Version May 2024
Erythropoiesis-stimulating agents (ESAs) increase the risk of death, myocardial infarction (MI), stroke, venous thromboembolism, thrombosis of vascular access.
In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a hemoglobin level of more than 11 g/dL.
No trial has identified a hemoglobin target level, darbepoetin alfa dose, or dosing strategy that does not increase these risks.
Use the lowest darbepoetin alfa dose sufficient to reduce the need for red blood cell (RBC) transfusions.
ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.
To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic reactions, use the lowest dose needed to avoid RBC transfusion.
Use ESAs only for treatment of anemia from myelosuppressive chemotherapy.
ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
Discontinue following the completion of a chemotherapy course.
Note: Dose rounding: Doses are often rounded to the nearest unit dose (eg, a vial or combination of vials). Iron supplementation: Ensure adequate iron stores prior to initiating and throughout therapy. The manufacturer recommends supplemental iron be administered if serum ferritin is <100 ng/mL or serum transferrin saturation is <20%; however, the threshold for iron replacement should be individualized based on clinical considerations (eg, trends in hemoglobin level, darbepoetin alfa dose, goals of therapy) and may vary by indication. Most patients with chronic kidney disease will require iron supplementation (Ref).
Anemia due to chemotherapy in patients with cancer: 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.
SUBQ: Initial: 2.25 mcg/kg once weekly or 500 mcg once every 3 weeks until completion of a chemotherapy course.
Dosage adjustments:
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.
Anemia due to chronic kidney disease:
Initial dose:
Patients not currently taking an erythropoiesis-stimulating agent:
Note: Generally initiated when Hb is <10 g/dL; however, the decision to initiate therapy must be individualized based on patient-specific factors (eg, rate of Hb decline, risks of repeat RBC transfusion, symptom severity) (Ref). Individualize initial dose within ranges shown below according to baseline Hb concentration and risk of adverse effects (eg, cardiovascular) (Ref). An optimal initial dosing algorithm has not been established; refer to institutional protocols.
Patients with chronic kidney disease ON dialysis:
IV, SUBQ: 0.45 mcg/kg once weekly or 0.75 mcg/kg once every 2 weeks.
Patients with chronic kidney disease NOT on dialysis:
IV, SUBQ (preferred route): 0.45 mcg/kg once every 2 to 4 weeks (Ref).
Patients converting from epoetin alfa:
Note: The following table may be used to convert the current total weekly epoetin alfa dose to darbepoetin alfa. The dose conversion in the following table does not accurately estimate once-monthly doses of darbepoetin alfa in patients with chronic kidney disease not on dialysis.
|
Total weekly epoetin alfa dose |
Initial darbepoetin alfa doseb | |
|---|---|---|
|
Epoetin alfa currently dosed 2 to 3 times per weeka |
Epoetin alfa currently dosed once weekly | |
|
a In patients receiving epoetin alfa 2 to 3 times per week, use the total weekly dose of epoetin alfa for conversion. | ||
|
b In patients receiving epoetin alfa 2 to 3 times per week, administer the equivalent initial darbepoetin alfa dosage once weekly. In patients receiving epoetin alfa once weekly, administer the equivalent initial darbepoetin alfa dose every 2 weeks. | ||
|
≤2,499 units/week |
≤1,249 units/week |
6.25 mcg per dose |
|
2,500 to 4,999 units/week |
1,250 to 2,499 units/week |
12.5 mcg per dose |
|
5,000 to 10,999 units/week |
2,500 to 5,499 units/week |
25 mcg per dose |
|
11,000 to 17,999 units/week |
5,500 to 8,999 units/week |
40 mcg per dose |
|
18,000 to 33,999 units/week |
9,000 to 16,999 units/week |
60 mcg per dose |
|
34,000 to 89,999 units/week |
17,000 to 44,999 units/week |
100 mcg per dose |
|
≥90,000 units/week |
≥45,000 units/week |
200 mcg per dose |
Dosage adjustment: Use the lowest maintenance dose necessary to reduce the need for RBC transfusions and manage symptoms (Ref). Target Hb range suggested by Kidney Disease: Improving Global Outcomes (KDIGO) is 10 to 11.5 g/dL, while manufacturer’s labeling recommends a range of 10 to 11 g/dL for patients on dialysis and not exceeding 10 g/dL for patients not on dialysis. Target should be individualized for anticipated benefits and risks (Ref). An optimal dosage adjustment algorithm has not been identified. The following provides general guidance; refer also to institutional protocols.
