Medication Guide App

Epoetin Alfa

Pronunciation
( Erythropoietin ; EPO )

Pronunciation: e-POE-e-tin AL-fa
Class: Recombinant human erythropoietin

Trade Names

Epogen
- Injection, solution 2,000 units/mL
- Injection, solution 3,000 units/mL
- Injection, solution 4,000 units/mL
- Injection, solution 10,000 units/mL
- Injection, solution 20,000 units/mL

Procrit
- Injection, solution 2,000 units/mL
- Injection, solution 3,000 units/mL
- Injection, solution 4,000 units/mL
- Injection, solution 10,000 units/mL
- Injection, solution 20,000 units/mL
- Injection, solution 40,000 units/mL

Eprex (Canada)

Pharmacology

Stimulates RBC production.

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Pharmacokinetics

Absorption

T max is 5 to 24 h (subcutaneous).

Elimination

Elimination half-life is approximately 4 to 13 h (IV) for chronic kidney disease patients and approximately 16 to 67 h (subcutaneous) for anemic cancer patients.

Special Populations

Elderly

Pharmacokinetic data indicate no apparent difference in half-life among adult patients older or younger than 65 y.

Children

Pharmacokinetic profile in children and adolescents is similar to that of adults. Vd was 1.5 to 2 times higher and Cl was 3 times higher in preterm neonates than in healthy adults.

Indications and Usage

Treatment of anemia due to concomitant myelosuppressive chemotherapy in patients with nonmyeloid malignancies; anemia due to chronic kidney disease in dialysis and nondialysis patients to decrease the need for RBC transfusion; anemia due to zidovudine administered at 4,200 mg or less per week in HIV patients with endogenous serum erythropoietin levels of 500 milliunits/mL or less; to reduce the need for allogeneic RBC transfusions among patients with perioperative Hgb greater than 10 to 13 or less g/dL who are high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery.

Unlabeled Uses

Anemia associated with critically ill patients, CHF, chronic disease (eg, rheumatoid arthritis), postpartum anemia, sickle cell disease, thalassemia, multiple myeloma, Jehovah's Witnesses, radiation treatment, epidermolysis bullosa, and porphyria; for athletic enhancement, sexual dysfunction, transfusional iron overload, uremic pruritus.

Contraindications

Uncontrolled hypertension; pure red cell aplasia (PRCA) that begins after treatment with epoetin alfa or other erythropoietin protein drugs; serious allergic reactions to epoetin alfa.

Multidose vials

Neonates, infants, pregnant women, and breast-feeding women.

Dosage and Administration

Cancer Patients
Adults

Subcutaneous 150 units/kg 3 times weekly, or 40,000 units weekly, until the completion of a chemotherapy course. Initiate epoetin only if the Hgb is less than 10 g/dL, and if there is a minimum of 2 additional mo of planned chemotherapy. Reduce dose by 25% if Hgb increases greater than 1 g/dL in any 2-wk period or Hgb reaches a level needed to avoid RBC transfusion. Withhold dose if Hgb exceeds a level needed to avoid RBC transfusion and reinitiate at a dose 25% below the previous dose when Hgb approaches a level in which RBC transfusion may be required. After the initial 4 wk, if Hgb increases by less than 1 g/dL and remains below 10 g/dL, increase dosage to 300 units/kg 3 times weekly or 60,000 units weekly. After 8 wk, if there is no response as measured by Hgb levels or if RBC transfusions are still required, discontinue therapy.

Children 5 to 18 y of age

IV Weekly dosing: 600 units/kg weekly. Reduce dose by 25% if Hgb increases greater than 1 g/dL in any 2-wk period or Hgb reaches a level needed to avoid RBC transfusion. Withhold dose if Hgb exceeds a level needed to avoid RBC transfusion and reinitiate at a dose 25% below the previous dose when Hgb approaches a level where RBC transfusion may be required. After the initial 4 wk, if Hgb increases by less than 1 g/dL and remains below 10 g/dL, increase dosage to 900 units/kg weekly (max, 60,000 units). After 8 wk, if there is no response as measured by Hgb levels or if RBC transfusions are still required, discontinue therapy.

