1.1 Anemia Due to Chronic Kidney Disease

PROCRIT is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell (RBC) transfusion.

1.2 Anemia Due to Zidovudine in Patients with HIV Infection

PROCRIT is indicated for the treatment of anemia due to zidovudine administered at ≤ 4200 mg/week in patients with HIV Infection with endogenous serum erythropoietin levels of ≤ 500 mUnits/mL.

1.3 Anemia Due to Chemotherapy in Patients with Cancer

PROCRIT is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy.

1.4 Reduction of Allogeneic Red Blood Cell Transfusions in Patients Undergoing Elective, Noncardiac, Nonvascular Surgery

PROCRIT is indicated to reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin > 10 to ≤ 13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. PROCRIT is not indicated for patients who are willing to donate autologous blood pre-operatively.

1.5 Limitations of Use

PROCRIT has not been shown to improve quality of life, fatigue, or patient well-being.

PROCRIT is not indicated for use:

• In patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy.
• In patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
• In patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion.
• In patients scheduled for surgery who are willing to donate autologous blood.
• In patients undergoing cardiac or vascular surgery.
• As a substitute for RBC transfusions in patients who require immediate correction of anemia.

2.1 Important Dosing Information

2.2 Patients with Chronic Kidney Disease

In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a hemoglobin level of greater than 11 g/dL. No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks. Individualize dosing and use the lowest dose of PROCRIT 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 reactions [see Boxed Warningand Clinical Studies (14)].

2.3 Zidovudine-treated Patients with HIV Infection

2.4 Patients on Cancer Chemotherapy

Initiate PROCRIT in patients on cancer chemotherapy only if the hemoglobin is less than 10 g/dL, and if there is a minimum of two additional months of planned chemotherapy.

Use the lowest dose of PROCRIT necessary to avoid RBC transfusions.

2.5 Surgery Patients

The recommended PROCRIT regimens are:

• 300 Units/kg per day subcutaneously for 15 days total: administered daily for 10 days before surgery, on the day of surgery, and for 4 days after surgery.
• 600 Units/kg subcutaneously in 4 doses administered 21, 14, and 7 days before surgery and on the day of surgery.

Deep venous thrombosis prophylaxis is recommended during PROCRIT therapy [see Warnings and Precautions (5.1)] .

2.6 Preparation and Administration

• Do not shake. Do not use PROCRIT that has been shaken or frozen.
• Protect vials 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.
• Discard unused portions of PROCRIT in preservative-free vials. Do not re-enter preservative-free vials.
• Store unused portions of PROCRIT in multiple-dose vials at 36°F to 46°F (2°C to 8°C). Discard 21 days after initial entry.
• Do not dilute. Do not mix with other drug solutions except for admixing as described below:
  Preservative-free PROCRIT from single-dose vials may be admixed in a syringe with bacteriostatic 0.9% sodium chloride injection, USP, with benzyl alcohol 0.9% (bacteriostatic saline) in a 1:1 ratio using aseptic technique at the time of administration. Do not mix PROCRIT with bacteriostatic saline when administering to pregnant women, lactating women, neonates, and infants [see Use in Specific Populations (8.1, 8.2, 8.4)].

5.1 Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism

• In controlled clinical trials of patients with CKD comparing higher hemoglobin targets (13 – 14 g/dL) to lower targets (9 – 11.3 g/dL), PROCRIT and other ESAs increased the risk of death, myocardial infarction, stroke, congestive heart failure, thrombosis of hemodialysis vascular access, and other thromboembolic events in the higher target groups.
• Using ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit [see Clinical Studies (14.1)] . Use caution in patients with coexistent cardiovascular disease and stroke [see Dosage and Administration (2.2)] . Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks.
• In controlled clinical trials of patients with cancer, PROCRIT and other ESAs increased the risks for death and serious adverse cardiovascular reactions. These adverse reactions included myocardial infarction and stroke.
• In controlled clinical trials, ESAs increased the risk of death in patients undergoing coronary artery bypass graft surgery (CABG) and the risk of deep venous thrombosis (DVT) in patients undergoing orthopedic procedures.

