Data from FDA - Curated by EPG Health - Last updated 04 September 2018

Indication(s)

1 INDICATIONS AND USAGE RETACRIT is an erythropoiesis-stimulating agent (ESA) indicated for: Treatment of anemia due to Chronic Kidney Disease (CKD) in patients on dialysis and not on dialysis (1.1). Zidovudine in patients with HIV-infection (1.2). 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 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 chemotherapy when the anticipated outcome is cure. In patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion. In patients scheduled for surgery who are willing to donate autologous blood. In patients undergoing cardiac or vascular surgery. As a substitute for RBC transfusions in patients who require immediate correction of anemia.

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Advisory information

contraindications
4 CONTRAINDICATIONS 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)]. 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)
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 Trial 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 Warnings and Precautions (5.1)]. 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 4. Adverse Reactions in Patients with CKD Not on Dialysis Adverse Reactions Epoetin alfa-treated Patients (n = 131) Placebo-treated Patients (n = 79) Hypertension 13.7% 10.1% Arthralgia 12.2% 7.6% Additional serious adverse reactions that occurred in less than 5% of epoetin alfa-treated patients not on dialysis and greater than placebo were erythema (0.8% epoetin alfa and 0% placebo) and myocardial infarction (0.8% epoetin alfa and 0% placebo) [see Warnings and Precautions (5.1)]. Pediatric Patients In pediatric patients with CKD on dialysis, the pattern of adverse reactions was similar to that found in adults. Zidovudine-treated Patients with HIV-infection A total of 297 zidovudine-treated patients with HIV-infection were studied in 4 placebo-controlled studies. A total of 144 (48%) patients were randomly assigned to receive epoetin alfa and 153 (52%) patients were randomly assigned to receive placebo. Epoetin alfa was administered at doses between 100 and 200 Units/kg 3 times weekly subcutaneously for up to 12 weeks. For the combined epoetin alfa treatment groups, a total of 141 (98%) men and 3 (2%) women between the ages of 24 and 64 years were enrolled. The racial distribution of the combined epoetin alfa treatment groups was as follows: 129 (90%) white, 8 (6%) black, 1 (1%) Asian, and 6 (4%) other. In double-blind, placebo-controlled studies of 3 months duration involving approximately 300 zidovudine-treated patients with HIV-infection, adverse reactions with an incidence of ≥ 1% in patients treated with epoetin alfa were: Table 5. Adverse Reactions in Zidovudine-treated Patients with HIV-infection Adverse Reaction Epoetin alfa (n = 144) Placebo (n = 153) Pyrexia 42% 34% Cough 26% 14% Rash 19% 7% Injection site irritation 7% 4% Urticaria 3% 1% Respiratory tract congestion 1% Not reported Pulmonary embolism 1% Not reported Patients with cancer on Chemotherapy The data below were obtained in Study C1, a 16-week, double-blind, placebo-controlled study that enrolled 344 patients with anemia secondary to chemotherapy. There were 333 patients who were evaluable for safety; 168 of 174 patients (97%) randomized to epoetin alfa received at least 1 dose of study drug, and 165 of 170 patients (97%) randomized to placebo received at least 1 placebo dose. For