Darbepoetin alfa

Patients with Chronic Kidney Disease In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL. No trial has identified a hemoglobin target level, Aranesp dose, or dosing strategy that does not increase these risks.

Individualize dosing and use the lowest dose of Aranesp sufficient to reduce the need for RBC transfusions [see Warnings and Precautions] . Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events [see Boxed Warning and Clinical Studies ] .

For all patients with CKD When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.

Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments. If the hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the dose of Aranesp by 25% or more as needed to reduce rapid responses. For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%.

For patients who do not respond adequately over a 12-week escalation period, increasing the Aranesp dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue Aranesp if responsiveness does not improve.

For adult patients with CKD on dialysis : Initiate Aranesp treatment when the hemoglobin level is less than 10 g/dL. If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of Aranesp. The recommended starting dose is 0.45 mcg/kg intravenously or subcutaneously as a weekly injection or 0.75 mcg/kg once every 2 weeks as appropriate.

The intravenous route is recommended for patients on hemodialysis. For adult patients with CKD not on dialysis : Consider initiating Aranesp treatment only when the hemoglobin level is less than 10 g/dL and the following considerations apply: ° The rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and , ° Reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal.

If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of Aranesp, and use the lowest dose of Aranesp sufficient to reduce the need for RBC transfusions. The recommended starting dose is 0.45 mcg/kg body weight intravenously or subcutaneously given once at four week intervals as appropriate. For pediatric patients with CKD : Initiate Aranesp treatment when the hemoglobin level is less than 10 g/dL.

If the hemoglobin level approaches or exceeds 12 g/dL, reduce or interrupt the dose of Aranesp. The recommended starting dose for pediatric patients (less than 18 years) is 0.45 mcg/kg body weight administered as a single subcutaneous or intravenous injection once weekly; patients not receiving dialysis may be initiated at a dose of 0.75 mcg/kg once every 2 weeks.

When treating patients who have chronic kidney disease and cancer, physicians should refer to Warnings and Precautions ( 5.1 and 5.2 ) . Conversion from Epoetin alfa to Aranesp in patients with CKD on dialysis Aranesp is administered less frequently than epoetin alfa. Administer Aranesp once weekly in patients who were receiving epoetin alfa 2 to 3 times weekly.

Administer Aranesp once every 2 weeks in patients who were receiving epoetin alfa once weekly. Estimate the starting weekly dose of Aranesp for adults and pediatric patients on the basis of the weekly epoetin alfa dose at the time of substitution (see Table 1). Maintain the route of administration (intravenous or subcutaneous injection). [See table below.] 200 *For pediatric patients receiving a weekly epoetin alfa dose of < 1,500 Units/week, the available data are insufficient to determine an Aranesp conversion dose.

Conversion from Epoetin alfa to Aranesp in patients with CKD not on dialysis Refer to Table 1. The dose conversion depicted in Table 1 does not accurately estimate the once monthly dose of Aranesp.

Preparation and Administration The needle cover of the prefilled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions. Do not shake. Do not use Aranesp that has been shaken or frozen. Protect vials and prefilled syringes from light. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Do not use any vials or prefilled syringes exhibiting particulate matter or discoloration. Discard unused portion of Aranesp in vials or prefilled syringes. Do not re-enter vial. Do not dilute Aranesp and do not administer in conjunction with other drug solutions. Self-Administration of the Prefilled Syringe Training should aim to demonstrate to those patients and caregivers how to measure the dose of Aranesp, and the focus should be on ensuring that a patient or caregiver can successfully perform all of the steps in the Instructions for Use for a prefilled syringe.

If a patient or caregiver is not able to demonstrate that they can measure the dose and administer the product successfully, you should consider whether the patient is an appropriate candidate for self-administration of Aranesp or whether the patient would benefit from a different Aranesp presentation. If a patient or caregiver experiences difficulty measuring the required dose, especially if it is other than the entire contents of the Aranesp prefilled syringe, use of the Aranesp vial may be considered.