darbepoetin


Also found in: Dictionary, Wikipedia.

darbepoetin

(dar-be-poh-e-tin) ,

Aranesp

(trade name)

Classification

Therapeutic: antianemics
Pharmacologic: hormones
Pregnancy Category: C

Indications

Anemia associated with chronic kidney disease (CKD).Chemotherapy-induced anemia in patients with non-myeloid malignancies.

Action

Stimulates erythropoiesis (production of red blood cells).

Therapeutic effects

Maintains and may elevate red blood cell counts, decreasing the need for transfusions.

Pharmacokinetics

Absorption: 30–50% following subcut administration; IV administration results in complete bioavailability.
Distribution: Confined to the intravascular space.
Metabolism and Excretion: Unknown.
Half-life: Subcut—49 hr; IV—21 hr.

Time/action profile (↑ in RBCs)

ROUTEONSETPEAKDURATION
IV, Subcut2–6 wkunknownunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Uncontrolled hypertension;Patients receiving chemotherapy when anticipated outcome is cure.
Use Cautiously in: Cardiovascular disease or stroke;Underlying hematologic diseases, including hemolytic anemia, sickle-cell anemia, thalassemia and porphyria (safety not established); Obstetric / Lactation / Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • seizures (life-threatening)
  • dizziness (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)
  • weakness

Respiratory

  • cough (most frequent)
  • dyspnea (most frequent)
  • bronchitis

Cardiovascular

  • HF (life-threatening)
  • mi (life-threatening)
  • stroke (life-threatening)
  • thromboembolic events (especially with hemoglobin >11 g/dL) (life-threatening)
  • edema
  • hypertension (most frequent)
  • hypotension (most frequent)
  • chest pain

Gastrointestinal

  • abdominal pain (most frequent)
  • nausea (most frequent)
  • diarrhea (most frequent)
  • vomiting (most frequent)
  • constipation

Dermatologic

  • pruritus

Hematologic

  • pure red cell aplasia

Musculoskeletal

  • myalgia (most frequent)
  • arthralgia
  • back pain
  • limb pain

Miscellaneous

  • fever (most frequent)
  • allergic reactions, flu-like syndrome
  • sepsis
  • ↑ mortality and ↑ tumor growth (with hemoglobin ≥12 g/dL)

Interactions

Drug-Drug interaction

None reported.

Route/Dosage

Anemia due to Chronic Renal Failure

(Do not initiate if hemoglobin ≥10 g/dL)
Intravenous Subcutaneous (Adults) Starting treatment with darbepoetin (no previous epoetin)—0.45 mcg/kg once weekly (may start with 0.75 mcg/kg q 2 wk in patients not on dialysis); use lowest dose sufficient to ↓ the need for red blood cell transfusions (do not exceed hemoglobin of 10 g/dL [patients on dialysis] or 11 g/dL [patients not on dialysis]); if Hgb ↑ by >1.0 g/dL in 2 wk, ↓ dose by 25%; if Hgb ↑ by <1.0 g/dL after 4 wk of therapy (with adequate iron stores), ↑ dose by 25%; do not ↑ dose more frequently than q 4 wk. Conversion from epoetin to darbepoetin—weekly epoetin dose <2500 units = 6.25 mcg/week darbepoetin, weekly epoetin dose 2500–4999 units = 12.5 mcg/week darbepoetin, weekly epoetin dose 5000–10,999 units = 25 mcg/week darbepoetin, weekly epoetin dose 11,000–17,999 units = 40 mcg/week darbepoetin, weekly epoetin dose 18,000–33,999 units = 60 mcg/week darbepoetin, weekly epoetin dose 34,000–89,999 units = 100 mcg/week darbepoetin, weekly epoetin dose >90,000 units = 200 mcg/week darbepoetin.

Anemia due to Chemotherapy

(Use only for chemotherapy-related anemia and discontinue when chemotherapy course is completed; do not initiate if hemoglobin ≥10 g/dL.)
Subcutaneous (Adults) 2.25 mcg/kg weekly or 500 mcg q 3 wk; target Hgb should not exceed 12 g/dL. If Hgb ↑ by >1.0 g/dL in 2 wk or or reaches a level needed to avoid red blood cell transfusions, ↓ dose by 40%; if Hgb ↑ by <1.0 g/dL after 6 wk of therapy, ↑ dose to 4.5 mcg/kg weekly.

