Trade Names:Aranesp- (as polysorbate or albumin solution) Injection 25 mcg per 0.42 mL- Injection 25 mcg/mL- Injection 40 mcg per 0.4 mL- Injection 40 mcg/mL- Injection 60 mcg per 0.3 mL- Injection 60 mcg/mL- Injection 100 mcg per 0.5 mL- Injection 100 mcg/mL- Injection 150 mcg per 0.3 mL- Injection 150 mcg per 0.75 mL- Injection 200 mcg per 0.4 mL- Injection 200 mcg/mL- Injection 300 mcg per 0.6 mL- Injection 300 mcg/mL- Injection 500 mcg/mL
Stimulates red blood cell production.
Absorption is slow and rate-limiting, with C max at 48 h. T max is approximately 34 h. Bioavailability is approximately 37%.
Distribution half-life is approximately 1.4 h (IV).
The terminal half-life is approximately 21 h (IV) and approximately 74 h (subcutaneous).
Bioavailability is 54% (subcutaneous).
Treatment of anemia associated with chronic renal failure (CRF), whether or not the patient is on dialysis; treatment of anemia in patients with nonmyeloid malignancies in whom anemia is caused by coadministered chemotherapy.
Treatment of anemia associated with malignancy.
Uncontrolled hypertension; hypersensitivity to the active substance or the excipients.
IV/Subcutaneous 0.45 mcg/kg as a single dose once weekly. Alternatively, in patients not receiving dialysis, start with 0.75 mcg/kg as a single subcutaneous injection once every 2 weeks. Individualize the dose to maintain Hgb levels within the range of 10 to 12 g/dL.Cancer Patients Receiving ChemotherapyAdults
Subcutaneous The recommended starting dose for once-weekly administration is 2.25 mcg/kg. The recommended starting dose for administration once every 3 wk is 500 mcg. Therapy should not be initiated at Hgb levels of 10 g/dL or more. For both dosing schedules, the dose should be adjusted for each patient to maintain the lowest Hgb level sufficient to avoid RBC transfusion. If the rate of Hgb increase is more than 1 g/dL per 2-wk period, or when the Hgb reaches a level needed to avoid transfusion, the dose should be reduced by 40% of the previous dose. If the Hgb exceeds a level needed to avoid transfusion, temporarily hold treatment until the Hgb approaches a level where transfusions may be required. At this point, reinstate therapy at a dose 40% below the previous dose. For patients receiving weekly administration, if there is less than a 1 g/dL increase in Hgb after 6 wk of therapy, the dose should be increased to 4.5 mcg/kg. Discontinue treatment if, after 8 wk of therapy, there is no response as measured by Hgb levels or if transfusions are still required. Discontinue the drug following completion of a chemotherapy course.Dosage Adjustment
Do not increase dose of darbepoetin alfa more frequently than once a month. If the Hgb is increasing and approaching 12 g/dL, reduce dose by approximately 25%. If Hgb continues to increase, withhold doses temporarily until Hgb begins to decrease, then reinstate dose by approximately 25% below the previous dose. If Hgb increases by more than 1 g/dL in a 2-wk period, decrease dose by approximately 25%. If the increase in Hgb is less than 1 g/dL over 4 weeks, the dose may be increased by 25%.Conversion from Epoetin AlfaAdults
IV/Subcutaneous If the epoetin alfa dose is less than 2,500 units/wk, start with darbepoetin alfa 6.25 mcg/wk; if dose is 2,500 to 4,999 units/wk, start with darbepoetin alfa 12.5 mcg/wk; if dose is 5,000 to 10,999 units/wk, start with darbepoetin alfa 25 mcg/wk; if dose is 11,000 to 17,999 units/wk, start with darbepoetin alfa 40 mcg/wk; if dose is 18,000 to 33,999 units/wk, start with darbepoetin alfa 60 mcg/wk; if dose is 34,000 to 89,999 units/wk, start with darbepoetin alfa 100 mcg/wk; if dose is 90,000 units/wk or more, start with darbepoetin alfa 200 mcg/wk.Children
IV/Subcutaneous If the epoetin alfa dose is less than 1,500 units/wk, the available data are insufficient to determine the darbepoetin alfa conversion dose; if dose is 1,500 to 2,499 units/wk, start with darbepoetin alfa 6.25 mcg/wk; if dose is 2,500 to 4,999 units/wk, start with darbepoetin alfa 10 mcg/wk; if dose is 5,000 to 10,999 units/wk, start with darbepoetin alfa 20 mcg/wk; if dose is 11,000 to 17,999 units/wk, start with darbepoetin alfa 40 mcg/wk; if dose is 18,000 to 33,999 units/wk, start with darbepoetin alfa 60 mcg/wk; if dose is 34,000 to 89,999 units/wk, start with darbepoetin alfa 100 mcg/wk; if dose is 90,000 or more units/wk, start with darbepoetin alfa 200 mcg/wk.
Store vials in refrigerator (36° to 46°F). Do not freeze or shake. Protect from light.
None well documented.
None well documented.
Hypertension, hypotension (20%); angina pectoris/cardiac chest pain, cardiac arrhythmias/cardiac arrest (8%); thrombosis, thrombosis vascular access, thrombotic events (6%); CHF (5%); acute MI, stroke (2%); pulmonary embolism (1%).
Fatigue (33%); headache (15%); dizziness (7%); asthenia (5%); seizures, transient ischemic attacks (1%).
Diarrhea, vomiting (14%); nausea (11%); abdominal pain (10%); constipation (5%).
Injection-site pain (6%).
Peripheral edema (10%); fluid overload (6%).
Muscle spasm (17%); arthralgia (9%); limb pain, myalgia (8%); back pain (7%).
Upper respiratory tract infection (15%); dyspnea (10%); cough (9%); bronchitis (5%).
Infection (24%); access hemorrhage, fever (7%); access infection, chest pain, death, influenza-like symptoms (6%).
Erythropoiesis-stimulating agents (ESAs) shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non–small cell lung, head and neck, lymphoid, and cervical cancers. To decrease these risks, as well as the risks of serious CV and thrombovascular events, use the lowest dose needed to avoid RBC transfusion. Use ESAs only for treatment of anemia caused by concomitant myelosuppressive chemotherapy. ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure. Discontinue following the completion of a chemotherapy course.Renal failure
In 2 clinical studies, patients experienced greater risks for death and serious CV events when given ESAs to target higher verses lower Hgb levels (eg, 13.5 vs 11.3 g/dL; 14 vs 10 g/dL).
Monitor BP and presence of premonitory neurologic symptoms closely during the first several months of therapy. Ensure that serum ferritin or transferrin saturation is determined before and during therapy. Determine Hgb weekly until it has stabilized and maintenance dose has been established. After a dose adjustment, 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. During the transition period onto dialysis, monitor Hgb or BP carefully, and determine whether patients need to have their maintenance doses adjusted to maintain Hgb levels within the 10 to 12 g/dL range.
Category C .
Safety and efficacy not established in children younger than 1 yr of age.Cancer
Safety and efficacy not established.
No overall differences in safety and efficacy were observed between patients 65 yr of age and older compared with younger patients.
Anaphylactic reactions, skin rashes, and urticaria may occur.
Darbepoetin formulated with albumin is derived from human blood and carries an extremely remote risk of transmission of viral diseases.
Patients with CRF not yet requiring dialysis may require lower maintenance doses than patients receiving dialysis.
Darbepoetin treatment may reduce dialysis efficiency; it may be necessary to adjust the dialysis prescription in patients who are marginally dialyzed.
Allow sufficient time to determine a patient's responsiveness to a dose before adjusting it.
Ensure that BP is controlled before initiating therapy.
The needle cover of the prefilled syringe contains dry natural rubber.
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 darbepoetin, accompanied by severe anemia and low reticulocyte count, for the etiology of the loss of effect. Withhold darbepoetin if anti-erythropoietin antibody–associated anemia is suspected. Permanently discontinue darbepoetin in patients with antibody-mediated anemia.
Seizures may occur.
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