"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 "...
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]. Use caution in patients with coexistent cardiovascular disease and stroke [see DOSAGE AND ADMINISTRATION]. 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.
Table 1: Randomized Controlled
Trials Showing Adverse Cardiovascular Outcomes in Patients With CKD
|Normal Hematocrit Study (NHS)
(N = 1265)
(N = 1432)
(N = 4038)
|Time Period of Trial||1993 to 1996||2003 to 2006||2004 to 2009|
|Population||CKD patients on hemodialysis with coexisting CHF or CAD, hematocrit 30 ± 3% on epoetin alfa||CKD patients not on dialysis with hemoglobin < 11 g/dL not previously administered epoetin alfa||CKD patients not on dialysis with type II diabetes, hemoglobin ≤ 11 g/dL|
|Hemoglobin Target; Higher vs. Lower (g/dL)||14.0 vs. 10.0||13.5 vs. 11.3||13.0 vs. > 9.0|
|Median (Q1, Q3) Achieved Hemoglobin level (g/dL)||12.6 (11.6, 13.3) vs.
10.3 (10.0, 10.7)
|13.0 (12.2, 13.4) vs.
11.4 (11.1, 11.6)
|12.5 (12.0, 12.8) vs.
10.6 (9.9, 11.3)
|Primary Endpoint||All-cause mortality or non-fatal MI||All-cause mortality, MI, hospitalization for CHF, or stroke||All-cause mortality, MI, myocardial ischemia, heart failure, and stroke|
|Hazard Ratio or Relative Risk (95% CI)||1.28 (1.06 - 1.56)||1.34 (1.03 - 1.74)||1.05 (0.94 - 1.17)|
|Adverse Outcome for Higher Target Group||All-cause mortality||All-cause mortality||Stroke|
|Hazard Ratio or Relative Risk (95% CI)||1.27 (1.04 - 1.54)||1.48 (0.97 - 2.27)||1.92 (1.38 - 2.68)|
Patients With Chronic Kidney Disease
Normal Hematocrit Study (NHS): A prospective, randomized, open-label study of 1265 patients with chronic kidney disease on dialysis with documented evidence of congestive heart failure or ischemic heart disease was designed to test the hypothesis that a higher target hematocrit (Hct) would result in improved outcomes compared with a lower target Hct. In this study, patients were randomized to epoetin alfa treatment targeted to a maintenance hemoglobin of either 14 ± 1 g/dL or 10 ± 1 g/dL. The trial was terminated early with adverse safety findings of higher mortality in the high hematocrit target group. Higher mortality (35% vs. 29%) was observed for the patients randomized to a target hemoglobin of 14 g/dL than for the patients randomized to a target hemoglobin of 10 g/dL. For all-cause mortality, the HR = 1.27; 95% CI (1.04, 1.54); p = 0.018. The incidence of nonfatal myocardial infarction, vascular access thrombosis, and other thrombotic events was also higher in the group randomized to a target hemoglobin of 14 g/dL.
CHOIR: A randomized, prospective trial, 1432 patients with anemia due to CKD who were not undergoing dialysis and who had not previously received epoetin alfa therapy were randomized to epoetin alfa treatment targeting a maintenance hemoglobin concentration of either 13.5 g/dL or 11.3 g/dL. The trial was terminated early with adverse safety findings. A major cardiovascular event (death, myocardial infarction, stroke, or hospitalization for congestive heart failure) occurred in 125 of the 715 patients (18%) in the higher hemoglobin group compared to 97 of the 717 patients (14%) in the lower hemoglobin group [hazard ratio (HR) 1.34, 95% CI: 1.03, 1.74; p = 0.03].
TREAT: A randomized, double-blind, placebo-controlled, prospective trial of 4038 patients with: CKD not on dialysis (eGFR of 20 – 60 mL/min), anemia (hemoglobin levels ≤ 11 g/dL), and type 2 diabetes mellitus, patients were randomized to receive either darbepoetin alfa treatment or a matching placebo. Placebo group patients also received darbepoetin alfa when their hemoglobin levels were below 9 g/dL. The trial objectives were to demonstrate the benefit of darbepoetin alfa treatment of the anemia to a target hemoglobin level of 13 g/dL, when compared to a “placebo” group, by reducing the occurrence of either of two primary endpoints: (1) a composite cardiovascular endpoint of all-cause mortality or a specified cardiovascular event (myocardial ischemia, CHF, MI, and CVA) or (2) a composite renal endpoint of all-cause mortality or progression to end stage renal disease. The overall risks for each of the two primary endpoints (the cardiovascular composite and the renal composite) were not reduced with darbepoetin alfa treatment (see Table 1), but the risk of stroke was increased nearly two-fold in the darbepoetin alfa-treated group versus the placebo group: annualized stroke rate 2.1% vs. 1.1%, respectively, HR 1.92; 95% CI: 1.38, 2.68; p < 0.001. The relative risk of stroke was particularly high in patients with a prior stroke: annualized stroke rate 5.2% in the darbepoetin alfa-treated group and 1.9% in the placebo group, HR 3.07; 95% CI: 1.44, 6.54. Also, among darbepoetin alfa-treated subjects with a past history of cancer, there were more deaths due to all causes and more deaths adjudicated as due to cancer, in comparison with the control group.
