Evaluation of Iron Stores and Nutritional Factors

Evaluate the iron status in all patients before and during treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20%. The majority of patients with CKD will require supplemental iron during the course of ESA therapy.

Monitoring of Response to Therapy

Correct or exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) before initiating RETACRIT. Following initiation of therapy and after each dose adjustment, monitor hemoglobin weekly until the hemoglobin level is stable and sufficient to minimize the need for RBC transfusion.

Selection of Formulation

In pregnant women, lactating women, neonates, and infants use only single-dose vials (the benzyl alcohol-free formulation) [see Contraindications (4)andUse in Specific Populations (8.1, and 8.4)].

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 RETACRIT 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 RETACRIT 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 RETACRIT if responsiveness does not improve.

For adult patients with CKD on dialysis:

•

Initiate RETACRIT 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 RETACRIT.

•

The recommended starting dose for adult patients is 50 to 100 Units/kg 3 times weekly intravenously or subcutaneously. The intravenous route is recommended for patients on hemodialysis.

For adult patients with CKD not on dialysis:

•

Consider initiating RETACRIT treatment only when the hemoglobin level is less than 10 g/dL and the following considerations apply:

o

The rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion
and,

o

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 RETACRIT, and use the lowest dose of RETACRIT sufficient to reduce the need for RBC transfusions.

•

The recommended starting dose for adult patients is 50 to 100 Units/kg 3 times weekly intravenously or subcutaneously.

For pediatric patients with CKD:

•

Initiate RETACRIT treatment only 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 RETACRIT .

•

The recommended starting dose for pediatric patients (ages 1 month or older) is 50 Units/kg 3 times weekly intravenously or subcutaneously.

When treating patients who have chronic kidney disease and cancer, physicians should refer to Warnings and Precautions (5.1 and 5.2).

Starting Dose

The recommended starting dose in adults is 100 Units/kg as an intravenous or subcutaneous injection 3 times per week.

Dose Adjustment

•

If hemoglobin does not increase after 8 weeks of therapy, increase RETACRIT dose by approximately 50 to 100 Units/kg at 4- to 8-week intervals until hemoglobin reaches a level needed to avoid RBC transfusions or 300 Units/kg.

•

Withhold RETACRIT if hemoglobin exceeds 12 g/dL. Resume therapy at a dose 25% below the previous dose when hemoglobin declines to less than 11 g/dL.

Discontinue RETACRIT if an increase in hemoglobin is not achieved at a dose of 300 Units/kg for 8 weeks.

Recommended Starting Dose

Dose Reduction

Reduce dose by 25% if:

•

Hemoglobin increases greater than 1 g/dL in any 2-week period or

•

Hemoglobin reaches a level needed to avoid RBC transfusion.

Withhold dose if hemoglobin exceeds a level needed to avoid RBC transfusion. Reinitiate at a dose 25% below the previous dose when hemoglobin approaches a level where RBC transfusions may be required.

Dose Increase

After the initial 4 weeks of RETACRIT therapy, if hemoglobin increases by less than 1 g/dL and remains below 10 g/dL, increase dose to:

•

300 Units/kg three times per week in adults or

•

60,000 Units weekly in adults

•

900 Units/kg (maximum 60,000 Units) weekly in pediatric patients

After 8 weeks of therapy, if there is no response as measured by hemoglobin levels or if RBC transfusions are still required, discontinue RETACRIT.