(dar be POE e tin AL fa)
- Darbepoetin Alfa Polysorbate
- Erythropoiesis-Stimulating Agent (ESA)
- Erythropoiesis-Stimulating Protein
- Novel Erythropoiesis-Stimulating Protein
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection [preservative free]:
Aranesp (Albumin Free): 10 mcg/0.4 mL (0.4 mL); 25 mcg/mL (1 mL); 40 mcg/mL (1 mL); 60 mcg/mL (1 mL); 100 mcg/mL (1 mL); 150 mcg/0.75 mL (0.75 mL [DSC]); 200 mcg/mL (1 mL); 300 mcg/mL (1 mL) [albumin free; contains mouse protein (murine) (hamster), polysorbate 80]
Solution Prefilled Syringe, Injection [preservative free]:
Aranesp (Albumin Free): 25 mcg/0.42 mL (0.42 mL); 40 mcg/0.4 mL (0.4 mL); 60 mcg/0.3 mL (0.3 mL); 100 mcg/0.5 mL (0.5 mL); 150 mcg/0.3 mL (0.3 mL); 200 mcg/0.4 mL (0.4 mL); 300 mcg/0.6 mL (0.6 mL); 500 mcg/mL (1 mL) [albumin free; contains mouse protein (murine) (hamster), polysorbate 80]
Brand Names: U.S.
- Aranesp (Albumin Free)
- Colony Stimulating Factor
- Erythropoiesis-Stimulating Agent (ESA)
- Hematopoietic Agent
Induces erythropoiesis by stimulating the division and differentiation of committed erythroid progenitor cells; induces the release of reticulocytes from the bone marrow into the bloodstream, where they mature to erythrocytes. There is a dose-response relationship with this effect. This results in an increase in reticulocyte counts followed by a rise in hematocrit and hemoglobin levels. When administered SubQ or IV, darbepoetin alfa's half-life is ~3 times that of epoetin alfa concentrations.
Vd: 0.06 L/kg
Onset of Action
Increased hemoglobin levels not generally observed until 2 to 6 weeks after initiating treatment
Time to Peak
CKD: Adults: 48 hours (range: 12 to 72 hours; independent of dialysis); Children: 36 hours (range: 10 to 58 hours)
Cancer: Adults: 71 to 90 hours (range: 28 to 123 hours); Children: 71 hours (range: 21 to 143 hours)
Note: Darbepoetin alfa half-life is approximately 3-fold longer than epoetin alfa following IV administration
IV: 21 hours
SubQ: Nondialysis patients: 70 hours (range: 35 to 139 hours); Dialysis patients: 46 hours (range: 12 to 89 hours)
Cancer: Adults: SubQ: 74 hours (range: 24 to 144 hours); Children: 49 hours
Special Populations: Children
Bioavailability is 54% (subcutaneous).
Use: Labeled Indications
Anemia: Treatment of anemia due to concurrent myelosuppressive chemotherapy in patients with cancer (nonmyeloid malignancies) receiving chemotherapy (palliative intent) for a planned minimum of 2 additional months of chemotherapy; treatment of anemia due to chronic kidney disease (including patients on dialysis and not on dialysis)
Limitations of use: In clinical trials, darbepoetin alfa has not demonstrated improved quality of life, fatigue, or well-being. Darbepoetin alfa is not indicated for use under the following conditions:
- Cancer patients receiving hormonal therapy, therapeutic biologic products, or radiation therapy unless also receiving concurrent myelosuppressive chemotherapy
- Cancer patients receiving myelosuppressive chemotherapy when the expected outcome is curative
- As a substitute for red blood cell (RBC) transfusion in patients requiring immediate correction of anemia
Treatment of symptomatic anemia in myelodysplastic syndrome (MDS)
Serious allergic reaction to darbepoetin alfa or any component of the formulation; uncontrolled hypertension; pure red cell aplasia (PRCA) that begins after treatment with darbepoetin alfa or other erythropoietin protein drugs
Note: Evaluate iron status in all patients before and during treatment and maintain iron repletion.
Anemia associated with chronic kidney disease (CKD): Individualize dosing and use the lowest dose necessary to reduce the need for red blood cell (RBC) transfusions.
