Darbepoetin Alfa

Pronunciation

Class: Hematopoietic Agents
VA Class: BL400
Chemical Name: Erythropoietin [30-asparagine, 32-threonine, 87-valine, 88-asparagine, 90-threonine] (human)
Molecular Formula: C800H1300N228O224S5
CAS Number: 209810-58-2
Brands: Aranesp

Warning(s)

  • Risk of Increased Mortality and Serious Adverse Events
  • Increased risk of death, serious cardiovascular events, and stroke reported in patients with chronic kidney disease (CKD) receiving therapy with darbepoetin alfa or other erythropoiesis-stimulating agents (ESAs) targeted to hemoglobin concentrations >11 g/dL in controlled clinical studies.1 19 20 21 22 23 24 25 30 31 38 39 40 45 620 622 624 (See Increased Mortality and Cardiovascular and Thromboembolic Events under Cautions.)

  • No trial has identified a hemoglobin target, ESA dosage, or dosing strategy that does not increase these risks.1 624

  • Use lowest ESA dosage sufficient to reduce need for RBC transfusion in patients with CKD.1 624

    ESA therapy shortened overall survival and/or increased risk of tumor progression or recurrence in some studies in patients with breast, non-small cell lung, head and neck, lymphoid, or cervical cancers.1 24 25 28 29 34 35 38 39 40 41 42 43 49 (See Increased Mortality and/or Tumor Progression under Cautions.)

  • To decrease these risks and risk of serious cardiovascular and thromboembolic events in anemic patients with cancer, use lowest ESA dosage sufficient to avoid RBC transfusion.1 20 21 22 23 24 25 28 29

  • Darbepoetin alfa may be prescribed and/or dispensed to cancer patients only by clinicians and institutions enrolled in the ESA APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs) Oncology program.1 619 (See REMS and see also Restricted Distribution Program in Oncology under Dosage and Administration.)

  • Use ESAs in cancer patients only for treatment of anemia caused by concomitant myelosuppressive chemotherapy.1 24 25 28 29 38 39 40 41

  • ESAs not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure of the underlying malignancy.1 28 29 54

  • Discontinue ESAs following completion of a course of chemotherapy.1 28 29

REMS:

FDA approved a REMS for darbepoetin to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of darbepoetin and consists of the following: medication guide, elements to assure safe use, communication plan, and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center (). Also see Restricted Distribution Program in Oncology under Dosage and Administration.

Introduction

Biosynthetic (recombinant DNA origin) form of the glycoprotein hormone erythropoietin, a hematopoietic agent that principally affects erythropoiesis.1 2 9 10

Uses for Darbepoetin Alfa

Anemia of Chronic Kidney Disease

Treatment of anemia associated with CKD in patients who currently are undergoing hemodialysis or peritoneal dialysis therapy, as well as those who do not yet require maintenance dialysis (predialysis patients).1 4 5 9 13

Some evidence suggests once-weekly darbepoetin alfa has similar safety and efficacy as equivalent doses of epoetin alfa given 2 or 3 times weekly in patients with CKD who are undergoing hemodialysis or peritoneal dialysis.1 6 7 9 11 12 In addition, administration of darbepoetin alfa once every other week appears to have similar efficacy as equivalent doses of sub-Q epoetin alfa administered once weekly.11 58 59 60

ESAs, including darbepoetin alfa, may increase risk for death, stroke, and serious cardiovascular events when targeted to hemoglobin concentrations >11 g/dL in patients with CKD.1 19 20 21 22 23 28 29 30 620 622 624 (See Boxed Warning.) FDA has issued public health advisories regarding these risks.19 20 21 22 23 24 25 38 39 40 624 Weigh potential benefits of ESAs in reducing RBC transfusions against risk of serious cardiovascular events in patients with CKD.1 624 Individualize therapy and use lowest possible dosage that will reduce the need for transfusion.1 624