If Hb does not increase by >1 g/dL after 4 weeks: Increase dose by 25%; do not increase dose more frequently than every 4 weeks.
Note: In patients who have no Hb response after adequate titration phase (generally over 4 to 12 weeks), or who have not met Hb targets despite high doses (eg, 1.5 mcg/kg per week) in the presence of adequate iron stores, reassess for other underlying causes of anemia; further dose increases are unlikely to improve response and may increase cardiovascular risks and mortality (Ref).
If Hb increases >1 g/dL in any 2-week period or >2 g/dL in any 4-week period: Reduce dose by 25% to 50% or hold therapy depending on Hb level and rate of Hb increase (Ref).
If Hb is increasing and approaching the upper target threshold: Reduce dose by 25%; if Hb continues to increase, hold therapy until Hb begins to decrease and then reinitiate at 75% of the previous dose (Ref).
Loss of efficacy (ie, acquired hyporesponsiveness): If an acute Hb decrease occurs in a patient who previously achieved target Hb levels on a stable darbepoetin dose, identify and treat underlying cause for acute Hb decrease prior to adjusting darbepoetin dose. If patient remains hyporesponsive, may cautiously use the minimum dose to avoid RBC transfusions; refer also to institutional protocols (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney impairment (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (large molecular weight): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (large molecular weight): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Darbepoetin alfa: Pediatric drug information")
Note: Dosing schedules need to be individualized and careful monitoring of patients receiving the drug is recommended. Use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.
Anemia associated with chronic kidney disease (CKD), ON dialysis: Note: 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 12 g/dL (if <18 years of age) or 11 g/dL (if ≥18 years of age):
Initial: IV (preferred), SubQ:
Infants, Children, and Adolescents <18 years: 0.45 mcg/kg once weekly
Adolescents ≥18 years: 0.45 mcg/kg once weekly or 0.75 mcg/kg once every 2 weeks
Dosage adjustment: Infants, Children, and Adolescents: IV (preferred), SubQ: 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 red blood cell transfusions and evaluate patient for other causes of anemia; discontinue treatment if responsiveness does not improve.
Anemia associated with chronic kidney disease (CKD), NO dialysis: Note: Initiate 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 12 g/dL (if age <18 years) or 10 g/dL (if age ≥18 years):
Initial: IV, SubQ:
Infants, Children, and Adolescents <18 years: 0.45 mcg/kg once weekly or 0.75 mcg/kg once every 2 weeks
Adolescents ≥18 years: 0.45 mcg/kg once every 4 weeks
Dosage adjustment: Infants, Children, and Adolescents: IV, SubQ: 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 red blood cell transfusions and evaluate patient for other causes of anemia; discontinue treatment if responsiveness does not improve
Conversion from epoetin alfa to darbepoetin alfa: Infants, Children, and Adolescents: Determination of weekly darbepoetin dose is based on the weekly epoetin dose at time of conversion; see the following table.
|
Previous Weekly Epoetin Alfa Dose (units/week) |
Weekly Darbepoetin Alfa Dosage | |
|---|---|---|
|
Age 1 month to <18 years (mcg/week) |
Age ≥ 18 years (mcg/week) | |
|
Note: Due to the longer serum half-life of darbepoetin alfa, when converting from epoetin alfa, administer darbepoetin alfa once weekly if the patient was receiving epoetin alfa 2 to 3 times weekly and administer darbepoetin alfa once every 2 weeks if the patient was receiving epoetin alfa once weekly. | ||
|
<1,500 |
Not established |
6.25 |
|
1,500 to 2,499 |
6.25 |
6.25 |
|
2,500 to 4,999 |
10 |
12.5 |
|
5,000 to 10,999 |
20 |
25 |
|
11,000 to 17,999 |
40 |
40 |
|
18,000 to 33,999 |
60 |
60 |
|
34,000 to 89,999 |
100 |
100 |
|
≥90,000 |
200 |
200 |
Infants, Children, and Adolescents: No dosage adjustment necessary.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions occurred in adults with chronic kidney disease unless otherwise specified.
