DrugindexOnline^{2nd edition}

( Erythropoietin ; EPO ) Pronouncation: (e-POE-e-tin AL-fa)
Class: Recombinant human erythropoietin

Trade Names:
Epogen
- Injection 2,000 units/mL
- Injection 3,000 units/mL
- Injection 4,000 units/mL
- Injection 10,000 units/mL
- Injection 20,000 units/mL
- Injection 40,000 units/mL

Trade Names:
Procrit
- Injection 2,000 units/mL
- Injection 3,000 units/mL
- Injection 4,000 units/mL
- Injection 10,000 units/mL
- Injection 20,000 units/mL
- Injection 40,000 units/mL

Eprex (Canada)

Mechanism of Action

Pharmacology

Stimulates RBC production.

Pharmacokinetics

Absorption

T _max is 5 to 24 h (subcutaneous).

Elimination

Elimination t _½ is approximately 4 to 13 h (IV).

Indications and Usage

Treatment of anemia related to chronic renal failure (CRF), zidovudine therapy in HIV-infected patients, and nonmyeloid malignancies; reduction of allogeneic blood transfusions in surgery patients.

Unlabeled Uses

Anemia associated with critically ill patients, CHF, chronic disease (eg, rheumatoid arthritis), postpartum anemia, sickle cell disease, thalassemia, multiple myeloma, Jehovah's Witnesses, radiation treatment, epidermolysis bullosa, porphyria, for athletic enhancement, sexual dysfunction, transfusional iron overload.

Contraindications

Hypersensitivity to mammalian cell–derived products or human albumin; uncontrolled hypertension.

Dosage and Administration

Cancer Patients
Adults 3 times/wk dosing

Subcutaneous 150 units/kg 3 times/wk. Reduce dose when Hgb approaches 12 g/dL or Hgb increases by more than 1 g/dL in any 2-wk period. Withhold dose when Hgb exceeds 12 g/dL, until the Hgb falls below 11 g/dL, then restart dose at 25% below the previous dose. Increase dose to 300 units/kg 3 times/wk if response is not satisfactory after 8 wk.

Weekly dosing

Subcutaneous 40,000 units/wk. If, after 4 wk of therapy, the Hgb has not increased by 1 g/dL or more in the absence of RBC transfusion, increase dose to 60,000 units/wk. Withhold dose if Hgb exceeds 12 g/dL, and, when Hgb falls to less than 11 g/dL, restart dose 25% below the previous dose. Reduce dose by 25% when Hgb approaches 12 g/dL or Hgb increases more than 1 g/dL in any 2-wk period.

Children

Weekly dosing is recommended.

Initial dose

IV 600 units/kg (max 40,000 units). If, after 4 weeks of therapy, Hgb has not increased by 1 g/dL or more in the absence of RBC transfusions, increase dose to 900 units/kg (max 60,000 units).

CRF
Adults

IV/Subcutaneous

Initial dose

50 to 100 units/kg 3 times/wk.

Children (1 mo of age and older)

IV/Subcutaneous

Initial dose

50 units/kg 3 times/wk.

Do not adjust dose more frequently than once monthly, unless clinically indicated. After any dose adjustment, determine the Hgb twice weekly for at least 2 to 6 wk. If the Hgb is increasing and approaching 12 g/dL, reduce the dose approximately 25%. If Hgb continues to increase, temporarily withhold the dose until Hgb begins to decrease, at which point, reinitiate therapy at a dose approximately 25% below the previous dose. If Hgb increases by more than 1 g/dL in a 2-wk period, decrease the dose by about 25%. If the increase in Hgb is less than 1 g/dL over 4 wk and iron stores are adequate, increase the dose by approximately 25% of the previous dose. Further increase may be made at 4-wk intervals until the specified Hgb is obtained.

Surgery
Adults

Subcutaneous 300 units/kg/day for 10 days before surgery, on the day of surgery, and for 4 days after surgery.

Alternate dose schedule

Subcutaneous 600 units/kg once/wk doses (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery.

Zidovudine-Treated HIV-Infected Patients
Adults

IV/Subcutaneous

Initial dose

100 units/kg 3 times/wk for 8 wk; increase by 50 to 100 units/kg 3 times/wk until appropriate maintenance dose is reached. If Hgb exceeds 12 g/dL, stop the dose until Hgb drops below 11 g/dL. When resuming treatment, reduce the dose by 25%, then titrate to maintain desired Hgb.

General Advice

• For subcutaneous or IV bolus administration only. Not for intradermal, IM, or intraarterial administration. IV route recommended for patients on hemodialysis.
• Do not shake or vigorously agitate vial. Prolonged vigorous shaking may denature the glycoprotein, rendering it biologically inactive.
• Do not administer if particulate matter, cloudiness, or discoloration is noted.
• If transferrin saturation is less than 20%, give supplemental iron.
• IV dose may be administered into venous line at end of dialysis procedure to obviate need for additional venous access.
• Rotate subcutaneous injection sites.
• Single-dose vials contain no preservative. Use only 1 dose/vial. Do not reenter vial. Discard any unused portion. Do not combine unused portions or save unused portions for later use.
• Do not administer in conjunction with other drug solutions. However, at time of subcutaneous administration, single-dose vial may be admixed in syringe with bacteriostatic sodium chloride 0.9% with benzyl alcohol at a 1:1 ratio. Multidose vials contain benzyl alcohol and admixing is not necessary.
• Adjust dose to achieve and maintain lowest Hgb level sufficient to avoid the need for RBC transfusion and not to exceed 12 g/dL.

