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Procrit

"The U.S. Food and Drug Administration approved a risk management program to inform healthcare providers and their patients about the risks of a class of drugs called Erythropoiesis-Stimulating Agents (ESAs). For patients with cancer, the program "...

Procrit

Indications
Dosage
How Supplied

INDICATIONS

Treatment of Anemia of Chronic Renal Failure Patients

PROCRIT® (epoetin alfa) is indicated for the treatment of anemia associated with CRF, including patients on dialysis and patients not on dialysis. PROCRIT® (epoetin alfa) 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® (epoetin alfa) is not intended for patients who require immediate correction of severe anemia. PROCRIT® (epoetin alfa) 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® (epoetin alfa) therapy, and must be closely monitored and controlled during therapy.

Treatment of Anemia in Zidovudine-treated HIV-infected Patients

PROCRIT® (epoetin alfa) is indicated for the treatment of anemia related to therapy with zidovudine in HIV-infected patients. PROCRIT® (epoetin alfa) 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® (epoetin alfa) 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® (epoetin alfa) use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.

PROCRIT® (epoetin alfa) , 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® (epoetin alfa) is indicated for the treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown a reduction in the need for RBC transfusions in patients with metastatic, non-myeloid malignancies receiving chemotherapy for a minimum of 2 months. Studies to determine whether PROCRIT® (epoetin alfa) increases mortality or decreases progression-free/recurrence-free survival are ongoing.

  • PROCRIT® (epoetin alfa) is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy.
  • PROCRIT® (epoetin alfa) is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure due to the absence of studies that adequately characterize the impact of PROCRIT (epoetin alfa) ® on progression-free and overall survival (see WARNINGS: Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence).
  • PROCRIT (epoetin alfa) ® 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 (see PRECAUTIONS: Lack or Loss of Response).
  • PROCRIT (epoetin alfa) ® use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.

Reduction of Allogeneic Blood Transfusion in Surgery Patients

PROCRIT® (epoetin alfa) 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® (epoetin alfa) is not indicated for anemic patients who are willing to donate autologous blood (see BOXED WARNINGS and DOSAGE AND ADMINISTRATION).

Clinical Experience: Response To PROCRIT® (epoetin alfa)

Chronic Renal Failure Patients

When dosed with PROCRIT® (epoetin alfa) , patients responded with an increase in hematocrit.5 After 3 months on study, more than 95% of patients were transfusion-independent.

In the presence of adequate iron stores (see Iron Evaluation), the time to reach the target hematocrit is a function of the baseline hematocrit and the rate of hematocrit rise.

The rate of increase in hematocrit is dependent upon the dose of PROCRIT® (epoetin alfa) administered and individual patient variation. In clinical trials at starting doses of 50 to 150 Units/kg TIW, adult patients responded with an average rate of hematocrit rise of:

  Hematocrit Increase
Starting Dose
(TIW IV)
Points/Da V Points/2 Weeks
50 Units/kg 0.11 1.5
100 Units/kg 0.18 2.5
150 Units/kg 0.25 3.5

In a 26 week, double-blind, placebo-controlled trial, 118 anemic dialysis patients with an average hemoglobin of approximately 7 g/dL were randomized to either PROCRIT® (epoetin alfa) or placebo. By the end of the study, average hemoglobin increased to approximately 11 g/dL in the PROCRIT® (epoetin alfa) -treated patients and remained unchanged in patients receiving placebo. PROCRIT® (epoetin alfa) -treated patients experienced improvements in exercise tolerance and patient-reported physical functioning at month 2 that was maintained throughout the study.

Adult Patients on Dialysis: Thirteen clinical studies were conducted, involving IV administration to a total of 1010 anemic patients on dialysis for 986 patient-years of PROCRIT® (epoetin alfa) therapy. In the three largest of these clinical trials, the median maintenance dose necessary to maintain the hematocrit between 30% to 36% was approximately 75 Units/kg TIW. In the US multicenter phase 3 study, approximately 65% of the patients required doses of 100 Units/kg TIW, or less, to maintain their hematocrit at approximately 35%. Almost 10% of patients required a dose of 25 Units/kg, or less, and approximately 10% required a dose of more than 200 Units/kg TIW to maintain their hematocrit at this level.

