Full Prescribing Information » Dosage & Administration
Dosage & Administration

Chronic Renal Failure Patients

The recommended range for the starting dose of EPOETINŽ is 50 to 100 Units/kg TIW for adult patients. The recommended starting dose for pediatric CRF patients on dialysis is 50 Units/kg TIW. Individualize dosing to achieve and maintain hemoglobin levels between 10-12 g/dL. The dose of EPOETINŽ should be reduced as the hemoglobin approaches 12 g/dL or increases by more than 1 g/dL in any 2-week period. If hemoglobin excursions outside the recommended range occur, the EPOETINŽ dose should be adjusted as described below.

EPOETINŽ may be given either as an IV or SC injection. In patients on hemodialysis, the IV route is recommended (see WARNINGS: Pure Red Cell Aplasia). While the administration of EPOETINŽ is independent of the dialysis procedure, EPOETINŽ may be administered into the venous line at the end of the dialysis procedure to obviate the need for additional venous access. In adult patients with CRF not on dialysis, EPOETINŽ may be given either as an IV or SC injection.

Patients who have been judged competent by their physicians to self-administer EPOETINŽ without medical or other supervision may give themselves either an IV or SC injection. The table below provides general therapeutic guidelines for patients with CRF:

Individually titrate to achieve and maintain hemoglobin levels between 10 to 12 g/dL.

Starting Dose: Adults
Pediatric Patients

50 to 100 Units/kg TIW; IV or SC
50 Units/kg TIW; IV or SC

Increase Dose by 25% If:

1. Hemoglobin is < 10 g/dL and has not increased by 1 g/dL after 4 weeks of therapy or
2. Hemoglobin decreases below 10 g/dL

Reduce Dose by 25% When:

1. Hemoglobin approaches 12 g/dL or,
2. Hemoglobin increases > 1 g/dL in any 2-week period

During therapy, hematological parameters should be monitored regularly. Doses must be individualized to ensure that hemoglobin is maintained at an appropriate level for each patient.

For patients whose hemoglobin does not attain a level within the range of 10 to 12 g/dL despite the use of appropriate EPOETINŽ dose titrations over a 12-week period:

  • do not administer higher EPOETINŽ doses and use the lowest dose that will maintain a hemoglobin level sufficient to avoid the need for recurrent RBC transfusions,
  • evaluate and treat for other causes of anemia (see PRECAUTIONS: Lack or Loss of Response), and
  • thereafter, hemoglobin should continue to be monitored and if responsiveness improves, EPOETINŽ dose adjustments should be made as described above; discontinue EPOETINŽ if responsiveness does not improve and the patient needs recurrent RBC transfusions.

Pretherapy Iron Evaluation: Prior to and during EPOETINŽ therapy, the patient's iron stores, including transferrin saturation (serum iron divided by iron binding capacity) and serum ferritin, should be evaluated. Transferrin saturation should be at least 20%, and ferritin should be at least 100 ng/mL. Virtually all patients will eventually require supplemental iron to increase or maintain transferrin saturation to levels that will adequately support erythropoiesis stimulated by EPOETINŽ.

Dose Adjustment: The dose should be adjusted for each patient to achieve and maintain hemoglobin levels between 10 to 12 g/dL.

Increases in dose should not be made more frequently than once a month. If the hemoglobin is increasing and approaching 12 g/dL, the dose should be reduced by approximately 25%. If the hemoglobin continues to increase, dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at a dose approximately 25% below the previous dose. If the hemoglobin increases by more than 1 g/dL in a 2-week period, the dose should be decreased by approximately 25%.

If the increase in the hemoglobin is less than 1 g/dL over 4 weeks and iron stores are adequate (see PRECAUTIONS: Laboratory Monitoring), the dose of EPOETINŽ may be increased by approximately 25% of the previous dose. Further increases may be made at 4-week intervals until the specified hemoglobin is obtained.

