Treatment of Anemia of Chronic Renal Failure Patients

PROCRIT® is indicated for the treatment of anemia associated with CRF, including patients on dialysis and patients not on dialysis. PROCRIT® is indicated to elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients.

Non-dialysis patients with symptomatic anemia considered for therapy should have a hemoglobin less than 10 g/dL.

PROCRIT® is not intended for patients who require immediate correction of severe anemia. PROCRIT® may obviate the need for maintenance transfusions but is not a substitute for emergency transfusion.

Prior to initiation of therapy, the patient's iron stores should be evaluated. Transferrin saturation should be at least 20% and ferritin at least 100 ng/mL. Blood pressure should be adequately controlled prior to initiation of PROCRIT® therapy, and must be closely monitored and controlled during therapy.

Treatment of Anemia in Zidovudine-treated HIV-infected Patients

PROCRIT® is indicated for the treatment of anemia related to therapy with zidovudine in HIV-infected patients. PROCRIT® is indicated to elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients. PROCRIT® is not indicated for the treatment of anemia in HIV-infected patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding, which should be managed appropriately. PROCRIT® use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.

PROCRIT®, at a dose of 100 Units/kg TIW, is effective in decreasing the transfusion requirement and increasing the red blood cell level of anemic, HIV-infected patients treated with zidovudine, when the endogenous serum erythropoietin level is ≤ 500 mUnits/mL and when patients are receiving a dose of zidovudine ≤ 4200 mg/week.

Treatment of Anemia in Cancer Patients on Chemotherapy

PROCRIT® is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy. PROCRIT® is indicated to decrease the need for transfusions in patients who will be receiving concomitant chemotherapy for a minimum of 2 months. PROCRIT® is not indicated for the treatment of anemia in cancer patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding, which should be managed appropriately. PROCRIT® use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.

PROCRIT® is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy.

Reduction of Allogeneic Blood Transfusion in Surgery Patients

PROCRIT® is indicated for the treatment of anemic patients (hemoglobin > 10 to ≤ 13 g/dL) who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery to reduce the need for allogeneic blood transfusions.^17-19 PROCRIT® is not indicated for anemic patients who are willing to donate autologous blood (see BOXED WARNINGS and DOSAGE AND ADMINISTRATION).

IMPORTANT: See BOXED WARNINGS and WARNINGS: Increased Mortality, Serious Cardiovascular and Thromboembolic Events.

Chronic Renal Failure Patients

The recommended range for the starting dose of PROCRIT® 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 PROCRIT® 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 PROCRIT® dose should be adjusted as described below.

PROCRIT® may be given either as an IV or SC injection. In patients on hemodialysis, the IV route is recommended (see WARNNGS: Pure Red Cell Aplasia). While the administration of PROCRIT® is independent of the dialysis procedure, PROCRIT® 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, PROCRIT® may be given either as an IV or SC injection.

Patients who have been judged competent by their physicians to self-administer PROCRIT® 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.

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 PROCRIT® dose titrations over a 12-week period:

• do not administer higher PROCRIT® 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, PROCRIT® dose adjustments should be made as described above; discontinue PROCRIT® if responsiveness does not improve and the patient needs recurrent RBC transfusions.

Pretherapy Iron Evaluation: Prior to and during PROCRIT® 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 PROCRIT®.

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 PROCRIT® 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 PROCRIT® 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. PROCRIT® 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 PROCRIT®, 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 PROCRIT® .

In zidovudine-treated HIV-infected patients the dosage of PROCRIT® 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 PROCRIT® 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 PROCRIT® 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 a PROCRIT® dose of 300 Units/kg TIW, it is unlikely that they will respond to higher doses of PROCRIT®.

Maintenance Dose: After attainment of the desired response (ie, reduced transfusion requirements or increased hemoglobin), the dose of PROCRIT® 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 PROCRIT® 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 PROCRIT® therapy until hemoglobin becomes stable. The dose of PROCRIT® 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 PROCRIT® in adults is 150 Units/kg SC TIW or 40,000 Units SC Weekly. The initial recommended dose of PROCRIT®in pediatric patients is 600 Units/kg IV weekly. Discontinue PROCRIT®following the completion of a chemotherapy course (see BOXED WARNINGS: Cancer).

Dose Modification

TIW Dosing

Weekly Dosing

Surgery Patients

Prior to initiating treatment with PROCRIT® a hemoglobin should be obtained to establish that it is > 10 to ≤ 13 g/dL.¹⁷ The recommended dose of PROCRIT® 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 PROCRIT® 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 PROCRIT® and should continue throughout the course of therapy. Deep venous thrombosis prophylaxis should be strongly considered (see BOXED WARNINGS).

PREPARATION AND ADMINISTRATION OF PROCRIT®

1. Do not shake. It is not necessary to shake PROCRIT®. 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 PROCRIT®, 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 PROCRIT® 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 PROCRIT® containing benzyl alcohol.

PROCRIT®, containing Epoetin alfa, is available in vials containing color coded labels and caps. Each dosage form is supplied in the following packages:

1 mL Single-Dose, Preservative-free Solution Cartons containing six (6) single-dose vials:

2000 Units/mL (NDC 59676-302-01) (Purple)
3000 Units/mL (NDC 59676-303-01) (Magenta)
4000 Units/mL (NDC 59676-304-01) (Green)
10,000 Units/mL (NDC 59676-310-01) (Red)

Cartons containing four (4) single-dose vials:

40,000 Units/mL (NDC 59676-340-01) (Orange)

Trays containing twenty-five (25) single-dose vials:

2000 Units/mL (NDC 59676-302-02) (Purple)
3000 Units/mL (NDC 59676-303-02) (Magenta)
4000 Units/mL (NDC 59676-304-02) (Green)
10,000 Units/mL (NDC 59676-310-02) (Red)

2 mL Multidose, Preserved Solution

Cartons containing four (4) multidose vials:

10,000 Units/mL (NDC 59676-312-04) (Blue)

Cartons containing six (6) multidose vials:

10,000 Units/mL (NDC 59676-312-01) (Blue)

1 mL Multidose, Preserved Solution

Cartons containing four (4) multidose vials:

20,000 Units/mL (NDC 59676-320-04) (Lime)

Cartons containing six (6) multidose vials:

20,000 Units/mL (NDC 59676-320-01) (Lime)

Storage

Store at 2° to 8° C (36° to 46° F). Do not freeze or shake.

This product's after this insert was used in production.label may have been For further product information and the current package insert, please visit www.procrit.com or call our Medical Information Group toll-free at 1 888 2ASK OBI or 1-888-227-5624.

REFERENCES

17. deAndrade JR and Jove M. Baseline Hemoglobin as a Predictor of Risk of Transfusion and Response to Epoetin alfa in Orthopedic Surgery Patients. Am. J. of Orthoped. 1996;25 (8): 533-542.

18. Goldberg MA and McCutchen JW. A Safety and Efficacy Comparison Study of Two Dosing Regimens of Epoetin alfa in Patients Undergoing Major Orthopedic Surgery. Am. J. of Orthoped. 1996;25 (8): 544-552.

Manufactured by: Amgen Inc, One Amgen Center Drive Thousand Oaks, CA 91320-1799, Distributed by: Ortho Biotech Products, L.P. Raritan, New Jersey 08869-0670, Revised March 2008. FDA rev date: 3/7/2008

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