Availability

Albumin solution for injection: 25 mcg/mL 1-mL vial, 40 mcg/mL 1-mL vial, 60 mcg/mL 1-mL vial, 100 mcg/mL 1-mL vial, 150 mcg/mL 0.75-mL vial, 200 mcg/mL 1-mL vial, 300 mcg/mL 1-mL vial, 500 mcg/mL 1-mL vial
Pre-filled syringes: 25 mcg/0.42 mL, 40 mcg/0.4 mL, 60 mcg/0.3 mL, 100 mcg/0.5 mL, 150 mcg/0.3 mL, 200 mcg/0.4 mL, 300 mcg/0.6 mL, 500 mcg/1 mL

Nursing implications

Nursing assessment

  • Monitor BP before and during therapy. Inform health care professional if severe hypertension is present or if BP begins to increase. Additional antihypertensive therapy may be required during initiation of therapy.
  • Monitor response for symptoms of anemia (fatigue, dyspnea, pallor).
  • Monitor dialysis shunts (thrill and bruit) and status of artificial kidney during hemodialysis. May need to increase heparin dose to prevent clotting. Monitor patients with underlying vascular disease for impaired circulation.
  • Monitor for allergic reactions (rash, utricaria). Discontinue darbepoetin if signs of anaphylaxis (dyspnea, laryngeal swelling) occur.
  • Lab Test Considerations: May cause ↑ in WBCs and platelets. May ↓ bleeding times.
    • Monitor serum ferritin, transferrin, and iron levels prior to and during therapy to assess need for concurrent iron therapy. Administer supplemental iron therapy if transferrin saturation <20% or serum ferritin is <100 mcg/mL.
  • Monitor hemoglobin before and weekly during initial therapy, for 4 wk after a change in dose, and regularly after target range has been reached and maintenance dose is determined. Monitor other hematopoietic parameters (CBC with differential and platelet count) before and periodically during therapy. If hemoglobin ↑ of more than 1.0 g/dL in any 2-wk period or hemoglobin reaches a level needed to avoid RBC transfusion, ↓ dose by 40%. If hemoglobin exceeds a level needed to avoid RBC transfusion, withhold dose until hemoglobin approaches level where RBC transfusions may be required and reinitiate at a dose 40% below the previous dose. If hemoglobin ↑ by less than 1 g/dL and remains below 10 g/dL after 6 wk of therapy, ↑ dose to 4.5 mcg/kg/wk (if on weekly therapy) or do not adjust dose (if on every 3 wk schedule). If there is no response as measured by hemoglobin levels or if RBC transfusions are still required after 8 wks of therapy, following completion of a chemotherapy course, discontinue darbepoetin. Hemoglobin >11 g/dL increases the likelihood of life-threatening cardiovascular complications, cardiac arrest, neurologic events (seizures, stroke), hypertensive reactions, HF, vascular thrombosis/ischemia/infarction, acute MI, and fluid overload/edema.
    • Only prescribers and hospitals enrolled in the ESA APPRISE Oncology Program can provide darbepoetin for patients with cancer. Visit www.esa-apprise.com or call 1-866-284-8089.
    • If ↑ in hemoglobin is less than 1 g/dL over 4 wk and iron stores are adequate, dose may be ↑ by 25% of previous dose. Use the lowest dose possible to avoid transfusions.
    • Monitor renal function studies and electrolytes closely; resulting increased sense of well-being may lead to decreased compliance with other therapies for renal failure.

Potential Nursing Diagnoses

Activity intolerance (Indications)

Implementation

  • Transfusions are still required for severe symptomatic anemia. Supplemental iron should be initiated with darbepoetin and continued during therapy. Correct deficiencies of folic acid or vitamin B12 prior to therapy.
    • Institute seizure precautions in patients who experience greater than a 1.0 g/dL increase in hemoglobin in a 2-wk period or exhibit any change in neurologic status.
    • For conversion from epoetin alfa to darbepoetin, if epoetin was administered 2–3 times/wk administer darbepoetin once a week. If patient was receiving epoetin once/wk, darbepoetin may be administered once every 2 wk. Route of administration should remain consistent.
    • Dose adjustments should not be more frequent than once/month.
    • Do not shake vial; inactivation of medication may occur. Do not administer vials containing solution that is discolored or contains particulate matter. Discard vial immediately after withdrawing dose. Do not pool unused portions.
  • Subcutaneous: This route is often used for patients not requiring dialysis.
  • Intravenous Administration
  • pH: 6.0–6.4.
  • Administer undiluted.
  • Rate: May be administered as direct injection or bolus over 1–3 min into IV tubing or via venous line at end of dialysis session.
  • Y-Site Incompatibility: Do not administer in conjunction with other drugs or solutions.

