Usual Adult Dose for Anemia Associated with Chronic Renal Failure

Patients NOT on Dialysis:

Not currently on erythropoiesis-stimulating agents (ESAs):
Initial dose: 0.6 mcg/kg, intravenously (IV) or subcutaneously (SC), once every 2 weeks
Maintenance dose (when hemoglobin is stabilized): Administer once monthly, using twice the every 2 week dose; titrate as needed

Conversion From Epoetin alfa (EA):
EA dose under 8000 units/week: 60 mcg every 2 weeks OR 120 mcg monthly

EA dose 8000 to 16,000 units/week: 100 mcg every 2 weeks OR 200 mcg monthly

EA dose over 16,000 units/week: 180 mcg every 2 weeks OR 360 mcg monthly

Conversion From Darbepoetin alfa:
Darbepoetin alfa dose under 40 mcg/week: 60 mcg every 2 weeks OR 120 mcg monthly

Darbepoetin alfa dose 40 to 80 mcg /week: 100 mcg every 2 weeks OR 200 mcg monthly

Darbepoetin alfa dose over 80 mcg /week: 180 mcg every 2 weeks OR 360 mcg monthly

Comments:

• Use is neither indicated or recommended for anemia from cancer chemotherapy.
• Use is neither indicated or recommended as a substitute for red blood cell (RBC) transfusions when immediate correction of anemia is required.
• Improvements in symptoms, physical function, or health related quality of life have not been shown.
• Initiate therapy when hemoglobin is under 10 g/dL, the rate of hemoglobin decline is likely to require a RBC infusion, and reducing RBC transfusion related risks, including alloimmunization, is a goal.
• If hemoglobin exceeds 10 g/dL, reduce or interrupt dose.
• Use the lowest dose necessary to reduce the need for red blood cell transfusions.

Use: Anemia due to chronic kidney disease

Renal Dose Adjustments

See Usual Adult Dosing

Liver Dose Adjustments

Data not available

Dose Adjustments

General:

• Do not increase the dose more often than every 4 weeks.
• Dose reductions can be more frequent.
• Avoid frequent dose changes.

Rapid Hemoglobin Rise (over 1 g/dL in any 14-day period): Reduce dose by 25% or more as necessary to reduce rapid responses.

Inadequate Response (hemoglobin increased 1 g/dL or less after 4 weeks of therapy): Increase dose by 25%

• Patients without adequate response despite a 12-week dose escalation are unlikely to respond to more dose increases, but are at greater risk of adverse events.
• Use the lowest dose necessary to reduce the need for red blood cell transfusions.

Hemoglobin Exceeds 10 g/dL: Reduce or interrupt dosing; use the lowest dose necessary to reduce the need for red blood cell transfusions.

Geriatrics: Clinical studies did not include enough patients over 65 years to determine if they react differently than younger patients.

• Dose selection should be cautious, usually starting on the lower end of the dosing range, reflecting the increased likelihood of hepatic, renal, or cardiac dysfunction as well as other conditions and concomitant medications.

Precautions

US BOXED WARNING(S):
Chronic Kidney Disease:

• In controlled trials, patients given erythropoiesis-stimulating agents (ESAs) had greater risks of death, serious adverse cardiovascular reactions, and stroke, when a hemoglobin level of 11 g/dL or higher was targeted.
• No target hemoglobin level, ESA dose, or dosing strategy has been found that doesn't increase the risk.
• Use the lowest dose necessary to reduce the need for red blood cell transfusions.

Cancer:

• Use is neither indicated or recommended for anemia due to cancer chemotherapy.
• A dose-ranging study terminated early due to increased deaths in patients on this drug versus another ESA.
• ESAs shortened overall survival, and increased the tumor progression or recurrence risk in breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.

CONTRAINDICATIONS:

• Uncontrolled hypertension
• Pure red cell aplasia (PRCA) that begins after treatment with this or another ESA
• Serious allergic reactions to this product (e.g. anaphylaxis, angioedema, bronchospasm, skin rash, urticaria)

Safety and efficacy have not been established in patients younger than 5 years.

Consult WARNINGS section for additional precautions.

Dialysis

Adult Dialysis patients:
Not currently on erythropoiesis-stimulating agents (ESAs):
Initial dose: 0.6 mcg/kg, intravenously (IV) or subcutaneously (SC), once every 2 weeks
Maintenance dose (when hemoglobin is stabilized): Administer once monthly, using twice the every 2 week dose; titrate as needed

• Initiate therapy when hemoglobin is under 10 g/dL.
• If hemoglobin nears or exceeds 11 g/dL, reduce or interrupt dose.
• IV administration is preferred for dialysis patients, as immunogenicity may be less.

Pediatric Hemodialysis (5 to 17 years); for patients with hemoglobin stabilized on another ESA transferring to this drug:
Dose based on previous ESA dose that stabilized hemoglobin.

Transferring from epoetin alfa: 4 times the previous epoetin alfa dose/125, IV every 4 weeks (e.g. 4 x 1500 Units epoetin alfa per week/125 = 48 mcg epoetin beta-methoxy polyethylene glycol)

Transferring from darbepoetin alfa: 4 times the previous darbepoetin alfa dose/0.55, IV every 4 weeks (e.g. 4 x 20 Units darbepoetin alfa per week/0.55 = 145.5 mcg epoetin beta-methoxy polyethylene glycol every 4 weeks)

Peritoneal dialysis:

• Safety and efficacy of have not been established in pediatric patients on peritoneal dialysis.

Other Comments

Administration advice:

• May be administered subcutaneously (SC) or intravenously(IV) in adults.
• IV is preferred for dialysis patients, as immunogenicity may be less.
• IV is the only approved route in pediatric patients.
• Safety and efficacy of SC administration have not been established in pediatric patients.

Storage requirements:

• Refrigerate; keep in original carton to protect from light
• May be kept at room temperature in the original carton for up to 30 days by the end user; discard after 30 days
• Avoid vigorous shaking

IV compatibility:

• Do not mix with parenteral solutions.

Monitoring:

• Monitor hemoglobin at least weekly until stable when initiating or adjusting therapy.
• Monitor hemoglobin at least monthly once stable.