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Epoetin Alfa-Epbx

FDA Drug Information • Also known as: Retacrit

Brand Names
Retacrit
Route
INTRAVENOUS, SUBCUTANEOUS
Dosage Form
INJECTION, SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE See full prescribing information for complete boxed warning. Chronic Kidney Disease:

  • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL ( 5.1 ).
  • No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks ( 2.2 ).
  • Use the lowest RETACRIT dose sufficient to reduce the need for red blood cell (RBC) transfusions ( 5.1 ). Cancer:
  • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers ( 5.2 ).
  • Use the lowest dose to avoid RBC transfusions ( 2.4 ).
  • Use ESAs only for anemia from myelosuppressive chemotherapy ( 1.3 ).
  • ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure ( 1.5 ).
  • Discontinue following the completion of a chemotherapy course ( 2.4 ). Perisurgery:
  • Due to increased risk of deep venous thrombosis (DVT), DVT prophylaxis is recommended ( 5.1 ). Chronic Kidney Disease:
  • In controlled trials, patients with chronic kidney disease (CKD) experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL [see Warnings and Precautions (5.1) ] .
  • No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks [see Dosage and Administration (2.2) ] .
  • Use the lowest RETACRIT dose sufficient to reduce the need for red blood cell (RBC) transfusions [see Warnings and Precautions (5.1) ] . Cancer:
  • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers [see Warnings and Precautions (5.2) ] .
  • To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic reactions, use the lowest dose needed to avoid RBC transfusions [see Dosage and Administration (2.4) ] .
  • Use ESAs only for anemia from myelosuppressive chemotherapy [see Indications and Usage (1.3) ] .
  • ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure [see Indications and Usage (1.5) ] .
  • Discontinue following the completion of a chemotherapy course [see Dosage and Administration (2.4) ] . Perisurgery:
  • Due to increased risk of deep venous thrombosis (DVT), DVT prophylaxis is recommended [see Dosage and Administration (2.5) , Warnings and Precautions (5.1) ] .

    • Description

    11 DESCRIPTION Epoetin alfa-epbx is an erythropoiesis-stimulating agent. Epoetin alfa-epbx is a 165-amino acid glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced in Chinese Hamster Ovary (CHO) cell line. The product contains the identical amino acid sequence of isolated natural erythropoietin. RETACRIT (epoetin alfa-epbx) injection for intravenous or subcutaneous administration is a sterile, clear, colorless solution in vials in multiple formulations. Each 1 mL single-dose vial of 2,000, 3,000, 4,000, and 10,000 Units of epoetin alfa-epbx contains calcium chloride dihydrate (0.01 mg), glycine (7.5 mg), isoleucine (1 mg), leucine (1 mg), L-glutamic acid (0.25 mg), phenylalanine (0.5 mg), polysorbate 20 (0.1 mg), sodium chloride (2.4 mg), sodium phosphate dibasic anhydrous (4.9 mg), sodium phosphate monobasic monohydrate (1.3 mg), and threonine (0.25 mg), in Water for Injection, USP. Sodium hydroxide and hydrochloric acid may be added to adjust the pH (pH 7.0 – 7.5). Each 1 mL multiple-dose vial of 20,000 Units of epoetin alfa-epbx contains benzyl alcohol (8.5 mg), L-methionine (0.45 mg), polysorbate 20 (0.04 mg), sodium phosphate dibasic anhydrous (0.09 mg), sodium phosphate monobasic monohydrate (2.67 mg), and sucrose (60 mg) in Water for Injection, USP. Sodium hydroxide and hydrochloric acid may be added to adjust the pH (pH 5.6 – 6.6). Each 2 mL multiple-dose vial of 20,000 Units (10,000 Units/mL) of epoetin alfa-epbx contains benzyl alcohol (17 mg), L-methionine (0.9 mg), polysorbate 20 (0.08 mg), sodium phosphate dibasic anhydrous (0.18 mg), sodium phosphate monobasic monohydrate (5.34 mg), and sucrose (120 mg) in Water for Injection, USP. Sodium hydroxide and hydrochloric acid may be added to adjust the pH (pH 5.6 – 6.6).