Chronic Kidney Disease
Adults

IV/Subcutaneous 50 to 100 units/kg 3 times weekly. Initiate when the Hgb level is less than 10 g/dL in dialysis patients; consider initiating therapy in patients not on dialysis when the Hgb is less than 10 g/dL, the rate of Hgb decline indicates the likelihood of requiring a RBC transfusion, and reducing RBC transfusion–related risks is a goal. If the Hgb increases by more than 1 g/dL in a 2-wk period, reduce the dose by 25% or more as needed to reduce rapid responses. If the Hgb level exceeds 10 g/dL (patients not on dialysis) or approaches or exceeds 11 g/dL (patients on dialysis), reduce or interrupt the dose. After the initial 4 wk, if Hgb has not increased by more than 1 g/dL, increase the dose by 25%. Do not increase the dose more frequently than once every 4 wk; decreases in dose can occur more frequently. Discontinue therapy in patients who do not respond over a 12-wk escalation period.

Children 1 mo to 16 y of age on dialysis

IV/Subcutaneous 50 units/kg 3 times weekly. If the Hgb increases by more than 1 g/dL in a 2-wk period, reduce the dose by 25% or more as needed to reduce rapid responses. If the Hgb level approaches or exceeds 11 g/dL, reduce or interrupt the dose. After the initial 4 wk, if Hgb has not increased by more than 1 g/dL, increase the dose by 25%. Do not increase the dose more frequently than once every 4 wk; decreases in dose can occur more frequently. Discontinue therapy in patients who do not respond over a 12-wk escalation period.

Surgery
Adults

Subcutaneous 300 units/kg/day for 10 days before surgery, on the day of surgery, and for 4 days after surgery; or 600 units/kg in once-weekly doses (21, 14, and 7 days before surgery), plus a fourth dose on the day of surgery. Concomitant deep venous thrombosis (DVT) prophylaxis is recommended.

Zidovudine-Treated HIV-Infected Patients
Adults

IV/Subcutaneous 100 units/kg 3 times weekly. Withhold therapy if Hgb exceeds 12 mg/dL and resume at a dose of 25% below the previous dose when Hgb is less than 11 g/dL. If Hgb does not increase after 8 wk of therapy, the dosage of epoetin alfa can be increased by 50 to 100 units/kg at 4- to 8-wk intervals until Hgb reaches a level needed to avoid RBC transfusion or 300 units/kg. Discontinue therapy if an increase in Hgb is not achieved at doses of 300 units/kg for 8 weeks.

General Advice

  • For subcutaneous or IV administration only. Not for intradermal, IM, or intra-arterial administration. IV route recommended for patients on hemodialysis.
  • Do not shake or vigorously agitate vial. Prolonged, vigorous shaking may denature the glycoprotein, rendering it biologically inactive.
  • Rotate subcutaneous injection sites.
  • Single-dose vials contain no preservative. Use only 1 dose/vial. Do not reenter vial. Discard any unused portion. Do not combine unused portions or save unused portions for later use.
  • Do not administer in conjunction with other drug solutions. However, at time of subcutaneous administration, single-use vials may be admixed in a syringe with bacteriostatic sodium chloride 0.9% with benzyl alcohol 0.9% at a 1:1 ratio. Multidose vials contain benzyl alcohol and admixing is not necessary.
  • Individualize dosing and use the lowest dose sufficient to reduce the need for blood transfusions.
  • When adjusting therapy, consider Hgb rate of rise, rate of decline, ESA responsiveness, and Hgb variability. A single Hgb excursion may not require a dosing change.
  • Evaluate the iron status in all patients before and during treatment and maintain iron repletion.

Storage/Stability

Store vials in refrigerator between 36° and 46°F. Do not freeze or shake. Protect from light. Multidose vials may be stored in refrigerator between 36° and 46°F for up to 21 days after initial entry.

Drug Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (28%); vascular access thrombosis (8%); DVT (6%); thrombosis (5%); MI, pulmonary embolism (1%).

CNS

Headache (18%); dizziness (10%); insomnia (6%); depression (5%); seizures (postmarketing).

Dermatologic

Pruritus (21%); rash (19%); urticaria (3%); erythema (1%).

GI

Nausea (56%); vomiting (28%); stomatitis (10%); dysphagia (5%).

Hematologic

Leukopenia (8%); porphyria, PRCA (postmarketing).

Hypersensitivity

Serious allergic reactions (postmarketing).

Local

Injection-site pain (13%); injection-site irritation (7%).

Metabolic

Weight decrease (9%); hyperglycemia (6%); hypokalemia (5%); edema (3%).

Musculoskeletal

Arthralgia (16%); myalgia (10%); bone pain, muscle spasm (7%).

Respiratory

Cough (26%); upper respiratory tract infection (7%); respiratory tract congestion (1%).