Slideshow: HealthQuiz: Basics About Stroke Signs and Symptoms

Not intended for patients with CKD who require acute correction of severe anemia; do not use as a substitute for emergency transfusion.1

Not established that ESAs improve quality of life, fatigue, or patient well-being.1

Chemotherapy-induced Anemia in Patients with Nonmyeloid Malignancies

Treatment of chemotherapy-induced anemia in patients with nonmyeloid malignancies in whom chemotherapy is planned for at least 2 additional months;1 used to decrease the need for blood transfusions in such patients.1 14 62

ESAs not indicated in patients with chemotherapy-induced anemia when the anticipated outcome is cure of the underlying malignancy.1 54 ESAs not shown to improve outcomes of cancer chemotherapy (e.g., in terms of greater tumor shrinkage, delayed tumor progression, increased survival).1 24 25 34 35 38 39 40 43 44 49 Not established that ESAs improve quality of life, fatigue, or patient well-being.1

Not intended for patients who require acute correction of severe anemia; do not use as a substitute for emergency transfusion.1

Chronic Anemia Associated with Malignancy

Darbepoetin alfa and other ESAs not indicated for use in anemic patients with active malignant disease who are not receiving cancer chemotherapy.1 28 29 ESAs have been shown to decrease overall survival in certain cancer patients not receiving chemotherapy or radiation therapy.1

Darbepoetin Alfa Dosage and Administration

General

  • In controlled trials of patients with CKD, ESA therapy targeted to hemoglobin concentrations >11 g/dL did not provide additional benefit beyond that achieved with lower targets and was associated with greater risk of death, stroke, and serious adverse cardiovascular events; no trial to date has identified a target hemoglobin, ESA dosage, or dosing strategy that decreases these risks.1 624 (See Boxed Warning.) Weigh benefits of darbepoetin alfa against these risks in patients with CKD.1 624 Use lowest dosage necessary to reduce need for RBC transfusions.1 624

  • To decrease risks of shortened survival, tumor progression or recurrence in patients with cancer, use lowest dosage sufficient to avoid RBC transfusion and discontinue following completion of a chemotherapy course.1

  • Evaluate iron status (i.e., transferrin saturation, serum ferritin) prior to and during therapy.1 Administer supplemental iron if serum ferritin <100 mcg/L or transferrin saturation <20%.1

  • Exclude or correct other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding) prior to initiating therapy.1

Restricted Distribution Program in Oncology

  • A required risk management plan (Risk Evaluation and Mitigation Strategy, REMS) has been developed for all ESAs.1 619

  • The APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs) Oncology program has been created to minimize risk of decreased survival and poor tumor response in cancer patients receiving ESAs.1 619 Clinicians and institutions must enroll in and comply with all requirements of the program (e.g., training module, signed acknowledgment of patient counseling) before they can prescribe and/or dispense ESAs to patients with cancer; participants must re-enroll every 3 years.1 619 For additional information or to enroll in the ESA APPRISE Oncology program, contact 866-284-8089 or visit www.esa-apprise.com.1 619

Administration

Administer by IV or sub-Q injection.1 8 9

IV or Sub-Q Administration

Do not expose to light, shake, or freeze prior to use.1

Do not dilute injection further prior to administration.1

Do not administer in conjunction with other drug solutions.1

Discard any unused portions of drug in the vials or prefilled syringes; do not re-enter vials.1

Sub-Q injections are preferred by some clinicians for predialysis and peritoneal dialysis patients because of the lack of existing accessible IV sites in such patients.8

Darbepoetin alfa may be self-administered in a home-care setting by patients if they are judged competent to do so by their clinician.1 For sub-Q injection using a vial and a disposable syringe or prefilled syringe, inject into the outer area of the upper arms, abdomen (except the 2-inch area around the navel), front of middle thighs, or upper outer areas of the buttocks.32 33 Do not inject into areas where skin is tender, bruised, red, or hard.32 Avoid injecting into areas with scars or stretch marks.33