A multicenter unit dose study was also conducted in 119 patients receiving peritoneal dialysis who self-administered PROCRIT® (epoetin alfa) subcutaneously for approximately 109 patient-years of experience. Patients responded to PROCRIT® (epoetin alfa) administered SC in a manner similar to patients receiving IV administration.20

Pediatric Patients on Dialysis: One hundred twenty-eight children from 2 months to 19 years of age with CRF requiring dialysis were enrolled in 4 clinical studies of PROCRIT® (epoetin alfa) . The largest study was a placebo-controlled, randomized trial in 113 children with anemia (hematocrit ≤ 27%) undergoing peritoneal dialysis or hemodialysis. The initial dose of PROCRIT® (epoetin alfa) was 50 Units/kg IV or SC TIW. The dose of study drug was titrated to achieve either a hematocrit of 30% to 36% or an absolute increase in hematocrit of 6 percentage points over baseline.

At the end of the initial 12 weeks, a statistically significant rise in mean hematocrit (9.4% vs 0.9%) was observed only in the PROCRIT® (epoetin alfa) arm. The proportion of children achieving a hematocrit of 30%, or an increase in hematocrit of 6 percentage points over baseline, at any time during the first 12 weeks was higher in the PROCRIT® (epoetin alfa) arm (96% vs 58%). Within 12 weeks of initiating PROCRIT® (epoetin alfa) therapy, 92.3% of the pediatric patients were transfusion-independent as compared to 65.4% who received placebo. Among patients who received 36 weeks of PROCRIT® (epoetin alfa) , hemodialysis patients required a higher median maintenance dose (167 Units/kg/week [n = 28] vs 76 Units/kg/week [n = 36]) and took longer to achieve a hematocrit of 30% to 36% (median time to response 69 days vs 32 days) than patients undergoing peritoneal dialysis.

Patients With CRF Not Requiring Dialysis

Four clinical trials were conducted in patients with CRF not on dialysis involving 181 patients treated with PROCRIT® (epoetin alfa) for approximately 67 patient-years of experience. These patients responded to PROCRIT® (epoetin alfa) therapy in a manner similar to that observed in patients on dialysis. Patients with CRF not on dialysis demonstrated a dose-dependent and sustained increase in hematocrit when PROCRIT® (epoetin alfa) was administered by either an IV or SC route, with similar rates of rise of hematocrit when PROCRIT® (epoetin alfa) was administered by either route. Moreover, PROCRIT® (epoetin alfa) doses of 75 to 150 Units/kg per week have been shown to maintain hematocrits of 36% to 38% for up to 6 months.21-22

Zidovudine-treated HIV-infected Patients

Efficacy in HIV-infected patients with anemia related to therapy with zidovudine was demonstrated based on reduction in the requirement for RBC transfusions.

PROCRIT® (epoetin alfa) has been studied in four placebo-controlled trials enrolling 297 anemic (hematocrit < 30%) HIV-infected (AIDS) patients receiving concomitant therapy with zidovudine (all patients were treated with Epoetin alfa manufactured by Amgen Inc). In the subgroup of patients (89/125 PROCRIT® (epoetin alfa) and 88/130 placebo) with prestudy endogenous serum erythropoietin levels ≤ 500 mUnits/mL, PROCRIT® (epoetin alfa) reduced the mean cumulative number of units of blood transfused per patient by approximately 40% as compared to the placebo group.24 Among those patients who required transfusions at baseline, 43% of patients treated with PROCRIT® (epoetin alfa) versus 18% of placebo-treated patients were transfusion-independent during the second and third months of therapy. PROCRIT® (epoetin alfa) therapy also resulted in significant increases in hematocrit in comparison to placebo. When examining the results according to the weekly dose of zidovudine received during month 3 of therapy, there was a statistically significant (p < 0.003) reduction in transfusion requirements in patients treated with PROCRIT® (epoetin alfa) (n = 51) compared to placebo treated patients (n = 54) whose mean weekly zidovudine dose was ≤ 4200 mg/week.23

