(epoetin alfa-epbx)

Prescribing Information
Download Prescribing Information

8 USE IN SPECIFIC POPULATIONS

8 USE IN SPECIFIC POPULATIONS

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 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

RETACRIT from multiple-dose vials contains benzyl alcohol and is contraindicated in lactating women [see Contraindications (4), Warnings and Precautions (5.9)]. Advise a lactating woman not to breastfeed for at least 2 weeks after the last dose. The preservative benzyl alcohol has been associated with serious adverse reactions and death when administered intravenously to neonates and infants [see Use in Specific Populations (8.4)]. There is a potential for similar risks to infants exposed to benzyl alcohol through human milk.

Do not mix RETACRIT with bacteriostatic saline containing benzyl alcohol, if administering RETACRIT to a lactating woman [see Dosage and Administration (2.1)].

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

The multiple-dose vials are formulated with benzyl alcohol and are contraindicated for use in neonates and infants [see Contraindications (4), Warnings and Precautions (5.9)]. When therapy with RETACRIT is needed in neonates and infants, use the single-dose vial, which is a benzyl alcohol-free formulation. Do not mix the single-dose vials with bacteriostatic saline when administering RETACRIT to neonates or infants because it contains benzyl alcohol [see Dosage and Administration (2.6)].

Serious adverse reactions including fatal reactions and the "gasping syndrome" occurred in premature neonates and infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known [see Warnings and Precautions (5.9)].

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 RETACRIT in pediatric patients with CKD not requiring dialysis is supported by efficacy of epoetin alfa 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.

Medication Guide

MEDICATION GUIDE

This Medication Guide has been approved by the U.S. Food and Drug Administration.     Revised: 6/2024

MEDICATION GUIDE
RETACRIT® (Ret-uh-krit)
(epoetin alfa-epbx)

Read this Medication Guide:

•
before you start RETACRIT.
•
if you are told by your healthcare provider that there is new information about RETACRIT.
•
if you are told by your healthcare provider that you may inject RETACRIT at home, read this Medication Guide each time you receive a new supply of medicine.

This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment. Talk with your healthcare provider regularly about the use of RETACRIT and ask if there is new information about RETACRIT.

What is the most important information I should know about RETACRIT?

RETACRIT may cause serious side effects that can lead to death, including:

For people with cancer:

•
Your tumor may grow faster and you may die sooner if you choose to take RETACRIT. Your healthcare provider will talk with you about these risks.

For all people who take RETACRIT, including people with cancer or chronic kidney disease:

•
Serious heart problems, such as heart attack or heart failure, and stroke. You may die sooner if you are treated with RETACRIT to increase red blood cells (RBCs) to near the same level found in healthy people.
•
Blood clots. Blood clots may happen at any time while taking RETACRIT. If you are receiving RETACRIT for any reason and you are going to have surgery, talk to your healthcare provider about whether or not you need to take a blood thinner to lessen the chance of blood clots during or following surgery. Blood clots can form in blood vessels (veins), especially in your leg (deep venous thrombosis or DVT). Pieces of a blood clot may travel to the lungs and block the blood circulation in the lungs (pulmonary embolus).
•
Call your healthcare provider or get medical help right away if you have any of these symptoms:
o
Chest pain
o
Trouble breathing or shortness of breath
o
Pain in your legs, with or without swelling
o
A cool or pale arm or leg
o
Sudden confusion, trouble speaking, or trouble understanding others' speech
o
Sudden numbness or weakness in your face, arm, or leg, especially on one side of your body
o
Sudden trouble seeing
o
Sudden trouble walking, dizziness, loss of balance or coordination
o
Loss of consciousness (fainting)
o
Hemodialysis vascular access stops working

See "What are the possible side effects of RETACRIT?" below for more information.

If you decide to take RETACRIT, your healthcare provider should prescribe the smallest dose of RETACRIT that is necessary to reduce your chance of needing RBC transfusions.

What is RETACRIT?

RETACRIT is a prescription medicine used to treat anemia. People with anemia have a lower-than-normal number of RBCs. RETACRIT works like the human protein called erythropoietin to help your body make more RBCs. RETACRIT is used to reduce or avoid the need for RBC transfusions.

RETACRIT may be used to treat anemia if it is caused by:

•
Chronic kidney disease (you may or may not be on dialysis).
•
Chemotherapy that will be used for at least two months after starting RETACRIT.
•
A medicine called zidovudine (AZT) used to treat HIV infection.

