Usual Adult Dose for Anemia Associated with Chronic Renal Failure

Chronic Kidney Disease (CKD) Patients Not on Dialysis:
Initial dose: 0.45 mcg/kg IV or subcutaneously once every 4 weeks as appropriate

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: 0.45 mcg/kg IV or subcutaneously once a week or 0.75 mcg/kg once every 2 weeks as appropriate

Comments:

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

Usual Adult Dose for Anemia Associated with Chemotherapy

Initial dose: 2.25 mcg/kg subcutaneously once a week or 500 mcg subcutaneously once every 3 weeks

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 Pediatric Dose for Anemia Associated with Chronic Renal Failure

Less than 18 Years:
Initial dose:

• Chronic Kidney Disease (CKD) Patients Not on Dialysis: 0.45 mcg/kg IV or subcutaneously once a week or 0.75 mcg/kg once every 2 weeks
• CKD Patients on Dialysis: 0.45 mcg/kg IV or subcutaneously once a week

Comments: Initiate treatment when hemoglobin is less than 10 g/dL.

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.

Pediatric CKD patients:

• If hemoglobin approaches or exceeds 12 g/dL, reduce or interrupt the dose of this drug.

Conversion from epoetin alfa to this drug in CKD patients on dialysis:

• Maintain the route of administration when converting.
• Administer this drug once weekly in patients who were receiving epoetin alfa 2 to 3 times weekly; administer once every 2 weeks in patients who were receiving epoetin alfa once weekly.
• Previous weekly epoetin alfa dose (units/week): Darbepoetin alfa dose (mcg/week)
• Less than 1500: Adults: 6.25; Pediatric: Unknown
• 1500 to 2499: Adults: 6.25; Pediatric: 6.25
• 2500 to 4999: Adults: 12.5; Pediatric: 10
• 5000 to 10999: Adults: 25; Pediatric: 20
• 11000 to 17999: Adults: 40; Pediatric: 40
• 18000 to 33999: Adults: 60; Pediatric: 60
• 34000 to 89999: Adults: 100; Pediatric: 100
• 90000 or greater: Adults: 200; Pediatric: 200

Conversion from epoetin alfa to this drug in CKD patients not on dialysis:

• Refer to doses for CKD patients on dialysis. Dose conversion does not accurately estimate the once monthly dose of this drug.

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 40%.
• 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 40% below the previous dose.
• If hemoglobin increases by less than 1 g/dL and remains below 10 g/dL after 6 weeks of therapy, increase dose to 4.5 mcg/kg/week, if on the weekly dosing schedule. If on the every 3 week dosing schedule, no dose adjustment is recommended.
• If there is no response as measured by hemoglobin levels or if RBC transfusions are still required after 8 weeks of therapy, or if chemotherapy course is complete, discontinue this drug.

Precautions

US BOXED WARNING(S):

• CHRONIC KIDNEY DISEASE: 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.

CONTRAINDICATIONS:

• Uncontrolled hypertension
• Pure red cell aplasia (RCA) that starts after use of this or other erythropoietin protein drugs
• Serious allergic reaction to this drug

Safety and efficacy have not been established in cancer patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

ANEMIA ASSOCIATED WITH CHRONIC KIDNEY DISEASE (CKD):
Adult:
Initial dose: 0.45 mcg/kg IV or subcutaneously once a week or 0.75 mcg/kg once every 2 weeks as appropriate

Comments:

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

Pediatric (Less than 18 Years):
Initial dose: 0.45 mcg/kg IV or subcutaneously once a week

Comments: Initiate treatment when hemoglobin is less than 10 g/dL.

Other Comments

Administration advice: The manufacturer product information should be consulted.

Storage requirements:

• Refrigerate at 36 to 46F (2 to 8C). Do not freeze.
• Protect from light.

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 portion in vials or prefilled syringes. Do not re-enter vial.

IV compatibility: Do not administer in conjunction 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 (1-800-77-AMGEN) to perform assays for binding and neutralizing antibodies.

Monitoring:

• 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.

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 of the need to have regular laboratory tests for hemoglobin.