Approximately 17% of the patients with endogenous serum erythropoietin levels ≤ 500 mUnits/mL receiving PROCRIT® (epoetin alfa) in doses from 100 to 200 Units/kg TIW achieved a hematocrit of 38% without administration of transfusions or significant reduction in zidovudine dose. In the subgroup of patients whose prestudy endogenous serum erythropoietin levels were > 500 mUnits/mL, PROCRIT® (epoetin alfa) therapy did not reduce transfusion requirements or increase hematocrit, compared to the corresponding responses in placebo-treated patients.

In a 6 month open-label PROCRIT® (epoetin alfa) study, patients responded with decreased transfusion requirements and sustained increases in hematocrit and hemoglobin with doses of PROCRIT® (epoetin alfa) up to 300 Units/kg TIW.23-25

Responsiveness to PROCRIT® (epoetin alfa) therapy may be blunted by intercurrent infectious/inflammatory episodes and by an increase in zidovudine dosage. Consequently, the dose of PROCRIT® (epoetin alfa) must be titrated based on these factors to maintain the desired erythropoietic response.

Cancer Patients on Chemotherapy

Adult Patients

Efficacy in patients with anemia due to concomitant chemotherapy was demonstrated based on reduction in the requirement for RBC transfusions.

Three-Times Weekly (TIW) Dosing

PROCRIT® (epoetin alfa) administered TIW has been studied in a series of six placebo-controlled, double-blind trials that enrolled 131 anemic cancer patients receiving PROCRIT® (epoetin alfa) or matching placebo. Across all studies, 72 patients were treated with concomitant non cisplatin-containing chemotherapy regimens and 59 patients were treated with concomitant cisplatin-containing chemotherapy regimens. Patients were randomized to PROCRIT® (epoetin alfa) 150 Units/kg or placebo subcutaneously TIW for 12 weeks in each study.

The results of the pooled data from these six studies are shown in the table below. Because of the length of time required for erythropoiesis and red cell maturation, the efficacy of PROCRIT® (epoetin alfa) (reduction in proportion of patients requiring transfusions) is not manifested until 2 to 6 weeks after initiation of PROCRIT® (epoetin alfa) .

Proportion of Patients Transfused During Chemotherapy (Efficacy Populationa)

Chemotherapy Regimen On Studyb During Months 2 and 3c
PROCRIT® Placebo PROCRIT® Placebo
Regimens without cisplatin 44% (15/34) 44% (16/36) 21% (6/29) 33% (11/33)
Regimens containing cisplatin 50% (14/28) 63% (19/30) 23% (5/22)d 56% (14/25)
Combined 47% (29/62) 53% (35/66) 22% (11/51)d 43% (25/58)
a Limited to patients remaining on study at least 15 days (1 patient excluded from PROCRIT® (epoetin alfa) , 2 patients excluded from placebo).
b Includes all transfusions from day 1 through the end of study.
c Limited to patients remaining on study beyond week 6 and includes only transfusions during weeks 5-12.
d Unadjusted 2-sided p < 0.05

Intensity of chemotherapy in the above trials was not directly assessed, however the degree and timing of neutropenia was comparable across all trials. Available evidence suggests that patients with lymphoid and solid cancers respond similarly to PROCRIT® (epoetin alfa) therapy, and that patients with or without tumor infiltration of the bone marrow respond similarly to PROCRIT® (epoetin alfa) therapy.