RETACRIT may also be used to reduce the chance you will need RBC transfusions if you are scheduled for certain surgeries where a lot of blood loss is expected.

If your hemoglobin level stays too high or if your hemoglobin goes up too quickly, this may lead to serious health problems which may result in death. These serious health problems may happen if you take RETACRIT, even if you do not have an increase in your hemoglobin level.

RETACRIT has not been proven to improve quality of life, fatigue, or well-being.

RETACRIT should not be used for treatment of anemia:

•
If you have cancer and you will not be receiving chemotherapy that may cause anemia.
•
If you have a cancer that has a high chance of being cured. Talk with your healthcare provider about the kind of cancer you have.
•
If your anemia caused by chemotherapy treatment can be managed by RBC transfusion.
•
In place of emergency treatment for anemia (RBC transfusions).

RETACRIT should not be used to reduce the chance you will need RBC transfusions if:

•
You are scheduled for surgery on your heart or blood vessels.
•
You are able and willing to donate blood prior to surgery.

It is not known if RETACRIT is safe and effective in treating anemia in children less than 1 month old who have chronic kidney disease and in children less than 5 years old who have anemia caused by chemotherapy.

Who should not take RETACRIT?

Do not take RETACRIT if you:

•
Have cancer and have not been counseled by your healthcare provider about treatment with RETACRIT.
•
Have high blood pressure that is not controlled (uncontrolled hypertension).
•
Have been told by your healthcare provider that you have or have ever had a type of anemia called Pure Red Cell Aplasia (PRCA) that starts after treatment with RETACRIT or other erythropoietin protein medicines.
•
Have had a serious allergic reaction to RETACRIT or other epoetin alfa products.

Do not give RETACRIT from multiple-dose vials to:

•
Pregnant or breastfeeding women
•
Babies

Before taking RETACRIT, tell your healthcare provider about all of your medical conditions, including if you:

•
Have heart disease.
•
Have high blood pressure.
•
Have had a seizure (convulsion) or stroke.
•
Have phenylketonuria. RETACRIT contains phenylalanine (a component of aspartame).
•
Receive dialysis treatment.
•
Are pregnant or plan to become pregnant. It is not known if RETACRIT may harm your unborn baby. Talk to your healthcare provider about possible pregnancy and birth control choices that are right for you.
•
Are breastfeeding or plan to breastfeed. It is not known if RETACRIT passes into breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I take RETACRIT?

•
If you or your caregiver has been trained to give RETACRIT shots (injections) at home:
o
Be sure that you read, understand, and follow the "Instructions for Use" that come with RETACRIT.
o
Take RETACRIT exactly as your healthcare provider tells you to. Do not change the dose of RETACRIT unless told to do so by your healthcare provider.
o
Your healthcare provider will show you how much RETACRIT to use, how to inject it, how often it should be injected, and how to safely throw away the used vials, syringes, and needles.
o
If you miss a dose of RETACRIT, call your healthcare provider right away and ask what to do.
o
If you take more than the prescribed dose of RETACRIT, call your healthcare provider right away.
•
During treatment with RETACRIT, continue to follow your healthcare provider's instructions for diet and medicines.
•
Have your blood pressure checked as instructed by your healthcare provider.

What are the possible side effects of RETACRIT?

RETACRIT may cause serious side effects, including:

•
See "What is the most important information I should know about RETACRIT?"
•
High blood pressure. High blood pressure is a common side effect of RETACRIT in people with chronic kidney disease. Your blood pressure may go up or be difficult to control with blood pressure medicine while taking RETACRIT. This can happen even if you have never had high blood pressure before. Your healthcare provider should check your blood pressure often. If your blood pressure does go up, your healthcare provider may prescribe new or more blood pressure medicine.
•
Seizures. If you have any seizures while taking RETACRIT, get medical help right away and tell your healthcare provider.
•
Antibodies to RETACRIT. Your body may make antibodies to RETACRIT. These antibodies can block or lessen your body's ability to make RBCs and cause you to have severe anemia. Call your healthcare provider if you have unusual tiredness, lack of energy, dizziness, or fainting. You may need to stop taking RETACRIT.
•
Serious allergic reactions. Serious allergic reactions can cause a skin rash, itching, shortness of breath, wheezing, dizziness and fainting because of a drop in blood pressure, swelling around your mouth or eyes, fast pulse, or sweating. If you have a serious allergic reaction, stop using RETACRIT and call your healthcare provider or get medical help right away.
•
Severe skin reactions. Signs and symptoms of severe skin reactions with RETACRIT may include: skin rash with itching, blisters, skin sores, peeling, or areas of skin coming off. If you have any signs or symptoms of a severe skin reaction, stop using RETACRIT and call your healthcare provider or get medical help right away.
•
Dangers of using RETACRIT from multiple-dose vials in newborns, infants, and pregnant or breastfeeding women. Do not use RETACRIT from multiple-dose vials in newborns, infants, pregnant or breastfeeding women because the RETACRIT in these vials contains benzyl alcohol. Benzyl alcohol has been shown to cause brain damage, other serious side effects, and death in newborn and premature babies. If you use RETACRIT from multiple-dose vials you should not breastfeed for at least 2 weeks after the last dose. RETACRIT that comes in single-dose vials does not contain benzyl alcohol. See "Who should not take RETACRIT?"

