The FDA has strengthened warning labels for the controversial abortion pill Mifeprex, better known as RU-486 (search), following an August report of a 22-year-old woman who died after taking the drug.

The agency released new alerts warning doctors and patients of a risk of severe bacterial infections and heavy bleeding associated with RU-486. The drug’s distributor is also changing its label to remind doctors that the drug should not be prescribed to women who have ectopic pregnancies, which are pregnancies that develop in the fallopian tubes instead of the uterus.

Danco Laboratories, which markets and distributes RU-486 under the brand name Mifeprex (search), reported to FDA officials in August that they received a report of a California woman who died of a widespread bacterial infection while trying to medically terminate a seven-week pregnancy in January.

The report was the third reported in the U.S. since the drug went on the market in 2000. An 18-year-old San Francisco woman died of a similar infection after taking RU-486 in September 2003. A 38-year-year old woman died in 2001 after taking the drug during an ectopic pregnancy.

FDA officials say complications with RU-486 remain rare and that they have no evidence directly connecting it to any of the deaths, but they want doctors and patients to be aware of the risk of infection or heavy bleeding.

“We have not been able to link any of them in terms of the drug causing the event,” says Steven Gallson, MD, acting director of the agency’s Center for Drug Evaluation and Research.

RU-486 was approved under the brand name Mifeprex in 2000, more than four years after an FDA advisory panel recommended its clearance. The drug has remained at the center of the U.S. abortion debate.

Gallson says the FDA’s decision to strengthen safety warnings connected to RU-486 was based on scientific concerns and that Bush administration officials did not try to influence the decision. “There was absolutely no political pressure on this. This was a science-based decision,” he says.

RU-486 is approved for the termination of normal pregnancies seven weeks or less in duration, but the drug is commonly used to terminate longer-term pregnancies.

More than 360,000 women have taken RU-486 since 2000, according to Danco. Regulators have received more than 600 reports of adverse events in women taking RU-486 but stress that those reports do not prove that RU-486 caused the events.

Still, officials say they grew concerned that doctors and patients needed more information warning that infection or severe bleeding can occur.

Some women taking RU-486 don’t seek medical attention for severe bleeding or cramping since those symptoms almost always occur, says Phillip G. Stubblefield, a professor of obstetrics and gynecology at Boston University School of Medicine who has researched medical abortion and its potential complications.

“Physicians providing the care need to know that this sort of thing can happen,” Stubblefield says in an interview. Women who take RU-486 typically bleed heavily for about one hour, but if the bleeding continues for three to four hours, “then she needs to get help,” he says.

Studies show that RU-486 is effective in inducing a full abortion 92 to 95 percent of the time. Three to four women in 100 who take the drug require surgery to resolve an incomplete abortion, Stubblefield says.

Danco Laboratories (search) markets and distributes RU-486 under an agreement that requires it to keep the drug’s manufacturer secret. Danco is sending out letters to thousands of doctors alerting them to the new warnings and also urging emergency room doctors to be on the lookout for severe bleeding and infections that can occur after miscarriages and abortions.

Previous Warnings

The letters are not the first that Danco has sent to doctors. The company sent out letters in 2000 warning of an infection risk and urging treating doctors to avoid prescribing RU-486 to women with ectopic pregnancies.

Cynthia Summers, PhD, a Danco spokeswoman, says the company is in favor of providing “as much accurate information as possible” to patients and doctors.

Concerned Women for America, a conservative group that opposes abortion, petitioned the FDA in 2002 to pull RU-486 off the market because it posed a health risk to women who took it. The group issued a statement Tuesday saying that the label changes did not go far enough.

“When women’s lives are at stake, this is unacceptable. While the label changes implicitly admit the dangerous nature of the drug, trusting abortionists to follow the warnings is a futile effort and does nothing to make the drug itself safe,” says Wendy Wright, the group’s senior policy director.

Asked about the petition, Gallson said, “We’re working on it.”

By Todd Zwillich, reviewed by Michael W. Smith, MD

SOURCES: Steven Gallson, acting director, Center for Drug Evaluation and Research, FDA. Phillip G. Stubblefield, professor of obstetrics and gynecology, Boston University School of Medicine. Cynthia Summers, PhD, spokeswoman, Danco Laboratories. Wendy Wright, senior policy director, Concerned Women for America.