dosage

Potency of epoetin alfa has been expressed in units of activity per mg of protein as tested against the WHO Second International Reference Preparation of human urinary erythropoietin.

Pediatric Patients

Anemia of Chronic Kidney Disease
IV or Sub-Q

Children and infants ≥1 month of age on dialysis: 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 11 g/dL.

Children ≥3 months of age who do not require dialysis: 50–250 units/kg 1–3 times weekly has been used.

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. Avoid frequent dosage changes.

Monitor hemoglobin concentration at least weekly following initiation of therapy and after each dosage adjustment until stable, then at least monthly thereafter.

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. (See Boxed Warning.) Use lowest dosage sufficient to reduce need for RBC transfusions; discontinue drug if responsiveness does not improve.

Zidovudine-associated Anemia in HIV-infected Patients
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.

Chemotherapy-induced Anemia 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 course of chemotherapy. (See Boxed Warning.)

Dosage Modifications

Monitor hemoglobin concentrations at least weekly following initiation of therapy and after each dosage adjustment until stable and sufficient to minimize need for RBC transfusions.

If the hemoglobin has not increased 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. (See Boxed Warning.)

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. (See Boxed Warning.)

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. Avoid frequent dosage changes.

Monitor hemoglobin concentration at least weekly following initiation of therapy and after each dosage adjustment until stable, then at least monthly thereafter.

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. (See Lack or Loss of Response to Therapy under Cautions.) 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. (See Boxed Warning.)

Zidovudine-associated Anemia in HIV-infected Patients
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

Monitor hemoglobin concentration at least weekly following initiation of therapy and after each dosage adjustment until stable and sufficient to minimize need for RBC transfusions.

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.

Chemotherapy-induced Anemia 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 Allogeneic RBC Transfusions in Anemic Surgical 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.

Prescribing Limits

Pediatric Patients

Chemotherapy-induced Anemia in Patients with Nonmyeloid Malignancies
IV

Maximum 60,000 units once weekly.

Adults

Zidovudine-associated Anemia in HIV-infected Patients
IV or Sub-Q

Patients not responding to 300 units/kg 3 times weekly are unlikely to respond to higher dosages.

Special Populations

Geriatric Patients

Patients with CKD: Individualize dosing.

Cancer patients receiving concomitant chemotherapy: Dosage requirements similar to those in younger adults.

Surgical patients: Dosage requirements similar to those in younger adults.

Cautions for Epoetin Alfa

Contraindications

  • Uncontrolled hypertension.

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

  • Serious allergic reactions to epoetin alfa.

Warnings/Precautions

Warnings

Increased Mortality and Cardiovascular and Thromboembolic Events

Increased risk of death and serious cardiovascular events reported in patients with CKD receiving therapy with epoetin alfa and other ESAs targeted to hemoglobin concentrations >11 g/dL. (See Boxed Warning.) In controlled clinical studies comparing higher (13–14 g/dL) to lower (9–11.3 g/dL) hemoglobin targets, an increased risk of death, MI, stroke, CHF, hemodialysis vascular access thrombosis, and other thromboembolic events was observed in the higher target groups. Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at greater risk. Increases in hemoglobin >1 g/dL during any 2-week period also may contribute to these risks.

Increased mortality reported in patients (without CKD) undergoing coronary artery bypass and receiving perioperative epoetin alfa; death associated with thrombotic events reported during drug administration. ESAs are not indicated for reduction of allogeneic RBC transfusions in patients undergoing cardiac surgery.

Increased mortality and incidence of fatal thrombotic vascular events reported in women with metastatic breast cancer receiving cancer chemotherapy and ESAs targeted to hemoglobin concentrations of 12–14 g/dL. (See Boxed Warning.)

Increased incidence of thromboembolic events also observed in patients undergoing orthopedic surgical procedures without prophylactic anticoagulation and receiving epoetin alfa to reduce allogeneic RBC transfusion requirements. Antithrombotic prophylaxis strongly recommended when ESAs are used in such patients.

Correction of hemoglobin to concentrations >11 g/dL may increase risk of serious and life-threatening cardiovascular events in patients with CKD. The manufacturer and FDA recommend that treatment be initiated in patients with CKD only when hemoglobin concentration <10 g/dL. Use lowest dosage sufficient to reduce the need for transfusions.

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

Increased Mortality and/or Tumor Progression

Risk of increased mortality and tumor progression or recurrence in patients with cancer. (See Boxed Warning.)

Decreased overall survival observed in patients with non-small-cell lung cancer receiving only palliative radiotherapy or no active therapy and epoetin alfa targeted to a hemoglobin concentration of 12–14 g/dL.

Shortened time to tumor progression observed in patients with advanced head and neck cancer receiving only radiation therapy and an ESA.

An increased risk of death and no reduction in transfusion requirements observed in patients with cancer-related anemia who were not receiving cancer chemotherapy or radiation therapy while receiving another ESA, darbepoetin alfa.