Chronic kidney disease patients ON dialysis (IV route is preferred for hemodialysis patients; initiate treatment when hemoglobin is <10 g/dL; reduce dose or interrupt treatment if hemoglobin approaches or exceeds 11 g/dL [adult patients] or 12 g/dL [pediatric patients]):
Pediatrics: IV, SubQ: Initial: 0.45 mcg/kg once weekly or conversion from epoetin alfa: Epoetin alfa doses of 1,500 to ≥90,000 units per week may be converted to darbepoetin alfa doses ranging from 6.25 to 200 mcg per week (see pediatric column in conversion table below).
Adults: IV, SubQ: Initial: 0.45 mcg/kg once weekly or 0.75 mcg/kg once every 2 weeks or conversion from epoetin alfa: Epoetin alfa doses of <1,500 to ≥90,000 units per week may be converted to darbepoetin alfa doses ranging from 6.25 to 200 mcg per week (see adult column in conversion table below).
Chronic kidney disease patients NOT on dialysis (consider initiating treatment when hemoglobin is <10 g/dL; use only if rate of hemoglobin decline would likely result in RBC transfusion and desire is to reduce risk of alloimmunization or other RBC transfusion-related risks; reduce dose or interrupt treatment if hemoglobin exceeds 10 g/dL [adult patients] or 12 g/dL [pediatric patients]):
Pediatrics: IV, SubQ: Initial: 0.45 mcg/kg once weekly or 0.75 mcg/kg once every 2 weeks
Adults: IV, SubQ: Initial: 0.45 mcg/kg once every 4 weeks
Dosage adjustments for chronic kidney disease patients (either on dialysis or not on dialysis): Do not increase dose more frequently than every 4 weeks (dose decreases may occur more frequently).
If hemoglobin increases >1 g/dL in any 2-week period: Decrease dose by ≥25%
If hemoglobin does not increase by >1 g/dL after 4 weeks: Increase dose by 25%
Inadequate or lack of response: If adequate response is not achieved over 12 weeks, further increases are unlikely to be of benefit and may increase the risk for adverse events; use the minimum effective dose that will maintain a hemoglobin level sufficient to avoid RBC transfusions and evaluate patient for other causes of anemia; discontinue treatment if responsiveness does not improve
Anemia due to chemotherapy in cancer patients: Initiate treatment only if hemoglobin <10 g/dL and anticipated duration of myelosuppressive chemotherapy is at least 2 additional months. Titrate dosage to use the minimum effective dose that will maintain a hemoglobin level sufficient to avoid RBC transfusions. Discontinue darbepoetin alfa following completion of chemotherapy.
Adults: SubQ: Initial: 2.25 mcg/kg once weekly or 500 mcg once every 3 weeks until completion of chemotherapy
Increase dose: If hemoglobin does not increase by 1 g/dL and remains below 10 g/dL after initial 6 weeks (for patients receiving weekly therapy only), increase dose to 4.5 mcg/kg once weekly (no dosage adjustment if using every-3-week dosing).
Reduce dose by 40% if hemoglobin increases >1 g/dL in any 2-week period or hemoglobin reaches a level sufficient to avoid RBC transfusion.
Withhold dose if hemoglobin exceeds a level needed to avoid RBC transfusion. Resume treatment with a 40% dose reduction when hemoglobin approaches a level where transfusions may be required.
Discontinue: On completion of chemotherapy or if after 8 weeks of therapy there is no hemoglobin response or RBC transfusions still required
Symptomatic anemia associated with myelodysplastic syndromes (off-label use): Adults: SubQ: 150 to 300 mcg once weekly (Giraldo 2006; Stasi 2005) or 500 mcg once every 2 to 3 weeks (Gabrilove 2008)
Conversion from epoetin alfa to darbepoetin alfa in chronic kidney disease (CKD) (on dialysis): See table.
Previous Dosage of Epoetin Alfa
Darbepoetin Alfa Dosage
Darbepoetin Alfa Dosage
Note: In patients receiving epoetin alfa 2 to 3 times per week, darbepoetin alfa is administered once weekly. In patients receiving epoetin alfa once weekly, darbepoetin alfa is administered once every 2 weeks. The darbepoetin alfa dose to be administered every 2 weeks is derived by adding together 2 weekly epoetin alfa doses and then converting to the appropriate darbepoetin alfa dose. Titrate dose to hemoglobin response thereafter. The dose conversion in this table does not accurately estimate the once-monthly dose in chronic kidney disease (CKD) patients not on dialysis.