Before using the prefilled syringe, check to see that the needle cover is on and the yellow needle guard is covering the barrel of the syringe.33 If the needle guard is covering the needle, discard the syringe.33 Do not slide the needle guard over the needle cover before injection; the sliding motion will lock the needle guard prematurely.33

Following administration from the prefilled syringe, activate the needle guard to prevent accidental needle sticks.1 33 To activate the needle guard, hold the finger grip of the syringe with one hand and grasp the needle guard with the other hand.33 Slide the guard completely over the needle until the needle guard clicks into place.33

The manufacturer recommends IV administration in patients with CKD undergoing hemodialysis.1

When switching from epoetin alfa to darbepoetin alfa, administer darbepoetin alfa by the same route of administration (IV or sub-Q) that epoetin alfa was administered.1 9 Administer darbepoetin alfa once weekly if epoetin alfa was administered 2 or 3 times weekly.1 9 Administer darbepoetin alfa once every 2 weeks if epoetin alfa was administered once weekly.1 9 Administer first dose of darbepoetin alfa in place of epoetin alfa at the time of the next scheduled dose.8

Dosage

Pediatric Patients

Anemia of Chronic Kidney Disease
IV or Sub-Q

In pediatric patients >1 year of age currently receiving epoetin alfa, the manufacturer of darbepoetin alfa recommends the following initial dosage of darbepoetin alfa based on the weekly epoetin alfa dosage at the time of substitution (See Table 1):1

For pediatric patients receiving a weekly epoetin alfa dosage of <1500 units/week, data are insufficient to determine initial darbepoetin alfa dosage.

Table 1.

Previous Weekly Epoetin Alfa Dosage (units/week)

Initial Weekly Darbepoetin Alfa Dosage (mcg/week)

<1500

1500–2499

6.25

2500–4999

10

5000–10,999

20

11,000–17,999

40

18,000–33,999

60

34,000–89,999

100

≥90,000

200

Adjust subsequent dosage based on hemoglobin concentrations.1 Consider rate of hemoglobin increase or decrease, ESA responsiveness, and hemoglobin variability when determining whether a dosage adjustment is needed; a single hemoglobin excursion may not require a dosage change.1 Avoid frequent dosage changes.1

Monitor hemoglobin concentration at least weekly following initiation of therapy and after each dosage adjustment until stable, then monitor at least monthly.1

If hemoglobin concentration increases by >1 g/dL in any 2-week period, reduce dosage by 25% or more as necessary to reduce risk of a rapid response.1

If hemoglobin has not increased by >1 g/dL after 4 weeks of therapy, increase dosage by 25%.1 Do not increase dosage more frequently than once every 4 weeks.1 If an adequate response not obtained within 12 weeks, evaluate for other causes of anemia.1 (See Lack or Loss of Response to Therapy under Cautions.) Further dosage increases not likely to improve patient response and may increase risks of therapy; use lowest dosage sufficient to reduce need for RBC transfusions and discontinue drug if responsiveness does not improve.1 (See Boxed Warning.)

Adults

Anemia of Chronic Kidney Disease
IV or Sub-Q

Patients on dialysis: Initially, 0.45 mcg/kg administered IV or sub-Q once weekly or 0.75 mcg/kg administered IV or sub-Q once every 2 weeks as appropriate; IV administration recommended in patients undergoing hemodialysis.1 9 Initiate therapy when hemoglobin concentration <10 g/dL.1 624 Reduce or interrupt therapy if hemoglobin approaches or exceeds 11 g/dL.1 (See Boxed Warning.)

Patients not on dialysis: Initially, 0.45 mcg/kg administered IV or sub-Q once every 4 weeks as appropriate.1 Consider initiating therapy when hemoglobin <10 g/dL and the following 2 conditions apply: rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion, and a goal of therapy is to reduce risk of alloimmunization and/or other risks associated with RBC transfusions.1 Reduce or interrupt therapy if hemoglobin >10 g/dL.1 (See Boxed Warning.)