    What Is Epoetin Alfa-Epbx Used For?

    1 INDICATIONS AND USAGE RETACRIT is an erythropoiesis-stimulating agent (ESA) indicated for:

  • Treatment of anemia due to o Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis ( 1.1 ). o Zidovudine in patients with Human Immunodeficiency Virus (HIV) infection ( 1.2 ). o The effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy ( 1.3 ).
  • Reduction of allogeneic red blood cell (RBC) transfusions in patients undergoing elective, noncardiac, nonvascular surgery ( 1.4 ). Limitations of Use RETACRIT has not been shown to improve quality of life, fatigue, or patient well-being ( 1.5 ). RETACRIT is not indicated for use:
  • In patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy ( 1.5 ).
  • In patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure ( 1.5 ).
  • In patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion ( 1.5 ).
  • In patients scheduled for surgery who are willing to donate autologous blood ( 1.5 ).
  • In patients undergoing cardiac or vascular surgery ( 1.5 ).
  • As a substitute for RBC transfusions in patients who require immediate correction of anemia ( 1.5 ). 1.1 Anemia Due to Chronic Kidney Disease RETACRIT is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion. 1.2 Anemia Due to Zidovudine in Patients with HIV Infection RETACRIT is indicated for the treatment of anemia due to zidovudine administered at ≤ 4,200 mg/week in patients with HIV infection with endogenous serum erythropoietin levels of ≤ 500 mUnits/mL. 1.3 Anemia Due to Chemotherapy in Patients with Cancer RETACRIT is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. 1.4 Reduction of Allogeneic Red Blood Cell Transfusions in Patients Undergoing Elective, Noncardiac, Nonvascular Surgery RETACRIT is indicated to reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin > 10 to ≤ 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. RETACRIT is not indicated for patients who are willing to donate autologous blood pre-operatively. 1.5 Limitations of Use RETACRIT has not been shown to improve quality of life, fatigue, or patient well-being. RETACRIT is not indicated for use:
  • In patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy.
  • In patients with cancer receiving myelosuppressive...

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION

  • Evaluate iron status before and during treatment and maintain iron repletion. Correct or exclude other causes of anemia before initiating treatment ( 2.1 ).
  • In pregnant women, lactating women, neonates, infants: Use only single-dose vials ( 2.1 ).
  • Patients with CKD: Initial dose: 50 to 100 Units/kg 3 times weekly (adults) and 50 Units/kg 3 times weekly (pediatric patients). Individualize maintenance dose. Intravenous route recommended for patients on hemodialysis ( 2.2 ).
  • Patients on Zidovudine due to HIV infection: 100 Units/kg 3 times weekly ( 2.3 ).
  • Patients with Cancer on Chemotherapy: 40,000 Units weekly or 150 Units/kg 3 times weekly (adults); 600 Units/kg intravenously weekly (pediatric patients ≥ 5 years) ( 2.4 ).
  • Surgery Patients: 300 Units/kg per day daily for 15 days or 600 Units/kg weekly ( 2.5 ). 2.1 Important Dosing Information Evaluation of Iron Stores and Nutritional Factors Evaluate the iron status in all patients before and during treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%. The majority of patients with CKD will require supplemental iron during the course of ESA therapy. Monitoring of Response to Therapy Correct or exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) before initiating RETACRIT. Following initiation of therapy and after each dose adjustment, monitor hemoglobin weekly until the hemoglobin level is stable and sufficient to minimize the need for RBC transfusion. Selection of Formulation In pregnant women, lactating women, neonates, and infants use only single-dose vials (the benzyl alcohol-free formulation) [see Contraindications (4) and Use in Specific Populations (8.1 , 8.2 , and 8.4) ] . 2.2 Patients with Chronic Kidney Disease In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a hemoglobin level of greater than 11 g/dL. No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks. Individualize dosing and use the lowest dose of RETACRIT sufficient to reduce the need for RBC transfusions [see Warnings and Precautions (5.1) ] . Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse reactions [see Boxed Warning and Clinical Studies (14) ] . For all patients with CKD: When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.
  • Do not increase the dose more frequently than once every 4 weeks. Decreases...

    • Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label:

  • Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism [see Warnings and Precautions (5.1) ]
  • Increased mortality and/or increased risk of tumor progression or recurrence in Patients with Cancer [see Warnings and Precautions (5.2) ]
  • Hypertension [see Warnings and Precautions (5.3) ]
  • Seizures [see Warnings and Precautions (5.4) ]
  • PRCA [see Warnings and Precautions (5.6) ]
  • Serious allergic reactions [see Warnings and Precautions (5.7) ]
  • Severe Cutaneous Reactions [see Warnings and Precautions (5.8) ]
  • Patients with CKD: Adverse reactions in ≥ 5% of epoetin alfa-treated patients in clinical studies were hypertension, arthralgia, muscle spasm, pyrexia, dizziness, medical device malfunction, vascular occlusion, and upper respiratory tract infection ( 6.1 ).
  • Patients on Zidovudine due to HIV infection: Adverse reactions in ≥ 5% of epoetin alfa-treated patients in clinical studies were pyrexia, cough, rash, and injection site irritation ( 6.1 ).
  • Patients with Cancer on Chemotherapy: Adverse reactions in ≥ 5% of epoetin alfa-treated patients in clinical studies were nausea, vomiting, myalgia, arthralgia, stomatitis, cough, weight decrease, leukopenia, bone pain, rash, hyperglycemia, insomnia, headache, depression, dysphagia, hypokalemia, and thrombosis ( 6.1 ).
  • Surgery Patients: Adverse reactions in ≥ 5% of epoetin alfa-treated patients in clinical studies were nausea, vomiting, pruritus, headache, injection site pain, chills, deep vein thrombosis, cough, and hypertension ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc., a Pfizer Company, at 1-800-438-1985, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice. Patients with Chronic Kidney Disease Adult Patients Three double-blind, placebo-controlled studies, including 244 patients with CKD on dialysis, were used to identify the adverse reactions to epoetin alfa. In these studies, the mean age of patients was 48 years (range: 20 to 80 years). One hundred and thirty-three (55%) patients were men. The racial distribution was as follows: 177 (73%) patients were white, 48 (20%) patients were black, 4 (2%) patients were Asian, 12 (5%) patients were other, and racial information was missing for 3 (1%) patients. Two double-blind, placebo-controlled studies, including 210 patients with CKD not on dialysis, were used to identify the adverse reactions to epoetin alfa. In these studies, the mean age of patients was 57 years (range: 24 to 79 years). One hundred and twenty-one (58%) patients were men. The racial distribution was as follows: 164 (78%) patients were white, 38 (18%) patients were black, 3 (1%) patients were Asian, 3 (1%) patients were other, and racial information was missing for 2 (1%) patients. The adverse reactions with a reported incidence of ≥ 5% in epoetin alfa-treated patients and that occurred at a ≥ 1% higher frequency than in placebo-treated patients are shown in the table below: Table 3. Adverse Reactions in Patients with CKD on Dialysis Adverse Reaction Epoetin alfa-treated Patients (n = 148) Placebo-treated Patients (n = 96) Hypertension 27.7% 12.5% Arthralgia 16.2% 3.1% Muscle spasm 7.4% 6.3% Pyrexia 10.1% 8.3% Dizziness 9.5% 8.3% Medical Device Malfunction (artificial kidney clotting during dialysis) 8.1% 4.2% Vascular Occlusion (vascular access thrombosis) 8.1% 2.1% Upper respiratory tract infection 6.8% 5.2% An additional serious adverse reaction that occurred in less than 5% of epoetin alfa-treated dialysis patients and greater than placebo was thrombosis (2.7% epoetin alfa and 1% placebo) [see...