Hypertension and Seizures

Risk of new or worsening hypertension in patients with CKD, particularly during early phase of therapy. May require initiation of or increases in antihypertensive therapy. (See Advice to Patients.)

Monitor and appropriately control BP prior to and during therapy; reduce or withhold epoetin alfa if BP becomes difficult to control. Contraindicated in patients with uncontrolled hypertension.

Seizures and hypertensive encephalopathy reported; risk appears greater in patients with CKD. Monitor closely for premonitory neurologic symptoms during first several months of therapy. (See Advice to Patients.)

Potential for Transmission of Viral Diseases

Contains albumin, a derivative of human blood; risk of transmitting viral diseases and/or Creutzfeldt-Jakob Disease (CJD) appears to be extremely remote. No cases of transmission of viral diseases or CJD ever identified for albumin.

Pure Red Cell Aplasia

PRCA and severe anemia with or without other cytopenias reported in association with neutralizing antibodies to endogenous erythropoietin.

PRCA occurred predominantly in patients with CKD receiving ESAs by sub-Q administration. PRCA also reported in patients with hepatitis C virus (HCV) infection receiving ESAs for anemia related to hepatitis treatment (non-FDA-labeled indication).

Withhold therapy in any patient who develops severe anemia and low reticulocyte counts; evaluate for presence of neutralizing antibodies to erythropoietin. Contact the manufacturer (Janssen Biotech [formerly Centocor Ortho Biotech] at 800-457-6399, Amgen at 800-772-6436) to perform assays for binding and neutralizing antibodies.

Discontinue permanently in any patient with PRCA. (See Contraindications.) Do not switch to another ESA.

Sensitivity Reactions

Risk of severe allergic reactions, including anaphylactic reactions, angioedema, respiratory symptoms, skin rash, and urticaria. Discontinue immediately and initiate appropriate therapy if a serious allergic or anaphylactic reaction occurs; do not reinitiate.

General Precautions

Patient Monitoring

Monitor hemoglobin concentrations weekly following initiation of therapy and after each dosage change until stable and sufficient to minimize RBC transfusions.

Regularly monitor CBC, including reticulocyte count, blood cell differential, platelet count, and determination of erythrocyte indices (Wintrobe indices).

Evaluate iron stores (i.e., transferrin saturation, serum ferritin) prior to and during therapy. Administer supplemental iron if transferrin saturation <20% or serum ferritin concentration <100 mcg/L. Virtually all patients with CKD will require supplemental iron.

Lack or Loss of Response to Therapy

Evaluate patients who fail to respond or experience a loss of hemoglobin response for potential causative factors (e.g., iron deficiency, infection, inflammation, bleeding).

In the absence of another etiology, evaluate for PRCA and test for presence of antibodies to erythropoietins. (See Pure Red Cell Aplasia under Cautions.)

Specific Populations

Pregnancy

Category C. Use during pregnancy only when potential benefits justify risks to the fetus; if used, use only single-dose formulation without benzyl alcohol. Women who become pregnant during epoetin alfa therapy are encouraged to enroll in the manufacturer’s Pregnancy Surveillance Program by calling 800-772-6436.

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.

Pediatric Use

Safety and efficacy for treatment of anemia of CKD established in children and infants ≥1 month of age undergoing dialysis. Pattern of adverse effects similar to that reported in adults. Safety and efficacy not established in pediatric patients with CKD not on dialysis.

Safety and efficacy established for the treatment of chemotherapy-induced anemia in pediatric patients ≥5 years of age. Adverse effects similar to those experienced in adults.

Has been used for treatment of zidovudine-associated anemia in pediatric patients 8 months to 17 years of age.

Has been used in pediatric patients for the treatment of anemia of prematurity.

Commercially available multidose vials of epoetin alfa contain benzyl alcohol as a preservative, which has been associated with neurologic and other toxicity in neonates. Do not use epoetin alfa from multidose vials or from single-dose vials that have been admixed with bacteriostatic saline preserved with benzyl alcohol in neonates or infants.

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.

Although special precautions usually not necessary, careful monitoring of blood chemistry and BP may be necessary because of a general increased risk of renal and/or cardiovascular complications in geriatric patients.

Common Adverse Effects

Patients with CKD: Hypertension, arthralgias , muscle spasm, pyrexia, dizziness, medical device malfunction, vascular occlusion, upper respiratory tract infection.

HIV-infected patients: Pyrexia, cough, rash, injection-site irritation.

Cancer patients: Nausea, vomiting, myalgia, arthralgia, stomatitis, cough, weight decrease, leukopenia, bone pain, rash, hyperglycemia, insomnia, headache, depression, dysphagia, hypokalemia, thrombosis.

Patients undergoing surgery: Nausea, vomiting, pruritus, injection-site pain, chills, deep-vein thrombosis, cough, hypertension, headache.

