darbepoetin alfa (Rx)

Brand and Other Names:Aranesp
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 25mcg/mL
  • 40mcg/mL
  • 60mcg/mL
  • 100mcg/mL
  • 200mcg/mL
  • 300mcg/mL
  • 500mcg/mL

prefilled syringe

  • 25mcg
  • 40mcg
  • 60mcg
  • 100mcg
  • 150mcg
  • 200mcg
  • 300mcg
  • 500mcg
more...

Chronic Kidney Disease-Associated Anemia

CKD not on dialysis

  • Consider initiating ESA treatment only when the hemoglobin level is <10 g/dL and the following considerations apply:
  • 1) The rate of hemoglobin decline indicates the likelihood of requiring a red blood cell transfusion; and
  • 2) Reducing the risk of alloimmunization and/or other red blood cell transfusion-related risks is a goal
  • If the hemoglobin level exceeds 10 g/dL, reduce or interrupt ESA dose and use the lowest dose sufficient to reduce the need for red blood cell transfusions
  • Recommended starting dose: 0.45 mcg/kg IV/SC q4weeks  

CKD on dialysis

  • Initiate ESA treatment when the hemoglobin level is <10 g/dL
  • If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of ESA
  • Recommended starting dose: 0.45 mcg/kg IV or SC qWeek or 0.75 mcg/kg q2weeks; the IV route is recommended for patietns on hemodialysis 
  • Intravenous route recommended for patients on hemodialysis

Dose adjustment & monitoring

  • Evaluate iron status before and during treatment and maintain iron repletion
  • When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly
  • When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability
  • A single hemoglobin excursion may not require a dosing change
  • Do not increase the dose more frequently than once every 4 weeks
  • Decreases in dose can occur more frequently; avoid frequent dose adjustment
  • If the hemoglobin rises rapidly (eg, more than 1 g/dL in any 2-week period), reduce the dose by 25% or more as needed to reduce rapid responses
  • For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%

Dosing information

  • For patients who do not respond adequately over a 12-week escalation period, increasing the dose further is unlikely to improve response and may increase risks
  • Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions
  • Evaluate other causes of anemia
  • Discontinue if responsiveness does not improve
  • Hemoglobin target removed from labeling: The drug label previously recommended that ESAs should be dosed to achieve and maintain hemoglobin levels within the target range of 10-12 g/dL in CKD patients; this target concept is now removed from the labeling
  • Withhold dose if Hgb continues to increase after dosage decrease
  • Monitor: Hgb, iron, Hct, renal function

Chemotherapy-Related Anemia with Nonmyeloid Malignancies

2.25 mcg/kg SC qWeek OR 500 mcg SC q3Weeks 

If Hgb increases <1 g/dL after 6 weeks, may increase dose no more than 4.5 mcg/kg

Reduce dose by 40% if rapid increase in Hgb (eg, >1 g/dL in 2-week period)

Discontinue if no response after 8 weeks

Dosage Forms & Strengths

injectable solution

  • 25mcg/mL
  • 40mcg/mL
  • 60mcg/mL
  • 100mcg/mL
  • 200mcg/mL
  • 300mcg/mL
  • 500mcg/mL

prefilled syringe

  • 25mcg
  • 40mcg
  • 60mcg
  • 100mcg
  • 150mcg
  • 200mcg
  • 300mcg
  • 500mcg
more...

Chronic Kidney Disease-Associated Anemia

≥1 month:

Initiate treatment when the hemoglobin level is <10 g/dL

If the hemoglobin level approaches or exceeds 12 g/dL, reduce or interrupt the dose

Recommended starting dose for pediatric patients (<18 yr) is 0.45 mcg/kg SC or IV qWeek

Patients not receiving dialysis may also be initiated at a dose of 0.75 mcg/kg q2Week

Conversion from epoetin alfa

  • EPO 1500-2499 unit/week: 6.25 mcg/week SC
  • EPO 2500-4999 unit/week: 10 mcg/week SC
  • EPO 5000-10,999 unit/week: 20 mcg/week SC
  • EPO 11,000-17,999 unit/week: 40 mcg/week SC
  • EPO 18,000-33,999 unit/week: 60 mcg/week SC
  • EPO 34,000-89,999 unit/week: 100 mcg/week SC
  • EPO 90,000 unit/week or greater: 200 mcg/week SC

Dosage modification

  • Reduce dose by 25% if rapid increase in Hgb (eg, >1 g/dL in 2-week period)
  • If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of ESA

Chemotherapy-related Anemia

Safety and efficacy not established

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Adverse Effects

>10%

Cancer patients

  • Fatigue (33%)
  • Diarrhea (22%)
  • Edema (21%)
  • Fever (19%)
  • Dizziness (14%)
  • Arthralgia (13%)
  • Headache (12%)
  • Death (10%)

Chronic renal failure patients

  • Infectious disease (24%)
  • Hyper/Hypotension (20%)
  • Spasm (17%)
  • Upper respiratory infection, Headache (15%)
  • Diarrhea, Vomiting (14%)
  • Nausea (11%)
  • Peripheral edema, Dyspnea (10%)
  • Abdominal pain (10%)