Conversion of epoetin alfa therapy to darbepoetin alfa in CKD patients on dialysis: In patients currently receiving epoetin alfa, the manufacturer of darbepoetin alfa recommends the following initial dosage of darbepoetin alfa based on the weekly epoetin alfa dosage at the time of substitution (See Table 2):1 9

Table 2.

Previous Weekly Epoetin Alfa Dosage (units/week)

Initial Weekly Darbepoetin Alfa Dosage (mcg/week)

<1500

6.25

1500–2499

6.25

2500–4999

12.5

5000–10,999

25

11,000–17,999

40

18,000–33,999

60

34,000–89,999

100

≥90,000

200

Adjust subsequent dosage based on hemoglobin concentrations.1 Consider rate of hemoglobin increase or decrease, responsiveness to the ESA, and hemoglobin variability when determining whether a dosage adjustment is needed; a single hemoglobin excursion may not require a dosage change.1 Avoid frequent dosage adjustments.1

Monitor hemoglobin concentration at least weekly following initiation of therapy and after each dosage adjustment until stable, then monitor at least monthly.1

If hemoglobin increases by >1 g/dL in any 2-week period, reduce dosage by 25% or more as necessary to reduce risk of a rapid response.1

If hemoglobin has not increased by >1 g/dL after 4 weeks of therapy, increase dosage by 25%.1 Do not increase dosage more frequently than once every 4 weeks.1 If an adequate response not obtained within 12 weeks, evaluate for other causes of anemia.1 (See Lack or Loss of Response to Therapy under Cautions.) Further dosage increases not likely to improve patient response and may increase risks of therapy; use lowest dosage sufficient to reduce need for RBC transfusions and discontinue drug if responsiveness does not improve.1 (See Boxed Warning.)

Chemotherapy-induced anemia in Patients with Nonmyeloid Malignancies
Sub-Q

Initially, 2.25 mcg/kg once weekly.1

Alternatively, 500 mcg once every 3 weeks.1

Initiate only if hemoglobin concentration <10 g/dL and at least 2 additional months of chemotherapy is planned.1 Discontinue following completion of a chemotherapy course.1

Once-weekly dosage regimen: If hemoglobin concentration increases by <1 g/dL after 6 weeks of therapy and remains below 10 g/dL, increase dosage to 4.5 mcg/kg weekly.1

Once-weekly or every-3-weeks dosage regimen: If hemoglobin concentration increases by >1 g/dL in any 2-week period or reaches a level sufficient to avoid RBC transfusions, decrease dosage by 40%.1

Once-weekly or every-3-weeks dosage regimen: If hemoglobin concentration exceeds a level needed to avoid RBC transfusions, withhold therapy until hemoglobin concentration decreases to a level at which transfusions may be required.1 Reinstitute at a dosage 40% below the previous dosage.1

Discontinue therapy after 8 weeks if no response based on hemoglobin concentrations or if RBC transfusions are still required.1

Cautions for Darbepoetin Alfa

Contraindications

  • Uncontrolled hypertension.1 33 (See Hypertension and Seizures under Cautions.)

  • Pure red cell aplasia (PRCA) that begins after treatment with darbepoetin alfa or other erythropoietin proteins.1 55

  • Serious allergic reactions to darbepoetin alfa.1 55

Warnings/Precautions

Warnings

Increased Mortality and Cardiovascular and Thromboembolic Events

Increased risk of death and serious cardiovascular events in patients with CKD receiving ESAs targeted to hemoglobin concentrations >11 g/dL.1 20 21 23 30 31 55 620 622 624 625 (See Boxed Warning.) In controlled clinical studies comparing higher (13–14 g/dL) to lower (9–11.3 g/dL) hemoglobin targets, an increased risk of death, MI, stroke, CHF, hemodialysis vascular access thrombosis, and other thromboembolic events was observed in the higher target hemoglobin groups.1 20 45 620 624 625 Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at greater risk for cardiovascular events and mortality.1 Increases in hemoglobin >1 g/dL during any 2-week period also may contribute to these risks.1