    • Contraindications

    4 CONTRAINDICATIONS

  • Uncontrolled hypertension ( 4 ).
  • Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs ( 4 ).
  • Serious allergic reactions to RETACRIT or other epoetin alfa products ( 4 ).
  • Use of the multiple-dose vials containing benzyl alcohol in neonates, infants, pregnant women, and lactating women ( 4 ). RETACRIT is contraindicated in patients with:
  • Uncontrolled hypertension [see Warnings and Precautions (5.3) ] .
  • Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT or other erythropoietin protein drugs [see Warnings and Precautions (5.6) ] .
  • Serious allergic reactions to RETACRIT or other epoetin alfa products [see Warnings and Precautions (5.7) ] . RETACRIT from multiple-dose vials contains benzyl alcohol and is contraindicated in:
  • Neonates, infants, pregnant women, and lactating women [see Warnings and Precautions (5.9) , Use in Specific Populations (8.1 , 8.2 and 8.4) ] .

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary RETACRIT from multiple-dose vials contains benzyl alcohol and is contraindicated in pregnant women [see Contraindications (4) ] . When therapy with RETACRIT is needed during pregnancy, use a benzyl alcohol-free formulation (i.e., single-dose vial). Do not mix RETACRIT with bacteriostatic saline when administering to pregnant women because it contains benzyl alcohol (see Clinical Considerations ) [see Dosage and Administration (2.1) ] . The limited available data on epoetin alfa use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. In animal reproductive and developmental toxicity studies, adverse fetal effects including embryo-fetal death, skeletal anomalies, and growth defects occurred when pregnant rats received epoetin alfa at doses approximating the clinical recommended starting doses (see Data ) . Consider the benefits and risks of RETACRIT single-dose vials for the mother and possible risks to the fetus when prescribing RETACRIT to a pregnant woman. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions The multiple-dose vials of RETACRIT contain benzyl alcohol. The preservative benzyl alcohol has been associated with serious adverse reactions and death when administered intravenously to neonates and infants [see Warnings and Precautions (5.9) , Use in Specific Populations (8.4) ] . There is a potential for similar risks to fetuses exposed to benzyl alcohol in utero. Data Human Data There are reports of pregnant women with anemia alone or anemia associated with severe renal disease and other hematologic...

    Overdosage

    10 OVERDOSAGE RETACRIT overdosage can cause hemoglobin levels above the desired level, which should be managed with discontinuation or reduction of RETACRIT dosage and/or with phlebotomy, as clinically indicated [see Clinical Pharmacology (12.2) ] . Cases of severe hypertension have been observed following overdose with ESAs [see Warnings and Precautions (5.3) ] .

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING RETACRIT (epoetin alfa-epbx) injection is a sterile, clear, and colorless solution in single-dose and multiple-dose vials available as: Unit of Sale Strength Each Single Unit of Use NDC 59353-002-10 Carton containing 10 vials 2,000 Units/mL NDC 59353-002-01 1 mL Single-dose vial NDC 59353-003-10 Carton containing 10 vials 3,000 Units/mL NDC 59353-003-01 1 mL Single-dose vial NDC 59353-004-10 Carton containing 10 vials 4,000 Units/mL NDC 59353-004-01 1 mL Single-dose vial NDC 59353-010-10 Carton containing 10 vials 10,000 Units/mL NDC 59353-010-01 1 mL Single-dose vial NDC 59353-120-10 Carton containing 10 vials with a freeze strip indicator 20,000 Units/mL NDC 59353-120-01 1 mL Multiple-dose vial NDC 59353-220-10 Carton containing 10 vials with a freeze strip indicator 20,000 Units/ 2 mL (10,000 Units/mL) NDC 59353-220-01 2 mL Multiple-dose vial Store refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. When exposed to freezing temperatures, the green area of the freeze strip indicator in the carton of the multiple-dose vials will show signs of cloudy or white discoloration. Do not shake. Do not use RETACRIT that has been shaken or frozen or if the green area of the freeze strip indicator is cloudy or white. Store RETACRIT vials in the original carton until use to protect from light. The vial stopper used for RETACRIT is not made with natural rubber latex.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.