June 24th, 2011

FDA Recommends More-Conservative Dosing of ESAs

The FDA today said that it was recommending more-conservative dosing of ESAs (erythropoiesis-stimulating agents) in patients with chronic kidney disease (CKD). The possible beneficial effects of the drugs to decrease the need for transfusions in CKD patients should be weighed against the increased risk for cardiovascular events, the FDA said. ESA therapy should be given at the lowest possible dose to reduce the need for transfusions. Currently available ESAs include epoetin alfa, marketed as Epogen (Amgen) and Procrit (J&J), and darbepoetin alfa, marketed as Aranesp (Amgen).

The FDA action follows last October’s advisory committee meeting, which itself followed the publication of the TREAT trial in the previous year. Here is the FDA summary of the label change:

The ESA labels now warn:

  • In controlled trials with CKD patients, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when given ESAs to achieve a target hemoglobin level of greater than 11 g/dL.
  • No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.

The ESA labels now recommend:

  • For patients with CKD, consider starting ESA treatment when the hemoglobin level is less than 10 g/dL. This advice does not define how far below 10 g/dL is appropriate for an individual to initiate. This advice also does not recommend that the goal is to achieve a hemoglobin level of 10 g/dL or a hemoglobin level above 10 g/dL. Individualize dosing and use the lowest dose of ESA sufficient to reduce the need for red blood cell transfusions. Adjust dosing as appropriate.

The drug label previously recommended that ESAs should be dosed to achieve and maintain hemoglobin levels within the target range of 10 to 12 g/dL in CKD patients. This target concept has been removed from the label.

The FDA said that a hemoglobin level above 11 g/dL raises the risk for serious adverse cardiovascular events and has never been shown to provide additional benefit. The FDA further noted that “no clinical trial to date has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase” the risk for cardiovascular events.

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