Interactions for Epoetin Alfa

Specific Drugs

Drug

Interaction

Comments

Androgens

Possible increase in the sensitivity of erythroid progenitors

Has been used for therapeutic effect

Desmopressin

Potential decrease in bleeding time

Probenecid

Possible pharmacokinetic interaction

Epoetin Alfa Pharmacokinetics

Absorption

Bioavailability

Following sub-Q administration, peak plasma concentrations achieved within 5–24 hours.

Serum concentrations peak sooner and are substantially higher with IV compared with sub-Q injection, concentrations are less sustained; IV route of administration generally offers no clinical advantage.

Sub-Q injection 3 times weekly can produce a hemoglobin response similar to that following IV injection but at lower dosages; dosages required for maintenance therapy generally are lower with sub-Q than IV injection.

Onset

Increase in hemoglobin concentrations: 2–6 weeks.

Distribution

Extent

Not fully elucidated.

Not known whether epoetin alfa crosses the placenta or is distributed into milk.

Special Populations

In preterm neonates, distribution volume approximately 1.5–2 times larger than in healthy adults.

Elimination

Metabolism

Metabolic fate of endogenous erythropoietin and the recombinant hormone (i.e., epoetin alfa) poorly understood. Hepatic metabolism contributes only minimally to elimination of the intact hormone.

Elimination Route

Approximately ≤10% is excreted unchanged in urine.

Half-life

IV administration in healthy individuals and in patients with CKD: 4–16 hours.

Special Populations

Elimination half-life does not appear to be affected by hemodialysis. The elimination characteristics of epoetin alfa appear to be similar in patients undergoing hemodialysis or peritoneal dialysis.

Half-life similar in adults >65 or <65 years of age.

In preterm neonates, clearance approximately 3 times higher than in healthy adults.

Stability

Storage

Parenteral

Injection

Refrigerate at 2–8°C; do not freeze or shake. Protect from light.

Store unused portions of multidose vial at 2–8°C and discard 21 days after initial entry into vial.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 10% in water with albumin human 0.05 or 0.1%

Incompatible

Dextrose 10% in water

Dextrose 10% in water with albumin human 0.01%

Sodium chloride 0.9%

Actions

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

Advice to Patients

  • Importance of informing patients about the increased risks of death, serious cardiovascular effects, thromboembolic events, and tumor progression in certain patient populations. (See Increased Mortality and Cardiovascular and Thromboembolic Events under Cautions and also see Boxed Warning.)

  • Patient instructions for use and medication guide must be provided prior to initiating therapy and each time drug is dispensed.

  • If the patient or caregiver is to administer epoetin alfa, provide careful instructions regarding proper, safe use of the drug in this setting, including information on aseptic techniques and on storage and disposal of the drug and administration equipment. Advise such patients to follow the manufacturer’s “Patient Instructions for Use”.

  • Importance of informing clinicians of heart disease, high BP, history of seizures or strokes, and blood disorders (e.g., sickle cell anemia, clotting disorders) prior to treatment initiation.

  • Importance of informing patients of the risks associated with benzyl alcohol (preservative in some epoetin alfa formulations) in neonates, infants, pregnant and nursing women.

  • Importance of informing patients of possible adverse effects, including signs and symptoms of allergic drug reactions. Importance of informing clinicians immediately if serious allergic reaction occurs (e.g., whole body rash, shortness of breath, wheezing, decreases in BP, swelling around mouth or eyes, fast pulse, sweating). Importance of advising patients of appropriate actions to take if adverse effects occur.

  • Importance of reporting 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 BP.

  • Risk of seizures; importance of patients contacting a clinician if any new-onset seizures, premonitory symptoms, or change in seizure frequency occurs.

  • Importance of informing clinician of redness, swelling, or itching at the injection site.

  • Importance of adherence to antihypertensive treatment and dietary restrictions.

  • Importance of regular monitoring of BP and hemoglobin concentration and of keeping appointments for determination of hemoglobin concentrations.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

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.

Epoetin Alfa (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV or subcutaneous use

2000 units/mL

Epogen

Amgen

Procrit

Janssen Biotech, (formerly Centocor Ortho Biotech)

3000 units/mL

Epogen

Amgen

Procrit

Janssen Biotech, (formerly Centocor Ortho Biotech)

4000 units/mL

Epogen

Amgen

Procrit

Janssen Biotech, (formerly Centocor Ortho Biotech)

10,000 units/mL

Epogen

Amgen

Procrit

Janssen Biotech, (formerly Centocor Ortho Biotech)

20,000 units/mL

Epogen

Amgen

Procrit

Janssen Biotech, (formerly Centocor Ortho Biotech)

40,000 units/mL

Epogen

Amgen

Procrit

Janssen Biotech, (formerly Centocor Ortho Biotech)

AHFS DI Essentials™. © Copyright 2021, Selected Revisions October 23, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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