1,500 to 2,499
2,500 to 4,999
5,000 to 10,999
11,000 to 17,999
18,000 to 33,999
34,000 to 89,999
Table has been converted to the following text.
Conversion From Epoetin Alfa to Darbepoetin Alfa in Chronic Kidney Disease (Estimated Initial Dose)
Note: In patients receiving epoetin alfa 2 to 3 times/week, darbepoetin alfa is administered once weekly. In patients receiving epoetin alfa once weekly, darbepoetin alfa should be administered once every 2 weeks. The darbepoetin alfa dose to be administered every 2 weeks is derived by adding together 2 weekly epoetin alfa doses and then converting to the appropriate darbepoetin alfa dose. Titrate dose to hemoglobin response thereafter. The dose conversion in this table does not accurately estimate the once-monthly dose in chronic kidney disease (CKD) patients not on dialysis.
Previous dosage of epoetin alfa:
• <1500 units/week, then darbepoetin alfa:
Children: Not established
Adults: 6.25 mcg/weekly
• 1,500 to 2,499 units/week, then darbepoetin alfa:
Children: 6.25 mcg/weekly
Adults: 6.25 mcg/weekly
• 2,500 to 4,999 units/week, then darbepoetin alfa:
Children: 10 mcg/weekly
Adults: 12.5 mcg/weekly
• 5,000 to 10,999 units/week, then darbepoetin alfa:
Children: 20 mcg/weekly
Adults: 25 mcg/weekly
• 11,000 to 17,999 units/week, then darbepoetin alfa:
Children: 40 mcg/weekly
Adults: 40 mcg/weekly
• 18,000 to 33,999 units/week, then darbepoetin alfa:
Children: 60 mcg/weekly
Adults: 60 mcg/weekly
• 34,000 to 89,999 units/week, then darbepoetin alfa:
Children: 100 mcg/weekly
Adults: 100 mcg/weekly
• ≥90,000 units/week, then darbepoetin alfa:
Children: 200 mcg/weekly
Adults: 200 mcg/weekly
Dosage adjustment in renal impairment: No dosage adjustment necessary.
Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling.
May be administered by SubQ or IV injection. The IV route is recommended in hemodialysis patients. Do not shake; vigorous shaking may denature darbepoetin alfa, rendering it biologically inactive. Do not dilute or administer in conjunction with other drug solutions. Discard any unused portion of the vial; do not pool unused portions.
Supplemental iron intake may be required in patients with low iron stores.
Do not dilute or administer with other solutions.
Store at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Protect from light. Store in original carton until use. The following stability information has also been reported: May be stored at room temperature for up to 7 days (Cohen 2007).
Lenalidomide: Erythropoiesis-Stimulating Agents may enhance the thrombogenic effect of Lenalidomide. Monitor therapy
Nandrolone: May enhance the stimulatory effect of Erythropoiesis-Stimulating Agents. Specifically, nandrolone may enhance the erythropoiesis stimulatory effect of Erythropoiesis-Stimulating Agents. Monitor therapy
Thalidomide: Erythropoiesis-Stimulating Agents may enhance the thrombogenic effect of Thalidomide. Monitor therapy
Cardiovascular: Hypertension (31%), peripheral edema (17%), edema (6% to 13%)
Gastrointestinal: Abdominal pain (10% to 13%)
Respiratory: Dyspnea (17%), cough (12%)
1% to 10%:
Cardiovascular: Angina pectoris, hypotension, myocardial infarction, pulmonary embolism, thromboembolism, thrombosis of vascular graft (arteriovenous), vascular injury (vascular access complications)
Central nervous system: Cerebrovascular disease
Dermatologic: Erythema, skin rash
Endocrine & metabolic: Hypervolemia
<1% (Limited to important or life-threatening): Anaphylaxis, anemia (associated with neutralizing antibodies; severe; with or without other cytopenias), angioedema, bronchospasm, cerebrovascular accident, hypersensitivity reaction, hypertensive encephalopathy, pure red cell aplasia, seizure, tumor growth (progression/recurrence; cancer patients), urticaria
Concerns related to adverse effects:
• Cardiovascular events: [US Boxed Warning]: Erythropoiesis-stimulating agents (ESAs) increased the risk of serious cardiovascular events, myocardial infarction, stroke, venous thromboembolism, vascular access thrombosis, and mortality in clinical studies when administered to target hemoglobin levels >11 g/dL (and provide no additional benefit); a rapid rise in hemoglobin (>1 g/dL over 2 weeks) may also contribute to these risks.
