Epogen

Erythropoietin Agents

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Epoetin alfa should be clear and colorless.
Protect vials from light.
Do not shake or freeze.
Do not reenter preservative-free vials. Multidose vials with preservatives are available.
Do not dilute. Do not administer with other drug solutions in general; however, preservative-free epoetin alfa may be admixed in a syringe with bacteriostatic 0.9% Sodium Chloride Injection, USP, with benzyl alcohol 0.9% (bacteriostatic saline) in a 1:1 ratio using aseptic technique at the time of administration. Do not use bacteriostatic saline when administering to neonates, infants, and pregnant or lactating women.
Storage: Discard unused epoetin alfa in preservative-free vials. Multidose vials can be kept refrigerated at 2 to 8 degrees C (36 to 46 degrees F) for 21 days once opened.[30100] [63174]

Intermittent IV Infusion
May be injected directly into a vein or via the venous return line of the dialysis tubing at the end of a dialysis session.

Inject subcutaneously taking care not to inject intradermally.

pulmonary embolism / Delayed / 1.0-1.0
seizures / Delayed / Incidence not known
red cell aplasia / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
stroke / Early / Incidence not known
thromboembolism / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
porphyria / Delayed / Incidence not known

hypertension / Early / 3.0-27.7
stomatitis / Delayed / 10.0-10.0
leukopenia / Delayed / 8.0-8.0
bone pain / Delayed / 7.0-7.0
hyperglycemia / Delayed / 6.0-6.0
depression / Delayed / 5.0-5.0
dysphagia / Delayed / 5.0-5.0
hypokalemia / Delayed / 5.0-5.0
edema / Delayed / 1.0-3.0
erythema / Early / 0.8-0.8
encephalopathy / Delayed / Incidence not known
antibody formation / Delayed / Incidence not known
anemia / Delayed / Incidence not known
phlebitis / Rapid / Incidence not known

nausea / Early / 35.0-56.0
fever / Early / 10.1-42.0
vomiting / Early / 12.0-28.0
cough / Delayed / 4.0-26.0
pruritus / Rapid / 12.0-21.0
rash / Early / 2.0-19.0
headache / Early / 5.0-18.0
arthralgia / Delayed / 10.0-16.2
injection site reaction / Rapid / 7.0-13.0
myalgia / Early / 10.0-10.0
dizziness / Early / 9.5-9.5
weight loss / Delayed / 9.0-9.0
chills / Rapid / 4.0-7.0
insomnia / Early / 6.0-6.0
urticaria / Rapid / 3.0-3.0
infection / Delayed / Incidence not known
vitamin B6 deficiency / Delayed / Incidence not known

In controlled trials, patients with chronic kidney disease (CKD) such as renal impairment or renal failure experienced greater risks for mortality, myocardial infarction, congestive heart failure, thromboembolism, and stroke when administered epoetin alfa and other erythropoiesis-stimulating agents (ESAs) to a target hemoglobin concentration greater than 11 g/dL. No trial has identified a hemoglobin target concentration, ESA dose, or dosing strategy that does not increase these risks. Use the lowest dose sufficient to reduce the need for red blood cell transfusions. For patients with CKD either on or off dialysis, a hemoglobin less than 10 g/dL is advised before treatment initiation. Use caution in patients with coexistent cardiac disease, stroke, and cardiovascular disease such as angina. Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of more than 1 g/dL over 2 weeks may contribute to these risks; a dose reduction is warranted. During hemodialysis, patients treated with epoetin alfa may require increased anticoagulant therapy with heparin to prevent clotting of the dialysis machine.

In controlled clinical trials, erythropoiesis-stimulating agents (ESAs) increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of thromboembolism (deep venous thrombosis [DVT]) in patients undergoing orthopedic procedures. Epoetin alfa is not indicated for use in patients undergoing cardiac or vascular surgery and should not be used in patients scheduled for surgery who are willing to donate autologous blood. However, guidelines suggest it is reasonable to use ESAs with iron supplementation several days before cardiac surgery to increase red cell mass in patients who have preoperative anemia, refuse blood cell transfusion, or are deemed high-risk for postoperative anemia; studies have reported no adverse effects associated with short-term ESA pretreatment. Weigh the anticipated benefits of epoetin alfa in any patient with a history of thromboembolic disease against the potential risks; the risk of thromboembolism is increased in many populations. Due to increased risk of DVT, prophylaxis is strongly recommended when ESAs are used for the reduction of allogeneic red blood cell transfusions in surgical patients.