The design and overall results of the 3 large trials comparing higher and lower hemoglobin targets are shown in Table 1.

5.2 Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence in Patients with Cancer

ESAs resulted in decreased locoregional control/progression-free survival (PFS) and/or overall survival (OS) (see Table 2).

Adverse effects on PFS and/or OS were observed in studies of patients receiving chemotherapy for breast cancer (Studies 1, 2, and 4), lymphoid malignancy (Study 3), and cervical cancer (Study 5); in patients with advanced head and neck cancer receiving radiation therapy (Studies 6 and 7); and in patients with non-small cell lung cancer or various malignancies who were not receiving chemotherapy or radiotherapy (Studies 8 and 9).

5.3 Hypertension

PROCRIT is contraindicated in patients with uncontrolled hypertension. Following initiation and titration of PROCRIT, approximately 25% of patients on dialysis required initiation of or increases in antihypertensive therapy; hypertensive encephalopathy and seizures have been reported in patients with CKD receiving PROCRIT.

Appropriately control hypertension prior to initiation of and during treatment with PROCRIT. Reduce or withhold PROCRIT if blood pressure becomes difficult to control. Advise patients of the importance of compliance with antihypertensive therapy and dietary restrictions [see Patient Counseling Information (17)] .

5.4 Seizures

PROCRIT increases the risk of seizures in patients with CKD. During the first several months following initiation of PROCRIT, monitor patients closely for premonitory neurologic symptoms. Advise patients to contact their healthcare practitioner for new-onset seizures, premonitory symptoms or change in seizure frequency.

5.5 Lack or Loss of Hemoglobin Response to PROCRIT

For lack or loss of hemoglobin response to PROCRIT, initiate a search for causative factors (e.g., iron deficiency, infection, inflammation, bleeding). If typical causes of lack or loss of hemoglobin response are excluded, evaluate for PRCA [see Warnings and Precautions (5.6)] . In the absence of PRCA, follow dosing recommendations for management of patients with an insufficient hemoglobin response to PROCRIT therapy [see Dosage and Administration (2.2)] .

5.6 Pure Red Cell Aplasia

Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin have been reported in patients treated with PROCRIT. This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration. PRCA has also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (an indication for which PROCRIT is not approved).

If severe anemia and low reticulocyte count develop during treatment with PROCRIT, withhold PROCRIT and evaluate patients for neutralizing antibodies to erythropoietin. Contact Janssen Products, LP at 1-800-JANSSEN (1-800-526-7736) to perform assays for binding and neutralizing antibodies. Permanently discontinue PROCRIT in patients who develop PRCA following treatment with PROCRIT or other erythropoietin protein drugs. Do not switch patients to other ESAs.

5.7 Serious Allergic Reactions

Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria may occur with PROCRIT. Immediately and permanently discontinue PROCRIT and administer appropriate therapy if a serious allergic or anaphylactic reaction occurs.

5.8 Severe Cutaneous Reactions

Blistering and skin exfoliation reactions including Erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with ESAs (including PROCRIT) in the postmarketing setting. Discontinue PROCRIT therapy immediately if a severe cutaneous reaction, such as SJS/TEN, is suspected.

5.9 Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative

PROCRIT from multiple-dose vials contains benzyl alcohol and is contraindicated for use in neonates, infants, pregnant women, and lactating women [see Contraindications (4)] . In addition, do not mix PROCRIT with bacteriostatic saline (which also contains benzyl alcohol) when administering PROCRIT to these patient populations [see Dosage and Administration (2)].

Serious and fatal reactions including "gasping syndrome" can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including PROCRIT multiple-dose vials. The "gasping syndrome" is characterized by central nervous system (CNS) depression, metabolic acidosis, and gasping respirations. There is a potential for similar risks to fetuses and infants exposed to benzyl alcohol in uteroor in breast-fed milk, respectively. PROCRIT multiple-dose vials contain 11 mg of benzyl alcohol per mL. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known [see Use in Specific Populations (8.1, 8.2, and 8.4)] .

