Information for Healthcare Providers
In recent years, there has been an increase in reports of possible antibody-mediated pure red cell aplasia (PRCA) predominantly in patients with chronic kidney disease (CKD) receiving recombinant erythropoiesis stimulating proteins (ESPs). In response to questions concerning this subject, Amgen has established this website to provide physicians with information surrounding this issue. Amgen intends to update this Web site on a semiannual basis.
Major Manufacturers of Erythropoiesis Stimulating Proteins
There are several manufacturers of erythropoietic proteins worldwide. Not all products are available in all regions. The major erythropoietic products, their manufacturers, and their regions of availability are:
EPOGEN/Procrit and Eprex share the same International Non-proprietary Name (Epoetin alfa), however, Eprex is not equivalent to EPOGEN/Procrit. The products are manufactured by different companies in different facilities, using different methods and formulations. Epoetin beta is a different product than Epoetin alfa, manufactured by different processes and with different formulations. Darbepoetin alfa is a different product from Epoetin alfa and Epotein beta, manufactured by different processes and with different formulations.
Identification and Reporting of Pure Red Cell Aplasia (PRCA) and Severe Anemia with Neutralizing Antibodies
Pure red cell aplasia (PRCA) is a rare condition that has been associated with autoimmune, viral and neoplastic diseases. It has also occurred as an adverse consequence of certain therapies. Antibody-mediated PRCA develops when antibodies form to block or reduce the body’s ability to make red blood cells, causing severe anemia. One cause of antibody-mediated PRCA occurs when a patient develops neutralizing antibodies against an ESP. In other cases, antibody-mediated PRCA occurs spontaneously without any prior exposure to ESPs.
Recently, the FDA’s interpretation of anemia associated with neutralizing antibodies has evolved to include both PRCA and severe anemia, with or without a decrease in white blood cells or platelets, associated with neutralizing antibodies. The FDA’s updated interpretation has resulted in a class label change for all three ESP products marketed in the U.S.; consistent information about PRCA will be added to the adverse event profile section of all ESP products’ labels in the U.S. If a patient fails to respond or maintain a response to the prescribed ESP, an evaluation for causative factors should be undertaken. If anti-erythropoietin antibody-associated anemia is suspected, physicians should withhold the prescribed ESP and other erythropoietic proteins and contact Amgen (1-800-77-AMGEN) or online at http://www.amgenmedinfo.com/ to perform assays for binding and neutralizing antibodies. If anemia associated with neutralizing antibodies is confirmed, the prescribed ESP should be permanently discontinued.
Cross-Reactivity of Anti-Erythropoietin Antibodies
Amgen scientists have demonstrated that neutralizing antibodies produced in response to any ESP may cross-react with other ESPs. As a result, Amgen recommends that patients who are suspected of having antibody-mediated PRCA not be switched to any other ESP.
Conclusion
Both EPOGEN and Aranesp have improved the lives of patients and have clinical practice experience of more than three million and 800,000 patient years, respectively (as of June, 2005). Amgen is committed to the highest standards of drug quality and patient safety and will continue to maintain a robust safety-surveillance program.
For additional information on EPOGEN and Aranesp, please refer to the product Web sites.
(Posted October 26, 2005)
