Darbepoetin Alfa

Approved Indications:

• Anemia of Chronic Kidney Disease (CKD):
• Treatment of anemia associated with CKD in adult patients on dialysis or not on dialysis.
• Anemia in Patients with Cancer:
• To reduce the need for red blood cell transfusions in patients with non-myeloid malignancies receiving chemotherapy where anemia is due to the chemotherapy.
• Anemia Associated with Zidovudine Therapy in HIV-infected Patients:
• To treat anemia in patients receiving zidovudine therapy.

Clinically Accepted Off-label Uses:

• Anemia in other chronic diseases where erythropoiesis stimulation is indicated.

Adults with CKD:

• Initial dose:
• 0.45 mcg/kg body weight administered subcutaneously once weekly, or
• 0.75 mcg/kg administered once every two weeks.
• Dose adjustments based on hemoglobin response, typically at 4-week intervals.

Adults with Chemotherapy-Induced Anemia:

• 500 mcg administered subcutaneously every 3 weeks.
• Dose adjustments individualized to maintain target hemoglobin levels.

Pediatrics:

• Safety and efficacy not well established.

Elderly:

• No specific dose adjustments recommended but monitor for adverse effects.

Renal/Hepatic Impairment:

• No dose adjustment required; monitor hemoglobin closely.

Administration Route:

• Subcutaneous injection.
• Can be given intravenously in dialysis patients if necessary.

Darbepoetin alfa is a synthetic analog of erythropoietin with additional glycosylation sites, which prolong its half-life compared to endogenous erythropoietin. It binds to erythropoietin receptors on erythroid progenitor cells in the bone marrow, stimulating proliferation and differentiation into mature red blood cells. By enhancing erythropoiesis, darbepoetin alfa increases hemoglobin levels and reduces the need for blood transfusions.

Absorption:

• Administered subcutaneously or intravenously; subcutaneous administration results in slower absorption and prolonged half-life.

Distribution:

• Distributed primarily to the vascular compartment; volume of distribution is approximately 30-50 mL/kg.

Metabolism:

• Cleared primarily by receptor-mediated endocytosis and degradation in the reticuloendothelial system.

Elimination:

• Terminal half-life after subcutaneous administration: approximately 49 hours (longer than epoetin alfa).
• After intravenous administration, half-life is approximately 21 hours.

• Pregnancy:
• FDA Category C; animal studies show adverse effects at high doses; use only if clearly needed.
• Lactation:
• Unknown if excreted in human milk; caution advised.

• Primary Class: Hematopoietic growth factor
• Subclass: Erythropoiesis-stimulating agent (ESA)

• Known hypersensitivity to darbepoetin alfa or any component of the formulation.
• Uncontrolled hypertension.
• Pure red cell aplasia (PRCA) that begins after treatment with erythropoietin products.

• Cardiovascular Risks: Increased risk of hypertension, stroke, myocardial infarction, and thromboembolism; monitor blood pressure closely.
• Pure Red Cell Aplasia: Rare cases reported with ESA therapy; monitor for loss of response.
• Tumor Progression: Possible risk in cancer patients; use lowest dose needed to avoid transfusions.
• Seizures: May occur in CKD patients during therapy; monitor neurologic status.
• Monitoring: Regularly monitor hemoglobin, hematocrit, and iron status.

Common:

• Hypertension
• Headache
• Arthralgia
• Injection site reactions
• Fatigue

Serious/Rare:

• Thromboembolic events (deep vein thrombosis, stroke)
• Pure red cell aplasia
• Seizures
• Allergic reactions, including anaphylaxis

• No significant direct pharmacokinetic interactions reported.
• Use caution with antihypertensive agents due to possible changes in blood pressure.
• Iron supplementation often required to optimize response.

• Updated guidelines recommend individualized hemoglobin targets to minimize cardiovascular risk.
• FDA warnings emphasize cautious use to avoid hemoglobin levels above 11 g/dL in CKD patients.
• Emphasis on monitoring for PRCA and thrombotic events.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Do not freeze.
• Protect from light.
• Keep in original carton until use.
• Discard any unused portion after withdrawal.