Darbepoetin Alfa

Dosage Forms

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); 300 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]

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Absorption

SubQ: Slow

Distribution

V_d:

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)

Onset of Action

Increased hemoglobin levels not generally observed until 2 to 6 weeks after initiating treatment

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)

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)

Use: Labeled Indications

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

Use: Off Label

Myelodysplastic syndromes, lower-risk (symptomatic anemia management)byes

Data from 4 studies, a meta-analysis, and a systematic review support the use of darbepoetin alfa (initially as a single agent and then in combination with growth-colony stimulating factor after single-agent failure) in the management of anemia in patients with lower-risk myelodysplastic syndromes Gabrilove 2008, Giraldo 2006, Park 2008, Park 2016, Park 2019, Stasi 2005.

Based on guidelines from the American Society of Clinical Oncology (ASCO) and the American Society of Hematology (ASH) for management of cancer-associated anemia with erythropoiesis-stimulating agents, erythropoiesis-stimulating agents may be an option for management of anemia in patients with lower-risk myelodysplastic syndromes who have an erythropoietin level ≤500 mU/mL.

Contraindications

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

Dosage and Administration

Dosing: Adult

Note: Evaluate iron status in all patients before and during treatment. The manufacturer recommends supplemental iron be administered if serum ferritin is <100 ng/mL or serum transferrin saturation (TSAT) is <20%. Most patients with CKD will require iron supplementation.

Anemia due to 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): 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 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): 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.

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.

Myelodysplastic syndromes, lower-risk, symptomatic anemia management (off-label use): SubQ: 150 to 300 mcg once weekly (Giraldo 2006; Park 2008; Stasi 2005) or 500 mcg once every 2 to 3 weeks (Gabrilove 2008).

Conversion from epoetin alfa to darbepoetin alfa in CKD (on dialysis): See table.

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:

• <1,500 units/week, then darbepoetin alfa: 6.25 mcg/weekly
• 1,500 to 2,499 units/week, then darbepoetin alfa: 6.25 mcg/weekly
• 2,500 to 4,999 units/week, then darbepoetin alfa: 12.5 mcg/weekly
• 5,000 to 10,999 units/week, then darbepoetin alfa: 25 mcg/weekly
• 11,000 to 17,999 units/week, then darbepoetin alfa: 40 mcg/weekly
• 18,000 to 33,999 units/week, then darbepoetin alfa: 60 mcg/weekly
• 34,000 to 89,999 units/week, then darbepoetin alfa: 100 mcg/weekly
• ≥90,000 units/week, then darbepoetin alfa: 200 mcg/weekly

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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.

Table has been converted to the following text:

Conversion from Epoetin Alfa to Darbepoetin Alfa (IV or SubQ) (maintain the same route of administration for the conversion):

Previous weekly epoetin alfa dose: <1,500 units/week, then weekly darbepoetin alfa dose: Age 1 month to <18 years: Not established; Age ≥18 years: 6.25 mcg/week

Previous weekly epoetin alfa dose: 1,500 to 2,499 units/week, then weekly darbepoetin alfa dose: Age 1 month to <18 years: 6.25 mcg/week; Age ≥18 years: 6.25 mcg/week

Previous weekly epoetin alfa dose: 2,500 to 4,999 units/week, then weekly darbepoetin alfa dose: Age 1 month to <18 years: 10 mcg/week; Age ≥18 years: 12.5 mcg/week

Previous weekly epoetin alfa dose: 5,000 to 10,999 units/week, then weekly darbepoetin alfa dose: Age 1 month to <18 years: 20 mcg/week; Age ≥18 years: 25 mcg/week

Previous weekly epoetin alfa dose: 11,000 to 17,999 units/week, then weekly darbepoetin alfa dose: Age 1 month to <18 years: 40 mcg/week; Age ≥18 years: 40 mcg/week

Previous weekly epoetin alfa dose: 18,000 to 33,999 units/week, then weekly darbepoetin alfa dose: Age 1 month to <18 years: 60 mcg/week; Age ≥18 years: 60 mcg/week

Previous weekly epoetin alfa dose: 34,000 to 89,999 units/week, then weekly darbepoetin alfa dose: Age 1 month to <18 years: 100 mcg/week; Age ≥18 years: 100 mcg/week

Previous weekly epoetin alfa dose: ≥90,000 units/week, then weekly darbepoetin alfa dose: Age 1 month to <18 years: 200 mcg/week; Age ≥18 years: 200 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.

Administration

IV, SubQ: 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.

Dietary Considerations

Supplemental iron intake may be required in patients with low iron stores.

Storage

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. Extended storage information at room temperature may be available; contact product manufacturer to obtain current recommendations.

Drug Interactions

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

Pomalidomide: Erythropoiesis-Stimulating Agents may enhance the thrombogenic effect of Pomalidomide. Monitor therapy

Thalidomide: Erythropoiesis-Stimulating Agents may enhance the thrombogenic effect of Thalidomide. Monitor therapy

Adverse Reactions

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

Warnings/Precautions

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 (the IV route is preferred for hemodialysis patients). 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 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 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.
• CKD patients: [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.
• 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 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.

- 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/Heart Failure Society of America (ACCF/AHA/HFSA) 2017 Heart Failure Guidelines recommend that patients with heart failure and anemia should NOT be administered erythropoietin-stimulating agents to improve morbidity and mortality due to lack of benefit and increased adverse events (ACCF/AHA/HFSA [Yancy 2017]).

• 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.

Monitoring Parameters

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; 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 treatment, assess iron status with total iron-binding capacity, and transferrin saturation or ferritin levels.

Pregnancy

Pregnancy Considerations

Use of darbepoetin alfa in pregnancy has been described in case reports (Ghosh 2007; Goshorn 2005; Macciò 2009; Sobiło-Jarek 2006).

Patient Education

What is this drug used for?

• It is used to treat anemia.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Cough
• Abdominal pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes
• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood
• Fast heartbeat
• Confusion
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Dizziness
• Passing out
• Vision changes
• Seizures
• Severe headache
• Sweating a lot
• Severe loss of strength and energy
• Pale skin
• Cool arm or leg
• Abnormal gait
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.