(epoetin alfa-epbx)

Prescribing Information
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6 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)]

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 ReactionEpoetin 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 ReactionsEpoetin 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 ReactionEpoetin 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 Patients with Cancer
Adverse ReactionEpoetin 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 ReactionStudy S1Study S2
Epoetin alfa
300 U/kg		Epoetin alfa
100 U/kg		PlaceboEpoetin alfa
600 U/kg × 4 weeks		Epoetin alfa
300 U/kg × 15 days
(n = 112)*(n = 101)*(n = 103)*(n = 73)†(n = 72)†
*
Study included patients undergoing orthopedic surgery treated with epoetin alfa or placebo for 15 days.
†
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.
‡
DVTs were determined by clinical symptoms.

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%‡

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

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of epoetin alfa or of other epoetin alfa products.

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)].

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.

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US License No. 1974
Distributed by Pfizer Labs, division of Pfizer Inc., New York, NY 10001 USA

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

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