1-10%

Cancer patients

  • Myalgia (8%)
  • Hypertension (3.7%)
  • Pneumonia (3%)
  • Dyspnea (2%)
  • Vomiting (2%)
  • Pulmonary embolism (1.3%)

Chronic renal failure patients

  • Arthralgia, Cough, Fatigue (9%)
  • Limb pain (8%)
  • Dizziness, Fever (7%)
  • Death (6%)
  • Edema (6%)
  • Anemia, DVT, red cell aplasia (5.6%)
  • Cardiac arrest, Cardiac dysrhythmia, Congestive heart failure (5%)
  • Myocardial infarction, CVA (2%)

<1%

Cancer patients

  • Hypertensive encephalopathy (0.6%)
  • Seizure (0.6%)

Chronic renal failure patients

  • Hypertensive encephalopathy (<1%)
  • Seizure (<1%)
  • Transient ischemic attack (<1% )

Frequency Not Defined

Tumor progression

Venous thromboembolism

Immune hypersensitivity reaction (rare )

Injection site thrombosis

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Warnings

Black Box Warnings

Chronic kidney disease (CKD)

  • In controlled trials with CKD patients, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to a target hemoglobin level of greater than 11 g/dL
  • No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks
  • Use the lowest dose sufficient to reduce the need for red blood cell (RBC) transfusions

Cancer

  • ESAs shortened overall survival and/or increased the risk of tumor progression in some clinical studies in patients with breast, head, and neck; lymphoid; non-small cell lung; and cervical cancers
  • Prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense ESAs to patients with cancer
  • Use the lowest dose to avoid RBC transfusions
  • Use ESAs only for 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

Cardiovascular Events

  • Increased risk of serious cardivascular events including stroke and thromboembolic  events

Contraindications

Uncontrolled hypertension

Hypersensitivity to any component

Cancer patients whose anemia is due to causes other than chemotherapy

Cautions

Increased mortality, myocardial infarction, stroke, and thromboembolism: Using ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit (see Black Box Warnings)

Known porphyria, sickle cell anemia, thalassemia

Decrease dose if Hgb increase exceeds 1 g/dL in any 2 wk period

Increased mortality and/or increased risk of tumor progression or recurrence in patients with cancer

Increases the risk for seizures in patients with CKD; increase monitoring of these patients for changes in seizure frequency or premonitory symptoms

If severe anemia and low reticulocyte count develop during treatment, withhold therapy and evaluate for pure red cell aplasia

Two different excipients available: polysorbate 80 or human albumin

May use supplemental iron if serum ferritin <100 mcg/L [0.225 pmol/L] or serum transferrin saturation <20%

IV route preferred for patients on hemodialysis

Autoinjector for SC administration only

Dose increase no more frequently than once monthly

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Pregnancy & Lactation

Pregnancy

Limited available data on pregnant women are insufficient to determine a drug-associated risk of major birth defects or miscarriage; in animal reproductive and developmental toxicity studies, drug increased early post-implantation loss at doses approximating clinical recommended starting doses; consider benefits and risks for the mother and possible risks to fetus when prescribing to a pregnant woman

Animal data

  • When Aranesp was administered intravenously during organogenesis to pregnant rats (gestational days 6 to 15) and rabbits (gestational days 6 to 18), there was no evidence of embryofetal toxicity or other adverse outcomes at intravenous doses tested, up to 20 mcg/kg/day; no significant placental transfer was observed in rats; placental transfer was not evaluated in rabbits
  • In a peri/postnatal development study, pregnant female rats received therapy intravenously every other day from implantation (day 6) throughout pregnancy and lactation (day 23); the lowest dose tested, 0.5 mcg/kg, did not cause fetal toxicity; this dose is approximately equivalent to clinical recommended starting dose; at maternal doses of 2.5 mcg/kg and higher, pups had decreased fetal body weights, which correlated with a slight increase in the incidence of fetal deaths, as well as delayed eye opening and delayed preputial separation; the offspring (F1 generation) of treated rats were observed postnatally; rats from F1 generation reached maturity and were mated; no treatment related effects were apparent for their offspring (F2 generation fetuses)

Lactation

There is no information regarding presence of drug in human milk, effects on breastfed child, or on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

more...
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Pharmacology

Mechanism of Action

Recombinant human erythropoietin with sialic acid additions to enhance stability; stimulates erythropoiesis via division & differentation of progenitor cells in bone marrow to induce the release of reticulocytes from the bone marrow into the bloodstream to become erythrocytes.

Pharmacokinetics

Half-Life: 46 hr (SC), 21 hr (IV)

Peak Plasma Time: 34 hr (SC)

Vd: 0.06 L/kg

Absorption: Slow (SC)

Bioavailability: 37% (SC; adults); 54% (SC; children)

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Administration

IV Incompatibilities

Do not dilute or administer with other solutions

IV Administration

May be administered SC or IV bolus

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

Discontinue immediately if signs/symptoms of anaphylaxis occur

Storage

Store at 2-8°C (36-46°F)

Do not freeze or shake

Protect from light

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Images

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

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Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.