• Hypersensitivity: Potentially serious allergic reactions have been reported (rarely), including anaphylactic reactions, angioedema, bronchospasm, rash, and urticaria. Discontinue immediately (and permanently) in patients who experience serious allergic/anaphylactic reactions.
• Pure red cell aplasia (PRCA): Cases of severe anemia and PRCA (with or without other cytopenias) have been reported, predominantly in patients with chronic kidney disease receiving SubQ darbepoetin alfa (the intravenous [IV] route is preferred for hemodialysis patients). Cases have also been reported in patients with hepatitis C who were receiving ESAs, interferon, and ribavirin. Patients with a sudden loss of response to darbepoetin alfa (with severe anemia and a low reticulocyte count) should be evaluated for PRCA with associated neutralizing antibodies to erythropoietin; discontinue treatment (permanently) in patients with PRCA secondary to neutralizing antibodies to erythropoietin. Antibodies may cross-react; do not switch to another ESA in patients who develop antibody-mediated anemia.
• Cancer patients: [US Boxed Warning]: A shortened overall survival and/or increased risk of time to tumor progression or recurrence has been reported in studies with breast, cervical, head and neck, lymphoid, and non–small cell lung cancer patients. It is of note that in these studies, patients received ESAs to a target hemoglobin of ≥12 g/dL; although risk has not been excluded when dosed to achieve a target hemoglobin of <12 g/dL. [US Boxed Warnings]: To decrease these risks, and risk of cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions. Use ESAs in cancer patients only for the treatment of anemia related to concurrent myelosuppressive chemotherapy; discontinue ESA following completion of the chemotherapy course. ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is curative. A dosage modification is appropriate if hemoglobin levels rise >1 g/dL per 2-week time period during treatment (Rizzo 2010). Use of ESAs has been associated with an increased risk of venous thromboembolism (VTE) without a reduction in transfusions in patients >65 years of age with cancer (Hershman 2009). Improved anemia symptoms, quality of life, fatigue, or well-being have not been demonstrated in controlled clinical trials.
• Chronic kidney disease patients: [US Boxed Warning]: An increased risk of death, serious cardiovascular events, and stroke was reported in chronic kidney disease patients administered ESAs to target hemoglobin levels ≥11 g/dL; use the lowest dose sufficient to reduce the need for RBC transfusions. An optimal target hemoglobin level, dose, or dosing strategy to reduce these risks has not been identified in clinical trials. Hemoglobin rising >1 g/dL in a 2-week period may contribute to the risk (dosage reduction recommended). Chronic kidney disease patients who exhibit an inadequate hemoglobin response to ESA therapy may be at a higher risk for cardiovascular events and mortality compared to other patients. ESA therapy may reduce dialysis efficacy (due to increase in red blood cells and decrease in plasma volume); adjustments in dialysis parameters may be needed. Chronic kidney disease patients not requiring dialysis may have a better response to darbepoetin alfa and may require lower doses. Patients treated with ESAs may require increased heparinization during dialysis to prevent clotting of the extracorporeal circuit.
• Hypertension: Use with caution in patients with a history of hypertension; use is contraindicated in patients with uncontrolled hypertension. An excessive rate of rise of hemoglobin may be associated with exacerbation of hypertension; decrease the darbepoetin alfa dose if the hemoglobin increase exceeds 1 g/dL in any 2-week period. Blood pressure should be controlled prior to start of therapy and monitored closely throughout treatment. Hypertensive encephalopathy has been reported with patients receiving erythropoietic therapy.
• Perisurgical patients: Increased mortality was observed in patients undergoing coronary artery bypass surgery who received epoetin; these deaths were associated with thrombotic events. An increased risk of deep vein thrombosis has been observed in patients treated with epoetin undergoing surgical orthopedic procedures. Darbepoetin alfa is not approved for reduction in allogeneic red blood cell transfusions in patients scheduled for surgical procedures.