Increased incidence of thromboembolic events, some serious and life-threatening, in cancer patients receiving darbepoetin alfa or other ESAs (epoetin alfa).1 24 25 46 (See Boxed Warning.) Increased incidence of fatal thromboembolic/vascular events and overall mortality reported in women with metastatic breast cancer who received epoetin alfa targeted to a hemoglobin concentration of 12–14 g/dL.1 24 25

Increased incidence of thromboembolism in patients undergoing surgical procedures without prophylactic anticoagulation and receiving another ESA, epoetin alfa, to reduce allogeneic RBC transfusion requirements.1 24 25 47 Darbepoetin alfa not FDA-labeled for reduction of allogeneic RBC transfusions in patients undergoing surgery.1

Correction of hemoglobin to concentrations >11 g/dL may increase risk of serious and life-threatening cardiovascular events in patients with CKD.1 19 20 21 23 61 624 The manufacturer and FDA recommend that treatment be initiated in patients with CKD only when hemoglobin concentration <10 g/dL.1 624 Use lowest dosage sufficient to reduce the need for RBC transfusions.1 624

Increased anticoagulation with heparin may be needed during dialysis to prevent clotting of the extracorporeal circuit in patients receiving darbepoetin alfa.1

Increased Mortality and/or Tumor Progression

Risk of increased mortality and tumor progression or recurrence in patients with cancer.1 (See Boxed Warning.)

Decreased overall survival observed in patients with non-small-cell lung cancer receiving only palliative radiation therapy or no active therapy and another ESA (epoetin alfa) targeted to a hemoglobin concentration of 12–14 g/dL.1

A shortened time to tumor progression observed in patients with advanced head and neck cancer receiving radiation therapy alone and an ESA.1 24 34 35

Increased risk of death in patients with cancer-related anemia who were not receiving cancer chemotherapy or radiation therapy while receiving darbepoetin alfa.1 24 25 46 ESAs are not FDA-labeled for use in patients with cancer-related anemia who are not receiving myelosuppressive chemotherapy.1 24 25 38 39 40 41

ESAs, including darbepoetin alfa, can only be prescribed and dispensed to cancer patients by authorized clinicians and institutions enrolled in the ESA APPRISE Oncology program.1 619 (See Risk Management Plan under Dosage and Administration and also see Boxed Warning.)

Hypertension and Seizures

Risk of new or worsening hypertension in patients with CKD, particularly during early phase of therapy.1 May require initiation of or increases in antihypertensive therapy.1 (See Advice to Patients.)

Contraindicated in patients with uncontrolled hypertension; BP should be under control before initiation of therapy.1 Monitor and control BP during therapy.1 If BP becomes difficult to control, reduce dosage of or withhold darbepoetin alfa.1

Seizures and hypertensive encephalopathy reported; risk appears greater in patients with CKD.1 Monitor closely for premonitory neurologic symptoms during the first several months of therapy.1 (See Advice to Patients.)

Pure Red Cell Aplasia

PRCA and severe anemia with or without other cytopenias in association with neutralizing antibodies to endogenous erythropoietin reported during postmarketing experience in a limited number of patients.1 16 56 57 PRCA occurred predominantly in patients with CKD receiving ESAs by sub-Q administration.1 16

PRCA also reported in patients with hepatitis C virus (HCV) infection receiving ESAs for anemia related to hepatitis treatment (non-FDA-labeled indication).1 56 57

Withhold therapy in any patient who develops severe anemia and low reticulocyte counts; evaluate for presence of neutralizing antibodies to erythropoietin.1 Contact the manufacturer (1-800-77AMGEN) to perform assays for binding and neutralizing antibodies.1 16 56

Discontinue permanently in any patient with PRCA.1 16 56 (See Contraindications.) Do not switch to another ESA.1 16 56

