ESA warnings riling practice

April 16, 2007

New warnings the Food & Drug Administration has issued about erythropoiesis-stimulating agents (ESAs) have prompted many practitioners to change the way they practice, while others remain unconvinced.

In March, the FDA said recent studies have revealed increased risk for serious adverse effects, tumor growth, and death associated with ESA use. The agency explained that while the studies evaluated individual products, the results apply to all ESAs because they have the same mechanism of action. The three ESAs currently marketed are Epogen and Procrit (epoetin alfa, Amgen/Ortho Biotech LP), and Aranesp (darbepoetin alfa, Amgen).

Amgen and the FDA announced last month that the labels for all three antianemia agents have been updated to reflect the new safety information. Paramount among the changes is the need for hemoglobin level monitoring for all patients receiving ESAs.

One group with reservations about the warnings is the Renal Physicians Association (RPA). In a guidance to nephrology care providers, RPA said the warnings "may be misleading and only partly applicable to CKD patients, and as a result have caused considerable confusion in the kidney community." It maintains that overreaction to the FDA advisory should not interfere with best clinical judgment.

The new information isn't necessarily surprising, said Kamakshi V. Rao, Pharm.D., BCOP, hematology oncology clinical specialist at the University of North Carolina Hospitals. However, it is important for clinicians to pay attention to it. She hopes R.Ph.s, physicians, and physician extenders will begin to focus more on monitoring ESA therapy appropriately. It's time monitoring was made a priority, she said.

However, Rao also thinks it's important that clinicians and patients remember the value of ESAs when used as they are intended. "The use of ESAs has grown significantly, as their usefulness in a variety of settings and for various indications has been explored," she said. Patients have had clear quality-of-life improvements with earlier treatment at recommended doses.

Although many studies evaluate patients receiving ESAs for unapproved indications and at higher-than-recommended doses, Rao said most clinicians are using them at approved doses. The trend lately has been to dose toward the upper end of the recommended dosing limits. It will be interesting, she noted, to see whether physicians now start prescribing ESAs at lower doses.

The revised ESA labeling advises that the dose be sufficient to prevent the need for blood transfusion and low enough to keep hemoglobin below 12 gm/dl. Because of the ESAs' mechanism of action, response to therapy can take two to six weeks. Monitoring should be done accordingly.

The new information also provides an excellent opportunity for pharmacists to educate patients, Rao said. Past publicity about the ESAs' benefits had patients asking for treatment. Now, publicity about the risks of ESAs may cause them to be fearful. Pharmacists can explain the ESAs' benefits and risks and stress the importance of compliance and monitoring.

An aid to hemoglobin monitoring

Shortly after the FDA issued the public safety advisory about ESAs, OTN announced that its Lynx software could help. The Lynx Technology software is designed specifically for community-based oncologists. "Our Lynx Technology ... helps provide the best outcomes for patients," said John Amos, president/CEO of OTN.

Lynx software performs several functions, including inventory and office management, billing, and certain patient information documentation. Lynx can help document patients' hemoglobin levels and adjust ESA dosing, according to OTN.

THE AUTHOR is a clinical writer based in the Seattle area.