Use of epoetin alfa and other erythropoiesis stimulating agents (ESAs) shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with certain neoplastic disease: breast, non-small cell lung, head and neck, lymphoid, and cervical cancers. ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure. ESAs are not indicated for patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy. In addition, ESAs are not indicated for patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion. In patients with cancer, use ESAs only for anemia from myelosuppressive chemotherapy, and use the lowest dose needed to avoid red blood cell transfusions. Use of the lowest dose to avoid red blood cell transfusions will also help to decrease the risk of serious cardiovascular and thromboembolic reactions; in controlled clinical trials of patients with cancer, ESAs increased the risks for death and serious adverse cardiovascular reactions such as myocardial infarction and stroke. Discontinue the ESA after the completion of a chemotherapy course.

Epogen, Procrit, Retacrit

Rx

Recombinant form of the renal hormone erythropoietin
Used for treatment of anemia and for reduction of allogeneic red blood cell transfusions in surgical patients
Associated with increased risk of death, myocardial infarction, stroke, venous thromboembolism, vascular access thrombosis, and tumor progression or recurrence

50 to 100 units/kg/dose IV or subcutaneously 3 times weekly initially; for patients on dialysis, administer IV. For patients on dialysis, initiate treatment when hemoglobin (Hgb) is less than 10 g/dL. If Hgb approaches or exceeds 11 g/dL, reduce or interrupt the dose. For patients not on dialysis, consider initiating treatment only when Hgb is less than 10 g/dL and the rate of Hgb decline indicates the likelihood of requiring a RBC transfusion and reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal. If Hgb is more than 10 g/dL, reduce or interrupt the dose, and use the lowest dose sufficient to reduce the need for RBC transfusions. If the Hgb rises more than 1 g/dL in any 2-week period, reduce the dose by 25% or more as needed to reduce rapid responses. In contrast, if Hgb has not increased more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. Do not increase the dose more frequently than once every 4 weeks; decreases can occur more frequently. For patients who do not respond adequately over a 12-week escalation period, increasing the dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a Hgb concentration sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia, and discontinue if responsiveness does not improve.

50 to 100 units/kg/dose IV or subcutaneously 3 times weekly initially; for patients on dialysis, administer IV. For patients on dialysis, initiate treatment when hemoglobin (Hgb) is less than 10 g/dL. If Hgb approaches or exceeds 11 g/dL, reduce or interrupt the dose. For patients not on dialysis, consider initiating treatment only when Hgb is less than 10 g/dL and the rate of Hgb decline indicates the likelihood of requiring a RBC transfusion and reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal. If Hgb is more than 10 g/dL, reduce or interrupt the dose, and use the lowest dose sufficient to reduce the need for RBC transfusions. If the Hgb rises more than 1 g/dL in any 2-week period, reduce the dose by 25% or more as needed to reduce rapid responses. In contrast, if Hgb has not increased more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. Do not increase the dose more frequently than once every 4 weeks; decreases can occur more frequently. For patients who do not respond adequately over a 12-week escalation period, increasing the dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a Hgb concentration sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia, and discontinue if responsiveness does not improve.

50 units/kg/dose IV or subcutaneously 3 times weekly initially; for patients on dialysis, administer IV. Initiate treatment when hemoglobin (Hgb) is less than 10 g/dL. If Hgb approaches or exceeds 12 g/dL, reduce or interrupt the dose. If the Hgb rises more than 1 g/dL in any 2-week period, reduce the dose by 25% or more as needed to reduce rapid responses. In contrast, if Hgb has not increased more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. Do not increase the dose more frequently than once every 4 weeks; decreases can occur more frequently. For patients who do not respond adequately over a 12-week escalation period, increasing the dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a Hgb concentration sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia, and discontinue if responsiveness does not improve.

Initially, 100 units/kg/dose subcutaneously or IV 3 times weekly. If Hgb does not increase after 8 weeks, increase by 50 to 100 units/kg/dose at 4 to 8 week intervals until Hgb is at a concentration to avoid RBC transfusions or a dose of 300 units/kg is reached. If the Hgb is more than 12 g/dL, withhold epoetin and once Hgb is less than 11 g/dL, resume at a dose 25% below the previous dose. Patients receiving zidovudine with endogenous serum erythropoietin levels more than 500 mUnits/mL are unlikely to respond to epoetin alfa treatment.

