Darbagen SC Injection

Darbagen is indicated for the treatment of anemia due to:

• Chronic Kidney Disease (CKD) in patients on dialysis and patients not on dialysis.
• The effects of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy.

Darbepoetin alfa is an erythropoiesis-stimulating protein that is produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology. It is a 165-amino acid protein that differs from recombinant human erythropoietin in containing 5 N-linked oligosaccharide chains, whereas recombinant human erythropoietin contains 3 chains. The 2 additional N-glycosylation sites result from amino acid substitutions in the erythropoietin peptide backbone.

Treatment of symptomatic anemia in adult and pediatric chronic renal failure patients: Anemia symptoms and sequelae may vary with age, gender and overall burden of disease. It should be administered either subcutaneously or intravenously in order to increase hemoglobin to not greater than 12 g/dl (7.5 mmol/l). Subcutaneous use is preferable in patients who are not receiving hemodialysis to avoid the puncture of peripheral veins. Treatment with Darbepoetin alfa is divided into two stages; correction and maintenance phase. Guidance is given separately for adult and pediatric patients.

Adult patients with chronic renal failure:

Correction phase:

• The initial dose by subcutaneous or intravenous administration is 0.45 µg/kg body weight, as a single injection once weekly. Alternatively, in patients not on dialysis, the following initial doses can also be administered subcutaneously as a single injection: 0.75 µg/kg once every two weeks or 1.5 µg/kg once monthly.

Maintenance phase:

• In dialysis patients, Darbepoetin alfa may continue to be administered as a single injection once weekly or once every two weeks. Dialysis patients converting from once weekly to once every other week dosing with Darbepoetin alfa should initially receive a dose equivalent to twice the previous once weekly dose.
• In patients not on dialysis, Darbepoetin alfa may continue to be administered as a single injection once weekly or once every two weeks or once monthly. For patients treated with Darbepoetin alfa once every two weeks, after the target haemoglobin has been achieved, Darbepoetin alfa may then be administered subcutaneously once monthly using an initial dose equal to twice the previous once every two week dose.

Pediatric population with chronic renal failure: Treatment of pediatric patients younger than 1 year of age has not been studied in randomized clinical trials.

Correction Phase:

• For patients ≥1 year of age, the initial dose by subcutaneous or intravenous administration is 0.45 µg/kg body weight, as a single injection once weekly.
• Alternatively, in patients not on dialysis, an initial dose of 0.75 µg/kg may be administered subcutaneously as a single injection once every two weeks.

Maintenance phase:

• For paediatric patients ≥1 year of age, in the maintenance phase, Darbepoetin alfa may continue to be administered as a single injection once weekly or once every two weeks.
• Patients <6 years of age may need higher doses for maintenance of haemoglobin than patients above that age. Dialysis patients converting from once weekly to once every other week dosing with Darbepoetin alfa should initially receive a dose equivalent to twice the previous once weekly dose.
• In patients ≥11 years of age not on dialysis, once the target haemoglobin has been achieved with once every two week dosing, Darbepoetin alfa may be administered subcutaneously once monthly using an initial dose equal to twice the previous once every two week dose.

Treatment of symptomatic chemotherapy-induced anaemia in cancer patients: Darbepoetin alfa should be administered by the subcutaneous route to patients with anemia (e.g. hemoglobin concentration ≤ 10 g/dl (6.2 mmol/l) in order to increase hemoglobin to not greater than 12 g/dl (7.5 mmol/l). The recommended initial dose is 500 µg (6.75 µg/kg) given once every three weeks, or once weekly dosing can be given at 2.25 µg/kg body weight. If the clinical response of the patient (fatigue, hemoglobin response) is inadequate after nine weeks, further therapy may not be effective.

• Do not shake. Do not use Darbepoetin alfa that has been shaken or frozen.
• Protect pre-filled syringe from light.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any pre-filled syringe exhibiting particulate matter or discoloration.
• Discard unused portion of Darbepoetin alfa in pre-filled syringes.
• Do not dilute Darbepoetin alfa and do not administer in conjunction with other drug solutions.

No formal drug interaction studies have been conducted with Darbagen.

• Uncontrolled hypertension
• Pure Red Cell Aplasia (PRCA)
• Serious allergic reactions

Hypertension, stroke, thromboembolic events, convulsions, allergic reactions, rash/erythema and Pure Red Cell Aplasia (PRCA).

Pregnancy Category C. It is not known whether Darbepoetin alfa is excreted in human milk. Caution should be exercised when Darbepoetin alfa is administered to a nursing woman.

Darbagen should be used with caution in patients with controlled hypertension, seizures, Pure Red Cell Aplasia (PRCA) or suspected allergy to the product.

Over dosage with Darbagen can cause hemoglobin levels above the desired level, which should be managed with discontinuation or reduction of Darbagen dosage and/or with phlebotomy, as clinically indicated.

Haematopoietic Agents

Store at 2°C to 8°C. Do not freeze. Do not shake. Protect from light; store Darbagen in the carton until use. Do not use Darbagen that has been shaken or frozen.