FDA MedWatch - Epoetin alfa- Preliminary Safety Findings Show More Deaths In Patients Given Epoetin-alpha Versus Placebo

ROCKVILLE, Md., Sept. 26, 2008-FDA has been made aware of preliminary safety findings from a clinical trial conducted in Germany investigating the use of epoetin alfa to treat acute ischemic stroke. The clinical trial utilized doses of epoetin alfa that were considerably higher than the doses recommended for the treatment of anemia as described in the FDA-approved labeling for the product. Over a period of ninety days after the start of the trial, there were more deaths in the group of patients who received epoetin alfa compared to patients who received the placebo (16% versus 9%). Roughly half of all deaths in both groups occurred within the first seven days after starting the drug, with death from intracranial hemorrhage (bleeding within the brain) occurring among approximately 4% of patients who received epoetin alfa compared to 1% of patients in the placebo group.
 

FDA anticipates the receipt of additional data within the next several weeks. As soon as the review of these data is complete, FDA will communicate our conclusions and recommendations to the public. The finding of increased mortality in patients receiving epoetin alfa in the German trial suggests the need to closely monitor patients enrolled in other ongoing trials for adverse outcomes and to evaluate whether the potential benefits for enrolled patients outweigh the risks in these trials.

Read the entire 2008 MedWatch Safety Summary, including a link to the FDA's Early Communication About An Ongoing Safety Review regarding this issue.

http://www.fda.gov/medwatch/safety/2008/safety08.htm#ESA3

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Early Communication about an Ongoing Safety Review

Epoetin alfa

This information reflects FDA’s current analysis of available data concerning this drug. Posting this information does not mean that FDA has concluded there is a cause and effect relationship between the drug products and the emerging safety issue.  Nor does it mean that FDA is advising health care professionals to discontinue prescribing these products. FDA is considering, but has not reached a conclusion about whether this information warrants any regulatory action. FDA intends to update this document when additional information or analyses become available.

FDA has been made aware of preliminary safety findings from a clinical trial conducted in Germany investigating the use of epoetin alfa to treat acute ischemic stroke.  The drug used in this investigational study was Eprex, a brand of epoetin alfa not marketed in the United States.  Eprex is a member of the class of erythropoiesis stimulating agents (ESAs) that are approved by the FDA for use in the treatment of certain patients with anemia. 

Over a period of ninety days after the start of the trial, there were more deaths in the group of patients who received epoetin alfa compared to patients who received the placebo (16% versus 9%).  Roughly half of all deaths in both groups occurred within the first seven days after starting the drug, with death from intracranial hemorrhage (bleeding within the brain) occurring among approximately 4% of patients who received epoetin alfa compared to 1% of patients in the placebo group.  Treatment of anemia was not a goal of the trial and most patients were not anemic.  Additional trial baseline and outcome data are currently being analyzed.

This clinical trial was a double-blind, placebo-controlled, multicenter investigation in 522 adult patients with an MRI-confirmed ischemic stroke in the area of the middle cerebral artery.  Patients were randomized to either receive treatment with a placebo or epoetin alfa administered as an intravenous dose of 40,000 units daily for three days.  R-tPA, a medication used to help dissolve blood clots, and often used for acute strokes, was also used when clinically indicated.   The goal of this clinical trial was to determine whether a relatively high dose of epoetin alfa (40,000 units daily) administered for three days would improve the ability of patients to care for themselves after their strokes (functional outcome).

The clinical trial utilized doses of epoetin alfa that were considerably higher than the doses recommended for the treatment of anemia as described in the FDA-approved labeling for the product.  FDA is aware of other clinical trials using epoetin alfa for potential neuroprotective effects (improving the functional outcomes of patients after stroke).  The finding of increased mortality in patients receiving epoetin alfa in the German trial suggests the need to closely monitor patients enrolled in other ongoing trials for adverse outcomes and to evaluate whether the potential benefits for enrolled patients outweigh the risks in these trials.

FDA anticipates the receipt of additional data within the next several weeks. As soon as the review of these data is complete, FDA will communicate our conclusions and recommendations to the public.

This early communication is in keeping with FDA's commitment to inform the public about ongoing safety reviews of drugs.  FDA will work with the manufacturers of ESAs and other sponsors of clinical trials to evaluate the clinical parameters associated with the risks and benefits associated with the investigational uses of these products as potential neuroprotective agents.   

The FDA urges both healthcare professionals and patients to report side effects from the use of ESAs to the FDA's MedWatch Adverse Event Reporting program 

• on-line at [www.fda.gov/medwatch/report.htm];
• by returning the postage-paid FDA form 3500 available in PDF format at [www.fda.gov/medwatch/getforms.htm] to 5600 Fishers Lane, Rockville, MD 20852-9787;
• faxing the form to 1-800-FDA-0178; or
• by phone at 1-800-332-1088

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