Patients With Cancer
An increased incidence of thromboembolic reactions, some serious and life-threatening, occurred in patients with cancer treated with ESAs.
In a randomized,
placebo-controlled study (Study 1 in Table 2 [see Increased Mortality and/or Increased Risk of Tumor Progression
or Recurrence in Patients With Cancer]) of 939 women with metastatic breast cancer receiving chemotherapy, patients received either weekly epoetin alfa or placebo for up to a year. This study was designed to show that survival was superior when epoetin alfa was administered to prevent anemia (maintain hemoglobin levels between 12 and 14 g/dL or hematocrit between 36% and 42%). This study was terminated prematurely when interim results demonstrated a higher mortality at 4 months (8.7% vs. 3.4%) and a higher rate of fatal thrombotic reactions (1.1% vs. 0.2%) in the first 4 months of the study among patients treated with epoetin alfa. Based on Kaplan-Meier estimates, at the time of study termination, the 12-month survival was lower in the epoetin alfa group than in the placebo group (70% vs. 76%; HR 1.37, 95% CI: 1.07, 1.75; p = 0.012).
Patients Having Surgery
An increased incidence of deep venous thrombosis (DVT) in patients receiving epoetin alfa undergoing surgical orthopedic procedures was demonstrated [see ADVERSE REACTIONS]. In a randomized, controlled study, 680 adult patients, not receiving prophylactic anticoagulation and undergoing spinal surgery, were randomized to 4 doses of 600 Units/kg epoetin alfa (7, 14, and 21 days before surgery, and the day of surgery) and standard of care (SOC) treatment (n = 340) or to SOC treatment alone (n = 340). A higher incidence of DVTs, determined by either color flow duplex imaging or by clinical symptoms, was observed in the epoetin alfa group (16 [4.7%] patients) compared with the SOC group (7 [2.1%] patients). In addition to the 23 patients with DVTs included in the primary analysis, 19 [2.8%] patients (n = 680) experienced 1 other thrombovascular event (TVE) each (12 [3.5%] in the epoetin alfa group and 7 [2.1%] in the SOC group). Deep venous thrombosis prophylaxis is strongly recommended when ESAs are used for the reduction of allogeneic RBC transfusions in surgical patients [see DOSAGE AND ADMINISTRATION].
Increased mortality was observed in a randomized, placebo-controlled study of PROCRIT in adult patients who were undergoing CABG surgery (7 deaths in 126 patients randomized to PROCRIT versus no deaths among 56 patients receiving placebo). Four of these deaths occurred during the period of study drug administration and all 4 deaths were associated with thrombotic events.
Prescribing And Distribution Program For PROCRIT In Patients With Cancer
In order to prescribe and/or dispense PROCRIT to patients with cancer and anemia due to myelosuppressive chemotherapy, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program requirements. To enroll, visit www.esa-apprise.com or call 1-866-284-8089 for further assistance. Additionally, prior to each new course of PROCRIT in patients with cancer, prescribers and patients must provide written acknowledgment of a discussion of the risks of PROCRIT.
Increased Mortality And/Or Increased Risk Of Tumor Progression Or Recurrence In Patients With Cancer
ESAs resulted in decreased locoregional control/progression-free survival and/or overall survival (see Table 2). These findings were observed in studies of patients with advanced head and neck cancer receiving radiation therapy (Studies 5 and 6), in patients receiving chemotherapy for metastatic breast cancer (Study 1) or lymphoid malignancy (Study 2), and in patients with non-small cell lung cancer or various malignancies who were not receiving chemotherapy or radiotherapy (Studies 7 and 8).
