Darbepoetin Alfa

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

Pharmacology

Stimulates red blood cell production.

Pharmacokinetics

Absorption

Absorption is slow and rate-limiting, with C _max at 48 h. T _max is approximately 34 h. Bioavailability is approximately 37%.

Distribution

Distribution half-life is approximately 1.4 h (IV).

Elimination

The terminal half-life is approximately 21 h (IV) and approximately 74 h (subcutaneous).

Special Populations

Bioavailability is 54% (subcutaneous).

Indications and Usage

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.

Unlabeled Uses

Treatment of anemia associated with malignancy.

Contraindications

Uncontrolled hypertension; hypersensitivity to the active substance or the excipients.

Dosage and Administration

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.

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.

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%.

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.

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.

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 Hgb.

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, 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%).

CNS

Fatigue (33%); headache (15%); dizziness (7%); asthenia (5%); seizures, transient ischemic attacks (1%).

Dermatologic

Pruritus (6%).

GI

Diarrhea, vomiting (14%); nausea (11%); abdominal pain (10%); constipation (5%).

Local

Injection-site pain (6%).

Metabolic-Nutritional

Peripheral edema (10%); fluid overload (6%).

Musculoskeletal

Muscle spasm (17%); arthralgia (9%); limb pain, myalgia (8%); back pain (7%).

Respiratory

Upper respiratory tract infection (15%); dyspnea (10%); cough (9%); bronchitis (5%).

Miscellaneous

Infection (24%); access hemorrhage, fever (7%); access infection, chest pain, death, influenza-like symptoms (6%).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established in children younger than 1 yr of age.

Safety and efficacy not established.

Elderly

No overall differences in safety and efficacy were observed between patients 65 yr of age and older compared with younger patients.

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.

CRF patients not requiring dialysis

Patients with CRF not yet requiring dialysis may require lower maintenance doses than patients receiving dialysis.

Dialysis management

Darbepoetin treatment may reduce dialysis efficiency; it may be necessary to adjust the dialysis prescription in patients who are marginally dialyzed.

Hematology

Allow sufficient time to determine a patient's responsiveness to a dose before adjusting it.

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 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

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 how to dispose of used equipment and supplies.
• Remind patient that injection is administered once weekly.
• Advise patient that dose will be adjusted based upon measured Hgb level.
• Advise patient to continue to follow dietary and dialysis prescriptions while taking this medication.
• Advise patient to notify health care provider immediately if any of the following occur: hives; intolerable GI effects (eg, diarrhea, nausea, vomiting); palpitations; rash; severe headache; shortness of breath; signs of infection (eg, chills, fever); swelling of the eyes, mouth, or throat; swelling of feet or ankles.

Copyright © 2009 Wolters Kluwer Health.