darbepoetin

ROUTE	ONSET	PEAK	DURATION
IV, SUBQ	2–6 wk	unknown	unknown

Contraindicated in:

Hypersensitivity;
Uncontrolled hypertension;
Patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy;
Patients receiving chemotherapy when anticipated outcome is cure;
Patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion;
Patients who require immediate correction of anemia when RBC transfusions can be used instead.

Use Cautiously in:

Cardiovascular disease or stroke;
Underlying hematologic diseases, including hemolytic anemia, sickle-cell anemia, thalassemia, and porphyria (safety not established);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Safety not established in breastfeeding.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, hypotension, chest pain, DEEP VEIN THROMBOSIS (ESPECIALLY WITH HGB >11 G/DL), edema, HF, MI

Derm: ERYTHEMA MULTIFORME, pruritus, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

GI: abdominal pain, diarrhea, nausea, vomiting, constipation

Hemat: pure red cell aplasia

MS: myalgia, arthralgia, back pain, limb pain

Neuro: dizziness, fatigue, headache, SEIZURES, STROKE, weakness

Resp: cough, dyspnea, bronchitis, PULMONARY EMBOLISM (ESPECIALLY WITH HGB >11 G/DL)

Misc: fever, ↑MORTALITY AND ↑ TUMOR GROWTH (ESPECIALLY WITH HGB >11 G/DL), HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), sepsis

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

Anemia Due to Chronic Kidney Disease

(Do not initiate if Hgb ≥10 g/dL; should only consider initiating therapy in patients not on dialysis if rate of hemoglobin decline indicates likelihood of requiring a RBC transfusion and a goal is to reduce the risk of alloimmunization and/or RBC transfusion risks.)
IV SC (Adults ): Starting treatment with darbepoetin (no previous epoetin): 0.45 mcg/kg once weekly or 0.75 mcg/kg every 2 wk (for patients on dialysis); 0.45 mcg/kg every 4 wk (for patients not on dialysis); use lowest dose sufficient to ↓ the need for RBC transfusions (do not exceed Hgb of 10 g/dL [patients not on dialysis] or 11 g/dL [patients on dialysis]); if Hgb ↑ by >1 g/dL in 2 wk, ↓ dose by 25%; if Hgb ↑ by <1 g/dL after 4 wk of therapy (with adequate iron stores), ↑ dose by 25%; do not ↑ dose more frequently than every 4 wk. Conversion from epoetin to darbepoetin: weekly epoetin dose <2500 units = 6.25 mcg/wk darbepoetin; weekly epoetin dose 2500–4999 units = 12.5 mcg/wk darbepoetin; weekly epoetin dose 5000–10,999 units = 25 mcg/wk darbepoetin; weekly epoetin dose 11,000–17,999 units = 40 mcg/wk darbepoetin; weekly epoetin dose 18,000–33,999 units = 60 mcg/wk darbepoetin; weekly epoetin dose 34,000–89,999 units = 100 mcg/wk darbepoetin; weekly epoetin dose >90,000 units = 200 mcg/wk darbepoetin.
IV SC (Children ): Starting treatment with darbepoetin (no previous epoetin): 0.45 mcg/kg once weekly (may also start with 0.75 mcg/kg every 2 wk in patients not on dialysis); use lowest dose sufficient to ↓ the need for RBC transfusions (do not exceed Hgb of 12 g/dL; if Hgb ↑ by >1.0 g/dL in 2 wk, ↓ dose by 25%; if Hgb ↑ by <1 g/dL after 4 wk of therapy (with adequate iron stores), ↑ dose by 25%; do not ↑ dose more frequently than every 4 wk.

Anemia Due to Chemotherapy

(Use only for chemotherapy-related anemia and discontinue when chemotherapy course is completed; do not initiate if Hgb ≥10 g/dL.)
SC (Adults ): 2.25 mcg/kg weekly or 500 mcg every 3 wk; target Hgb should not exceed 12 g/dL. If Hgb ↑ by >1 g/dL in 2 wk or reaches a level needed to avoid RBC transfusions, ↓ dose by 40%; if Hgb ↑ by <1 g/dL after 6 wk of therapy, ↑ dose to 4.5 mcg/kg weekly.