A limited number of pediatric HIV-infected patients have been treated with epoetin alfa 50 to 400 units/kg/dose subcutaneously or IV 2 to 3 times per week. If the Hgb is more than 12 g/dL, withhold epoetin and once Hgb is less than 11 g/dL, resume at a dose 25% below the previous dose. Patients receiving zidovudine with endogenous serum erythropoietin levels more than 500 mUnits/mL are unlikely to respond to epoetin alfa treatment.

150 units/kg/dose subcutaneously 3 times weekly or 40,000 units subcutaneously once weekly only when the hemoglobin (Hgb) is less than 10 g/dL and only until the chemotherapy course is completed. Adjust the dose to maintain the lowest Hgb concentration sufficient to avoid RBC transfusions. If no rise in Hgb of at least 1 g/dL after 4 weeks of therapy and Hgb is less than 10 g/dL, the dosage may be increased to 300 units/kg/dose subcutaneously 3 times weekly or 60,000 units subcutaneously once weekly. Discontinue if after 8 weeks of therapy there is no response as measured by Hgb concentrations or if transfusions are still required. Reduce the dose by 25% if Hgb increases by more than 1 g/dL in any 2-week period or if Hgb reaches a concentration needed to avoid RBC infusion. If Hgb is increasing and exceeds a concentration necessary to avoid blood transfusions, hold therapy and reinstitute at a dose that is 25% lower when the Hgb reaches a concentration where transfusions may be needed.

600 units/kg/dose IV weekly only when the hemoglobin (Hgb) is less than 10 g/dL and only until the chemotherapy course is completed. Adjust the dose to maintain the lowest Hgb concentration sufficient to avoid RBC transfusions. If no rise in Hgb of at least 1 g/dL after 4 weeks of therapy and Hgb is less than 10 g/dL, the dosage may be increased to 900 units/kg/dose IV weekly (Max: 60,000 units). Discontinue if after 8 weeks there is no response as measured by Hgb concentrations or if transfusions are still required. Reduce the dose by 25% if Hgb increases by more than 1 g/dL in any 2-week period or if Hgb reaches a concentration needed to avoid RBC infusion. If the Hgb is increasing and exceeds a concentration necessary to avoid blood transfusions, hold therapy and reinstitute at a dose that is 25% lower when the Hgb reaches a concentration where transfusions may be needed.

300 units/kg/day subcutaneously for 10 days before surgery, on the day of surgery, and for 4 days after surgery (15 days total) plus deep vein thrombosis (DVT) prophylaxis. Alternatively, 600 units/kg/dose subcutaneously on days 21, 14, and 7 before surgery plus 1 dose on the day of surgery (4 total doses) plus DVT prophylaxis.

Various dosing regimens have been used in studies. Total weekly doses of 75 to 1,500 units/kg/week subcutaneously or IV divided into 3 to 7 doses for a total duration of 10 days to 6 weeks have been administered to premature neonates. The most commonly studied dosing regimen is 200 to 250 units/kg/dose subcutaneously or IV given 3 times weekly for up to 6 weeks. Oral iron 2 to 9 mg/kg/day was also administered in most studies.

150 to 300 units/kg/dose subcutaneously 3 times weekly has been shown to improve anemia in about 20% of patients with MDS. When epoetin alfa is given in combination with granulocyte-macrophage colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor (G-CSF), response increases to about 50% of MDS patients.

40,000 units subcutaneously once weekly maintained the ribavirin dose in anemic patients with chronic hepatitis C virus. After 4 weeks, if the hemoglobin (Hgb) had not increased by at least 1 g/dL, the weekly dose was increased to 60,000 units subcutaneously. Patients with Hgb of 12 g/dL or less who were being treated with ribavirin and interferon alfa were randomized to receive epoetin alfa (n = 93) or placebo (n = 92) for 8 weeks. The ribavirin dose was maintained in 88% of patients receiving epoetin alfa compared to 60% of patients receiving placebo (p less than 0.001). At randomization, the baseline Hgb was 10.8 g/dL; after 8 weeks of treatment, Hgb increased by an average of 2.2 +/- 1.3 g/dL in the epoetin group compared to 0.1 +/- 1.0 g/dL in the placebo group (p less than 0.001).