the once weekly epoetin alfa treatment group, a total of 76 men (45%) and 92 women (55%) between the ages of 20 and 88 years were treated. The racial distribution of the epoetin alfa-treatment group was 158 white (94%) and 10 black (6%). Epoetin alfa was administered once weekly for an average of 13 weeks at a dose of 20,000 to 60,000 IU subcutaneously (mean weekly dose was 49,000 IU). The adverse reactions with a reported incidence of ≥ 5% in epoetin alfa-treated patients that occurred at a higher frequency than in placebo-treated patients are shown in the table below: Table 6. Adverse Reactions in Cancer Patients with Cancer Adverse Reaction Epoetin alfa (n = 168) Placebo (n = 165) Nausea 35% 30% Vomiting 20% 16% Myalgia 10% 5% Arthralgia 10% 6% Stomatitis 10% 8% Cough 9% 7% Weight decrease 9% 5% Leukopenia 8% 7% Bone pain 7% 4% Rash 7% 5% Hyperglycemia 6% 4% Insomnia 6% 2% Headache 5% 4% Depression 5% 4% Dysphagia 5% 2% Hypokalemia 5% 3% Thrombosis 5% 3% Surgery Patients Four hundred sixty-one patients undergoing major orthopedic surgery were studied in a placebo-controlled study (S1) and a comparative dosing study (2 dosing regimens, S2). A total of 358 patients were randomly assigned to receive epoetin alfa and 103 (22%) patients were randomly assigned to receive placebo. Epoetin alfa was administered daily at a dose of 100 to 300 IU/kg subcutaneously for 15 days or at 600 IU/kg once weekly for 4 weeks. For the combined epoetin alfa treatment groups, a total of 90 (25%) men and 268 (75%) women between the ages of 29 and 89 years were enrolled. The racial distribution of the combined epoetin alfa treatment groups was as follows: 288 (80%) white, 64 (18%) black, 1 (< 1%) Asian, and 5 (1%) other. The adverse reactions with a reported incidence of ≥ 1% in epoetin alfa-treated patients that occurred at a higher frequency than in placebo-treated patients are shown in the table below: Table 7. Adverse Reactions in Surgery Patients Adverse Reaction Study S1 Study S2 Epoetin alfa 300 U/kg Epoetin alfa 100 U/kg Placebo Epoetin alfa 600 U/kg × 4 weeks Epoetin alfa 300 U/kg × 15 days (n = 112)Study included patients undergoing orthopedic surgery treated with epoetin alfa or placebo for 15 days. (n = 101) (n = 103) (n = 73)Study included patients undergoing orthopedic surgery treated with epoetin alfa 600 U/kg weekly for 4 weeks or 300 U/kg daily for 15 days. (n = 72) Nausea 47% 43% 45% 45% 56% Vomiting 21% 12% 14% 19% 28% Pruritus 16% 16% 14% 12% 21% Headache 13% 11% 9% 10% 18% Injection site pain 13% 9% 8% 12% 11% Chills 7% 4% 1% 1% 0% Deep vein thrombosis 6% 3% 3% 0%DVTs were determined by clinical symptoms. 0% Cough 5% 4% 0% 4% 4% Hypertension 5% 3% 5% 5% 6% Rash 2% 2% 1% 3% 3% Edema 1% 2% 2% 1% 3% 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of epoetin alfa. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Seizures [see Warnings and Precautions (5.4)] PRCA [see Warnings and Precautions (5.6)] Serious allergic reactions [see Warnings and Precautions (5.7)] Injection site reactions, including irritation and pain Porphyria Severe Cutaneous Reactions [see Warnings and Precautions (5.8)] 6.3 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to epoetin alfa with the incidence of antibodies to other products may be misleading. Neutralizing antibodies to epoetin alfa that cross-react with endogenous erythropoietin and other ESAs can result in PRCA or severe anemia (with or without other cytopenias) [see Warnings and Precautions (5.6)].