Weekly (QW) Dosing

PROCRIT® (epoetin alfa) was also studied in a placebo-controlled, double-blind trial utilizing weekly dosing in a total of 344 anemic cancer patients. In this trial, 61 (35 placebo arm and 26 in the PROCRIT® (epoetin alfa) arm) patients were treated with concomitant cisplatin containing regimens and 283 patients received concomitant chemotherapy regimens that did not contain cisplatinum. Patients were randomized to PROCRIT® (epoetin alfa) 40,000 Units weekly (n = 174) or placebo (n = 170) SC for a planned treatment period of 16 weeks. If hemoglobin had not increased by > 1 g/dL after 4 weeks of therapy or the patient received RBC transfusion during the first 4 weeks of therapy, study drug was increased to 60,000 Units weekly. Forty-three percent of patients in the Epoetin alfa group required an increase in PROCRIT® (epoetin alfa) dose to 60,000 Units weekly.23

Results demonstrated that PROCRIT® (epoetin alfa) therapy reduced the proportion of patients transfused in day 29 through week 16 of the study as compared to placebo. Twenty-five patients (14%) in the PROCRIT® (epoetin alfa) group received transfusions compared to 48 patients (28%) in the placebo group (p = 0.0010) between day 29 and week 16 or the last day on study.

Comparable intensity of chemotherapy for patients enrolled in the two study arms was suggested by similarities in mean dose and frequency of administration for the 10 most commonly administered chemotherapy agents, and similarity in the incidence of changes in chemotherapy during the trial in the two arms.

Pediatric Patients

The safety and effectiveness of PROCRIT® (epoetin alfa) were evaluated in a randomized, double-blind, placebo-controlled, multicenter study in anemic patients ages 5 to 18 receiving chemotherapy for the treatment of various childhood malignancies. Two hundred twenty-two patients were randomized (1:1) to PROCRIT® (epoetin alfa) or placebo. PROCRIT® (epoetin alfa) was administered at 600 Units/kg (maximum 40,000 Units) intravenously once per week for 16 weeks. If hemoglobin had not increased by 1g/dL after the first 4-5 weeks of therapy, PROCRIT® (epoetin alfa) was increased to 900 Units/kg (maximum 60,000 Units). Among the PROCRIT® (epoetin alfa) -treated patients 60% required dose escalation to 900 Units/kg/week.

The effect of PROCRIT® (epoetin alfa) on transfusion requirements is shown in the table below:

Percentage of Patients Transfused:
On Studya After 28 Days Post-Randomization
PROCRIT®
(n=111)
Placebo
(n=111)
PROCRIT®
(n= 111)
Placebo
(n=111)
65% (72)
77% (86) 51%(57)b 69% (77)
a Includes all transfusions from day 1 through the end of study
b Adjusted 2 sided p < 0.05

There was no evidence of an improvement in health-related quality of life, including no evidence of an effect on fatigue, energy or strength, in patients receiving PROCRIT® (epoetin alfa) as compared to those receiving placebo.

Surgery Patients

PROCRIT® (epoetin alfa) has been studied in a placebo-controlled, double-blind trial enrolling 316 patients scheduled for major, elective orthopedic hip or knee surgery who were expected to require ≥ 2 units of blood and who were not able or willing to participate in an autologous blood donation program. Based on previous studies which demonstrated that pretreatment hemoglobin is a predictor of risk of receiving transfusion,19,26 patients were stratified into one of three groups based on their pretreatment hemoglobin [ ≤ 10 (n = 2), > 10 to ≤ 13 (n = 96), and > 13 to ≤ 15 g/dL (n = 218)] and then randomly assigned to receive 300 Units/kg PROCRIT® (epoetin alfa) , 100 Units/kg PROCRIT® (epoetin alfa) or placebo by SC injection for 10 days before surgery, on the day of surgery, and for 4 days after surgery.17 All patients received oral iron and a low-dose post-operative warfarin regimen.17