Maintenance Dose: The maintenance dose must be individualized for each patient on dialysis. In the US phase 3 multicenter trial in patients on hemodialysis, the median maintenance dose was 75 Units/kg TIW, with a range from 12.5 to 525 Units/kg TIW. Almost 10% of the patients required a dose of 25 Units/kg, or less, and approximately 10% of the patients required more than 200 Units/kg TIW to maintain their hematocrit in the suggested target range. In pediatric hemodialysis and peritoneal dialysis patients, the median maintenance dose was 167 Units/kg/week (49 to 447 Units/kg per week) and 76 Units/kg per week (24 to 323 Units/kg/week) administered in divided doses (TIW or BIW), respectively to achieve the target range of 30% to 36%.

If the transferrin saturation is greater than 20%, the dose of EPOETINŽ may be increased. Such dose increases should not be made more frequently than once a month, unless clinically indicated, as the response time of the hemoglobin to a dose increase can be 2 to 6 weeks. Hemoglobin should be measured twice weekly for 2 to 6 weeks following dose increases. In adult patients with CRF not on dialysis, the dose should also be individualized to maintain hemoglobin levels between 10 to 12 g/dL. EPOETINŽ doses of 75 to 150 Units/kg/week have been shown to maintain hematocrits of 36% to 38% for up to 6 months.

Lack or Loss of Response: If a patient fails to respond or maintain a response, an evaluation for causative factors should be undertaken (see WARNINGS: Pure Red Cell Aplasia, PRECAUTIONS: Lack or Loss of Response, and PRECAUTIONS: Iron Evaluation). If the transferrin saturation is less than 20%, supplemental iron should be administered.

Zidovudine-treated HIV-infected Patients

Prior to beginning EPOETINŽ, it is recommended that the endogenous serum erythropoietin level be determined (prior to transfusion). Available evidence suggests that patients receiving zidovudine with endogenous serum erythropoietin levels > 500 mUnits/mL are unlikely to respond to therapy with EPOETINŽ.

In zidovudine-treated HIV-infected patients the dosage of EPOETINŽ should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion and not to exceed the upper safety limit of 12 g/dL.

Starting Dose: For adult patients with serum erythropoietin levels ≤ 500 mUnits/mL who are receiving a dose of zidovudine ≤ 4200 mg/week, the recommended starting dose of EPOETINŽ is 100 Units/kg as an IV or SC injection TIW for 8 weeks. For pediatric patients, see PRECAUTIONS: PEDIATRIC USE.

Increase Dose: During the dose adjustment phase of therapy, the hemoglobin should be monitored weekly. If the response is not satisfactory in terms of reducing transfusion requirements or increasing hemoglobin after 8 weeks of therapy, the dose of EPOETINŽ can be increased by 50 to 100 Units/kg TIW. Response should be evaluated every 4 to 8 weeks thereafter and the dose adjusted accordingly by 50 to 100 Units/kg increments TIW. If patients have not responded satisfactorily to an EPOETINŽ dose of 300 Units/kg TIW, it is unlikely that they will respond to higher doses of EPOETINŽ.

Maintenance Dose: After attainment of the desired response (ie, reduced transfusion requirements or increased hemoglobin), the dose of EPOETINŽ should be titrated to maintain the response based on factors such as variations in zidovudine dose and the presence of intercurrent infectious or inflammatory episodes. If the hemoglobin exceeds the upper safety limit of 12 g/dL, the dose should be discontinued until the hemoglobin drops below 11 g/dL. The dose should be reduced by 25% when treatment is resumed and then titrated to maintain the desired hemoglobin.

Cancer Patients on Chemotherapy

Although no specific serum erythropoietin level has been established which predicts which patients would be unlikely to respond to EPOETINŽ therapy, treatment of patients with grossly elevated serum erythropoietin levels (eg, > 200 mUnits/mL) is not recommended. The hemoglobin should be monitored on a weekly basis in patients receiving EPOETINŽ therapy until hemoglobin becomes stable. The dose of EPOETINŽ should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion and not to exceed the upper safety limit of 12 g/dL (See recommended Dose Modifications, below).

