INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS

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.

Anemia Due to Zidovudine in HIV-infected Patients

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

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.

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 preoperatively.

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 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.

Contraindications

PROCRIT^® is contraindicated in patients with:

• Uncontrolled hypertension
• Pure red cell aplasia (PRCA) that begins after treatment with PROCRIT^® or other erythropoietin protein drugs
• Serious allergic reactions to PROCRIT^®

PROCRIT^® from multidose vials contains benzyl alcohol and is contraindicated in:

• Neonates, infants, pregnant women, and nursing mothers. When therapy with PROCRIT^® is needed in neonates and infants, use single-dose vials; do not admix with bacteriostatic saline containing benzyl alcohol.

Additional Important Safety Information

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. Use caution in patients with coexistent cardiovascular disease and stroke. 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.

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. These findings were observed in studies of patients with advanced head and neck cancer receiving radiation therapy, in patients receiving chemotherapy for metastatic breast cancer or lymphoid malignancy, and in patients with non-small cell lung cancer or various malignancies who were not receiving chemotherapy or radiotherapy.

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.

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.

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. In the absence of PRCA, follow dosing recommendations for management of patients with an insufficient hemoglobin response to PROCRIT^® therapy.

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.

Laboratory Monitoring

• 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%. 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.

PROCRIT^® is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.

Anemia in Patients with Chronic Kidney Disease Not on Dialysis

• Consider initiating PROCRIT^® treatment only when the hemoglobin level is less than 10 g/dL and:
  • The patient’s rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion and
  • Reducing the risk of alloimmunization and/or other RBC transfusion related risks is a goal.
• If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of PROCRIT^®, and use the lowest dose of PROCRIT^® sufficient to reduce the need for RBC transfusions.
• When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.
  • Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.
  • If the hemoglobin rises rapidly (e.g. more than 1 g/dL in any 2-week period), reduce the dose of PROCRIT^® by 25% or more as needed to reduce rapid responses.
  • For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%.
  • For patients who do not respond adequately over a 12-week escalation period, increasing the PROCRIT^® dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue PROCRIT^® if responsiveness does not improve.
• Adverse reactions in ≥ 5% of PROCRIT^®-treated patients in clinical studies were hypertension and arthralgia.

Chemotherapy-Induced Anemia

• PROCRIT^® is not indicated for use in patients with cancer receiving hormonal agents, biologic products, or radiotherapy, unless also receiving concomitant myelosuppressive chemotherapy.
• PROCRIT^® is not indicated for use in patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure.
• 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.
• Reduce dose by 25% if:
  • Hemoglobin increases greater than 1 g/dL in any 2-week period or
  • Hemoglobin reaches a level needed to avoid RBC transfusion.
• Withhold dose if hemoglobin exceeds a level needed to avoid RBC transfusion. Reinitiate at a dose 25% below the previous dose when hemoglobin approaches a level where RBC transfusions may be required.
• Adverse reactions in ≥ 5% of PROCRIT^®-treated patients in clinical studies were nausea, vomiting, myalgia, arthralgia, stomatitis, cough, weight decrease, leukopenia, bone pain, rash, hyperglycemia, insomnia, headache, depression, dysphagia, hypokalemia, and thrombosis.

Surgery/Perisurgery

• PROCRIT^® is not indicated for use in patients scheduled for surgery who are willing to donate autologous blood.
• PROCRIT^® is not indicated for use in patients undergoing cardiac or vascular surgery.
• Deep venous thrombosis prophylaxis is recommended during PROCRIT^® therapy.
• Adverse reactions in ≥ 5% of PROCRIT^®-treated patients in clinical studies were nausea, vomiting, pruritus, headache, injection site pain, chills, deep vein thrombosis, cough, and hypertension.

Anemia in Zidovudine-treated HIV-infected Patients

• Withhold PROCRIT^® if hemoglobin exceeds 12 g/dL. Resume therapy at a dose 25% below the previous dose when hemoglobin declines to less than 11 g/dL.
• Discontinue PROCRIT^® if an increase in hemoglobin is not achieved at a dose of 300 Units/kg for 8 weeks.
• Adverse reactions in ≥ 5% of PROCRIT^®-treated patients in clinical studies were pyrexia, cough, rash, and injection site irritation.

These are not all of the possible side effects of PROCRIT^®. Your healthcare provider can give you a more complete list. Tell your healthcare provider about any side effects that bother you or that do not go away.

For medication information imquires or to report adverse events or product quality complaints related to our products, please contact the Jassen products Customer Communications Center at 1-800-457-6399 (9:00 am - 5:00 pm ET, Monday through Friday) or http://www.janssenmdecalinformation.com/.

Please read the Medication Guide and discuss with your doctor.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
1-800-FDA-1088 (1-800-332-1088).