Treatment with PROCRIT® (epoetin alfa) 300 Units/kg significantly (p = 0.024) reduced the risk of allogeneic transfusion in patients with a pretreatment hemoglobin of > 10 to ≤ 13; 5/31 (16%) of PROCRIT® (epoetin alfa) 300 Units/kg, 6/26 (23%) of PROCRIT® (epoetin alfa) 100 Units/kg, and 13/29 (45%) of placebo-treated patients were transfused.17 There was no significant difference in the number of patients transfused between PROCRIT® (epoetin alfa) (9% 300 Units/kg, 6% 100 Units/kg) and placebo (13%) in the > 13 to ≤ 15 g/dL hemoglobin stratum. There were too few patients in the ≤ 10 g/dL group to determine if PROCRIT® (epoetin alfa) is useful in this hemoglobin strata. In the > 10 to ≤ 13 g/dL pretreatment stratum, the mean number of units transfused per PROCRIT® (epoetin alfa) -treated patient (0.45 units blood for 300 Units/kg, 0.42 units blood for 100 Units/kg) was less than the mean transfused per placebo-treated patient (1.14 units) (overall p = 0.028). In addition, mean hemoglobin, hematocrit, and reticulocyte counts increased significantly during the presurgery period in patients treated with PROCRIT® (epoetin alfa) .17

PROCRIT® (epoetin alfa) was also studied in an open-label, parallel-group trial enrolling 145 subjects with a pretreatment hemoglobin level of ≥ 10 to ≤ 13 g/dL who were scheduled for major orthopedic hip or knee surgery and who were not participating in an autologous program.18 Subjects were randomly assigned to receive one of two SC dosing regimens of PROCRIT® (epoetin alfa) (600 Units/kg once weekly for 3 weeks prior to surgery and on the day of surgery, or 300 Units/kg once daily for 10 days prior to surgery, on the day of surgery and for 4 days after surgery). All subjects received oral iron and appropriate pharmacologic anticoagulation therapy.

From pretreatment to presurgery, the mean increase in hemoglobin in the 600 Units/kg weekly group (1.44 g/dL) was greater than observed in the 300 Units/kg daily group.18 The mean increase in absolute reticulocyte count was smaller in the weekly group (0.11 x 106/mm3) compared to the daily group (0.17 x 106/mm3). Mean hemoglobin levels were similar for the two treatment groups throughout the postsurgical period.

The erythropoietic response observed in both treatment groups resulted in similar transfusion rates [11/69 (16%) in the 600 Units/kg weekly group and 14/71 (20%) in the 300 Units/kg daily group].18 The mean number of units transfused per subject was approximately 0.3 units in both treatment groups.

DOSAGE AND ADMINISTRATION

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

Chronic Renal Failure Patients

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

PROCRIT® (epoetin alfa) 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 PROCRIT® (epoetin alfa) is independent of the dialysis procedure, PROCRIT® (epoetin alfa) 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® (epoetin alfa) may be given either as an IV or SC injection.

Patients who have been judged competent by their physicians to self-administer PROCRIT® (epoetin alfa) 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 PROCRIT® (epoetin alfa) dose titrations over a 12-week period:

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

Pretherapy Iron Evaluation: Prior to and during PROCRIT® (epoetin alfa) 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® (epoetin alfa) .

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® (epoetin alfa) 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® (epoetin alfa) 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® (epoetin alfa) 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® (epoetin alfa) , 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® (epoetin alfa) .

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

Maintenance Dose: After attainment of the desired response (ie, reduced transfusion requirements or increased hemoglobin), the dose of PROCRIT® (epoetin alfa) 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

Only prescribers enrolled in the ESA APPRISE Oncology Program may prescribe and/or dispense PROCRIT® (see WARNINGS: ESA APPRISE Oncology Program).

Although no specific serum erythropoietin level has been established which predicts which patients would be unlikely to respond to PROCRIT® (epoetin alfa) therapy, treatment of patients with grossly elevated serum erythropoietin levels (eg, > 200 mUnits/mL) is not recommended. Therapy should not be initiated at hemoglobin levels ≥ 10 g/dL. The hemoglobin should be monitored on a weekly basis in patients receiving PROCRIT® (epoetin alfa) therapy until hemoglobin becomes stable. The dose of PROCRIT® (epoetin alfa) should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion (see recommended Dose Modifications, below).