Sensitivity Reactions

Hypersensitivity Reaction

Risk of severe allergic reactions, including anaphylactic reactions, angioedema, respiratory symptoms, skin rash, and urticaria.1 If a serious hypersensitivity or anaphylactic reaction occurs, discontinue immediately and institute appropriate therapy; do not reinitiate.1

Latex Sensitivity

The needle cover of the prefilled syringe contains natural latex proteins in the form of dry natural rubber (latex).1 51 52 53 Individuals sensitive to latex should not handle the needle cover.1 51 52 53 Rarely, hypersensitivity reactions to natural latex proteins have been fatal.52 53

General Precautions

Lack or Loss of Response to Therapy

Evaluate patients who fail to respond or experience a loss of hemoglobin response for potential causative factors (e.g., iron deficiency, infection, inflammation, bleeding).1

In the absence of another etiology, evaluate for evidence of PRCA and test for presence of antibodies to erythropoietins.1 (See Pure Red Cell Aplasia under Cautions.)

Patient Monitoring

Evaluate iron stores in all patients prior to and periodically during therapy.1 8 9 Administer supplemental iron if serum ferritin concentration <100 mcg/L or serum transferrin saturation <20%.1 8 Most patients with CKD will require supplemental iron during ESA therapy.1

Monitor hemoglobin concentrations weekly following initiation of therapy and after each dosage change until stable and sufficient to minimize RBC transfusion.1 May perform subsequent monitoring less frequently provided hemoglobin concentrations remain stable; monitor at least monthly in patients with CKD.1

Dialysis Management

Patients undergoing dialysis may require adjustments in their dialysis prescriptions following initiation of darbepoetin alfa.1 Heparin anticoagulation requirements during hemodialysis may be increased.1 (See Increased Mortality and Cardiovascular and Thromboembolic Events under Cautions.).1

Specific Populations

Pregnancy

Category C.1

Women who become pregnant during darbepoetin alfa therapy are encouraged to enroll in the manufacturer’s Pregnancy Surveillance Program by calling 800-772-6436.1

Lactation

Not known whether darbepoetin alfa is distributed into milk;1 32 use with caution in nursing women.1

Pediatric Use

Safety and efficacy in the initial treatment of anemia of CKD not established.1 Safety and efficacy of transitioning to darbepoetin alfa therapy from epoetin alfa in pediatric patients >1 year of age with CKD similar to adults.1 Safety and efficacy of transitioning from another erythropoietin not established in pediatric patients <1 year of age.1

Safety and efficacy in pediatric cancer patients not established.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

Hepatic Impairment

Use with caution.8

Common Adverse Effects

Adults with CKD: Hypertension, dyspnea, peripheral edema, cough, procedural hypotension, angina pectoris, vascular access complications, fluid overload, rash/erythema, arteriovenous graft thrombosis.

Pediatric patients with CKD: Hypertension, injection-site pain, rash, convulsions.1

Patients with cancer: Abdominal pain, edema, thrombovascular events.

Interactions for Darbepoetin Alfa

No formal drug interaction studies have been performed.1

Darbepoetin Alfa Pharmacokinetics

Absorption

Bioavailability

Approximately 37% (range 30–50%) or 54% (range 32–70%) in adult or pediatric patients, respectively, with CKD following sub-Q administration.1

Absorption is slow and rate limiting following sub-Q administration.1

Distribution

Extent

Not known whether darbepoetin alfa is distributed into milk.1

Elimination

Half-life

Following sub-Q administration: 49 hours (range: 27–89 hours) in adult patients with CKD.1

Pediatric patients (3–16 years of age) with CKD with or without dialysis following a single IV or sub-Q dose: Half-life similar to that in adults.1

Patients with cancer following a single sub-Q dose: 74 hours (range: 24–144 hours).1

Following IV administration: Distribution half-life is approximately 1.4 hours and terminal half-life is approximately 21 hours.1

