Usage
Darbepoetin alfa is prescribed for the treatment of anemia associated with chronic kidney disease (CKD) in patients on dialysis and not on dialysis, and for chemotherapy-induced anemia in patients with non-myeloid malignancies. It is classified as an erythropoiesis-stimulating agent (ESA). Darbepoetin alfa stimulates erythropoiesis by binding to the erythropoietin receptor on erythroid progenitor cells in the bone marrow.
Alternate Names
Darbepoetin alfa is also known as INN-darbepoetin alfa. A popular brand name is Aranesp®.
How It Works
Pharmacodynamics: Darbepoetin alfa binds to the erythropoietin receptor on the surface of erythroid progenitor cells in the bone marrow. This binding activates intracellular signaling pathways that promote the proliferation, differentiation, and maturation of red blood cells, ultimately increasing red blood cell counts and hemoglobin levels.
Pharmacokinetics: Darbepoetin alfa can be administered intravenously or subcutaneously. Subcutaneous administration results in slower absorption and a bioavailability of approximately 37%. The terminal half-life is approximately 21 hours after intravenous administration and 49 hours after subcutaneous administration. Darbepoetin alfa is primarily eliminated through hepatic metabolism, with a small amount excreted by the kidneys.
Dosage
Standard Dosage
Adults:
Children:
- Chronic Kidney Disease-Associated Anemia (≥1 year of age): Similar dosing to adults, starting with 0.45 mcg/kg once weekly (IV or SC). Patients not receiving dialysis may also be initiated on a dose of 0.75 mcg/kg every two weeks. Children less than 6 years of age may require higher maintenance doses. Correction of anemia with once-monthly dosing has not been studied in children.
- Chemotherapy-Induced Anemia: Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: No specific dose adjustment recommended.
- Patients with Renal Impairment: Dose adjustments based on hemoglobin response are necessary.
- Patients with Hepatic Dysfunction: No specific dose adjustment recommended, but use with caution.
- Patients with Comorbid Conditions: Careful monitoring of blood pressure and other relevant parameters is necessary, especially in patients with uncontrolled hypertension or cardiovascular disease.
Clinical Use Cases
Darbepoetin alfa is not indicated for use in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is for the chronic management of anemia.
Dosage Adjustments
Dose adjustments are made based on hemoglobin response and should not be made more frequently than once a month. If hemoglobin increases rapidly (e.g., >1 g/dL in a 2-week period), reduce the dose by 25% or more. If the hemoglobin level approaches 12 g/dL, reduce the dose by approximately 25%. If hemoglobin continues to increase, temporarily withhold doses until it begins to decrease, then reinitiate therapy at a dose approximately 25% lower than the previous dose. For patients not responding adequately (hemoglobin hasn’t increased by more than 1 g/dL after 4 weeks), increase the dose by 25%. If no response after 8 weeks of therapy for chemotherapy-induced anemia, discontinue treatment. If no response after 12 weeks of escalating doses for CKD-associated anemia, increasing the dose further is unlikely to be beneficial.
Side Effects
Common Side Effects:
Hypertension, headache, dizziness, nausea, vomiting, diarrhea, edema, fatigue, injection site pain.
Rare but Serious Side Effects:
Myocardial infarction, stroke, thromboembolic events, seizures, pure red cell aplasia, hypersensitivity reactions (including anaphylaxis).
Long-Term Effects:
Worsening of hypertension, cardiovascular events.
Adverse Drug Reactions (ADR):
Pure red cell aplasia, severe hypertension, allergic reactions.
Contraindications
- Uncontrolled hypertension
- Hypersensitivity to darbepoetin alfa or any component of the formulation
- Pure red cell aplasia following treatment with any erythropoietin
Drug Interactions
- ACE inhibitors and angiotensin II receptor antagonists: Increased risk of hyperkalemia and antagonism of hypotensive effects.
- Cyclosporine and tacrolimus: Serum levels may be affected by changes in red blood cell counts.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C (data on use in pregnant women are insufficient to determine risk). Animal studies show increased early post-implantation loss at doses approximating clinical recommended starting doses. It is not known whether darbepoetin alfa is excreted in human milk. Exercise caution when administering to nursing women.
Drug Profile Summary
- Mechanism of Action: Stimulates erythropoiesis by binding to erythropoietin receptors.
- Side Effects: Hypertension, headache, dizziness, nausea, fatigue, injection site pain; rarely, serious cardiovascular and thromboembolic events, pure red cell aplasia.
- Contraindications: Uncontrolled hypertension, hypersensitivity, pure red cell aplasia following treatment with any erythropoietin.
- Drug Interactions: ACE inhibitors, angiotensin II receptor antagonists, cyclosporin, tacrolimus.
- Pregnancy & Breastfeeding: Category C; exercise caution.
- Dosage: Varies based on indication and patient characteristics.
- Monitoring Parameters: Hemoglobin, blood pressure, iron stores, electrolytes.
Popular Combinations
Iron supplementation is often given concomitantly with darbepoetin alfa to ensure adequate iron stores for erythropoiesis.
Precautions
Control hypertension before and during treatment. Monitor hemoglobin levels regularly. Monitor for signs of thromboembolic events and pure red cell aplasia. Evaluate iron stores.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Darbepoetin alfa?
A: Dosage varies based on indication and patient characteristics. See the Dosage section for specific details.
Q2: How is Darbepoetin alfa administered?
A: Darbepoetin alfa can be administered intravenously or subcutaneously.
Q3: What is the mechanism of action of Darbepoetin alfa?
A: Darbepoetin alfa stimulates erythropoiesis by binding to erythropoietin receptors on erythroid progenitor cells in the bone marrow.
Q4: What are the common side effects of Darbepoetin alfa?
A: Common side effects include hypertension, headache, dizziness, nausea, fatigue, and injection site pain.
Q5: What are the serious side effects of Darbepoetin alfa?
A: Serious side effects include myocardial infarction, stroke, thromboembolic events, seizures, pure red cell aplasia, and allergic reactions.
Q6: When should Darbepoetin alfa be avoided?
A: Darbepoetin alfa is contraindicated in patients with uncontrolled hypertension, hypersensitivity to the drug, or pure red cell aplasia following treatment with any erythropoietin.
Q7: What are the important drug interactions with Darbepoetin alfa?
A: Darbepoetin alfa may interact with ACE inhibitors, angiotensin II receptor antagonists, cyclosporine, and tacrolimus.
Q8: Can Darbepoetin alfa be used during pregnancy?
A: Darbepoetin alfa is a Pregnancy Category C drug. The risks and benefits must be carefully weighed. Animal studies suggest a potential risk of fetal harm.
Q9: Can Darbepoetin alfa be used during breastfeeding?
A: It is unknown whether darbepoetin alfa is excreted in human milk. Caution should be exercised when administering to nursing women.
Q10: How frequently should hemoglobin levels be monitored during Darbepoetin alfa treatment?
A: Hemoglobin should be monitored at least weekly until stable and then at least monthly.
