darbepoetin (dar-be-poh-e-tin) Aranesp

 Indications

Anemia associated with chronic kidney disease (CKD).

Chemotherapy-induced anemia in patients with nonmyeloid

malignancies when there is 2 additional mo

of planned chemotherapy.

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 (q in RBCs)

ROUTE ONSET PEAK DURATION

IV, Subcut 2–6 wk unknown unknown

Contraindications/Precautions

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, Lactation: Safety

not established.

Adverse Reactions/Side Effects

CNS: SEIZURES, dizziness, fatigue, headache, weakness.

Resp: cough, dyspnea, bronchitis. CV: HF, MI, STROKE,

THROMBOEMBOLIC EVENTS (especially with hemoglobin

11 g/dL), edema, hypertension, hypotension, chest

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

constipation. Derm: STEPHENS-JOHNSON SYNDROME,

TOXIC EPIDERMAL NECROLYSIS, pruritus. Hemat: pure

red cell aplasia. MS: myalgia, arthralgia, back pain,

limb pain. Misc: fever, allergic reactions, flu-like syndrome, sepsis,qmortality andqtumor growth

(with hemoglobin 12 g/dL).

Interactions

Drug-Drug: None reported.

Route/Dosage

Anemia due to Chronic Kidney Disease

(Do not initiate if hemoglobin 10 g/dL; should only

consider initiating therapy in patients not on dialysis if

rate of hemoglobin decline indicates likelihood of requiring

a red blood cell transfusion and a goal is to reduce

the risk of alloimmunization and/or red blood cell

transfusion risks).

IV, Subcut (Adults): Starting treatment with darbepoetin

(no previous epoetin)—0.45 mcg/kg once

weekly or 0.75 mcg/kg q 2 wk (for patients on dialysis);

0.45 mcg/kg q 4 wk (for patients not on dialysis);

use lowest dose sufficient topthe need for red blood

cell transfusions (do not exceed hemoglobin of 10 g/dL

[patients not on dialysis] or 11 g/dL [patients on dialysis]);

if Hgbqby 1.0 g/dL in 2 wk,pdose by 25%; if

Hgbqby 1.0 g/dL after 4 wk of therapy (with adequate

iron stores),qdose by 25%; do notqdose 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 units12.5 mcg/week darbepoetin,

weekly epoetin dose 5000–10,999 units25 mcg/

week darbepoetin, weekly epoetin dose 11,000–

17,999 units40 mcg/week darbepoetin, weekly

epoetin dose 18,000–33,999 units60 mcg/week

darbepoetin, weekly epoetin dose 34,000–89,999

units100 mcg/week darbepoetin, weekly epoetin

dose 90,000 units200 mcg/week darbepoetin.

IV, Subcut (Children): Starting treatment with darbepoetin

(no previous epoetin)—0.45 mcg/kg once

weekly (may also start with 0.75 mcg/kg q 2 wk in patients

not on dialysis); use lowest dose sufficient top

the need for red blood cell transfusions (do not exceed

hemoglobin of 12 g/dL; if Hgbqby 1.0 g/dL in 2 wk,

pdose by 25%; if Hgbqby 1.0 g/dL after 4 wk of

therapy (with adequate iron stores),qdose by 25%; do

notqdose more frequently than q 4 wk.

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.).

Subcut (Adults): 2.25 mcg/kg weekly or 500 mcg q 3

wk; target Hgb should not exceed 12 g/dL. If Hgbqby

1.0 g/dL in 2 wk or or reaches a level needed to avoid

red blood cell transfusions,pdose by 40%; if Hgbqby

1.0 g/dL after 6 wk of therapy,qdose to 4.5 mcg/kg

weekly.

Availability

Solution for injection (single-dose vials): 25 mcg/

1 mL, 40 mcg/1 mL, 60 mcg/1 mL, 100 mcg/1 mL, 150

mcg/0.75 mL, 200 mcg/1 mL, 300 mcg/1 mL, 500 mcg/

1 mL. Solution for injection (pre-filled 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.