5.10 Risk of Infectious Diseases Due to Albumin (Human) Content

PROCRIT contains albumin, a derivative of human blood [see Description (11)] . Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

5.11 Dialysis Management

Patients may require adjustments in their dialysis prescriptions after initiation of PROCRIT. Patients receiving PROCRIT may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis.

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of PROCRIT.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Seizures [see Warnings and Precautions (5.4)]
• PRCA [see Warnings and Precautions (5.6)]
• Serious Allergic Reactions [see Warnings and Precautions (5.7)]
• Injection Site Reactions, including irritation and pain
• Porphyria
• Severe Cutaneous Reactions [see Warnings and Precautions (5.8)]

6.3 Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to epoetin alfa with the incidence of antibodies to other products may be misleading.

Neutralizing antibodies to epoetin alfa that cross-react with endogenous erythropoietin and other ESAs can result in PRCA or severe anemia (with or without other cytopenias) [see Warnings and Precautions (5.6)] .

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The multiple-dose vials are formulated with benzyl alcohol and are contraindicated for use in neonates and infants [see Contraindications (4), Warnings and Precautions (5.9)] . When therapy with PROCRIT is needed in neonates and infants, use the single-dose vial, which is a benzyl alcohol-free formulation. Do not mix the single-dose vials with bacteriostatic saline when administering PROCRIT to neonates or infants because it contains benzyl alcohol [see Dosage and Administration (2.6)] .

Serious adverse reactions including fatal reactions and the "gasping syndrome" occurred in premature neonates and infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known [see Warnings and Precautions (5.9)] .

8.5 Geriatric Use

Of the 4553 patients who received PROCRIT in the 6 studies for treatment of anemia due to CKD not receiving dialysis, 2726 (60%) were age 65 years and over, while 1418 (31%) were 75 years and over. Of the 757 patients who received PROCRIT in the 3 studies of CKD patients on dialysis, 361 (47%) were age 65 years and over, while 100 (13%) were 75 years and over. No differences in safety or effectiveness were observed between geriatric and younger patients. Dose selection and adjustment for an elderly patient should be individualized to achieve and maintain the target hemoglobin [see Dosage and Administration (2)] .

Among 778 patients enrolled in the 3 clinical studies of PROCRIT for the treatment of anemia due to concomitant chemotherapy, 419 received PROCRIT and 359 received placebo. Of the 419 who received PROCRIT, 247 (59%) were age 65 years and over, while 78 (19%) were 75 years and over. No overall differences in safety or effectiveness were observed between geriatric and younger patients. The dose requirements for PROCRIT in geriatric and younger patients within the 3 studies were similar.

Among 1731 patients enrolled in the 6 clinical studies of PROCRIT for reduction of allogeneic RBC transfusions in patients undergoing elective surgery, 1085 received PROCRIT and 646 received placebo or standard of care treatment. Of the 1085 patients who received PROCRIT, 582 (54%) were age 65 years and over, while 245 (23%) were 75 years and over. No overall differences in safety or effectiveness were observed between geriatric and younger patients. The dose requirements for PROCRIT in geriatric and younger patients within the 4 studies using the 3 times weekly schedule and 2 studies using the weekly schedule were similar.

Insufficient numbers of patients age 65 years or older were enrolled in clinical studies of PROCRIT for the treatment of patients treated with zidovudine for HIV Infection to determine whether they respond differently from younger patients .

9.1 Controlled Substance

PROCRIT contains epoetin alfa, which is not a controlled substance.

9.2 Abuse

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Abuse of PROCRIT may be seen in athletes for the effects on erythropoiesis. Abuse of drugs that increase erythropoiesis, such as PROCRIT, by healthy persons may lead to life-threatening cardiovascular complications (e.g., stroke, myocardial infarction, or thromboembolism) [see Warnings and Precautions (5.1)].

In animal studies, epoetin alfa did not distribute to the CNS nor produce behavioral effects that are consistent with CNS activity.

12.1 Mechanism of Action

PROCRIT stimulates erythropoiesis by the same mechanism as endogenous erythropoietin.