NOTE: Epoetin alfa has been designated an orphan drug by the FDA for this indication.

Optimal regimen and place in therapy have not been defined; doses ranging from 300 to 2,500 units/kg/dose IV have been given daily or every other day for a short duration after birth. In a study of 167 term neonates with moderate to severe HIE, the use of erythropoietin (300 or 500 units/kg/dose every other day for 2 weeks beginning less than 48 hours after birth) resulted in improved neurological outcomes in patients with moderate (but not severe) HIE compared to conventional treatment (no erythropoietin). At 18 months of age, fewer patients in the erythropoietin group had experienced death or moderate/severe disability compared to the control group (24.6% vs. 43.8%, respectively; p = 0.017); neonates in the erythropoietin group also had fewer hospitalizations during the study period. No difference was found between the erythropoietin doses. In a prospective case-control study, the administration of erythropoietin 2,500 units/kg/dose subcutaneously for 5 days to neonates with mild/moderate HIE (n = 15) was associated with fewer neurologic and developmental abnormalities at 6 months of age compared to conventional therapy (no erythropoietin; n = 15). Erythropoietin was well tolerated.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

No dosage adjustment needed.

Androgens: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Danazol: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Esterified Estrogens; Methyltestosterone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Lenalidomide: (Moderate) Concomitant use of lenalidomide with erythropoietic agents such as epoetin alfa may increase the risk of thrombosis in patients with multiple myeloma patients who are also receiving dexamethasone. Use lenalidomide and erythropoietic agents with caution in these patients. Monitor for signs of thromboembolism (e.g., deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) and encourage patients to report symptoms such as shortness of breath, chest pain, or arm or leg swelling.
Methyltestosterone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Oxandrolone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Oxymetholone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Testosterone: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Thalidomide: (Moderate) Thalidomide and epoetin alfa should be used cautiously due an increased risk of thromboembolism.

Epogen/Procrit/Retacrit Intravenous Inj Sol: 1mL, 2000U, 3000U, 4000U, 10000U, 20000U, 40000U
Epogen/Procrit/Retacrit Subcutaneous Inj Sol: 1mL, 2000U, 3000U, 4000U, 10000U, 20000U, 40000U

Varies depending on indication, frequency of administration, and individual response; for patients with cancer, doses up to 60,000 units IV weekly until completion of chemotherapy.

Varies depending on indication, frequency of administration, and individual response; for patients with cancer, doses up to 60,000 units IV weekly until completion of chemotherapy.

Varies depending upon indication, frequency of administration, and individual response. For patients with cancer, 900 units/kg/week IV (Max: 60,000 units) until completion of chemotherapy. A limited number of HIV-infected adolescents have been treated off-label with doses up to 400 units/kg/dose subcutaneously/IV 3 times per week.

5 to 12 years: Varies depending upon indication, frequency of administration, and individual response. For patients with cancer, 900 units/kg/week IV (Max: 60,000 units) until completion of chemotherapy. A limited number of HIV-infected children have been treated off-label with doses up to 400 units/kg/dose subcutaneously/IV 3 times per week.
1 to 4 years: Varies depending upon indication, frequency of administration, and individual response; a limited number of HIV-infected children have been treated off-label with doses up to 400 units/kg/dose subcutaneously/IV 3 times per week.

8 to 11 months: Varies depending upon indication, frequency of administration, and individual response; a limited number of HIV-infected infants have been treated off-label with doses up to 400 units/kg/dose subcutaneously/IV 3 times per week.
1 to 7 months: Varies depending upon indication, frequency of administration, and individual response.

Safety and efficacy have not been established; however, doses up to 2,500 units/kg/dose subcutaneously/IV have been used off-label for hypoxic-ischemic encephalopathy.

Erythropoietin (EPO) is a glycoprotein that regulates the production of red blood cells by stimulating the division and differentiation of committed erythroid progenitor cells in the bone marrow. Epoetin alfa has the same biological activity as native EPO. In adults, almost 90% of EPO is produced in the kidney with the remainder produced by the liver. During fetal development, EPO is produced in the liver, and prior to birth at term, production is transferred to the kidney. Erythropoietin production in the kidney occurs in interstitial cells in the inner cortex that are in immediate proximity to the proximal tubules. More cells are activated as the hematocrit drops. Renal tubular cells may serve as oxygen sensors transmitting signals to the interstitial cells, possibly because they contain large amounts of heme protein that may function as an intracellular oxygen sensor and transducer.
 
