Usual Adult Dose for Anemia Associated with Zidovudine

Initial dose: 100 units/kg IV or subcutaneously 3 times a week

Use: Treatment of anemia due to zidovudine administered at 4200 mg/week or less in HIV-infected patients with endogenous serum erythropoietin levels of 500 milliunits/mL or less.

Usual Adult Dose for Anemia Associated with Chemotherapy

Initial dose: 150 units/kg subcutaneously 3 times a week or 40,000 units subcutaneously once a week

Duration of therapy: Until completion of chemotherapy course

Comments:

• Initiate treatment if hemoglobin is less than 10 g/dL and a minimum of 2 additional months of chemotherapy is planned.
• Use the lowest dose necessary to avoid RBC transfusions.

Use: Treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy.

Usual Adult Dose for Anemia Associated with Chronic Renal Failure

Chronic Kidney Disease (CKD) Patients Not on Dialysis:
Initial dose: 50 to 100 units/kg IV or subcutaneously 3 times a week

Comments:

• Initiate treatment only when hemoglobin is less than 10 g/dL, rate of hemoglobin decline indicates likelihood of requiring RBC transfusion, and reducing risk of alloimmunization and/or other RBC transfusion-related risks is a goal.

CKD Patients on Dialysis:
Initial dose: 50 to 100 units/kg IV or subcutaneously 3 times a week

Comments:

• Initiate treatment when hemoglobin is less than 10 g/dL.
• IV route is recommended for patients on hemodialysis.

Usual Adult Dose for Anemia Prior to Surgery

300 units/kg subcutaneously once a day starting 10 days before surgery, on day of surgery, and 4 days after surgery (15 days total) or 600 units/kg subcutaneously on days 21, 14, and 7 before surgery and on day of surgery (4 doses total)

Comments: Deep venous thrombosis (DVT) prophylaxis is recommended during treatment with this drug.

Use: To reduce the need for allogeneic RBC transfusions in patients with perioperative hemoglobin greater than 10 and less than or equal to 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. This drug is not indicated for patients who are willing to donate autologous blood preoperatively.

Usual Pediatric Dose for Anemia Associated with Chemotherapy

5 to 18 Years:
Initial dose: 600 units/kg IV once a week
Duration of therapy: Until completion of chemotherapy course

Comments:

• Benzyl alcohol-containing preparations of this drug are contraindicated in neonates and infants. Do not mix this drug with bacteriostatic saline as it also contains benzyl alcohol.
• Initiate treatment if hemoglobin is less than 10 g/dL and a minimum of 2 additional months of chemotherapy is planned.
• Use the lowest dose necessary to avoid RBC transfusions.

Usual Pediatric Dose for Anemia Associated with Chronic Renal Failure

CHRONIC KIDNEY DISEASE (CKD) PATIENTS ON DIALYSIS:
1 Month to 16 Years:
Initial dose: 50 units/kg IV or subcutaneously 3 times a week

Comments:

• Benzyl alcohol-containing preparations of this drug are contraindicated in neonates and infants. Do not mix this drug with bacteriostatic saline as it also contains benzyl alcohol.
• Initiate treatment when hemoglobin is less than 10 g/dL.
• IV route is recommended for patients on hemodialysis.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

All chronic kidney disease (CKD) patients:

• May increase dose no more than every 4 weeks; may decrease dose more frequently. Avoid frequent dose adjustments.
• If hemoglobin increases by more than 1 g/dL in 2 weeks, reduce dose by 25% or more as needed to reduce rapid responses.
• If hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase dose by 25%.
• For patients who do not respond adequately over a 12 week escalation period, further dose increases are unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce need for RBC transfusions. Evaluate other causes of anemia. Discontinue if responsiveness does not improve.

CKD patients on dialysis:

• If hemoglobin approaches or exceeds 11 g/dL, reduce or interrupt the dose of this drug.

CKD patients not on dialysis:

• If hemoglobin exceeds 10 g/dL, reduce or interrupt the dose and use the lowest dose sufficient to reduce need for RBC transfusions.

Zidovudine treated patients:

• If hemoglobin does not increase in 8 weeks, increase dose by 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.
• If hemoglobin does not increase with 300 units/kg for 8 weeks, discontinue treatment.
• If hemoglobin exceeds 12 g/dL, withhold treatment until hemoglobin decreases to less than 11 g/dL and resume at a dose 25% below the previous dose.

All chemotherapy patients:

• If hemoglobin increases greater than 1 g/dL in 2 weeks or reaches a level needed to avoid RBC transfusion, reduce dose by 25%.
• If hemoglobin exceeds a level needed to avoid RBC transfusion, withhold dose until hemoglobin approaches a level where RBC transfusions may be required and reinitiate at a dose 25% below the previous dose.
• If hemoglobin increases by less than 1 g/dL and remains below 10 g/dL after 4 weeks of therapy, increase dose to 300 units/kg 3 times a week or 60,000 units once a week in adults or 900 units/kg (60,000 units maximum) once a week in children.
• If there is no response as measured by hemoglobin levels or if RBC transfusions are still required after 8 weeks of therapy, discontinue this drug.