Table 2: Randomized,
Controlled Studies With Decreased Survival and/or Decreased Locoregional
|Study/Tumor/(n)||Hemoglobin Target||Achieved Hemoglobin (Median; Q1, Q3*)||Primary Efficacy Outcome||Adverse Outcome for ESA-containing Arm|
|Study 1 Metastatic breast cancer (n = 939)||12-14 g/dL||12.9 g/dL; 12.2, 13.3 g/dL||12-month overall survival||Decreased 12-month survival|
|Study 2 Lymphoid malignancy (n = 344||13-15 g/dL (M) 13-14 g/dL (F)||11 g/dL; 9.8, 12.1 g/dL||Proportion of patients achieving a hemoglobin response||Decreased overall survival|
|Study 3 Early breast cancer (n = 733)||12.5-13 g/dL||13.1 g/dL; 12.5, 13.7 g/dL||Relapse-free and overall survival||Decreased 3-year relapse-free and overall survival|
|Study 4 Cervical cancer (n = 114)||12-14 g/dL||12.7 g/dL; 12.1, 13.3 g/dL||Progression-free and overall survival and locoregional control||Decreased 3-year progression-free and overall survival and locoregional control|
|Study 5 Head and neck cancer (n = 351)||≥ 15 g/dL (M) ≥ 14 g/dL (F)||Not available||Locoregional progression-free survival||Decreased 5-year locoregional progression-free and overall survival|
|Study 6 Head and neck cancer (n = 522)||14-15.5 g/dL||Not available||Locoregional disease control||Decreased locoregional disease control|
|No Chemotherapy or Radiotherapy|
|Study 7 Non-small cell lung cancer (n = 70)||12-14 g/dL||Not available||Quality of life||Decreased overall survival|
|Study 8 Non-myeloid malignancy (n = 989)||12-13 g/dL||10.6 g/dL; 9.4, 11.8 g/dL||RBC transfusions||Decreased overall survival|
|*Q1= 25th percentile
Q3= 75th percentile
Decreased Overall Survival
Study 1 was described in the previous section [see Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism]. Mortality at 4 months (8.7% vs. 3.4%) was significantly higher in the epoetin alfa arm. The most common investigator-attributed cause of death within the first 4 months was disease progression; 28 of 41 deaths in the epoetin alfa arm and 13 of 16 deaths in the placebo arm were attributed to disease progression. Investigator-assessed time to tumor progression was not different between the 2 groups. Survival at 12 months was significantly lower in the epoetin alfa arm (70% vs. 76%; HR 1.37, 95% CI: 1.07, 1.75; p = 0.012).
Study 2 was a randomized, double-blind study (darbepoetin alfa vs. placebo) conducted in 344 anemic patients with lymphoid malignancy receiving chemotherapy. With a median follow-up of 29 months, overall mortality rates were significantly higher among patients randomized to darbepoetin alfa as compared to placebo (HR 1.36, 95% CI: 1.02, 1.82).
Study 7 was a multicenter, randomized, double-blind study (epoetin alfa vs. placebo) in which patients with advanced non-small cell lung cancer receiving only palliative radiotherapy or no active therapy were treated with epoetin alfa to achieve and maintain hemoglobin levels between 12 and 14 g/dL. Following an interim analysis of 70 patients (planned accrual 300 patients), a significant difference in survival in favor of the patients in the placebo arm of the study was observed (median survival 63 vs. 129 days; HR 1.84; p = 0.04).
Study 8 was a randomized, double-blind study (darbepoetin alfa vs. placebo) in 989 anemic patients with active malignant disease, neither receiving nor planning to receive chemotherapy or radiation therapy. There was no evidence of a statistically significant reduction in proportion of patients receiving RBC transfusions. The median survival was shorter in the darbepoetin alfa treatment group than in the placebo group (8 months vs. 10.8 months; HR 1.30, 95% CI: 1.07, 1.57).
Decreased Progression-free Survival And Overall Survival
Study 3 was a randomized, open-label, controlled, factorial design study in which darbepoetin alfa was administered to prevent anemia in 733 women receiving neo-adjuvant breast cancer treatment. A final analysis was performed after a median follow-up of approximately 3 years. The 3-year survival rate was lower (86% vs. 90%; HR 1.42, 95% CI: 0.93, 2.18) and the 3-year relapse-free survival rate was lower (72% vs. 78%; HR 1.33, 95% CI: 0.99, 1.79) in the darbepoetin alfa-treated arm compared to the control arm.