Erythropoietin is required for the transformation of the most mature erythroid progenitor cell, erythroid colony-forming unit (CFU-E), to a proerythroblast. In the absence of EPO, this transformation cannot occur and the CFU-E will die. Erythropoietin activates the synthesis of hemoglobin and other proteins found in normal erythroblasts. Erythropoietin also causes a shift of marrow reticulocytes into the circulation. Due to the length of time required for erythropoiesis, a clinically significant increase in hematocrit is usually not observed in less than 2 weeks and may take up to 6 weeks in some patients. Erythropoietin has little effect on early erythroid progenitor cells, erythroid burst-forming units (BFU-E), whose growth is more dependent upon interleukin-3 and granulocyte-macrophage colony stimulating factor (GM-CSF). The production and activity of EPO is linked in a negative feedback loop, which maintains optimal red cell mass for oxygen transport. There appears to be a plateau of optimal oxygen transport to tissues occurring around hematocrits of 35% to 55% with significant decreases in oxygen transport above and below these values. Epoetin alfa produces a dose-dependent increase in the hematocrit; an increase of 2% per week may be seen during the initial phase of therapy. The stimulation of erythropoiesis increases the demand for iron, making iron supplementation necessary for many patients.

Epoetin alfa is administered intravenously or subcutaneously. A dose-dependent response is seen with epoetin alfa doses of 50 to 300 units/kg 3 times a week; however, a greater response is not seen at doses more than 300 units/kg 3 times a week. Other factors affecting response to therapy include iron stores, baseline hematocrit, and concurrent medical conditions. As with the endogenous erythropoietin (EPO), epoetin alfa does not appear extravascularly in humans. Whether the drug crosses the placenta or is distributed into breast milk has not been evaluated. Metabolism and elimination of endogenous EPO or epoetin alfa are not fully understood. While the glycosylation of EPO does not affect its binding to target cells, it plays an important role in preventing the rapid clearance of the hormone from the bloodstream. Non-glycosylated erythropoietin has a half-life in vivo of a few minutes. About 10% of the dose appears to be excreted in the urine. In healthy volunteers, the half-life of epoetin alfa is approximately 20% shorter than the half-life in patients with chronic renal failure.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Administering epoetin alfa by the IV route results in a more rapid peak; however, the delayed systemic absorption from the subcutaneous route gives a more sustained response.

The subcutaneous route of administration produces peak plasma concentrations between 5 to 24 hours after the dose. Although the IV route gives a more rapid peak, the delayed systemic absorption from the subcutaneous route gives a more sustained response. Subcutaneous administration can result in some drug accumulation because of delayed absorption.

Multidose vials of epoetin alfa are contraindicated during pregnancy due to the use of benzyl alcohol as a preservative. When epoetin alfa therapy is needed during pregnancy, use a single-dose vial, which is benzyl alcohol-free. Consider the benefits and risks of epoetin alfa single-dose vials for the mother and possible risks to the fetus when prescribing epoetin alfa to a pregnant woman. The limited available data on epoetin alfa use in pregnant women are insufficient to determine a drug-associated risk of adverse developmental outcomes. There are reports of intrauterine growth restriction and polyhydramnios in women with chronic renal disease, which is associated with an increased risk for these adverse pregnancy outcomes. In animal reproductive and developmental toxicity studies, embryofetal death, skeletal anomalies, and growth defects occurred when pregnant rats received epoetin alfa at doses approximating the clinical recommended starting doses.[30100] [63174]

Multidose vials of epoetin alfa are contraindicated in breast-feeding due to the use of benzyl alcohol as a preservative. Advise breast-feeding women to not breast-feed for at least 2 weeks after the last dose of epoetin alfa, if a multidose vial was used. Do not mix epoetin alfa with bacteriostatic saline containing benzyl alcohol. Use caution when administering epoetin alfa from a single-dose vial to a breast-feeding woman. There is no information regarding the presence of epoetin alfa in human milk, the effects on the breast-fed infant, or the effects on milk production. Endogenous erythropoietin is present in human milk.