Usage information

Dosing 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). 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. 2.2 Patients with 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. 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 in dose can occur more frequently. Avoid frequent dose adjustments. If the hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the dose of RETACRIT by 25% or more as needed to reduce rapid responses. For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. For patients who do not respond adequately over a 12-week escalation period, increasing the RETACRIT dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue RETACRIT if responsiveness does not improve. For adult patients with CKD on dialysis: Initiate RETACRIT treatment when the hemoglobin level is less than 10 g/dL. If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of RETACRIT. The recommended starting dose for adult patients is 50 to 100 Units/kg 3 times weekly intravenously or subcutaneously. The intravenous route is recommended for patients on hemodialysis. For adult patients with CKD not on dialysis: Consider initiating RETACRIT treatment only when the hemoglobin level is less than 10 g/dL and the following considerations apply: The rate of hemoglobin 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 the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of RETACRIT, and use the lowest dose of RETACRIT sufficient to reduce the need for RBC transfusions. The recommended starting dose for adult patients is 50 to 100 Units/kg 3 times weekly intravenously or subcutaneously. For pediatric patients with CKD: Initiate RETACRIT treatment only when the hemoglobin level is less than 10 g/dL. If the hemoglobin level approaches or exceeds 12 g/dL, reduce or interrupt the dose of RETACRIT . The recommended starting dose for pediatric patients (ages 1 month or older) is 50 Units/kg 3 times weekly intravenously or subcutaneously. When treating patients who have chronic kidney disease and cancer, physicians should refer to Warnings and Precautions (5.1 and 5.2). 2.3 Zidovudine-treated Patients with HIV-infection Starting Dose The recommended starting dose in adults is 100 Units/kg as an intravenous or subcutaneous injection 3 times per week. Dose Adjustment If hemoglobin does not increase after 8 weeks of therapy, increase RETACRIT dose by approximately 50 to 100 Units/kg at 4- to 8-week intervals until hemoglobin reaches a level needed to avoid RBC transfusions or 300 Units/kg. Withhold RETACRIT if hemoglobin exceeds 12 g/dL. Resume therapy at a dose 25% below the previous dose when hemoglobin declines to less than 11 g/dL. Discontinue RETACRIT if an increase in hemoglobin is not achieved at a dose of 300 Units/kg for 8 weeks. 2.4 Patients on Cancer Chemotherapy Initiate RETACRIT in patients on cancer chemotherapy only if the hemoglobin is less than 10 g/dL, and if there is a minimum of two additional months of planned chemotherapy. Use the lowest dose of RETACRIT necessary to avoid RBC transfusions. Recommended Starting Dose Adults: 150 Units/kg subcutaneously 3 times per week until completion of a chemotherapy course or 40,000 Units subcutaneously weekly until completion of a chemotherapy course. Pediatric Patients (5 to 18 years): 600 Units/kg intravenously weekly until completion of a chemotherapy course. Dose Reduction Reduce dose by 25% if: Hemoglobin increases greater than 1 g/dL in any 2-week period or Hemoglobin reaches a level needed to avoid RBC transfusion. Withhold dose if hemoglobin exceeds a level needed to avoid RBC transfusion. Reinitiate at a dose 25% below the previous dose when hemoglobin approaches a level where RBC transfusions may be required. Dose Increase After the initial 4 weeks of RETACRIT therapy, if hemoglobin increases by less than 1 g/dL and remains below 10 g/dL, increase dose to: 300 Units/kg three times per week in adults or 60,000 Units weekly in adults 900 Units/kg (maximum 60,000 Units) weekly in pediatric patients After 8 weeks of therapy, if there is no response as measured by hemoglobin levels or if RBC transfusions are still required, discontinue RETACRIT. 2.5 Surgery Patients The recommended RETACRIT regimens are: 300 Units/kg per day subcutaneously for 15 days total: administered daily for 10 days before surgery, on the day of surgery, and for 4 days after surgery. 600 Units/kg subcutaneously in 4 doses administered 21, 14, and 7 days before surgery and on the day of surgery. Deep venous thrombosis prophylaxis is recommended during RETACRIT therapy [see Warnings and Precautions (5.1)]. 2.6 Preparation and Administration Do not shake. Do not use RETACRIT that has been shaken or frozen. Protect vials from light. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any vials exhibiting particulate matter or discoloration. Discard unused portions of RETACRIT in preservative-free vials. Do not re-enter preservative-free vials. Do not dilute. Do not mix with other drug solutions.
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary 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. Data Human Data There are reports of pregnant women with anemia alone or anemia associated with severe renal disease and other hematologic disorders who received epoetin alfa. Polyhydramnios and intrauterine growth restriction were reported in women with chronic renal disease, which is associated with an increased risk for these adverse pregnancy outcomes. Due to the limited number of exposed pregnancies and multiple confounding factors (such as underlying maternal conditions, other maternal medications, and gestational timing of exposure), these published case reports and studies do not reliably estimate the frequency, presence or absence of adverse outcomes. Animal Data When rats received epoetin alfa at doses greater than or equal to 100 Units/kg/day during mating and through early pregnancy (dosing stopped prior to organogenesis), there were slight increases in the incidences of pre- and post-implantation loss, and a decrease in live fetuses in the presence of maternal toxicity (red limbs/pinna, focal splenic capsular toxicity, increased organ weights). This animal dose level of 100 Units/kg/day may approximate the clinical recommended starting dose, depending on the treatment indication. When pregnant rats and rabbits received intravenous doses of up to 500 mg/kg/day of epoetin alfa only during organogenesis (gestational days 7 to 17 in rats and gestational days 6 to 18 in rabbits), no teratogenic effects were observed in the offspring. The offspring (F1 generation) of the treated rats were observed postnatally; rats from the F1 generation reached maturity and were mated; no epoetin alfa-related effects were apparent for their offspring (F2 generation fetuses). When pregnant rats received epoetin alfa at doses of 500 Units/kg/day late in pregnancy (after the period of organogenesis from day 17 of gestation through day 21 of lactation), pups exhibited decreased number of caudal vertebrae, decreased body weight gain, and delayed appearance of abdominal hair, eyelid opening, and ossification in the presence of maternal toxicity (red limbs/pinna, increased organ weights). This animal dose level of 500 U/kg/day is approximately five times the clinical recommended starting dose depending on the patient's treatment indication. 