Recommended Dose: The initial recommended dose of PROCRIT® (epoetin alfa) in adults is 150 Units/kg SC TIW or 40,000 Units SC Weekly. The initial recommended dose of PROCRIT® (epoetin alfa) in pediatric patients is 600 Units/kg IV weekly. Discontinue PROCRIT® (epoetin alfa) 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
TIW Hemoglobin reaches a level needed to avoid transfusion orincreases > 1 g/dL in any 2-week period.
Withhold Dose if: Hemoglobin exceeds a level needed to avoid transfusion. 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 transfusion requirements or rise in hemoglobin) after 4 weeks to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for RBC transfusion.
Discontinue: If after 8 weeks of therapy there is no response as measured by hemoglobin levels or if transfusions are still required.
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 a level needed to avoid transfusion 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 SCWeekly
For 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.
Discontinue: If after 8 weeks of therapy there is no response as measured by hemoglobin levels or if transfusions are still required.

Surgery Patients

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

Preparation And Administration Of Procrit® (epoetin alfa)

  1. Do not shake. It is not necessary to shake PROCRIT® (epoetin alfa) . Prolonged vigorous shaking may denature any glycoprotein, rendering it biologically inactive.
  2. Protect the solution from light. 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® (epoetin alfa) , 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® (epoetin alfa) 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® (epoetin alfa) containing benzyl alcohol.

HOW SUPPLIED

PROCRIT®, containing Epoetin alfa, is available 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)
3000 Units/mL (NDC 59676-303-01)
4000 Units/mL (NDC 59676-304-01)
10,000 Units/mL (NDC 59676-310-01)

Cartons containing four (4) single-dose vials:

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

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

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

2 mL Multidose, Preserved Solution

Cartons containing four (4) multidose vials:

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

Cartons containing six (6) multidose vials:

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

1 mL Multidose, Preserved Solution

Cartons containing four (4) multidose vials: 20,000 Units/mL (NDC 59676-320-04)

Cartons containing six (6) multidose vials: 20,000 Units/mL (NDC 59676-320-01)

Storage

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

REFERENCES

5. Eschbach JW, Abdulhadi MH, Browne JK, et al. Recombinant Human Erythropoietin in Anemic Patients with End-Stage Renal Disease. Ann Intern Med. 1989;111:992-1000.

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.

19. Faris PM and Ritter MA. The Effects of Recombinant Human Erythropoietin on Perioperative Transfusion Requirements in Patients Having a Major Orthopedic Operation. J. Bone and Joint Surgery. 1996;78-A:62-72.

20. Amgen Inc., data on file.

21. Eschbach JW, Kelly MR, Haley NR, et al. Treatment of the Anemia of Progressive Renal Failure with Recombinant Human Erythropoietin. NEJM. 1989;321:158-163.

22. The US Recombinant Human Erythropoietin Predialysis Study Group. Double-Blind, Placebo-Controlled Study of the Therapeutic Use of Recombinant Human Erythropoietin for Anemia Associated with Chronic Renal Failure in Predialysis Patients. Am J Kid Dis. 1991;18:50-59.

23. Ortho Biologics, Inc., data on file.

24. Danna RP, Rudnick SA, Abels RI. Erythropoietin Therapy for the Anemia Associated with AIDS and AIDS Therapy and Cancer. In: MB Garnick, ed. Erythropoietin in Clinical Applications - An International Perspective. New York, NY: Marcel Dekker; 1990:301-324.

25. Fischl M, Galpin JE, Levine JD, et al. Recombinant Human Erythropoietin for Patients with AIDS Treated with Zidovudine. NEJM. 1990;322:1488-1493.

26. Laupacis A. Effectiveness of Perioperative Recombinant Human Erythropoietin in Elective Hip Replacement. Lancet. 1993;341:1228-1232.

Manufactured by: Amgen Inc. One Amgen Center Drive, Thousand Oaks, CA 91320-1799. Manufactured for: Centocor Ortho Biotech Products, L.P. Raritan, New Jersey 08869-0670.

Last reviewed on RxList: 6/20/2012
This monograph has been modified to include the generic and brand name in many instances.

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