FDA has announced more conservative dosing recommendations for erythropoiesis-stimulating agents (ESAs) when they are used to treat anemia in patients with chronic kidney disease (CKD) because of increased risk of cardiovascular events such as stroke, thrombosis, and death.
FDA has announced more conservative dosing recommendations for erythropoiesis-stimulating agents (ESAs) when they are used to treat anemia in patients with chronic kidney disease (CKD) because of the increased risks of cardiovascular events such as stroke, thrombosis, and death.
ESA product labels up to now have recommended a target to keep hemoglobin level in the range of 10 to 12 g/dL for those patients. This has been removed from the labels.
The new guidelines say that although treatment should be individualized, for patients with CKD anemia who are not on dialysis, ESA treatment should be considered only when the level is less than 10 g/dL and certain other considerations apply. The ESA should be reduced or interrupted if the level goes above 10 g/dL, they say.
For similar patients who are on dialysis, ESA treatment should be started when the level is less than 10 g/dL, but it should be reduced or interrupted if it approaches or exceeds 11 g/dL, the FDA announcement stated.
In a conference call with reporters, Robert C. Kane, MD, FDA’s acting deputy director for safety in the Division of Hematology Products, said that findings from the large TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) trial had showed a clear indication of increased risk of stroke for patients treated to achieve the target level of 13 and that effect was even more evident in the patient treatment group with an underlying history of stroke.
“All of these things in total indicate a prothrombotic effect of ESAs. It is not clear at this point that there is a hemoglobin level below which you might not have any of these problems. It is also clear that as the hemoglobin target increases, the risk increases,” said Kane.
The release said that the changes in recommendation were based on findings from clinical trials, including the TREAT trial, which showed that using ESAs to target a hemoglobin level of greater than 11 g/dL increased the risk of serious adverse cardiovascular events, such as heart attack and stroke, and provided no additional benefit to patients.
In terms of cancer patients, these dose administration recommendations do not directly affect that population, said Kane.
But other parts of the new label, Kane said, specifically the warnings and precautions, the boxed warning, and the dosage and administration sections of the label that “reiterate and extend our concern about the risks, apply to all patients.”
Amgen, the maker of ESAs, said that it “is in ongoing discussions with the FDA regarding additional post-marketing required studies to further understand the benefit-risk profile of ESAs in CKD patients on dialysis and not on dialysis.”
FDA’s safety communication is posted at http://www.fda.gov/Drugs/DrugSafety/ucm259639.htm.