12.2 Pharmacodynamics

PROCRIT increases the reticulocyte count within 10 days of initiation, followed by increases in the RBC count, hemoglobin, and hematocrit, usually within 2 to 6 weeks. The rate of hemoglobin increase varies among patients and is dependent upon the dose of PROCRIT administered. For correction of anemia in hemodialysis patients, a greater biologic response is not observed at doses exceeding 300 Units/kg 3 times weekly.

12.3 Pharmacokinetics

In adult and pediatric patients with CKD, the elimination half-life (t 1/2) of plasma erythropoietin after intravenous administration of PROCRIT ranged from 4 to 13 hours. After subcutaneous administration, C maxwas achieved within 5 to 24 hours. The t 1/2in adult patients with serum creatinine greater than 3 mg/dL was similar between those not on dialysis and those maintained on dialysis. The pharmacokinetic data indicate no apparent difference in PROCRIT t 1/2among adult patients above or below 65 years of age.

A pharmacokinetic study comparing 150 Units/kg subcutaneous 3 times weekly to 40,000 Units subcutaneous weekly dosing regimen was conducted for 4 weeks in healthy subjects (n=12) and for 6 weeks in anemic cancer patients (n=32) receiving cyclic chemotherapy. There was no accumulation of serum erythropoietin after the 2 dosing regimens during the study period. The 40,000 Units weekly regimen had a higher C max(3- to 7-fold), longer T max(2- to 3-fold), higher AUC 0–168 h(2- to 3-fold) of erythropoietin and lower clearance (CL) (50%) than the 150 Units/kg 3 times weekly regimen. In anemic cancer patients, the average t 1/2was similar (40 hours with range of 16 to 67 hours) after both dosing regimens. After the 150 Units/kg 3 times weekly dosing, the values of T maxand CL were similar (13.3 ± 12.4 vs. 14.2 ± 6.7 hours, and 20.2 ± 15.9 vs. 23.6 ± 9.5 mL/hr/kg) between week 1 when patients were receiving chemotherapy (n=14) and week 3 when patients were not receiving chemotherapy (n=4). Differences were observed after the 40,000 Units weekly dosing with longer T max(38 ± 18 hours) and lower CL (9.2 ± 4.7 mL/hr/kg) during week 1 when patients were receiving chemotherapy (n=18) compared with those (22 ± 4.5 hours, 13.9 ± 7.6 mL/hr/kg, respectively) during week 3 when patients were not receiving chemotherapy (n=7).

The pharmacokinetic profile of PROCRIT in pediatric patients appeared similar to that of adults.

The pharmacokinetics of PROCRIT has not been studied in patients with HIV Infection.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of PROCRIT has not been evaluated.

PROCRIT was not mutagenic or clastogenic under the conditions tested: PROCRIT was negative in the in vitrobacterial reverse mutation assay (Ames test), in the in vitromammalian cell gene mutation assay (the hypoxanthine-guanine phosphoribosyl transferase [HGPRT] locus), in an in vitrochromosomal aberration assay in mammalian cells, and in the in vivomouse micronucleus assay.

When administered intravenously to male and female rats prior to and during mating, and to females through the beginning of implantation (up to gestational day 7; dosing stopped prior to the beginning of organogenesis), doses of 100 and 500 Units/kg/day of PROCRIT caused slight increases in pre-implantation loss, post-implantation loss and decreases in the incidence of live fetuses. It is not clear whether these effects reflect a drug effect on the uterine environment or on the conceptus. This animal dose level of 100 Units/kg/day approximates the clinical recommended starting dose, depending on the patient's treatment indication, but may be lower than the clinical dose in patients whose doses have been adjusted.