Study 4 was a randomized, open-label, controlled study that enrolled 114 of a planned 460 cervical cancer patients receiving chemotherapy and radiotherapy. Patients were randomized to receive epoetin alfa to maintain hemoglobin between 12 and 14 g/dL or to RBC transfusion support as needed. The study was terminated prematurely due to an increase in thromboembolic adverse reactions in epoetin alfa-treated patients compared to control (19% vs. 9%). Both local recurrence (21% vs. 20%) and distant recurrence (12% vs. 7%) were more frequent in epoetin alfa-treated patients compared to control. Progression-free survival at 3 years was lower in the epoetin alfa-treated group compared to control (59% vs. 62%; HR 1.06, 95% CI: 0.58, 1.91). Overall survival at 3 years was lower in the epoetin alfa-treated group compared to control (61% vs. 71%; HR 1.28, 95% CI: 0.68, 2.42).
Study 5 was a randomized, placebo-controlled study in 351 head and neck cancer patients where epoetin beta or placebo was administered to achieve target hemoglobins ≥ 14 and ≥ 15 g/dL for women and men, respectively. Locoregional progression-free survival was significantly shorter in patients receiving epoetin beta (HR 1.62, 95% CI: 1.22, 2.14; p = 0.0008) with medians of 406 days and 745 days in the epoetin beta and placebo arms, respectively. Overall survival was significantly shorter in patients receiving epoetin beta (HR 1.39, 95% CI: 1.05, 1.84; p = 0.02).
Decreased Locoregional Control
Study 6 was a randomized, open-label, controlled study conducted in 522 patients with primary squamous cell carcinoma of the head and neck receiving radiation therapy alone (no chemotherapy) who were randomized to receive darbepoetin alfa to maintain hemoglobin levels of 14 to 15.5 g/dL or no darbepoetin alfa. An interim analysis performed on 484 patients demonstrated that locoregional control at 5 years was significantly shorter in patients receiving darbepoetin alfa (RR 1.44, 95% CI: 1.06, 1.96; p = 0.02). Overall survival was shorter in patients receiving darbepoetin alfa (RR 1.28, 95% CI: 0.98, 1.68; p = 0.08).
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 INFORMATION].
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.
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 Pure Red Cell Aplasia]. In the absence of PRCA, follow dosing recommendations for management of patients with an insufficient hemoglobin response to PROCRIT therapy [see DOSAGE AND ADMINISTRATION].
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.
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.
PROCRIT contains albumin, a derivative of human blood [see DESCRIPTION]. 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.
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.
Evaluate transferrin saturation and serum ferritin prior to and during PROCRIT treatment. Administer supplemental iron therapy when serum ferritin is less than 100 mcg/L or when serum transferrin saturation is less than 20% [see DOSAGE AND ADMINISTRATION]. The majority of patients with CKD will require supplemental iron during the course of ESA therapy. Following initiation of therapy and after each dose adjustment, monitor hemoglobin weekly until the hemoglobin level is stable and sufficient to minimize the need for RBC transfusion.
Patient Counseling Information
See Medication Guide.
Prior to treatment, inform patients of the risks and benefits of PROCRIT.
Inform patients with cancer that they must sign the patient-healthcare provider acknowledgment form before the start of each treatment course with PROCRIT and that healthcare providers must enroll and comply with the ESA APPRISE Oncology Program in order to prescribe PROCRIT.
- To read the Medication Guide.
- Of the increased risks of mortality, serious cardiovascular reactions, thromboembolic reactions, stroke, and tumor progression [see WARNINGS AND PRECAUTIONS].
- To undergo regular blood pressure monitoring, adhere to prescribed anti-hypertensive regimen and follow recommended dietary restrictions.
- To contact their healthcare provider for new-onset neurologic symptoms or change in seizure frequency.
- Of the need to have regular laboratory tests for hemoglobin.
- Risks are associated with benzyl alcohol in neonates, infants, pregnant women, and nursing mothers [see Use in Specific Populations].
Instruct patients who self-administer PROCRIT of the:
- Importance of following the Instructions for Use.
- Dangers of reusing needles, syringes, or unused portions of single-dose vials.
- Proper disposal of used syringes, needles, and unused vials, and of the full container.
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 vitro bacterial reverse mutation assay (Ames test), in the in vitro mammalian cell gene mutation assay (the hypoxanthine-guanine phosphoribosyl transferase [HGPRT] locus), in an in vitro chromosomal aberration assay in mammalian cells, and in the in vivo mouse micronucleus assay.
Impairment Of Fertility
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.
Use In Specific Populations
The multidose vials are formulated with benzyl alcohol. Do not administer PROCRIT from multidose vials, or PROCRIT from single-dose vials admixed with bacteriostatic saline containing benzyl alcohol, to pregnant women. When therapy with PROCRIT is needed during pregnancy, use a benzyl alcohol-free formulation [see DOSAGE AND ADMINISTRATION and CONTRAINDICATIONS].