Precautions

US BOXED WARNINGS:

• CHRONIC KIDNEY DISEASE (CKD): 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, dose of this drug, or dosing strategy that does not increase these risks. Use the lowest dose of this drug sufficient to reduce the need for RBC transfusions.
• 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. Because of these risks, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense this drug to patients with cancer. To enroll in the ESA APPRISE Oncology Program, visit www.esa-apprise.com or call 1-866-284-8089 for further assistance. To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic reactions, use the lowest dose needed to avoid RBC transfusions. Use ESAs only for anemia from myelosuppressive chemotherapy. ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure. Discontinue following the completion of a chemotherapy course.
• PERISURGERY: Due to increased risk of Deep Venous Thrombosis (DVT), DVT prophylaxis is recommended.

CONTRAINDICATIONS:

• Uncontrolled hypertension
• Pure red cell aplasia (PRCA) that begins after treatment with this or other erythropoietin protein drugs
• Serious allergic reactions to this or other epoetin alpha products
• Use of multiple-dose/benzoyl alcohol-containing products in neonates, infants, pregnancy, or lactation

Safety and efficacy have not been established in CKD patients younger than 1 month; this drug is indicated for pediatric patients 1 month to 16 years for treatment of anemia associated with CKD requiring dialysis. Postmarketing reports do not indicate a difference in safety profiles of pediatric patients with CKD requiring dialysis and not requiring dialysis.
Safety and efficacy have not been established in cancer patients on chemotherapy younger than 5 years.

Consult WARNINGS section for additional precautions.

Dialysis

ANEMIA ASSOCIATED WITH CHRONIC KIDNEY DISEASE (CKD):
Adult:
Initial dose: 50 to 100 units/kg IV or subcutaneously 3 times a week

Comments:

• Initiate treatment when hemoglobin is less than 10 g/dL.
• IV route is recommended for patients on hemodialysis.

Pediatric (1 Month to 16 Years):
Initial dose: 50 units/kg IV or subcutaneously 3 times a week

Comments:

• Initiate treatment when hemoglobin is less than 10 g/dL.
• IV route is recommended for patients on hemodialysis.

Other Comments

Administration advice:

• Use only single dose (benzoyl alcohol free) formulations in neonates, infants, pregnancy, and lactation.
• The manufacturer product information should be consulted.

Storage requirements:

• Protect from light.
• Store (including unused portions of multidose vials) at 36 to 46F (2 to 8C). Do not freeze.
• Discard unused portions of preservative-free formulations; do not reenter these vials.
• Discard 21 days after initial entry.

Reconstitution/preparation techniques:

• Do not dilute.
• Do not shake. Do not use this drug if it has been shaken or frozen.
• Allow this drug to reach room temperature before injecting.
• Discard unused portions in preservative-free vials. Do not re-enter preservative-free vials.

IV compatibility: Do not mix with other drug solutions.

General:

• Women who become pregnant during treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN to enroll.
• Contact Amgen (1-800-AMGEN) OR Janssen (1-800-JANSSEN) to perform assays for binding and neutralizing antibodies.

Monitoring:

• Evaluate iron status before and during treatment; administer supplemental iron when serum ferritin is under 100 mcg/L or serum transferrin saturation is under 20%.
• The majority of chronic kidney disease patients will need supplemental iron during treatment.
• Correct or exclude other anemia causes (e.g. vitamin deficiency, inflammatory conditions, bleeding) prior to therapy.
• Following treatment initiation and dose adjustments, monitor hemoglobin weekly until stable and sufficient to minimize need for RBC transfusion. Monitor at least monthly thereafter provided hemoglobin remains stable.
• Monitor patients closely for premonitory neurologic symptoms during the first several months following initiation of this drug.
• Monitor platelet count regularly during the first 8 weeks of therapy.
• Monitor serum electrolytes in chronic renal failure patients.

Patient advice:

• Inform cancer patients that they must sign the patient-healthcare provider acknowledgment form before the start of each treatment course with this drug.
• Inform patients of the increased risks of mortality, serious cardiovascular reactions, thromboembolic reactions, stroke, and tumor progression.
• Advise patients of the importance of regular blood pressure monitoring and compliance with concomitant antihypertensive therapy and dietary restrictions.
• Advise patients to seek medical attention for new/different neurologic symptoms.
• Inform patients to stop using this drug and immediately contact their healthcare provider if they notice any signs or symptoms of severe skin reactions (e.g., itchy rash, blisters, sores, peeling, or skin coming off).
• Inform patients of the need to have regular laboratory tests for hemoglobin.

Frequently asked questions

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