>10%:
Cardiovascular: Hypertension (31%; children and adolescents: frequency not defined), peripheral edema (17%), edema (cancer patients: 13%)
Gastrointestinal: Abdominal pain (cancer patients: 13%)
Respiratory: Dyspnea (17%), cough (12%)
1% to 10%:
Cardiovascular: Procedural hypotension (10%), angina pectoris (8%), thrombosis (cancer patients: 5%), thrombosis of vascular graft (arteriovenous: 5%), thromboembolism (cancer patients, venous: 4%), pulmonary embolism (cancer patients: 2%), arterial thromboembolism (cancer patients: 1%)
Dermatologic: Erythema of skin (≤5%), skin rash (≤5%)
Endocrine & metabolic: Hypervolemia (7%)
Immunologic: Antibody development (children & adolescents: 4% to 6%, adults: <1%)
Frequency not defined:
Cardiovascular: Myocardial infarction, significant cardiovascular event
Central nervous system: Cerebrovascular disease
Local: Pain at injection site
<1%, postmarketing, and/or case reports: Anaphylaxis, angioedema, bronchospasm, cardiac failure, cerebrovascular accident, erythema multiforme, exfoliation of skin, hypertensive encephalopathy, pure red cell aplasia (occurs following development of antibodies to erythropoietin), seizure, severe dermatological reaction, severe hypersensitivity reaction, skin blister, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
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
Canadian labeling: Additional contraindications (not in the US labeling): Sensitivity to mammalian cell-derived products
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.
• Cutaneous reactions: Erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis have been reported with ESA use; discontinue immediately if a severe cutaneous reaction develops.
• 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 (CKD) receiving SUBQ darbepoetin alfa. Cases have also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (not an approved indication). 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.
Disease-related concerns:
• Cancer: [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 most of 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 RBC 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 ESA treatment (ASCO/ASH [Bohlius 2019]). A randomized, double-blind, placebo-controlled trial in patients with anemia receiving chemotherapy for non-small cell lung cancer demonstrated that treatment with darbepoetin alfa (up to a maximum hemoglobin of 12 g/dL) was noninferior to placebo for both overall survival and progression-free survival; thrombovascular events occurred more frequently in the darbepoetin alfa arm. Use of ESAs has been associated with an increased risk of venous thromboembolism 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: [US Boxed Warning]: An increased risk of death, serious cardiovascular events, and stroke was reported in CKD 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). CKD 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 RBCs and decrease in plasma volume); adjustments in dialysis parameters may be needed. CKD 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.
• Diabetes mellitus: ESAs may artificially lower HbA1c through increased circulation of immature erythrocytes in the peripheral blood stream (Kobayashi 2016; Rasche 2017).
• Heart failure: Avoid use; erythrocyte stimulating agents do not provide clinical benefit and may increase risk of thrombotic events, including stroke (AHA/ACC/HFSA [Heidenreich 2022]; Kang 2016; Swedberg 2013).
• 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: 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 RBC transfusions in patients scheduled for surgical procedures.
• Seizures: The risk for seizures is increased with darbepoetin alfa use in patients with CKD; 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.
Other warnings/precautions:
• Appropriate use:
- Oncology: The American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH) 2019 updates to the clinical practice guidelines for the use of ESAs in adult patients with cancer indicate that ESAs are appropriate when used according to the parameters identified within the FDA-approved labeling for epoetin and darbepoetin alfa (ASCO/ASH [Bohlius 2019]). ESAs are an option for chemotherapy-associated anemia in patients whose cancer treatment is not of curative intent and when the hemoglobin has fallen to <10 g/dL. ESAs should not be used when the intent of cancer chemotherapy is curative. ESAs should only be used in conjunction with concurrent myelosuppressive chemotherapy (except in the case of low-risk myelodysplastic syndromes). For patients with myeloma, non-Hodgkin lymphoma, or chronic lymphocytic leukemia, observe hematologic response to cancer treatment prior to considering an ESA. Consider risks versus benefits when there is an increased risk of thromboembolic complications. The recommended target hemoglobin level is the lowest hemoglobin concentration necessary to avoid or reduce the need for RBC transfusion. ESAs should be discontinued in patients who do not respond (eg, <1 to 2 g/dL increase in hemoglobin or no reduction in RBC transfusions within 6 to 8 weeks [evaluate non-responders for underlying tumor progression, iron deficiency, or other causes of anemia]). Iron replacement may be utilized to improve hemoglobin response or reduce RBC transfusions in patients with and without iron deficiency receiving ESAs.
