New Warnings by FDA on Anemia Drugs

Warning labels on three anemia drugs used by one million Americans undergoing chemotherapy or who have kidney failure have been strengthened to alert users about increased risk of heart attack, stroke, a worsening of their condition, and even death, said the manufacturers, Amgen and Johnson & Johnson earlier this week.

The decision, which has been made in consultation with the US Food and Drug Administration, affects Amgen's Epogen and Aranesp, and Johnson & Johnson's Procrit. These drugs belong to a class known as erythropoiesis-stimulating agents or ESAs.

ESAs are a bioengineered protein similar to one made in the kidneys that causes bone marrow to produce more red blood cells.

Concern about ESAs has been growing since a number of studies has revealed an increased risk of death in cancer patients with anemia that did not arise as a result of chemotherapy, that kidney dialysis patients could be overusing them, and that they increase tumour growth and reduce survival.

The US Food and Drug Administration (FDA) said yesterday, Thursday 8th November, that it had approved revised boxed warnings and other labelling changes for Aranesp, Epogen and Procrit because of the increased risks to patients with cancer and chronic kidney failure.

Epogen, Procrit and Aranesp are approved by the FDA for the treatment of anemia in certain cancer patients with anemia caused by chemotherapy, and for the treatment of anemia in patients with chronic kidney failure.

The three drugs are also FDA approved for treatment of certain cases of anemia in patients who are about to have major surgery, in order to reduce the need for blood transfusions. And they are also approved for HIV patients with anemia caused by zidovudine (AZT) therapy, said the FDA.

The new warnings add to the changes made in March this year, include advice from FDA advisory panels, and say that ESAs do not show reductions in symptoms of anemia, fatigue and quality of life in patients with cancer. The changes in March reflected the resuts of six studies that showed survival was reduced and tumours developed more rapidly when cancer patients were given ESAs targeted at hemoglobin levels of 12 grams per deciliter (g/dL) or more.

The latest warnings tell cancer patients that recent studies showed tumour growth and reduced survival in patients with advanced breast, head and neck, lymphoid and non small-cell lung cancer who took ESAs to reach a hemoglobin target of 12 g/dL or more.

The warnings also stress there is no evidence that the same risks are present for patients taking ESAs to reach lower targets than 12 g/dL, which is believed to be the more common level reached in clinical practice, said the FDA.

Doctors look at a patient's hemoglobin count and recommend the dose of ESA to raise that count to a certain target level.

Dr Janet Woodcock, the FDA's deputy commissioner for scientific and medical programs, who is also the chief medical officer and acting director of its Center for Drug Evaluation and Research, said that doctors prescribing ESAs for patients with cancer should take into account the risk of increased tumour growth and reduced survival.

"ESAs should be used in patients with cancer only when their anemia is due to chemotherapy and only at the lowest dose necessary to avoid the need for blood transfusions," she said.

The warnings specify that ESAs should not be used by cancer patients unless their anemia was caused by chemotherapy, and that they should stop taking ESAs once the chemotherapy has finished.

Further trials are to be carried out to test different doses of ESAs on a range of tumour types.

The new labels also warn there is no evidence that ESAs improved symptoms of anemia, quality of life, fatigue, or well-being in controlled trials with cancer patients or HIV patients on AZT therapy.

For kidney failure patients, the new warnings say that ESAs should not be used to attain a hemoglobin level above the 10 g/dL to 12 g/dL target range. They state that maintaining levels above this range increases the risk of stroke, heart attack, heart failure, and death.

They also contain precise instructions on dosage and hemoglobin monitoring for patients with chronic kidney failure whose hemoglobin levels are not responding well to ESA treatment.

A new Medication Guide will also be issued to update patients on the safety and effectiveness of ESAs.

[BonnieR]

Oh, great......it's always something!
But thanks for the head's up.

[tousled1]

Thanks for the update.

I just want to point out what I feel to be the most important part of the warning:

The warnings also stress there is no evidence that the same risks are present for patients taking ESAs to reach lower targets than 12 g/dL, which is believed to be the more common level reached in clinical practice, said the FDA

I have had and continue to have problems with my red blood counts (also white and platlets) while receiving chemo. I get Procrit shots every week but my oncologist is not trying to raise my hemoglobin above 12. With the Procrit shots my hemoglobin is maintaining at around 9.8. I would hate to think what it would be without the Procrit. I've also tried the Arnasep shots but they did not work. I'm just thankful that I can get the Procrit in order to avoid a transfusion.

[Sherryg683]

I saw that today and was shocked. My oncologist never gave me any of those shots. Can't believe that they could make the tumor grow faster..that's scary..sherry

[dlaxague]

From "MedicalNewsToday": "The warnings also stress there is no evidence that the same risks are present for patients taking ESAs to reach lower targets than 12 g/dL, which is believed to be the more common level reached in clinical practice, said the FDA."

The actual FDA alert ( http://www.fda.gov/cder/drug/infopage/RHE/default.htm) : "The changes for use in patients with cancer include a warning to state that the risks of shortened survival and tumor progression have not been excluded when ESAs are dosed to reach a hemoglobin value of <12 g/dL."

Debbie now: I guess that both are saying the same thing, but it certainly sounds worse if you read the FDA's version of it.

As Tousled said, this really puts women and providers in a hard spot. How to make this decision? Does anyone have a Dr. who does not use ESA's at all, but rather gives blood transfusions? And at what level - a certain number, or is it based on symptoms?

On the other hand, the research is not showing that people using ESA's are dropping like flies. The research is showing a fairly small decrease in survival time. And the research was done on those who were targeting ESA's great than 12g/dL. At that level, they often had a control group for whom nothing was done. At lower levels of Hgb, you can't do nothing, or the person could die from the anemia. For those people, further research could show that although the ESA may have a small tumorigenic effect, the benefit of prudent ESA use clearly outweighs the risk of not using it, right?

Debbie Laxague