Systemic Therapy Program

Search Again

Date



Disease Group



Cancer Type

Document Type

Drug Monographs
Treatment Regimens

Scientific Name:
DARBEPOETIN
Brand Name(s):
Aranesp®

Drug Monograph

Pharmacology

Mechanism of Action

Darbepoietin is an erythropoiesis stimulating protein closely related to epoietin. Darbepoetin induces erythropoiesis by stimulating the division and differentiation of committed erythroid progenitor cells; it induces the release of reticulocytes from the bone marrow into the blood stream, where they mature to erythrocytes in a dose-response manner.  Darbepoetin is a 165-amino acid protein that differs from recombinant human epoietin in containing 5 N-linked oligosaccharide chains, whereas recombinant human erythropoietin contains 3. The 2 additional N-glycosylation sites result from amino acid substitutions in the erythropoietin peptide backbone.

Pharmacokinetics

Absorption:
inactive orally
SC administration: absorption is slow and rate-limiting; bioavailability approximately 37% (range: 30% to 50%)
Distribution:
Onset of action: steady-state serum levels are achieved within 4 weeks
Distributes confined to the vascular space; biphasic serum concentration-time profiles
SC- peak concentration at 34 hours (range: 24 to 72 hours)
Excretion in breast-milk unknown
Cross blood brain barrier?  No information
Vd:  approx. 60 mL/kg
PPB: no information
Metabolism:
No information, but presumed to be similar to Epoietin
Excretion:
dose-linearity over therapeutic dose range
terminal t½  IV- approximately 21 hours; SC- 49 hours (range: 27 to 89 hours)
 approximately 3-fold longer terminal half-life than Epoetin alfa

Side Effects

IMMEDIATE ONSET (hours to days)

• angina/chest pain (8%)
• congestive heart failure (6%)
• cardiac arrythmias, cardiac arrest (10%)
• nausea (14%), vomiting (15%), diarrhea (16%)

EARLY ONSET  (days to weeks)

infection (27%)- includes sepsis, bacteremia, pneumonia, peritonitis, and
   abscess.
headache (16%), myalgia (21%), arthralgia (11%)
hypertension (23%)- increased hematocrit & blood viscosity; hypotension (24%)
• thrombosis vascular access (8%)
• bone pain (11%)

Therapeutics

Approved Indications

OTHER ONCOLOGY USES (Not Approved)
Treatment of anemia associated with chemotherapy for non-myeloid malignancies

Routes

Intravenous
Subcutaneous

Administration

• IV or SC as a single weekly injection
• dose should be adjusted for each patient to achieve and maintain a target hemoglobin level not to exceed 12 g/dL

IV Compatibility

No information

Dosing

Injection:
• Initial: 0.45µg/Kg IV/SC once weekly; titrate dose q2weeks to achieve target hemoglobin level (dosage used for chronic renal failure)
• Conversion from daily Epoetin Alfa to Darbepoetin:
Convert total Epoietin Alfa dose to weekly total, then find Darbepoietin equivalent dose
Epoietin- IU/week             5000-    11000-   18000-   34000-   >90000
                                       10999     17999     33999     89999
Darbepoietin- µg/week   25          25              40           100            200
(or µg/ 2 weeks)
• If Epoietin was given tiw, then give Darbepoetin q week; if Epoietin was given q week, then give Darbepoetin q 2 weeks

Adequate trial:  
• If hemoglobin does not increase by 1g/dL over 4 weeks from initial dose of Darbepoetin, then increase dose by about 25%.  Do not increase dose more often than once every 4 weeks
• If hemoglobin increases by >1g/dL in 2 weeks or less, decrease dose by 25%

Dose Adjustment Criteria

Estimated Darbepoietin Starting Doses (µg/week) Based on Previous Epoetin alfa Dose (Units/week)
Previous Weekly   Weekly Darbepoetin
Epoetin alfa Dose  Dose (µg/week)
(Units/week)
< 2,500                        6.25
2,500 to 4,999             12.5
5,000 to 10,999           25
11,000 to 17,999         40
18,000 to 33,999         60
34,000 to 89,999         100
> 90,000                      200

Contraindications

• Uncontrolled hypertension • Known hypersensitivity to the active substance or any of the excipients

Monitoring

Clinical Monitoring

RECOMMENDED CRITERIA
• Routine blood pressure monitoring during IV infusions, especially in hypertensive patients (or at regular clinic visits while darbepoetin therapy is recently started)
Hematocrit and iron status (serum ferritin and/or transferrin saturation levels) monitored regularly

Significant Interactions

None known to date.

Product Information

Commercial Product Description

Vials with 25µg, 40µg, 60µg, 100µg, or 200µg. Keep under refrigeration

Pharmaceutical Considerations

Injection:
Single dose vials with 25µg/mL, 40µg/mL, 60µg/mL, 100µg/mL, 150µg/0.75mL, 200µg/mL, 300µg/mL, 500µg/mL.  Single use vials.  Store in refrigerator at 2-8oC; do not freeze.  Do not shake vials.  Protect from light.  Do not dilute or administer with any other solutions.

Note

Pure Red Cell Aplasia (PRCA) and Severe Anemia with Neutralizing Antibodies
Pure red cell aplasia (PRCA) is a rare condition that has been associated with autoimmune, viral and neoplastic diseases. It has also occurred as an adverse consequence of certain therapies. Antibody-mediated PRCA develops when antibodies form to block or reduce the body’s ability to make red blood cells, causing severe anemia. One cause of antibody-mediated PRCA occurs when a patient develops neutralizing antibodies against an erythropoiesis stimulating proteins (ESP). In other cases, antibody-mediated PRCA occurs spontaneously without any prior exposure to ESPs.  If a patient fails to respond or maintain a response to the prescribed ESP, an evaluation for causative factors should be undertaken. If anti-erythropoietin antibody-associated anemia is suspected, physicians should withhold the prescribed ESP and other erythropoietic proteins.

Health Canada Advisories:
• Important safety information regarding risks of tumour progression and serious cardiovascular events (April 2007).
Serious Warnings and Precautions:
• Patients with uncontrolled hypertension should not receive Aranesp; blood pressure should be adequately controlled before initiating treatment with Aranesp.
• Erythropoiesis-stimulating proteins may increase the risk of thrombotic vascular events which can be fatal. Patients with existing vascular disease should be monitored closely. Patients on hemodialysis should be monitored closely for increased risk of vascular access thrombosis.
• Use with caution in patients with a history of seizures.
• Antibody-mediated Pure Red Cell Aplasia (PRCA) has been reported after months to years of treatment with recombinant erythropoietins.

Availability & Funding

Administrative Information (Nova Scotia)

• CCNS Provincial Formulary Status- Restricted as per CDHA criteria •• Pharmacare Formulary Status- Non-Formulary Go to "Additional Information" tab (above) for links to Privincial Formulary of Cancer Drugs.



© 2017 Cancer Care Nova Scotia    Sitemap | Privacy                                                                                                        Report broken links and errors to nshealth.ca