• 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection [preservative free]:
Aranesp (Albumin Free): 25 mcg/mL (1 mL); 40 mcg/mL (1 mL); 60 mcg/mL (1 mL); 100 mcg/mL (1 mL); 200 mcg/mL (1 mL) [albumin free; contains mouse (murine) and/or hamster protein, polysorbate 80]
Solution Prefilled Syringe, Injection [preservative free]:
Aranesp (Albumin Free): 10 mcg/0.4 mL (0.4 mL); 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 (murine) and/or hamster protein, polysorbate 80]
No
Solution (Aranesp (Albumin Free) Injection)
25 mcg/mL (per mL): $232.20
40 mcg/mL (per mL): $371.52
60 mcg/mL (per mL): $557.28
100 mcg/mL (per mL): $928.80
200 mcg/mL (per mL): $1,857.60
Solution Prefilled Syringe (Aranesp (Albumin Free) Injection)
10 mcg/0.4 mL (per 0.4 mL): $92.88
25 mcg/0.42 mL (per 0.42 mL): $232.20
40 mcg/0.4 mL (per 0.4 mL): $371.52
60 mcg/0.3 ml (per 0.3 mL): $557.28
100 mcg/0.5 mL (per 0.5 mL): $928.80
150 mcg/0.3 ml (per 0.3 mL): $1,393.20
200 mcg/0.4 mL (per 0.4 mL): $1,857.60
300 mcg/0.6 mL (per 0.6 mL): $2,786.40
500 mcg/mL (per mL): $4,644.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Aranesp: 10 mcg/0.4 mL (0.4 mL) [contains mouse (murine) and/or hamster protein, polysorbate 80]
Aranesp: 20 mcg/0.5 mL (0.5 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Injection:
Aranesp: 30 mcg/0.3 mL (0.3 mL); 40 mcg/0.4 mL (0.4 mL); 50 mcg/0.5 mL (0.5 mL); 60 mcg/0.3 mL (0.3 mL); 80 mcg/0.4 mL (0.4 mL); 100 mcg/0.5 mL (0.5 mL); 130 mcg/0.65 mL (0.65 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) [contains polysorbate 80]
IV, SUBQ: May be administered by SUBQ or IV injection. IV or SUBQ route can be used in hemodialysis patients (Ref). 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.
Parenteral: May be administered undiluted IV or SubQ. IV route preferred for hemodialysis patients. Do not shake as this may denature the glycoprotein rendering the drug biologically inactive. Do not administer in conjunction with other drug solutions. Discard any unused portion of the vial; do not pool unused portions.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/103951s5375lbl.pdf#page=25, must be dispensed with this medication.
Anemia due to chemotherapy in patients with cancer: Treatment of anemia in patients with nonmyeloid malignancies when anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of 2 additional months of planned chemotherapy.
Anemia due to chronic kidney disease: Treatment of anemia due to chronic kidney disease, including patients on dialysis and patients not on dialysis.