Stability

Storage

Parenteral

Injection

2–8°C; protect from light.1 32 33 Do not freeze or shake.1 32 33 Discard vial or prefilled syringe that has been frozen or shaken.1 32

Actions

  • Has pharmacologic actions identical to those of endogenous erythropoietin;1 2 10 interacts with progenitor stem cells to increase red cell production.1

  • Erythropoietin deficiency is the primary cause of anemia in patients with CKD.1

  • In patients with cancer receiving concomitant chemotherapy, etiology of anemia is multifactorial.1

Advice to Patients

  • Importance of informing patients about the increased risks of death, serious cardiovascular effects, thromboembolic events, and tumor progression in certain patient populations.1 32 33 (See Increased Mortality and Cardiovascular and Thromboembolic Events under Cautions and also see Boxed Warning.)

  • Manufacturer’s medication guide must be provided prior to initiating therapy and each time drug is dispensed.1 55 619

  • Importance of informing clinician of latex allergy.55 Importance of informing patients that the needle cover of the prefilled syringe contains natural dry rubber.1

  • If the patient or caregiver is to administer darbepoetin alfa, provide careful instructions regarding proper, safe use of the drug in this setting, including information on aseptic techniques, and on storage and disposal of the drug and administration equipment.1 32 33 Advise such patients to follow the manufacturer’s “Patient Instructions for Use.”1 32 33

  • Importance of patient informing clinicians of heart disease, high BP, history of seizures or strokes, and blood disorders (e.g., sickle cell anemia, clotting disorders) prior to treatment initiation.32 33

  • Importance of recognizing and reporting adverse effects of darbepoetin alfa (e.g., sensitivity reactions).1 32 33 Importance of informing clinicians immediately if serious allergic reaction occurs (e.g., whole body rash, shortness of breath, wheezing, decreases in BP, swelling around mouth or eyes, fast pulse, sweating).32 Importance of informing patients of appropriate actions to take if such adverse effects occur.1

  • Importance of reporting signs or symptoms of stroke, chest pain, irregular heartbeats, pain in the legs with or without swelling, seizures, confusion, dizziness or loss of consciousness, extreme tiredness, blood clots in hemodialysis vascular access ports, or increases in BP.19 22 32 33

  • Importance of informing clinician of redness, swelling, or itching at the injection site.32 33

  • Importance of adhering to antihypertensive treatment and dietary restrictions.1

  • Importance of regular monitoring of BP and hemoglobin.1 19 22 32 33

  • Importance of patients contacting a clinician if any new-onset seizures, premonitory symptoms, or change in seizure frequency occurs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 32 33

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Because of risks associated with use of erythropoiesis-stimulating agents (ESAs) in cancer patients, the APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs) Oncology program has been developed.1 619 For additional information, see Restricted Distribution Program in Oncology under Dosage and Administration: Administration.

Darbepoetin Alfa

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

25 mcg/0.42 mL

Aranesp (available as single-dose prefilled syringes)

Amgen

25 mcg/mL

Aranesp (available as single-dose vials)

Amgen

40 mcg/0.4 mL

Aranesp (available as single-dose prefilled syringes)

Amgen

40 mcg/mL

Aranesp (available as single-dose vials)

Amgen

60 mcg/0.3 mL

Aranesp (available as single-dose prefilled syringes)

Amgen

60 mcg/mL

Aranesp (available as single-dose vials)

Amgen

100 mcg/0.5 mL

Aranesp (available as single-dose prefilled syringes)

Amgen

100 mcg/mL

Aranesp (available as single-dose vials)

Amgen

150 mcg/0.3 mL

Aranesp (available as single-dose prefilled syringes)

Amgen

150 mcg/0.75 mL

Aranesp (available as single-dose vials)

Amgen

200 mcg/0.4 mL

Aranesp (available as single-dose prefilled syringes)

Amgen

200 mcg/mL

Aranesp (available as single-dose vials)

Amgen

300 mcg/0.6 mL

Aranesp (available as single-dose prefilled syringes)