Common side effects of RETACRIT include:

•
joint, muscle, or bone pain
•
fever
•
cough
•
dizziness
•
high blood sugar
•
low potassium levels in the blood
•
chills
•
redness and pain at the RETACRIT injection site
•
rash
•
nausea
•
vomiting
•
blood vessel blockage
•
low white blood cells
•
trouble sleeping
•
difficulty swallowing
•
soreness of mouth
•
itching
•
headache
•
respiratory infection
•
weight decrease
•
depression
•
muscle spasm

These are not all of the possible side effects of RETACRIT. Your healthcare provider can give you a more complete list. Tell your healthcare provider about any side effects that bother you or that do not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store RETACRIT?

•
Do not shake RETACRIT.
•
Store RETACRIT vials in the carton it comes in to protect from light.
•
Store RETACRIT in the refrigerator between 36°F to 46°F (2°C to 8°C).
•
Do not freeze RETACRIT. Do not use the carton of RETACRIT multiple-dose vials if it that has been frozen or if the green area on the freeze strip indicator inside the RETACRIT carton looks white or cloudy.
•
Throw away multiple-dose vials of RETACRIT no later than 21 days from the first day that you put a needle into the vial.
•
Single-dose vials of RETACRIT should be used only one time. Throw the vial away after use even if there is medicine left in the vial.

Keep RETACRIT and all medicines out of the reach of children.

General information about the safe and effective use of RETACRIT.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use RETACRIT for a condition for which it was not prescribed. Do not give RETACRIT to other people even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about RETACRIT that is written for healthcare professionals.

What are the ingredients in RETACRIT?

Active Ingredient: epoetin alfa-epbx

Inactive Ingredients:

•
Multiple-dose vials contain benzyl alcohol.
•
All single-dose vials contain calcium chloride dehydrate, glycine, isoleucine, leucine, L-glutamic acid, phenylalanine, polysorbate 20, sodium chloride, sodium phosphate dibasic anhydrous, sodium phosphate monobasic monohydrate, and threonine, in water for injection. Sodium hydroxide and hydrochloric acid may be added to adjust the pH.
•
All multiple-dose vials contain benzyl alcohol, L-methionine, polysorbate 20, sodium phosphate dibasic anhydrous, sodium phosphate monobasic monohydrate, and sucrose, in water for injection. Sodium hydroxide and hydrochloric acid may be added to adjust the pH.

Manufactured by Hospira, Inc., a Pfizer Company, Lake Forest, IL 60045 USA
US License No. 1974
Distributed by Pfizer Labs, division of Pfizer Inc., New York, NY 10001 USA

Pfizer logo

LAB-0827-9.0
For more information, go to www.pfizer.com or call 1-800-438-1985.

Additional Resources

Chat online with Pfizer Medical Information regarding your inquiry on a Pfizer medicine or vaccine.

Speak with a Pfizer Medical Information Professional regarding your Pfizer medicine or vaccine inquiry.

Available 9AM-5PM ET Monday to Friday; excluding holidays.

 

Submit a medical question for a Pfizer medicine or a vaccine. 

The submission will be reviewed during our standard business hours.

To report an adverse event related to a Pfizer product and you are not part of a clinical trial* for this medication, click the link below to submit your information: 
Pfizer Safety Reporting Site

*If you are involved in a clinical trial for either product, adverse events should be reported to your coordinating study site.

If you cannot use the above website to report an adverse event related to a Pfizer medication, please call (800) 438-1985.

You may also contact the U.S. Food and Drug Administration (FDA) directly to report adverse events or product quality concerns either online at www.fda.gov/medwatch or by calling (800) 332-1088.