Does Epogen (epoetin alfa) cause side effects?

Epogen (epoetin alfa) is a colony-stimulating factor used to treat anemia associated with chronic kidney failure for people who are or will be receiving dialysis. Epogen is also used to treat anemia in individuals with HIV infection and in patients with cancer who are receiving chemotherapy

Erythropoietin is a protein that normally is made in the body by the kidney. It causes the bone marrow to produce oxygen-carrying red blood cells. Under normal conditions, when the body senses a decrease in red blood cells or a deficiency in the supply of oxygen, more erythropoietin is produced, and this increases the number of red blood cells. 

When this natural mechanism is not working, it may become necessary to stimulate the bone marrow to produce red blood cells. The erythropoietin that is used for therapy, called epoetin alfa, is man-made. It does not cure the underlying cause of the anemia, and unless the underlying cause can be reversed, treatment with Epogen must be continued indefinitely. 

Colony-stimulating factors have the ability to stimulate cells in the bone marrow to multiply and form colonies of identical cells. Epogen and Procrit are both epoetin alfa, but they are marketed by two different pharmaceutical companies. 

Common side effects of Epogen in patients with kidney failure on dialysis include

In HIV-infected patients receiving zidovudine, the most common side effects with Epogen are

The most common side effects of Epogen in patients undergoing surgery with anemia are fever, nausea, constipation, skin reactions, vomiting and headaches

Among patients with cancer receiving chemotherapy, the most common side effects of Epogen are fever, diarrhea, tissue swelling, shortness of breath, abnormal sensations like burning or prickling, and upper respiratory infection.

Serious side effects of Epogen include

No clinical studies have been done to demonstrate Epogen drug interactions

There are no studies of Epogen use in pregnant women. Polyhydramnios and intrauterine growth restriction were reported in a small number of pregnant women who received Epogen. Multiple dose vials contain benzyl alcohol and should not be administered to pregnant women. 

It is unknown if Epogen is excreted into breast milk. Multiple dose vials contain benzyl alcohol and should not be administered to nursing mothers. Consult your doctor before breastfeeding.

What are the important side effects of Epogen (epoetin alfa)?

The most common side effects of epoetin alfa in patients with kidney failure on dialysis are:

Rare cases of stinging at the injection site, skin rash and flu-like symptoms (joint and muscle pain) have occurred within a few hours following administration.

Allergic reactions, seizures, and thrombotic events (for example, heart attacks, strokes, and pulmonary embolism ) rarely occur.

In HIV-infected patients receiving zidovudine, the most common side effects with epoetin alfa are fever, headache, rash, and nasal or chest congestion. Rare cases of seizures or severe rash have occurred in these patients.

The most common side effects in patients undergoing surgery with anemia are:

Blood clots in veins, referred to as a deep venous thrombosis, also may occur.

Among patients with cancer receiving chemotherapy, the most common side effects of epoetin alfa are:

  • fever,
  • diarrhea,
  • tissue swelling,
  • shortness of breath,
  • paresthesia (abnormal sensations like burning or prickling that may occur anywhere in the body), and
  • upper respiratory infection.

Treatment with epoetin alfa may increase the growth of several types of cancer and reduce survival, and, therefore, its use should be restricted to the conditions discussed previously.

Epogen (epoetin alfa) side effects list for healthcare professionals

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

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 Epogen. 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 Epogen. 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 Epogen-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 Epogen-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% Epogen and 1% placebo).

The adverse reactions with a reported incidence of ≥ 5% in Epogen-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 Epogen-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% Epogen and 0% placebo) and
  • myocardial infarction (0.8% Epogen and 0% placebo).
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 Epogen and 153 (52%) patients were randomly assigned to receive placebo. Epogen was administered at doses between 100 and 200 Units/kg 3 times weekly subcutaneously for up to 12 weeks.

For the combined Epogen 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 Epogen 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 Epogen were:

Table 5: Adverse Reactions in Zidovudine-treated Patients with HIV-infection

Adverse Reaction Epogen
(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 Epogen 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 Epogen-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 Epogen-treatment group was 158 white (94%) and 10 black (6%). Epogen 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 Epogen-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 Reaction Epogen
(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 Epogen and 103 (22%) patients were randomly assigned to receive placebo. Epogen 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 Epogen treatment groups, a total of 90 (25%) and 268 (75%) women between the ages of 29 and 89 years were enrolled. The racial distribution of the combined Epogen 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 Epogen-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
Epogen 300 U/kg
(n = 112)a
Epogen 100 U/kg
(n = 101)a
Placebo
(n = 103)a
Epogen 600 U/kg x 4 weeks
(n = 73)b
Epogen 300 U/kg x 15 days
(n = 72)b
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%c 0%c
Cough 5% 4% 0% 4% 4%
Hypertension 5% 3% 5% 5% 6%
Rash 2% 2% 1% 3% 3%
Edema 1% 2% 2% 1% 3%
aStudy included patients undergoing orthopedic surgery treated with Epogen or placebo for 15 days.
bStudy included patients undergoing orthopedic surgery treated with Epogen 600 U/kg weekly for 4 weeks or 300 U/kg daily for 15 days.
cDVTs were determined by clinical symptoms.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Epogen. 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
  • PRCA
  • Serious allergic reactions
  • Injection site reactions, including irritation and pain
  • Porphyria
  • Severe Cutaneous Reactions

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).

What drugs interact with Epogen (epoetin alfa)?

No information provided.

Treatment & Diagnosis

Medications & Supplements

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Medically Reviewed on 12/2/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.