Revision to the Posology Section (or Dosage and Administration Section) to state that the product should only be administered by the intravenous route in chronic renal failure patients, as further described below,

Reminder to healthcare professionals about handling of the product, in order to closely maintain storage conditions (e.g. 2o to 8oC) prior to administration.

Rare cases of antibody mediated PRCA have been reported from post-marketing experience in patients with chronic renal failure. As of September 30, 2002, the Company is aware of 112 post-marketing reports of anti-EPO antibody-mediated PRCA in patients treated with EPREX®. All of these cases were reported in patients with chronic renal failure treated by the subcutaneous route of administration, where route of administration was known. For those cases of antibody-mediated PRCA in which duration of treatment was reported, lack of efficacy was first observed between 4 and 25 months (median 9 months) following the start of treatment with EPREX®.

Of the total number of cases reported to date, there have also been a subset of antibody-mediated PRCA cases (17/112) in patients exposed to other erythropoietin products in conjunction with EPREX®. The Company has embarked on an extensive epidemiological study as part of the clinical program to monitor and evaluate the occurrence of antibody-mediated PRCA associated with epoetinums in chronic renal failure patients.

Revised route of administration and monitoring in chronic renal failure patients

The actions taken to date have already resulted in a substantial shift to intravenous use in chronic renal failure patients. To further ensure intravenous use in these patients, we have requested the Bureau of Food and Drugs to allow us to revise the product insert to reflect that EPREX® should only be administered by the intravenous route in chronic renal failure patients. It should be noted, this change to IV administration does not effect other patient populations for which EPREX® is approved.

Storage conditions

Healthcare professionals are reminded to properly handle the product, as is emphasized in the prescribing information (see Summary of Product Characteristics - Section 6.4), by storing the product at 2° to 8° C in its original outer package and not freezing. The cold chain should be closely maintained until administration to the patient. Clinicians are also advised to review the handling and storage information with their patients, as described in the Patient Information Leaflet. We have enclosed copies of materials on this topic for use by healthcare professionals, pharmacists, and patients.

Our Company Commitment

Our renal patients are important to us. Our focus is our patients and it is our duty and commitment to help you care for them. Janssen has 1.6 million patient-years of experience in anemia management and EPREXâ continues to provide timely, safe, effective and cost-effective treatment of anemia and fatigue in patients with chronic kidney disease or cancer when used in accordance with the label.

Being the company with the most experience in anemia management and in order to enhance understanding of PRCA in patients taking erythropoetin products, we are encouraging all companies marketing these products to conduct full retrospective safety reviews and case analyses of suspected PRCA cases, use a common and inclusive definition for this disorder, employ highly sensitive assay methodologies and publicly communicate their findings.

Should you have any questions or require additional information concerning the use of EPREX®, please contact the Medical Department at 8248944 or 8248945. You may also contact these numbers should you wish to report any adverse event related with EPREX®.

Sincerely,

Lilia M. Reyes, MD, MPH
Medical Director