Miscellaneous

Pyrexia (42%); artificial kidney clotting during dialysis (8%); chills (7%).

Precautions

Warnings

Erythropoiesis-stimulating agents (ESAs) increase the risk of death, MI, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.

Chronic kidney disease

Patients experienced greater risks for death, serious CV reactions, and stroke when administered ESAs to target a Hgb level of greater than 11 g/dL in controlled trials. No trial has identified a Hgb target level, ESA dose, or dosing strategy that does not increase these risks. Use the lowest dose sufficient to reduce the need for RBC transfusions.

Cancer

ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non–small cell lung, head and neck, lymphoid, and cervical cancers. Prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense epoetin alfa to patients with cancer. To decrease these risks, as well as the risk of serious CV and thrombovascular events, use the lowest dose needed to avoid RBC transfusions. Use ESAs only for treatment of anemia caused by concomitant myelosuppressive chemotherapy. ESAs are not indicated for patients receiving myelosuppressive therapy when anticipated outcome is cure. Discontinue following the completion of a chemotherapy course.

Perisurgery

Because of an increased risk of DVT, DVT prophylaxis is recommended.


Monitor

Evaluate transferrin saturation and serum ferritin prior to and during treatment. Administer supplemental iron when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%. Prior to initiation and after each dose adjustment, monitor Hgb weekly until the level is stable and sufficient to minimize the need for RBC transfusion. Thereafter, monitor Hgb at least monthly. Closely monitor and appropriately control BP. Closely monitor patients with preexisting CV disease. Closely monitor for premonitory neurologic symptoms during the first month of therapy.


Pregnancy

Category C (single-dose vials). Multidose vials are contraindicated for use in pregnant women because they contain benzyl alcohol as a preservative.

Lactation

Undetermined. Considered compatible with breast-feeding. Multidose vials are contraindicated in breast-feeding women because they contain benzyl alcohol as a preservative.

Children

Safety and efficacy not established in children younger than 1 mo for treatment of anemia in patients with chronic kidney disease on dialysis. Safety and effectiveness not established in children younger than 5 y for treatment of anemia due to concomitant myelosuppressive chemotherapy.

Hypersensitivity

Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria, may occur.

Special Risk Patients

Use caution in patients with CV disease and stroke.

Albumin

Epoetin alfa contains albumin, which is derived from human blood and carries an extremely remote risk for transmission of viral diseases.

Benzyl alcohol

Benzyl alcohol is a preservative present in some of these products (multidose vials) and has been associated with a fatal “gasping syndrome” in premature infants.

Dialysis management

Adjustments in the dialysis prescription and increased anticoagulation with heparin may be required to prevent clotting of the extracorporeal circuit during hemodialysis.

Hypertension

Not for use in patients with uncontrolled hypertension; control BP adequately before initiation of therapy. Hypertensive encephalopathy and seizures have been reported in patients with chronic kidney disease.

Lack or loss of Hgb response

Initiate a search for causative factors (eg, iron deficiency, infection, inflammation, bleeding). If typical causes are excluded, evaluate for PRCA.

Pure red cell aplasia

PRCA and severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported, especially in patients with chronic kidney disease. Permanently discontinue epoetin alfa in patients who develop PRCA.

Seizures

Risk of seizures is increased in patients with chronic kidney disease.

Overdosage

Symptoms

Elevated Hgb levels, severe hypertension.

Patient Information

  • Instruct patients to read the Medication Guide before starting therapy and at regular intervals during treatment.
  • Inform patients of the risks and benefits of epoetin alfa prior to treatment.
  • Inform patients with cancer that they must sign the patient-health care provider acknowledgement before the start of each treatment course with epoetin alfa.
  • Inform patients of the increase risks of mortality, serious CV reactions, thromboembolic reactions, stroke, and tumor progression.
  • Inform patients to undergo regular BP monitoring, adhere to prescribed antihypertensive regimen, and follow dietary restrictions.
  • Inform patients to contact their health care provider for new-onset neurologic symptoms or change in seizure frequency.
  • Inform patients of the need to have regular laboratory tests for Hgb.
  • Inform patients of the risks associated with benzyl alcohol in neonates, infants, pregnant women, and breast-feeding mothers.
  • Instruct patients who self-administer epoetin alfa of the importance of following instructions for use; dangers of reusing needles, syringes, or unused portions of single-dose vials; proper disposal of syringes, needles, and unused vials, and of the full container.

Copyright © 2009 Wolters Kluwer Health.

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