Availability ⬆ ⬇

Solution for injection (single-dose vials): 25 mcg/mL; 40 mcg/mL; 60 mcg/mL; 100 mcg/mL; 200 mcg/mL; 300 mcg/mL
Solution for injection (prefilled syringes): 10 mcg/0.4 mL; 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

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, urticaria). Discontinue darbepoetin if signs of anaphylaxis (dyspnea, laryngeal swelling) occur.
Assess patient for skin rash frequently during therapy. Discontinue darbepoetin at first sign of rash; may be life-threatening. SJS or TEN may develop. Treat symptomatically; may recur once treatment is stopped.
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 Hgb weekly until the Hgb level is stable and sufficient to minimize the need for RBC transfusion after starting therapy and after each dose adjustment.
Anemia due to Chemotherapy: Monitor Hgb 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 Hgb ↑ by more than 1 g/dL in any 2-wk period or Hgb reaches a level needed to avoid RBC transfusion,↓ dose by 40%. If Hgb exceeds a level needed to avoid RBC transfusion, withhold dose until Hgb approaches level where RBC transfusions may be required and reinitiate at a dose 40% below the previous dose. If Hgb ↑ 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 Hgb or if RBC transfusions are still required after 8 wk of therapy, following completion of a chemotherapy course, discontinue darbepoetin. Hgb >11 g/dL increases the likelihood of life-threatening cardiovascular complications, cardiac arrest, neurologic events (seizures, stroke), hypertensive reactions, HF, vascular thrombosis/ischemia/infarction, MI, and fluid overload/edema.
Anemia of CKD: Monitor Hgb at least weekly until stable, then at least monthly. Do not ↑ dose more frequently than once every 4 wk. Decreases in dose can be made more frequently. Avoid frequent dose adjustments. If Hgb ↑ by >1 g/dL in a 2-wk period,↓ dose by 25% or more. If Hgb ↑ by <1 g/dL over 4 wk (and iron stores are adequate),↑ dose by 25%. If no response after 12 wk of escalation, further dose ↑ is unlikely to improve response and may increase risks. Use lowest dose that will maintain Hgb level sufficient to reduce need for RBC transfusions.
- Adults with Anemia of CKD on DialysisStart darbepoetin when Hgb >10 g/dL. If Hgb ≥11 g/dL, reduce or hold dose.
- Adults with Anemia of CKD not on DialysisStart darbepoetin only when Hgb <10 g/dL AND rate of Hgb decline indicates likelihood of requiring a RBC transfusion AND reducing risk of alloimmunization and/or other RBC transfusion-related risks is a goal. If Hgb level >10 g/dL, reduce or hold dose, and use lowest darbepoetin dose sufficient to reduce need for RBC transfusions.
- Children with Anemia of CKDStart epoetin only when Hgb <10 g/dL. If Hgb level >12 g/dL, reduce or hold dose.
- Monitor renal function studies and electrolytes closely; resulting increased sense of well-being may lead to decreased compliance with other therapies for renal failure. Increases in BUN, serum creatinine, uric acid, phosphorus, and potassium may occur.

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 g/dL ↑ in Hgb 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 wk. 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/mo.
- 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.
SC: This route is often used for patients not requiring dialysis.

IV Administration:

IV Push: 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 ⬆ ⬇

Instruct patient to read the Medication Guide prior to beginning therapy and with each Rx refill in case of changes. Inform patients of risks and benefits of darbepoetin.
- Discuss ways of preventing self-injury in patients at risk for seizures. Driving and activities requiring continuous alertness should be avoided.
- Advise patient to stop darbepoetin and notify health care professional immediately if severe skin reactions (skin rash with itching, blisters, skin sores, peeling, areas of skin coming off) or signs and symptoms of serious allergic reactions (rash, itching, shortness of breath, wheezing, dizziness and fainting due to drop in blood pressure, swelling around mouth or eyes, fast pulse, sweating) occur.
- 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.
- Advise patient to notify health care professional of darbepoetin prior to surgery.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Anemia of CKD: 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