ROCKVILLE, Md. -- The FDA warned today that aggressive use of erythropoiesis-stimulating agents to raise hemoglobin to a target of 12 g/dL or higher was associated with "serious and life-threatening side-effects and or/death."
ROCKVILLE, Md., March 9 -- The FDA warned today that aggressive use of erythropoiesis-stimulating agents to raise hemoglobin to a target of 12 g/dL or higher was associated with "serious and life-threatening side-effects and or/death."
The agency ordered a black-box warning for the drugs that recommended the lowest possible dose to slowly raise the hemoglobin concentration to the lowest level that will avoid the need for a blood transfusion.
Moreover, the FDA said that there has never been any evidence to support claims made in direct-to-consumer advertising that treatment with darbepoetin (Aranesp), epoetin alfa (Epogen), or epoetin alfa (Procrit) could increase energy or ease fatigue in patients undergoing cancer therapy.
For cancer patients who are not on chemotherapy, the FDA said that erythropoiesis-stimulating agents did not benefit anemia. But they appeared to shorten time to death.
At a press briefing, Richard Pazdur, M.D., director of the Office of Oncology Drug Products at the FDA's Center for Drug Evaluation and Research, said that on the basis of data from several recently reported clinical trials, a black box warning had been added to the labels of the three drugs.
The warning states:
Karen Weiss, M.D., deputy director of the FDA's Office of Oncology Drug Products, said the FDA became concerned when it started to receive results from a number of trials investigating aggressive use of erythropoiesis-stimulating agents to raise hemoglobin to targets higher than the targets on the drug label.
The results of those "more is better" studies were uniformly bad-ranging from increased cardiovascular events to progression of cancer.
A puzzling aspect of the FDA action today was the acknowledgement that there was no evidence to support marketing claims that the drugs could restore energy or reduce fatigue for patient in chemotherapy or radiation therapy.
Rafel Dwain Rieves, M.D., acting director, division of medical imaging and hematology products, said those claims were an extension of quality-of-life labeling from studies in renal dialysis patients.
But Dr. Rieves said that even the renal labeling was not supported by good quality-of-life measures, but rather results of a series of questionnaires that asked open-ended questions about a wide range of topics including sex life, appetite, happiness, and energy.
Dr. Pazdur said that going forward, all patients should be started on the lowest possible dose of Aranesp, Epogen, or Procrit.
Additionally, for all patients, physicians should:
The label was also changed to include this evidence from recently reported clinical trials: