Darbepoetin Alfa
Pronouncation: (dar-be-POE-e-tin AL-fa)
Class: Recombinant human erythropoietin
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
Mechanism of Action
Pharmacology
Stimulates red blood cell production.
Pharmacokinetics
Absorption
Subcutaneous
Absorption is slow and rate-limiting. T max is approximately 34 h. Bioavailability is approximately 37%.
Distribution
Distribution t ½ is approximately 1.4 h (IV).
Elimination
The t ½ is approximately 21 h (IV) and approximately 49 h (subcutaneous).
Special Populations
Children
Bioavailability is 54% (subcutaneous).
Indications and Usage
Treatment of anemia associated with chronic renal failure, whether or not the patient is on dialysis; treatment of anemia in patients with nonmyeloid malignancies in whom anemia is caused by coadministered chemotherapy.
Contraindications
Uncontrolled hypertension; hypersensitivity to the active substance or the excipients.
Dosage and Administration
Anemia Associated With Chronic Renal Failure
Adults
IV/Subcutaneous Initial dose: 0.45 mcg/kg once weekly. Maintenance: Individually titrate to a target hemoglobin not to exceed 12 g/dL.
Dosage Adjustment
Do not increase dose of darbepoetin alfa more frequently than once a month. If the hemoglobin is increasing and approaching 12 g/dL, reduce dose approximately 25%. If hemoglobin continues to increase, withhold doses temporarily until hemoglobin begins to decrease, then reinstate dose approximately 25% below the previous dose. If hemoglobin increases by more than 1 g/dL in a 2-wk period, decrease dose approximately 25%. If the increase in hemoglobin is less than 1 g/dL over 4 weeks, the dose may be increased by 25%.
Conversion from Epoetin Alfa
Adults
IV/Subcutaneous If 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 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.
Cancer Patients Receiving Chemotherapy
Adults
Subcutaneous Initial dose: 2.25 mcg/kg/wk. Maintenance: Individually titrate to achieve a target hemoglobin. If there is less than a 1 g/dL increase in hemoglobin after 6 wk of therapy, increase the dose up to 4.5 mcg/kg. If hemoglobin increases more than 1 g/dL in a 2-wk period or if the hemoglobin exceeds 11 g/dL, reduce the dose approximately 40%. If the hemoglobin exceeds 12 g/dL, temporarily withhold doses until the hemoglobin falls to 11 g/dL. Reinitiate therapy at a dose approximately 40% below the previous dose.
General Advice
- Do not shake or vigorously agitate to prevent inactivation of medication.
- Do not administer if particulate matter, cloudiness, or discoloration is noted.
- Do not dilute solution.
- Discard any unused portion. Do not combine unused portions.
- Do not administer in conjunction with other drug solutions.
- Prescribed dose is administered once weekly.
- Rotate subcutaneous injection sites.
- An interval of 2 to 6 wk may occur between time of dose adjustment and a change in hemoglobin.
Storage/Stability
Store vials in refrigerator (36° to 46°F). Do not freeze or shake. Protect from light.
Drug Interactions
None well documented.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Hypertension (23%); hypotension (22%); cardiac arrhythmias/cardiac arrest (10%); angina pectoris/cardiac chest pain, thrombosis vascular access (8%); CHF, thrombosis (6%); acute MI (2%); pulmonary embolism, stroke, transient ischemic attack (1%).
CNS
Fatigue (33%); headache (16%); dizziness (14%); asthenia (5%); seizure (1%).
Dermatologic
Pruritus (8%); rash (7%).
GI
Diarrhea (22%); constipation (18%); vomiting (15%); nausea (14%); abdominal pain (12%).
Local
Injection-site pain (7%).
Metabolic-Nutritional
Fluid overload (6%); dehydration (5%).
Musculoskeletal
Myalgia (21%); arthralgia (13%); limb pain (10%); back pain (8%).
Respiratory
Upper respiratory tract infection (14%); dyspnea (12%); cough (10%); bronchitis (6%).
Miscellaneous
Infection (27%); edema (21%); fever (19%); peripheral edema (11%); death (7%), access hemorrhage, access infection, chest pain, influenza-like symptoms (6%).
Precautions
Warnings
Use the lowest dose of darbepoetin alfa that will gradually increase hemoglobin concentrations to the lowest level sufficient to avoid the need for RBC transfusion. Darbepoetin alfa increased the risk for death and serious CV events when administered to target a hemoglobin 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 a hemoglobin of greater than 12 g/dL, shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a hemoglobin of greater than 12 g/dL, and increased the risk of death when administered to target a hemoglobin 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 for reduction of RBC transfusions, a higher incidence of deep vein thrombosis occurred in patients receiving epoetin alfa who were not receiving prophylactic anticoagulation. Darbepoetin alfa is not approved for this indication.
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Monitor
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 hemoglobin weekly until it has stabilized and maintenance dose has been established. After a dose adjustment, determine hemoglobin weekly for at least 4 wk, until it has been determined that hemoglobin has stabilized in response to the dose change. Then, monitor at regular intervals.
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Pregnancy
Category C .
Lactation
Undetermined.
Children
Chronic renal failure: Safety and efficacy not established in children younger than 1 yr of age. Cancer: Safety and efficacy not established.
Hypersensitivity
Anaphylactic reactions, skin rashes, and urticaria may occur.
Albumin
Darbepoetin formulated with albumin is derived from human blood and carries an extremely remote risk of transmission of viral diseases.
Dialysis management
Darbepoetin treatment may reduce dialysis efficiency; it may be necessary to adjust the dialysis prescription in patients who are marginally dialyzed.
Hypertension
Ensure that BP is controlled before initiating therapy.
Latex allergy
The needle cover of the prefilled syringe contains dry natural rubber.
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 chronic renal failure. Any patient developing a loss of response to darbepoetin, accompanied by severe anemia and low reticulocyte count, should be evaluated for the etiology of the loss of effect. Withhold darbepoetin if anti-erythropoietin-associated anemia is suspected. Permanently discontinue darbepoetin in patients with antibody-mediated anemia.
Seizures
Seizures may occur.
Overdosage
Symptoms
Polycythemia.
Patient Information
- If patient or caregiver will be administering at home, review patient information leaflet with the patient or caregiver. Ensure that the patient or caregiver understands how to store, prepare, and administer the dose, and dispose of used equipment and supplies.
- Remind patient that injection is administered once a wk.
- Advise patient that dose will be adjusted based upon measured hemoglobin level.
- Advise patient to continue to follow dietary and dialysis prescriptions while taking this medication.
- Advise patient to notify the health care provider immediately if any of the following occur: hives; intolerable GI effects (eg, nausea, vomiting, diarrhea); palpitations; rash; severe headache; shortness of breath; signs of infection (eg, fever, chills); swelling of the eyes, mouth, or throat; swelling of feet or ankles.
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