The US Food and Drug Administration (FDA) is informing healthcare professionals in the US of modified dosing recommendations for the erythropoiesis-stimulating agents (ESAs), when used in the treatment of anaemia in patients with chronic kidney disease (CKD).

The more conservative dosing recommendations have been made to improve the safety of ESAs, as data have shown that there is an increased risk of cardiovascular events associated with their use of in this patient population, when they are dosed to achieve a normal (or nearly normal) haemoglobin level.  The modified product information removes the concept of a target haemoglobin range (previously 10 to 12g/dL) and recommends the following:

1) For patients with anaemia of chronic kidney disease NOT on dialysis:
• Consider starting ESA treatment only when the haemoglobin level is less than 10 g/dL and when certain other considerations apply
• If the haemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of ESA

2) For patients with anaemia of chronic kidney disease on dialysis:
• Initiate ESA treatment when the haemoglobin level is less than 10 g/dL
• If the haemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of ESA

This advice does not define how far below 10 g/dL is appropriate for an individual to initiate, and does not recommend that the goal is to achieve a haemoglobin ≥10 g/dL. Therapy should be individualised to the patient and the lowest possible ESA dose given to reduce the need for transfusions.  Healthcare professionals should weigh the possible benefits of using ESAs to decrease the need for red blood cell transfusions in CKD patients against the increased risks for serious cardiovascular events, and should inform their patients of the current understanding of potential risks and benefits.

The manufacturer has revised the Boxed Warning, Warnings and Precautions, and Dosage and Administration sections of the US labels for the ESAs to include this new information. The FDA will continue to evaluate the safety of ESAs and is requiring the manufacturer to conduct additional trials.

Please see the Drug Safety Communication at the link below for further information, including a summary of the clinical trials on which these new recommendations were based (TREAT; CHOIR; normal haematocrit study)