2.1 eva luation of Iron Stores and Nutritional Factors

eva luate the iron status in all patients before and during treatment and maintain iron repletion. Correct or exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) before initiating Aranesp [see Warnings and Precautions (5.10)].

2.2 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 (5.1)]. 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 (14)].

For all patientswith 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. eva luate other causes of anemia. Discontinue Aranesp if responsiveness does not improve.

For 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 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.

When treating patients who have chronic kidney disease and cancer, physicians should refer to Warnings and Precautions (5.1 and 5.3).

Refer patients who self-administer Aranesp to the Instructions for Use [see Patient Counseling Information (17)].

Conversion from Epoetin alfa to Aranesp in patients with CKD on dialysis

Aranesp is administered less frequently than epoetinalfa.

• Administer Aranesp once weekly in patients who were receiving epoetin alfa 2 to 3 times weekly.
• Administer Aranesp once every 2weeks 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).

Conversion from Epoetin alfa to Aranesp in patients with CKD not on dialysis

The dose conversion depicted in Table 1 does not accurately estimate the once monthly dose of Aranesp.