Amgen

300 mcg/mL

Aranesp (available as single-dose vials)

Amgen

500 mcg/mL

Aranesp (available as single-dose prefilled syringes)

Amgen

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Aranesp (Albumin Free) 100MCG/0.5ML Solution (AMGEN): 2/$2,332.03 or 6/$6,875.18

Aranesp (Albumin Free) 100MCG/ML Solution (AMGEN): 4/$2,423.46 or 12/$7,040.27

Aranesp (Albumin Free) 150MCG/0.75ML Solution (AMGEN): 3/$3,943.27 or 9/$10,624.19

Aranesp (Albumin Free) 25MCG/ML Solution (AMGEN): 1/$156.99 or 2/$313.98

Aranesp (Albumin Free) 300MCG/ML Solution (AMGEN): 1/$1,782.58 or 3/$5,153.89

Aranesp (Albumin Free) 60MCG/ML Solution (AMGEN): 1/$390.99 or 4/$1,557.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 30, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Amgen Inc. Aranesp (darbepoetin alfa) for injection prescribing information. Thousand Oaks, CA; 2011 Jun.

2. Joy MS. Novel erythropoiesis-stimulating protein: an erythropoietin analogue with an extended half-life and less frequent dosing. Formulary. 2001; 36:19-25.

3. Coyne D, Ling BN, Toto R et al. Novel erythropoiesis stimulating protein (NESP) corrects anemia in dialysis patients when administered at reduced dose frequency compared with recombinant-human erythropoietin (r-HuEPO). Paper presented at 33rd American Society of Nephrology annual meeting. Toronto, Canada: 2000 Oct. Abstract.

4. Locatelli F, Olivares J, Walker R et al., on behalf of the European/Australian NESP 980202 Study Group. Novel erythropoiesis stimulating protein for treatment of anemia in chronic renal insufficiency Kidney Int. 2001; 60:741-7.

5. Suranyi M, Walker R, Jackson L et al. Novel erythropoiesis stimulating protein (NESP) administered once every other week corrects anemia in patients with chronic renal insufficiency (CRI). Paper presented at 33rd American Society of Nephrology annual meeting. Toronto, Canada: 2000 Oct. Abstract 1873.

6. Nissenson AR, Swan SK, Lindberg JS et al. Novel erythropoiesis stimulating protein (NESP) safely maintains hemoglobin concentration levels in hemodialysis patients as effectively as r-HuEPO when administered once weekly. Paper presented at 33rd American Society of Nephrology annual meeting. Toronto, Canada: 2000 Oct. Abstract 1326.

7. Vanrenterghem P, Barany P, Mann J, on behalf of the European/Australian NESP 970290 Study Group. Novel erythropoiesis stimulating protein (NESP) maintains hemoglobin (Hgb) in ESRD patients when administered once weekly or once every other week. Paper presented at 32nd American Society of Nephrology annual meeting. Miami, FL: 1999 Nov. Abstract 1365.

8. NESP Usage Guidelines Group. Practical guidelines for the use of NESP in treating renal anaemia. Nephrol Dial Transplant. 2001; 16(Suppl 3):22-8.

9. Amgen Inc. Darbepoetin alfa: Summary of clinical publications. Thousand Oaks, CA; undated.

10. Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer. 2001; 84(Suppl 1):3-10. [PubMed 11308268]

11. Graf H, Lacombe JL, Braun J et al. Novel erythropoiesis stimulating protein (NESP) effectively maintains hemoglobin (Hgb) when administered at a reduced dose frequency compared with recombinant human erythropoietin (r-HuEPO) in ESRD patients. Paper presented at 33rd American Society of Nephrology annual meeting. Toronto, Canada: 2000 Oct. Abstract.

12. Anon. Darbepoetin (Aranesp)—a long-acting erythropoietin. Med Lett Drugs Ther. 2001; 43:109-10. [PubMed 11740411]

13. Amgen, Thousand Oaks, CA: Personal communication.

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