Procrit 

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HORSHAM, PA – (April 9, 2009) – Centocor Ortho Biotech Products, L.P. today updated the prescribing information for PROCRIT® (Epoetin alfa) to include a warning of the potential for antibody-mediated pure red cell aplasia (PRCA) when erythropoiesis-stimulating agents (ESAs) are administered to treat anemia associated with interferon or pegylated interferon and ribavirin therapy in patients with hepatitis C virus infection. ESAs are not approved by the U.S. Food and Drug Administration (FDA) for this use. This label update applies to all products in the ESA class of medicines.

PRCA is a known risk in treatment with ESAs in the approved indications and has been included as a warning in the prescribing information for PROCRIT since 2003. PRCA is a rare to very rare adverse drug reaction in which patients who are treated with ESAs develop antibodies to the ESA. These antibodies inactivate ESAs and naturally produced erythropoietin. The resulting anemia does not respond to treatment with an ESA. Patients with antibody-mediated PRCA need to receive red blood cell transfusions on a regular basis, typically over a number of months.

The WARNINGS section of the PROCRIT label has been revised and now reads:

Pure Red Cell Aplasia

Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients treated with PROCRIT. This has been reported predominantly in patients with chronic renal failure receiving ESAs by subcutaneous administration. PRCA has also been reported in patients receiving ESAs while undergoing treatment for hepatitis C with interferon and ribavirin.

As part of its ongoing commitment to rapid and transparent communication regarding emerging safety issues, Centocor Ortho Biotech Products, L.P. has worked with the FDA to monitor the issue and communicate the potential risk to physicians through multiple channels. The company reaffirms that, when used according to the product labeling, PROCRIT remains safe and effective.

About PROCRIT® (Epoetin alfa)

PROCRIT is used for the treatment of anemia in patients with most types of cancer receiving chemotherapy, with chronic renal failure who are on dialysis and those who are not on dialysis, who are being treated with zidovudine for HIV infection, and to reduce the need for transfusion in anemic patients who are scheduled for elective noncardiac, nonvascular surgery. Depending on the country in which Epoetin alfa is marketed, these indications may differ.

Important Safety Information

WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCE

Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.

Cancer:

ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers (see WARNINGS: Table 1).
To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion.
Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.
Discontinue following the completion of a chemotherapy course. 

Perisurgery: PROCRIT® (Epoetin alfa) increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.

Contraindications

PROCRIT is contraindicated in patients with uncontrolled hypertension or with known hypersensitivity to albumin (human) or mammalian cell-derived products.

 Additional Important Safety Information

Patients with chronic renal failure experienced greater risks for death and serious cardiovascular events (including myocardial infarction, stroke, congestive heart failure, and hemodialysis vascular access thrombosis) when administered ESAs to target higher versus lower hemoglobin levels (13.5 vs.11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies; these risks also increased in controlled clinical trials of patients with cancer. A rate of hemoglobin rise of >1 g/dL over 2 weeks may contribute to these risks.

Dose of PROCRIT

• Chronic renal failure patients: The dose of PROCRIT should be titrated for each patient to achieve and maintain hemoglobin levels between 10 to 12 g/dL. If a patient does not attain hemoglobin levels of 10 to 12 g/dL despite 12 weeks of appropriate PROCRIT therapy, see DOSAGE and ADMINISTRATION in the PROCRIT Prescribing Information.
• Cancer patients: PROCRIT therapy should not be initiated at hemoglobin levels ≥10 g/dL. The dose of PROCRIT should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion. Discontinue if after 8 weeks of therapy there is no response as measured by hemoglobin levels or if transfusions are still required (see recommended Dose Modification section in DOSAGE and ADMINISTRATION of the PROCRIT Prescribing Information).
• HIV patients: The dose of PROCRIT should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid transfusion and not to exceed the upper safety limit of 12 g/dL.

Monitor hemoglobin regularly during therapy, weekly until hemoglobin becomes stable.

Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients treated with PROCRIT predominantly in patients with chronic renal failure receiving PROCRIT by subcutaneous administration. PRCA has also been reported in patients receiving ESAs while undergoing treatment for Hepatitis C with interferon and ribavirin. If any patient develops a sudden loss of response to PROCRIT, accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT and other erythropoietic proteins. Contact ORTHO BIOTECH (1-888-2ASKOBI or 1-888-227-5624) to perform assays for binding and neutralizing antibodies. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT should be permanently discontinued and patients should not be switched to other erythropoietic proteins.

The safety and efficacy of PROCRIT therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes, or hypercoagulable disorders).

In some female patients, menses have resumed following PROCRIT therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.

Prior to and regularly during PROCRIT therapy monitor iron status; transferrin saturation should be ≥20% and ferritin should be ≥100 ng/mL. During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT.

Treatment of patients with grossly elevated serum erythropoietin levels (e.g., >200 mUnits/mL) is not recommended.

During PROCRIT therapy, blood pressure should be monitored carefully and aggressively managed, particularly in patients with an underlying history of hypertension or cardiovascular disease.

In studies, the most common side effects included fever (pyrexia), diarrhea, nausea, vomiting, swelling of hands or feet (edema), lack or loss of strength or weakness (asthenia, fatigue), shortness of breath, high blood pressure, headache, joint pain (arthralgias), abnormal skin sensations (as tingling or tickling or itching or burning; paresthesia), rash, constipation and upper respiratory infection.

Please visit www.procrit.com for the full Prescribing Information, including the Boxed WARNINGS, and for the Medication Guide and Patient Instructions for Use.