• Seizures: The risk for seizures is increased with darbepoetin alfa use in patients with chronic kidney disease; use with caution in patients with a history of seizures. Monitor closely for neurologic symptoms during the first several months of therapy.
• Severe anemia or acute blood loss: Due to the delayed onset of erythropoiesis, darbepoetin alfa is not recommended for acute correction of severe anemia or as a substitute for emergency transfusion.
Dosage form specific issues:
• Latex: The packaging of some formulations may contain latex.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.
• Appropriate use:
- Oncology: The American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH) 2010 updates to the clinical practice guidelines for the use of ESAs in patients with cancer indicate that ESAs are appropriate when used according to the parameters identified within the Food and Drug Administration (FDA)–approved labeling for epoetin and darbepoetin alfa (Rizzo 2010). ESAs are an option for chemotherapy-associated anemia when the hemoglobin has fallen to <10 g/dL to decrease the need for red blood cell transfusions. ESAs should only be used in conjunction with concurrent chemotherapy. Although the FDA label now limits ESA use to the palliative setting, the ASCO/ASH guidelines suggest using clinical judgment in weighing risks versus benefits as formal outcomes studies of ESA use defined by intent of chemotherapy treatment have not been conducted.
- Cardiovascular disease: The American College of Physicians recommends against the use of ESAs in patients with mild to moderate anemia and heart failure or coronary heart disease (ACP [Qaseem 2013]). The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013 Heart Failure Guidelines do not provide a clear recommendation on the use of ESAs in anemic heart failure patients. The effects of ESAs on quality of life measures, morbidity, and mortality are potentially modest and still unclear. The authors declined to provide an official recommendation regarding the use of ESAs pending the completion of ongoing randomized trials (ACCF/AHA [Yancy 2013]).
• Factors impairing erythropoiesis: Prior to treatment, correct or exclude deficiencies of iron, vitamin B12, and/or folate, as well as other factors that may impair erythropoiesis (inflammatory conditions, infections, bleeding). Poor response to therapy should prompt evaluation of potential factors impairing erythropoiesis, as well as possible malignant processes and hematologic disease (thalassemia, refractory anemia, myelodysplastic disorder), occult blood loss, hemolysis, osteitis fibrosa cystic, and/or bone marrow fibrosis.
• Iron supplementation: Prior to and during therapy, iron stores must be evaluated. Supplemental iron is recommended if serum ferritin <100 mcg/L or serum transferrin saturation <20%. Most patients with chronic kidney disease will require iron supplementation.
• REMS program: [US Boxed Warning]: Because of the risks of decreased survival and increased risk of tumor growth or progression, health care providers and hospitals must enroll and comply with the ESA APPRISE Oncology Program to prescribe or dispense ESAs to cancer patients. Prescribers and patients will have to provide written documentation of discussed risks prior to each new course.
Hemoglobin (at least once per week until maintenance dose established and after dosage changes; monitor less frequently once hemoglobin is stabilized); CKD patients should be also be monitored at least monthly following hemoglobin stability); iron stores (transferrin saturation and ferritin) prior to and during therapy; serum chemistry (CKD patients); blood pressure; fluid balance (CKD patients); seizures (CKD patients following initiation for first few months, includes new-onset or change in seizure frequency or premonitory symptoms)
Cancer patients: Examinations recommended by the ASCO/ASH guidelines (Rizzo 2010) prior to treatment include peripheral blood smear (in some situations a bone marrow exam may be necessary), assessment for iron, folate, or vitamin B12 deficiency, reticulocyte count, renal function status, and occult blood loss; during ESA treatment, assess baseline and periodic iron, total iron-binding capacity, and transferrin saturation or ferritin levels.
Pregnancy Risk Factor
Adverse events were observed in animal reproduction studies. Women who become pregnant during treatment with darbepoetin alfa are encouraged to enroll in Amgen’s Pregnancy Surveillance Program (800-772-6436).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience injection site irritation, cough, or abdominal pain. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), tachycardia, angina, arrhythmia, shortness of breath, excessive weight gain, swelling of arm or leg, severe dizziness, passing out, seizures, severe headache, loss of strength and energy, pale skin, coughing up blood, change in balance, or abnormal gait (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about darbepoetin alfa
- Other brands: Aranesp