Dosing and uses of Aranesp (darbepoetin alfa)
Adult dosage forms and 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
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
Pediatric dosage forms and 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
Chronic Kidney Disease-Associated Anemia
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
Aranesp (darbepoetin alfa) adverse (side) 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
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
CRF: Risk of seizures in early part of treatment
Associated with 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
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if excreted in breast milk, use caution
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.
Pharmacology of Aranesp (darbepoetin alfa)
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)
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