Recommended Dose: The initial recommended dose of EPOETINŽ in adults is 150 Units/kg SC TIW or 40,000 Units SC Weekly. The initial recommended dose of EPOETINŽ in pediatric patients is 600 Units/kg IV weekly. Discontinue EPOETINŽ following the completion of a chemotherapy course (see BOXED WARNINGS: Cancer).

Dose Modification

TIW Dosing
Starting Dose:
Adults Reduce Dose by 25% when:

150 Units/kg SC TIWHemoglobin reaches a level needed to avoid transfusion or increases > 1 g/dL in any 2-week period

Withhold Dose if:

Hemoglobin exceeds 12 g/dL and restart at 25% below the previous dose when the hemoglobin approaches a level where transfusions may be required

Increase Dose to 300 Units/kg TIW if:

Response is not satisfactory (no reduction in transfusionrequirements or rise in hemoglobin) after 8 weeks to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed the upper safety limit of 12 g/dL

Weekly Dosing
Starting Dose: Adults

40,000 Units SC

Pediatrics

600 Units/kg IV (maximum 40,000 Units)

Reduce Dose by 25% when:

Hemoglobin reaches a level needed to avoid transfusion or increases > 1 g/dL in any 2-weeks

Withhold Dose if:

Hemoglobin exceeds 12 g/dL and restart at 25% below the previous dose when the hemoglobin approaches a level where transfusions may be required

Increase Dose if:For Adults: 60,000 Units SCWeeklyFor Pediatrics: 900 Units/kg IV(maximum 60,000 Units) if:

Response is not satisfactory (no increase in hemoglobin by ≥ 1 g/dL after 4 weeks of therapy, in the absence of a RBC transfusion) to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for RBC transfusion and not to exceed the upper safety limit of 12 g/dL

Surgery Patients

Prior to initiating treatment with EPOETINŽ a hemoglobin should be obtained to establish that it is > 10 to ≤ 13 g/dL.17 The recommended dose of EPOETINŽ is 300 Units/kg/day subcutaneously for 10 days before surgery, on the day of surgery, and for 4 days after surgery.

An alternate dose schedule is 600 Units/kg EPOETINŽ subcutaneously in once weekly doses (21, 14, and 7 days before surgery) plus a fourth dose on the day of surgery.18

All patients should receive adequate iron supplementation. Iron supplementation should be initiated no later than the beginning of treatment with EPOETINŽ and should continue throughout the course of therapy. Deep venous thrombosis prophylaxis should be strongly considered (see BOXED WARNINGS).

PREPARATION AND ADMINISTRATION OF EPOETINŽ

1.                   Do not shake. It is not necessary to shake EPOETINŽ. Prolonged vigorous shaking may denature any glycoprotein, rendering it biologically inactive.

2.                   Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use any vials exhibiting particulate matter or discoloration.

3.                   Using aseptic techniques, attach a sterile needle to a sterile syringe. Remove the flip top from the vial containing EPOETINŽ, and wipe the septum with a disinfectant. Insert the needle into the vial, and withdraw into the syringe an appropriate volume of solution.

4.                   Single-dose: 1 mL vial contains no preservative. Use one dose per vial; do not re-enter the vial. Discard unused portions.
Multidose: 1 mL and 2 mL vials contain preservative. Store at 2° to 8° C after initial entry and between doses. Discard 21 days after initial entry.

5.                   Do not dilute or administer in conjunction with other drug solutions. However, at the time of SC administration, preservative-free EPOETINŽ from single-use vials may be admixed in a syringe with bacteriostatic 0.9% sodium chloride injection, USP, with benzyl alcohol 0.9% (bacteriostatic saline) at a 1:1 ratio using aseptic technique. The benzyl alcohol in the bacteriostatic saline acts as a local anesthetic which may ameliorate SC injection site discomfort. Admixing is not necessary when using the multidose vials of EPOETINŽ containing benzyl alcohol.

 
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