Darbepoetin Alfa

Darbepoetin alfa is an artificial protein used for the treatment of anemia associated with chronic kidney disease and chemotherapy treatment in non-myeloid malignancies.

• Darbepoetin alfa is available under the following different brand names: Aranesp

Adult and pediatric dosage

Injectable solution

• 25mcg/mL
• 40mcg/mL
• 60mcg/mL
• 100mcg/mL
• 200mcg/mL
• 300mcg/mL

Prefilled syringe

• 25mcg
• 40mcg
• 60mcg
• 100mcg
• 150mcg
• 200mcg
• 300mcg
• 500mcg

Chronic Kidney Disease-Associated Anemia

Adult dosage

• CKD not on dialysis: 0.45 mcg/kg IV/SC every 4 weeks
• CKD on dialysis: 0.45 mcg/kg IV or SC every week or 0.75 mcg/kg every 2 weeks; the IV route is recommended for patients on hemodialysis 

Pediatric dosage

• Children above 1 month: 0.45 mcg/kg SC or IV every week

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

Chemotherapy-Related Anemia with Nonmyeloid Malignancies

Adult dosage

• 2.25 mcg/kg SC every week OR 500 mcg SC every 3 weeks  
• If Hgb increases less than 1 g/dL after 6 weeks, may increase dose no more than 4.5 mcg/kg
• Reduce dose by 40% if a rapid increase in Hgb (e.g., more than 1 g/dL in a 2-week period)
• Discontinue if no response after 8 weeks

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Darbepoetin alfa include:

• low blood pressure during dialysis,
• cough, trouble breathing,
• stomach pain, or
• swelling in the arms or legs

Serious side effects of Darbepoetin alfa include:

• signs of an allergic reaction such as hives, wheezing, difficult breathing, severe dizziness or fainting, swelling in your face or throat
• severe skin reaction such as fever, sore throat, burning in your eyes, skin pain, a red or purple skin rash that spreads and causes blistering and peeling.
• heart attack symptoms like chest pain or pressure, shortness of breath, pain spreading to the jaw or shoulder, nausea, sweating;
• signs of a stroke--sudden numbness or weakness (especially on one side of the body), confusion, sudden severe headache, slurred speech, problems with vision or balance;
• signs of a blood clot--pain, swelling, warmth, redness, cold feeling, or pale appearance of an arm or leg; or
• increased blood pressure--severe headache, blurred vision, pounding in the neck or ears, anxiety, nosebleed.
• a light-headed feeling,
• unusual weakness or tiredness,
• a seizure (convulsions), or
• shortness of breath (even with mild exertion), 
• swelling, and
• rapid weight gain

Rare side effects of Darbepoetin alfa include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Darbepoetin alfa has no noted severe interactions with any other drugs
• Darbepoetin alfa has no noted serious interactions with any other drugs.
• Darbepoetin alfa has no noted moderate interactions with any other  drugs.
• Darbepoetin alfa has no noted minor interactions with any other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Uncontrolled hypertension
• Hypersensitivity to any component
• Pure red cell aplasia (PRCA) that begins after treatment with darbepoetin alfa or other erythropoietin protein drugs

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Darbepoetin alfa?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Darbepoetin alfa?”

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)
• Hypertensive encephalopathy and seizures reported in patients with CKD; appropriately control hypertension before initiation of and during treatment; reduce or withhold Aranesp if blood pressure becomes difficult to control; advise patients of the importance of compliance with antihypertensive therapy and dietary restrictions
• For lack or loss of hemoglobin response to therapy, initiate a search for causative factors (eg, iron deficiency, infection, inflammation, bleeding); if typical causes of lack or loss of hemoglobin response are excluded, evaluate for PRCA; in absence of PRCA, follow dosing recommendations for the management of patients with insufficient hemoglobin response to therapy
• Use caution in known porphyria, sickle cell anemia, thalassemia
• Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria may occur; immediately and permanently discontinue therapy and administer appropriate therapy if a serious allergic or anaphylactic reaction occurs
• Decrease dose if Hgb increase exceeds 1 g/dL in any 2 wk period
• Increased mortality and/or increased risk of tumor progression or recurrence in patients with cancer
• Increases the risk for seizures in patients with CKD; increase monitoring of these patients for changes in seizure frequency or premonitory symptoms
• If severe anemia and low reticulocyte count develop during treatment, withhold therapy and evaluate for pure red cell aplasia
• Blistering and skin exfoliation reactions including erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), reported in the post-marketing setting; discontinue therapy immediately if a severe cutaneous reaction, such as SJS/TEN, suspected
• Two different excipients are available: polysorbate 80 or human albumin
• May use supplemental iron if serum ferritin  is less than 100 mcg/L [0.225 pmol/L] or serum transferrin saturation is less than 20%
• IV route preferred for patients on hemodialysis
• Patients may require adjustments in their dialysis prescriptions after initiation of therapy; patients receiving treatment may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis
• Autoinjector for SC administration only
• Dose increase no more frequently than once monthly
• Pure red cell aplasia
  • Cases of PRCA and severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin reported predominantly in patients with CKD receiving ESAs by subcutaneous administration; also reported in patients receiving therapy for anemia related to hepatitis C treatment (indication not approved)
  • If severe anemia and low reticulocyte count develop during treatment, withhold therapy and evaluate patients for neutralizing antibodies to erythropoietin; contact Amgen (1-800-77-AMGEN) to perform assays for binding and neutralizing antibodies
  • Permanently discontinue therapy in patients who develop PRCA following treatment; do not switch patients to other ESA.

Pregnancy and Lactation

• Limited available data on pregnant women are insufficient to determine a drug-associated risk of major birth defects or miscarriage; in animal reproductive and developmental toxicity studies, the drug increased early post-implantation loss at doses approximating clinical recommended starting doses; consider benefits and risks for the mother and possible risks to a fetus when prescribing to a pregnant woman
• Lactation
  • There is no information regarding the presence of drugs in human milk, effects on the breastfed child, or milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from the drug or underlying maternal condition.