Pronunciation: DAR-be-POE-e-tin AL-fa
Class: Erythropoiesis-stimulating agent
- Injection, solution 25 mcg per 0.42 mL
- Injection, solution 25 mcg/mL
- Injection, solution 40 mcg per 0.4 mL
- Injection, solution 40 mcg/mL
- Injection, solution 60 mcg per 0.3 mL
- Injection, solution 60 mcg/mL
- Injection, solution 100 mcg per 0.5 mL
- Injection, solution 100 mcg/mL
- Injection, solution 150 mcg per 0.3 mL
- Injection, solution 150 mcg per 0.75 mL
- Injection, solution 200 mcg per 0.4 mL
- Injection, solution 200 mcg/mL
- Injection, solution 300 mcg per 0.6 mL
- Injection, solution 300 mcg/mL
- Injection, solution 500 mcg/mL
Stimulates red blood cell production.
Absorption is slow and rate-limiting, with T max at 48 h (chronic kidney disease patients) and 71 h (cancer patients). 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).
Special PopulationsHepatic Function Impairment
No data available.Children
Bioavailability is 54% (subcutaneous).
Indications and Usage
Treatment of anemia associated with chronic kidney disease, whether or not the patient is on dialysis; treatment of anemia in patients with nonmyeloid malignancies in whom anemia is caused by coadministered chemotherapy, and upon initiation, there is a minimum of 2 additional mo of planned chemotherapy.
Uncontrolled hypertension; pure red cell aplasia (PRCA) that begins after treatment with any erythropoietin protein drugs; hypersensitivity to the active drug or the excipients.
Dosage and AdministrationAnemia Associated With Chronic Kidney Disease on Dialysis
IV/Subcutaneous Initially, 0.45 mcg/kg as a weekly injection or 0.75 mcg/kg once every 2 weeks as appropriate. If the Hgb level approaches or exceeds 11 g/dL, reduce or interrupt the dose. If the Hgb rises rapidly (eg, more than 1 g/dL in any 2-wk period), reduce the dose by 25% or more as needed to reduce rapid responses. For patients who do not respond adequately, if the Hgb has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.Anemia Associated With Chronic Kidney Disease Not on Dialysis
IV/Subcutaneous Initially, 0.45 mcg/kg given once at 4-week intervals as appropriate. If the Hgb level exceeds 10 g/dL, reduce or interrupt the dose. If the Hgb rises rapidly (eg, more than 1 g/dL in any 2-week period), reduce the dose by 25% or more as needed to reduce rapid responses. For patients who do not respond adequately, if the Hgb has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.Amenia Associated With Cancer Chemotherapy
Subcutaneous 2.25 mcg/kg every week or 500 mcg every 3 weeks until completion of a chemotherapy course. 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 darbepoetin alfa if after 8 wk of therapy there is no response as measured by Hgb levels or transfusions are still required. Discontinue darbepoetin alfa following completion of a chemotherapy course.Conversion From Epoetin Alfa
Darbepoetin alfa should be administered once per week if a patient was receiving epoetin alfa 2 to 3 times weekly. Darbepoetin alfa should be administered once every 2 weeks if a patient was receiving epoetin alfa once per week. The same route of administration (IV or subcutaneous) should be maintained.Adults
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.
- Individualize dosing and use the lowest dose sufficient to reduce the need for RBC transfusions.
- Administer IV or subcutaneously. The IV route is recommended for patients on hemodialysis.
- Initiate treatment when the Hgb level is less than 10 g/dL.
- Do not shake or vigorously agitate the vials.
- Do not administer if particulate matter, cloudiness, or discoloration is noted.
- Do not dilute solution or administer in conjunction with other drug solutions.
- The needle cover of the prefilled syringe contains dry natural rubber (a derivative of latex).
- Evaluate the iron status in all patients before and during treatment and maintain iron repletion.
Store between 36° and 46°F. Do not freeze. Do not use darbepoetin alfa that has been frozen. Protect from light. Discard unused portion in vials or prefilled syringes. Do not reenter vial.
None well documented.
Hypertension (31%); procedural hypotension (10%); angina pectoris, thromboembolic adverse reactions, vascular access complaints (8%); arteriovenous graft thrombosis, cerebrovascular disorders (5%); MI (2%).
Peripheral edema (17%); edema (13%); fluid overload (7%); pulmonary embolism (2%).
Dyspnea (17%); cough (12%).
Abdominal pain (13%); rash/erythema (5%); convulsions; injection-site pain; PRCA, serious allergic reactions (postmarketing).
Erythropoiesis-stimulating agents (ESAs) increase the risk of death, MI, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence. Use the lowest darbepoetin alfa dose 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 in patients with breast, non–small cell lung, head and neck, lymphoid, and cervical cancers. Health care providers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense darbepoetin alfa to patients with cancer. To enroll in the ESA APPRISE Oncology Program, visit http://www.esa-apprise.com or call 1-866-284-8089 for further assistance. Use ESAs only for treatment of anemia caused by 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.Chronic kidney disease
In clinical trials, patients experienced greater risks for death, serious adverse CV reactions, and stroke when administered ESAs to target a Hgb level of more than 11 g/dL. No trial has identified a Hgb target level, darbepoetin alfa dose, or dosing strategy that does not increase these risks.
After initiation of therapy and after each dose adjustment, determine the Hgb weekly until it is stable and sufficient to minimize the need for RBC transfusion. Thereafter, Hgb may be monitored less frequently provided Hgb levels remain stable. Evaluate transferrin saturation and serum ferritin before and during therapy. Monitor BP and presence of premonitory neurologic symptoms closely during the first several months of therapy.
Category C .
Safety and efficacy not established.Chronic kidney disease
Safety and efficacy not established in children younger than 1 y.
Anaphylactic reactions, angioedema, bronchospasm, skin rashes, and urticaria may occur.
May require adjustment after initiation of therapy.
Ensure that BP is controlled before initiating therapy.
The needle cover of the prefilled syringe contains dry natural rubber.
Pure red cell aplasia
PRCA and severe anemia, with or without other cytopenias, that arise following the development of neutralizing antibodies to erythropoietin have been reported, especially in patients with chronic kidney disease. If severe anemia and low reticulocyte count develop during treatment with darbepoetin alfa, withhold darbepoetin alfa and evaluate patients for neutralizing antibodies to erythropoietin. Permanently discontinue darbepoetin alfa in patients with anemia who develop PRCA following treatment. Do not switch patients to other ESAs.
Seizures may occur.
Polycythemia, severe hypertension.
- Advise patients to read the Medication Guide before starting therapy and with each refill.
- 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.
- Inform patients of the increased risks of mortality, serious CV reactions, thromboembolic reactions, stroke, and tumor progression.
- Inform patient to undergo regular BP monitoring, adhere to prescribed antihypertensive regimen, and follow recommended dietary restrictions.
- Inform patients to contact their health care provider for new-onset neurologic symptoms or change in seizure frequency.
- Inform patients of the need to have regular laboratory tests for Hgb.
- Inform patients that the needle cover on the prefilled syringe contains dry natural rubber (a derivative of latex), which should not be handled by persons allergic to latex.
- Advise dialysis patients to continue to follow dietary and dialysis prescriptions while taking this medication.
- Advise patients to notify their 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 the feet or ankles.
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