Limitations of use: 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
- Cancer patients receiving myelosuppressive chemotherapy when anemia can be managed by transfusion
- As a substitute for red blood cell (RBC) transfusion in patients requiring immediate correction of anemia
Myelodysplastic syndromes, lower-risk (symptomatic anemia management)
Aranesp may be confused with Aralast, Aricept
Darbepoetin alfa may be confused with dalteparin, epoetin alfa, methoxy polyethylene glycol-epoetin beta
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Lenalidomide: Erythropoiesis-Stimulating Agents may enhance the thrombogenic effect of Lenalidomide. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Erythropoiesis-Stimulating Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Nandrolone: May enhance the stimulatory effect of Erythropoiesis-Stimulating Agents. Specifically, nandrolone may enhance the erythropoiesis stimulatory effect of Erythropoiesis-Stimulating Agents. Risk C: Monitor therapy
Pomalidomide: Erythropoiesis-Stimulating Agents may enhance the thrombogenic effect of Pomalidomide. Risk C: Monitor therapy
Roxadustat: May enhance the adverse/toxic effect of Erythropoiesis-Stimulating Agents. Risk X: Avoid combination
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Thalidomide: Erythropoiesis-Stimulating Agents may enhance the thrombogenic effect of Thalidomide. Risk C: Monitor therapy
Use of darbepoetin alfa in pregnancy has been described in case reports (Ghosh 2007; Goshorn 2005; Macciò 2009; Sobiło-Jarek 2006).
It is not known if darbepoetin alfa is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Supplemental iron intake may be required in patients with low iron stores.
Hemoglobin (at least once per week until maintenance dose established and after dosage changes; monitor less frequently once hemoglobin is stabilized); chronic kidney disease (CKD) patients should be also be monitored at least monthly following hemoglobin stability); iron stores (transferrin saturation and ferritin) prior to and during therapy to ensure adequate iron stores; serum chemistry (CKD patients); blood pressure; fluid balance (CKD patients); monitor for signs of seizures (CKD patients following initiation for first few months, includes new-onset or change in seizure frequency or premonitory symptoms)
Cancer patients: Examinations recommended prior to treatment include: Appropriate history, physical, and diagnostic tests to identify/rule out other causes of anemia including peripheral blood smear (in some situations a bone marrow exam may be necessary), assessment (if indicated) for iron, total iron-binding capacity, transferrin saturation, ferritin, folate, vitamin B12, or hemoglobinopathy screening, reticulocyte count, kidney function status, and occult blood loss; baseline erythropoietin level; in patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or a history of autoimmune disease, direct antiglobulin testing (eg, Coombs test) may be necessary (ASCO/ASH [Bohlius 2019]). During erythropoiesis-stimulating agent (ESA) treatment, assess iron status with total iron-binding capacity, and transferrin saturation or ferritin levels.
Diabetes: HbA1c is not useful as a glycemic indicator in patients treated with an ESA. Other monitoring parameters may be more useful.
Myelodysplastic syndromes (off-label use): Patients with baseline erythropoietin levels >500 mU/mL (SI: >500 U/L) are unlikely to respond to erythropoiesis-stimulating agents (ASCO/ASH [Bohlius 2019]).
Darbepoetin alfa 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.
Onset of action: Increased hemoglobin levels not generally observed until 2 to 6 weeks after initiating treatment
Absorption: SubQ: Slow
Distribution: Vd:
Children and Adolescents: Initial dose: 51.6 ± 13.7 mL/kg; Steady state: 80.9 ± 32.5 mL/kg (Lerner 2002)
Adults: 52.4 ± 2 mL/kg (Macdougall 1999)
Bioavailability: CKD: SubQ: Adults: ~37% (range: 30% to 50%); Children: 54% (range: 32% to 70%)
Half-life elimination: Note: Darbepoetin alfa half-life is approximately 3-fold longer than epoetin alfa following IV administration.
CKD:
Children and Adolescents (Lerner 2002):
IV: Terminal: 22.1 ± 4.8 hours
SubQ: Terminal: 42.8 ± 23 hours
Adults:
IV: 21 hours
SubQ: Nondialysis patients: 70 hours (range: 35 to 139 hours), Dialysis patients: 46 hours (range: 12 to 89 hours)
Cancer:
Children and Adolescents: SubQ: 49.4 ± 32 hours (Blumer 2007)
Adults: SubQ: 74 hours (range: 24 to 144 hours)
Time to peak: SubQ:
CKD:
Children and Adolescents: 36.2 ± 14.1 hours (Lerner 2002)
Adults: 48 hours (range: 12 to 72 hours; independent of dialysis)
Cancer:
Children and Adolescents: 87.5 ± 53 hours (Blumer 2007)
Adults: 71 hours (range: 28 to 120 hours)
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