8.2 Lactation Risk Summary There is no information regarding the presence of epoetin alfa products in human milk, the effects on the breastfed infant, or the effects on milk production. However, endogenous erythropoietin is present in human milk. Because many drugs are present in human milk, caution should be exercised when RETACRIT is administered to a lactating woman. 8.4 Pediatric Use Pediatric Patients with CKD RETACRIT is indicated in pediatric patients, ages 1 month to 16 years of age, for the treatment of anemia associated with CKD requiring dialysis. Safety and effectiveness in pediatric patients less than 1 month old have not been established [see Clinical Studies (14.1)]. Use of epoetin alfa products in pediatric patients with CKD not requiring dialysis is supported by efficacy in pediatric patients requiring dialysis. The mechanism of action of epoetin alfa products is the same for these two populations. Published literature also has reported the use of epoetin alfa in pediatric patients with CKD not requiring dialysis. Dose-dependent increases in hemoglobin and hematocrit were observed with reductions in transfusion requirements. The safety data from the pediatric studies and postmarketing reports are similar to those obtained from the studies of epoetin alfa in adult patients with CKD [see Warnings and Precautions (5) and Adverse Reactions (6.1)]. Postmarketing reports do not indicate a difference in safety profiles in pediatric patients with CKD requiring dialysis and not requiring dialysis. Pediatric Patients with Cancer on Chemotherapy RETACRIT is indicated in patients 5 to 18 years old for the treatment of anemia due to concomitant myelosuppressive chemotherapy. Safety and effectiveness in pediatric patients less than 5 years of age have not been established [see Clinical Studies (14.3)]. The safety data from these studies are similar to those obtained from the studies of epoetin alfa in adult patients with cancer [see Warnings and Precautions (5.1, 5.2) and Adverse Reactions (6.1)]. Pediatric Patients with HIV Infection Receiving Zidovudine Published literature has reported the use of epoetin alfa in 20 zidovudine-treated, anemic, pediatric patients with HIV infection, ages 8 months to 17 years, treated with 50 to 400 Units/kg subcutaneously or intravenously 2 to 3 times per week. Increases in hemoglobin levels and in reticulocyte counts and decreases in or elimination of RBC transfusions were observed. Pharmacokinetics in Neonates Limited pharmacokinetic data from a study of 7 preterm, very low birth weight neonates and 10 healthy adults given intravenous erythropoietin suggested that distribution volume was approximately 1.5 to 2 times higher in the preterm neonates than in the healthy adults, and clearance was approximately 3 times higher in the preterm neonates than in the healthy adults. 8.5 Geriatric Use Of the 4553 patients who received epoetin alfa in the 6 studies for treatment of anemia due to CKD not receiving dialysis, 2726 (60%) were age 65 years and over, while 1418 (31%) were 75 years and over. Of the 757 patients who received epoetin alfa in the 3 studies of CKD patients on dialysis, 361 (47%) were age 65 years and over, while 100 (13%) were 75 years and over. No differences in safety or effectiveness were observed between geriatric and younger patients. Dose selection and adjustment for an elderly patient should be individualized to achieve and maintain the target hemoglobin [see Dosage and Administration (2)]. Among 778 patients enrolled in the 3 clinical studies of epoetin alfa for the treatment of anemia due to concomitant chemotherapy, 419 received epoetin alfa and 359 received placebo. Of the 419 who received epoetin alfa, 247 (59%) were age 65 years and over, while 78 (19%) were 75 years and over. No overall differences in safety or effectiveness were observed between geriatric and younger patients. The dose requirements for epoetin alfa in geriatric and younger patients within the 3 studies were similar. Among 1731 patients enrolled in the 6 clinical studies of epoetin alfa for reduction of allogeneic RBC transfusions in patients undergoing elective surgery, 1085 received epoetin alfa and 646 received placebo or standard of care treatment. Of the 1085 patients who received epoetin alfa, 582 (54%) were age 65 years and over, while 245 (23%) were 75 years and over. No overall differences in safety or effectiveness were observed between geriatric and younger patients. The dose requirements for epoetin alfa in geriatric and younger patients within the 4 studies using the 3 times weekly schedule and 2 studies using the weekly schedule were similar. Insufficient numbers of patients age 65 years or older were enrolled in clinical studies of epoetin alfa for the treatment of patients treated with zidovudine for HIV-infection to determine whether they respond differently from younger patients.

More information

Category Value
Authorisation number BLA125545
Agency product number 64FS3BFH5W
Orphan designation No
Product NDC 59353-003,59353-002,59353-010,59353-004
Date Last Revised 07-06-2018
Type HUMAN PRESCRIPTION DRUG
RXCUI 2047606
Storage and handling Store at 36°F to 46°F (2°C to 8°C). Do not freeze. Do not shake. Do not use RETACRIT that has been shaken or frozen. Store RETACRIT vials in the original carton until use to protect from light.
Marketing authorisation holder Vifor (International) Inc.
Warnings 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. 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 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)] .