Storage/Stability

Store vials in refrigerator (36° to 46°F). Do not freeze or shake. Multidose vials may be stored in refrigerator for up to 21 days after initial entry.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (24%); deep venous thrombosis (10%).

CNS

Fatigue (25%); dizziness, insomnia (21%); headache (19%); asthenia (13%); anxiety, paresthesia (11%); seizure.

Dermatologic

Pruritus (22%); skin pain (18%); rash (16%).

GI

Nausea (58%); constipation (53%); vomiting (29%); diarrhea (21%); dyspepsia (11%).

Genitourinary

UTI (12%).

Local

Skin reaction at injection site (29%).

Musculoskeletal

Arthralgia (11%); trunk pain (3%).

Respiratory

Cough (18%); congestion (15%); shortness of breath (14%); upper respiratory tract infection (11%).

Miscellaneous

Pyrexia (51%); edema (17%); chest pain, clotted access (7%).

Precautions

Warnings Use the lowest dose of epoetin alfa that will gradually increase Hgb concentrations to the lowest level sufficient to avoid the need for RBC transfusion. Epoetin alfa increased the risk for death and serious CV events when administered to target an Hgb of greater than 12 g/dL. Erythropoiesis-stimulating agents (ESAs) shortened the time to tumor progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target an Hgb of greater than 12 g/dL; shortened overall survival and increased deaths attributed to disease progression at 4 mo in patients with metastatic breast cancer receiving chemotherapy when administered to target an Hgb of greater than 12 g/dL; and increased the risk of death when administered to target an Hgb of 12 g/dL in patients with active malignant disease receiving neither chemotherapy nor radiation therapy. ESAs are not indicated for this population. In patients receiving ESAs preoperatively for reduction of RBC transfusions, a higher incidence of deep vein thrombosis occurred in patients receiving epoetin alfa who were not receiving prophylactic anticoagulation.

Monitor Determine Hgb twice a week in CRF patients and once weekly in zidovudine-treated HIV patients until it has stabilized and the maintenance dose has been established. Then, determine Hgb weekly for at least 4 wk, until it has been determined that Hgb has stabilized in response to the dose change. Then, monitor at regular intervals. Closely monitor BP during therapy. Monitor iron stores, including transferrin saturation and serum ferritin, renal function, fluid and electrolyte balance, CBC with differential and platelet count, and serum chemistry regularly.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 1 mo of age.

Hypersensitivity

Anaphylactoid reactions, mild and transient skin rashes, and urticaria may occur.

Albumin

Epoetin alfa contains albumin, which is derived from human blood and carries an extremely remote risk for transmission of viral diseases.

Anemia

Because epoetin alfa may obviate the need for maintenance transfusion, it is not intended for CRF patients who require correction of severe anemia or for anemia in HIV-infected or cancer patients caused by other factors (eg, iron or folate deficiencies, hemolysis, GI bleeding).

Benzyl alcohol

Benzyl alcohol preservative present in some of these products has been associated with a fatal “gasping syndrome” in premature infants.

Dialysis management

Increased anticoagulation with heparin may be required to prevent clotting of the artificial kidney.

Hematologic response

An interval of 2 to 6 wk may occur between time of dose adjustment and a change in Hgb.

Hematology

Elevated bleeding time decreases toward normal after correction of anemia.

Hypertension

Not for use in patients with uncontrolled hypertension; control BP adequately before initiation of therapy.

Porphyria

May be exacerbated.

Pure red cell aplasia (PRCA)

PRCA and severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported, especially in patients with CRF. Evaluate any patient developing a loss of response to epoetin, accompanied by severe anemia and low reticulocyte count, for the etiology of the loss of effect. Withhold epoetin if anti-erythropoietin-associated anemia is suspected. Permanently discontinue epoetin in patients with antibody-mediated anemia.

Seizures

May occur; relationship to drug uncertain.

Thrombotic events

During hemodialysis, patients may need increased anticoagulation to prevent clotting of vascular access. Epoetin alfa also appears to increase the risk of thrombotic events and mortality in patients at risk.

Surgery patients

BP may rise in perioperative period; therefore, carefully monitor BP. Administer adequate iron supplementation throughout therapy.

Overdosage

Symptoms

Polycythemia.

Patient Information

• If patient or caregiver will be administering at home, review patient information leaflet with the patient or caregiver. Ensure patient or caregiver understands how to store, prepare, and administer the dose, and how to dispose of used equipment and supplies.
• Advise patient that dose will be adjusted based upon measured Hgb levels.
• Advise CRF patient to continue to follow dietary and dialysis prescriptions while taking this medication.
• Advise patient that iron supplementation will probably be needed and to take iron supplement as prescribed.
• Advise hypertensive patient to continue to take antihypertensive medications as prescribed and to follow dietary guidelines. Advise patient to continue to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
• Advise patient to notify health care provider immediately of the following: hives; intolerable GI effects (eg, nausea, vomiting, diarrhea); intolerable injection-site reaction; palpitations; rash; severe headache; shortness of breath; swelling of the eyes, mouth, or throat; or swelling of feet or ankles.
• Inform patient that drug may be associated with risk of seizures during first 90 days of treatment and to avoid driving or performing other hazardous tasks during this period.
• Caution women of childbearing potential that menses may resume following epoetin therapy. Advise patient that if this occurs to discuss risk of pregnancy and need for contraception with health care provider.