Patient/Family Teaching

  • Explain ESA APPRISE Oncology Program and the rationale for concurrent iron therapy (increased red blood cell production requires iron). Instruct patient to read the Medication Guide prior to beginning therapy. Inform patients of risks and benefits of darbepoetin. Inform patients with cancer that they must sign the patient-health care provider acknowledgment form before the start of each treatment course.
    • Discuss possible return of menses and fertility in women of child-bearing age. Patient should discuss contraceptive options with health care professional.
    • Discuss ways of preventing self-injury in patients at risk for seizures. Driving and activities requiring continuous alertness should be avoided.
    • Inform patient that use of darbepoetin may result in shortened overall survival and/or ↓ time to tumor progression. May also cause MI or stroke. Advise patient to notify health care professional immediately if chest pain; trouble breathing or shortness of breath; pain in legs, with or without swelling; a cool or pale arm or leg; sudden confusion, trouble speaking, or trouble understanding others’ speech; sudden numbness or weakness in face, arm, or leg, especially on one side of body; sudden trouble seeing; sudden trouble walking, dizziness, loss of balance or coordination; loss of consciousness (fainting); or hemodialysis vascular access stops working.
  • Anemia of Chronic Kidney Disease: Stress importance of compliance with dietary restrictions, medications, and dialysis. Foods high in iron and low in potassium include liver, pork, veal, beef, mustard and turnip greens, peas, eggs, broccoli, kale, blackberries, strawberries, apple juice, watermelon, oatmeal, and enriched bread. Darbepoetin will result in increased sense of well-being, but it does not cure underlying disease.
  • Home Care Issues: Home dialysis patients determined to be able to safely and effectively administer darbepoetin should be taught proper dose, administration technique with syringe, auto-injector or IV use, and disposal of equipment. Information for Patients and Caregivers should be provided to patient along with medication.

Evaluation/Desired Outcomes

  • Increase in hemoglobin not to exceed 11 g/dL with improvement in symptoms of anemia in patients with chronic renal failure or with chemotherapy-induced anemia.
References in periodicals archive ?
Amongst all synthetic erythropoietin products, Epoetin alfa and its advance version, Darbepoetin alfa, are the most popular drugs.
In addition, Amgen currently owns the patent Aranesp for Darbepoetin alfa; which is expected to expire by 2016, thus, calling for launch of Darbepoetin alfa biosimilars.
4% of those with a history of malignancy at baseline died from cancer in the darbepoetin arm compared to 0.
Darbepoetin alfa, marketed as Arandesp, and epoetin alfa, marketed as Epogen o and Procrit, are the ESAs approved in the United States; they are administered as often as one to three times per week.
American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer.
The study showed that darbepoetin alpha works no better than a placebo for improving cardiovascular and kidney outcomes, but it did lower the risk for blood transfusion and resulted in modest improvement in patient-reported outcomes among people with diabetes, kidney disease and anemia.
A proposed Amgen study of more than 6,000 patients with advanced breast, lung, or colorectal cancer will compare overall survival and progression-free survival in patients who receive darbepoetin alfa (dosed to target a 12-g/dL hemoglobin level) or placebo.
MIRCERA is the only drug to have compared itself in its registration program to three ESAs: epoetin alfa, beta and darbepoetin alfa.
Cancer treatment will represent the fastest growing application for biologics due to the ineffectiveness of many existing therapies and the increasing penetration of new recombinant proteins such as darbepoetin alfa, new monoclonal antibodies such as alemtuzumab and, in the long term, new preventive vaccines against most common malignancies.
Novel erythropoiesis-stimulating protein (Aranesp[TM]; darbepoetin alfa) is a glycoprotein hormone with a longer serum half-life than recombinant human erythropoietin (rHuEPO) (1).
The Food and Drug Administration (FDA) approved darbepoetin alfa (Aranesp) for treatment of anemia as sociated with chronic renal failure (CRF) in patients on dialysis and patients not on dialysis (1).
Disgraced Spanish cross country skier Johann Muehlegg is pleading innocence after testing positive for the blood-boosting drug darbepoetin (NESP).