Pregnancy Category C (single-dose vials only)
There are no adequate and well-controlled studies of PROCRIT use during pregnancy. There are limited data on PROCRIT use in pregnant women. In animal reproductive and developmental toxicity studies, adverse fetal effects occurred when pregnant rats received epoetin alfa at doses approximating the clinical recommended starting doses. Single-dose formulations of PROCRIT should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
There are reports of at least 33 pregnant women with anemia alone or anemia associated with severe renal disease and other hematologic disorders who received PROCRIT. Polyhydramnios and intrauterine growth restriction were reported in women with chronic renal disease, which is associated with an increased risk for these adverse pregnancy outcomes. There was 1 infant born with pectus excavatum and hypospadias following exposure during the first trimester. Due to the limited number of exposed pregnancies and multiple confounding factors (such as underlying maternal conditions, other maternal medications, and gestational timing of exposure), these published case reports and studies do not reliably estimate the frequency or absence of adverse outcomes.
When healthy rats received PROCRIT at doses of 100 Units/kg/day during mating and through early pregnancy (dosing stopped prior to organogenesis), there were slight increases in the incidences of pre- and post-implantation loss, and a decrease in live fetuses. This animal dose level of 100 Units/kg/day may approximate the clinical recommended starting dose, depending on the treatment indication. When healthy pregnant rats and rabbits received intravenous doses of up to 500 mg/kg/day of PROCRIT only during organogenesis, no teratogenic effects were observed in the offspring.
When healthy pregnant rats received PROCRIT at doses of 500 Units/kg/day late in pregnancy (after the period of organogenesis), offspring had decreased number of caudal vertebrae and growth delays [see Nonclinical Toxicology].
The multidose vials of PROCRIT are formulated with benzyl alcohol. Do not administer PROCRIT from multidose vials, or PROCRIT from single-dose vials admixed with bacteriostatic saline containing benzyl alcohol, to a nursing woman. When therapy with PROCRIT is needed in nursing women, use a benzyl alcohol-free formulation [see DOSAGE AND ADMINISTRATION and CONTRAINDICATIONS].
It is not known whether PROCRIT is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PROCRIT from single-dose vials is administered to a nursing woman.
The multidose vials are formulated with benzyl alcohol. Do not administer PROCRIT from multidose vials, or PROCRIT from single-dose vials admixed with bacteriostatic saline containing benzyl alcohol, to neonates or infants. When therapy with PROCRIT is needed in neonates and infants, use a benzyl alcohol-free formulation [see DOSAGE AND ADMINISTRATION and CONTRAINDICATIONS].
Benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome,” (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages > 99 mg/kg/day in neonates and low-birthweight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.
Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birthweight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all credits.
Pediatric Patients On Dialysis
PROCRIT is indicated in pediatric patients, ages 1 month to 16 years of age, for the treatment of anemia associated with CKD requiring dialysis. Safety and effectiveness in pediatric patients less than 1 month old have not been established [see Clinical Studies].
The safety data from these studies are similar to those obtained from the studies of PROCRIT in adult patients with CKD [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
Pediatric Cancer Patients On Chemotherapy
PROCRIT is indicated in patients 5 to 18 years old for the treatment of anemia due to concomitant myelosuppressive chemotherapy. Safety and effectiveness in pediatric patients less than 5 years of age have not been established [see Clinical Studies]. The safety data from these studies are similar to those obtained from the studies of PROCRIT in adult patients with cancer [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
Pediatric Patients With HIV Infection Receiving Zidovudine
Published literature has reported the use of PROCRIT in 20 zidovudine-treated, anemic, pediatric patients with HIV infection, ages 8 months to 17 years, treated with 50 to 400 Units/kg subcutaneously or intravenously 2 to 3 times per week. Increases in hemoglobin levels and in reticulocyte counts and decreases in or elimination of RBC transfusions were observed.
Pharmacokinetics In Neonates
Limited pharmacokinetic data from a study of 7 preterm, very low birth weight neonates and 10 healthy adults given intravenous erythropoietin suggested that distribution volume was approximately 1.5 to 2 times higher in the preterm neonates than in the healthy adults, and clearance was approximately 3 times higher in the preterm neonates than in the healthy adults.
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].
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 zidovudine in HIV-infected patients to determine whether they respond differently from younger patients.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 2/22/2017
Additional Procrit Information
Procrit - User Reviews
Procrit User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.