By David Brown
Washington Post Staff Writer
Saturday, March 10, 2007
The Food and Drug Administration warned yesterday that anemia-fighting drugs called erythropoietins, which had $10 billion in U.S. sales last year, are being used so aggressively that they may be harming some patients.
Recent studies have shown that when physicians use the hormone-like drugs to "cure" the anemia commonly seen in cancer and kidney-failure patients, some patients suffer complications and die earlier.
Some physicians are apparently using erythropoietins at doses beyond what the FDA-approved instructions recommend, as they are allowed to do.
Many have felt "in the past that more is better," Karen Weiss, a physician and FDA official, said in a news conference yesterday. "I think there is considerable off-label use of this drug."
The drugs will now carry a "black-box" warning -- the strongest possible -- saying they should be used at the lowest dose necessary to avoid the need for a blood transfusion. They should not be used to fully reverse anemia.
Erythropoietins, sold as Epogen, Procrit, and Aranesp, are the fifth-leading class of prescription pharmaceuticals sold in the United States. They are unusual in that they are advertised directly to consumers, even though they are extremely expensive and given only by injection.
"Life doesn't stop during chemotherapy," says one advertisement for Procrit, which shows a grandfather holding a baseball and standing next to a young boy. It appears to suggest that the drug, made by Ortho Biotech, will help reverse the fatigue common in patients undergoing chemotherapy.
However, Patricia Keegan, a physician in the FDA's Center for Drug Evaluation and Research, said the agency "has never had data that [erythropoietin] has effects on improvement of energy and fatigue" in cancer patients.
Anemia occurs when the level of oxygen-carrying hemoglobin falls too low. Normal hemoglobin in men is 13.5 to 17.5 milligrams per deciliter. For women it is 12 to 16. Most physicians do not transfuse patients until the hemoglobin level falls below 10, and the FDA officials suggested that was a reasonable target.
New studies show that when erythropoietins are prescribed to raise hemoglobin to 12, tumors grow faster in people undergoing radiation treatment for throat cancer. In women with metastatic breast cancer on chemotherapy, those taking the drug with that goal died more quickly.
The risk of death also increased in a variety of cancer patients not being actively treated -- a group that should not get erythropoietins at any dose, the FDA said. High doses of the drugs can also lead to blood clots in the legs and in the lungs, where they can be fatal, and the new labeling will warn against those complications.
The drugs have been shown to increase activity and to improve sleeping, eating and sexual activity in anemic kidney-failure patients. Over the years, those "quality of life" claims were allowed to bleed over into the marketing of the drugs to cancer patients. The FDA now has stricter standards for claims that are subjective and hard to measure.
"The oncology [cancer] claims would not be supported at this time," said Richard Pazdur, the FDA's director of oncology drug products. "That would not be allowed now."
Ortho Biotech spokeswoman Stephanie Fagan said that "all of our marketing claims are done in accordance with the label and are submitted to FDA for review."
How many people are taking erythropoietins in an effort to reverse their anemia completely is unknown.
In June 2005, 50 percent of people on dialysis had average hemoglobin levels above 12, including 20 percent with values above 13, according to data collected by the federal government, which pays for the treatment of people in total kidney failure.
Information on cancer patients is harder to find. However, Roger Perlmutter, executive vice president of Amgen, a California biotech company, said a survey of one medical system recently found that 86 percent of patients being treated for anemia caused by chemotherapy had hemoglobin levels below 12.
Amgen makes all the erythropoietin drugs sold in the United States. It sells two under its own label and licenses Procrit to Ortho Biotech, a division of pharmaceutical giant Johnson & Johnson.