14.1 Patients with Chronic Kidney Disease

14.2 Zidovudine-treated Patients with HIV Infection

The safety and efficacy of PROCRIT were evaluated in 4 placebo-controlled studies enrolling 297 anemic patients (hemoglobin < 10 g/dL) with HIV Infection receiving concomitant therapy with zidovudine. In the subgroup of patients (89/125 PROCRIT and 88/130 placebo) with pre-study endogenous serum erythropoietin levels ≤ 500 mUnits/mL, PROCRIT reduced the mean cumulative number of units of blood transfused per patient by approximately 40% as compared to the placebo group. Among those patients who required RBC transfusions at baseline, 43% of patients treated with PROCRIT versus 18% of placebo-treated patients were RBC transfusion-independent during the second and third months of therapy. PROCRIT therapy also resulted in significant increases in hemoglobin 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 reduction (p < 0.003) in RBC transfusion requirements in patients treated with PROCRIT (n=51) compared to placebo-treated patients (n=54) whose mean weekly zidovudine dose was ≤ 4200 mg/week.

Approximately 17% of the patients with endogenous serum erythropoietin levels ≤ 500 mUnits/mL receiving PROCRIT in doses from 100 to 200 Units/kg 3 times weekly achieved a hemoglobin of 12.7 g/dL without administration of RBC transfusions or significant reduction in zidovudine dose. In the subgroup of patients whose pre-study endogenous serum erythropoietin levels were > 500 mUnits/mL, PROCRIT therapy did not reduce RBC transfusion requirements or increase hemoglobin compared to the corresponding responses in placebo-treated patients.

14.3 Patients with Cancer on Chemotherapy

The safety and effectiveness of PROCRIT was assessed in two multicenter, randomized (1:1), placebo-controlled, double-blind studies (Study C1 and Study C2) and a pooled analysis of six additional randomized (1:1), multicenter, placebo-controlled, double-blind studies. All studies were conducted in patients with anemia due to concomitantly administered cancer chemotherapy. Study C1 enrolled 344 adult patients, Study C2 enrolled 222 pediatric patients, and the pooled analysis contained 131 patients randomized to epoetin alfa or placebo. In Studies C1 and C2, efficacy was demonstrated by a reduction in the proportion of patients who received an RBC transfusion, from week 5 through end of the study, with the last-known RBC transfusion status carried forward for patients who discontinued treatment. In the pooled analysis, efficacy was demonstrated by a reduction in the proportion of patients who received an RBC transfusion from week 5 through end of the study in the subset of patients who were remaining on therapy for 6 or more weeks.

14.4 Surgery Patients

The safety and efficacy of PROCRIT were evaluated in a placebo-controlled, double-blind study (S1) 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. Patients were stratified into 1 of 3 groups based on their pretreatment hemoglobin [≤ 10 g/dL (n=2), > 10 to ≤ 13 g/dL (n=96), and > 13 to ≤ 15 g/dL (n=218)] and then randomly assigned to receive 300 Units/kg PROCRIT, 100 Units/kg PROCRIT, or placebo by subcutaneous injection for 10 days before surgery, on the day of surgery, and for 4 days after surgery. All patients received oral iron and a low-dose, postoperative warfarin regimen.

Treatment with PROCRIT 300 Units/kg significantly (p=0.024) reduced the risk of allogeneic RBC transfusion in patients with a pretreatment hemoglobin of > 10 to ≤ 13 g/dL; 5/31 (16%) of patients treated with PROCRIT 300 Units/kg, 6/26 (23%) of patients treated with PROCRIT 100 Units/kg, and 13/29 (45%) of placebo-treated patients were transfused. There was no significant difference in the number of patients transfused between PROCRIT (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 is useful in this hemoglobin strata. In the > 10 to ≤ 13 g/dL pretreatment stratum, the mean number of units transfused per PROCRIT-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.

PROCRIT was also evaluated in an open-label, parallel-group study (S2) enrolling 145 patients 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. Patients were randomly assigned to receive 1 of 2 subcutaneous dosing regimens of PROCRIT (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 patients 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 that observed in the 300 Units/kg daily group. The mean increase in absolute reticulocyte count was smaller in the weekly group (0.11 × 10 6/mm 3) compared to the daily group (0.17 × 10 6/mm 3). Mean hemoglobin levels were similar for the 2 treatment groups throughout the postsurgical period.

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

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

Do not shake. Do not use PROCRIT that has been shaken or frozen.

Store PROCRIT vials in the original carton until use to protect from light.