LOS ANGELES (AP) _ Federal health investigators are baffled: Why have four California women died from a bloodstream infection after using a controversial abortion pill?
Two of the deaths _ one this year and one last year _ were reported last week by the Food and Drug Administration. The other two deaths occurred in 2003. All were caused by sepsis, a bloodstream infection, although the women didn't have all the usual symptoms for sepsis, such as fever, health officials say. Only one other U.S. death linked to the drug has been reported since it went on the market in 2000, and the cause of death in that case was different.
``On the surface, this appears unusual,'' said Dr. Marc Fischer, a medical epidemiologist at the federal Centers for Disease Control and Prevention in Atlanta. ``That's why we're investigating.''
Sold as Mifeprex, and also known as RU-486 or mifepristone, the drug is taken as two pills at different times. None of the women who died followed FDA-approved instructions for taking the drug, and authorities are looking into whether that may have played a role in their deaths.
The FDA said it believes Mifeprex is safe enough to stay on the market and that there is no proof it caused the deaths. However, the label will be updated to alert women and doctors in more detail to unusual, dangerous infections that are not always accompanied by fever.
More than 460,000 women in the United States have used Mifeprex since it was invented in France in the 1980s. The pill already contains a ``black-box'' warning highlighting the risk of bacterial infection, sepsis and death. Reports of fatal sepsis among the pill's users are rare, occurring one in 100,000 cases.
The drug's maker, New York-based Danco Laboratories, has defended the pill's record, saying there is no evidence Mifeprex caused bacterial infection and sepsis. However, the company agreed to change the warning label so patients and doctors know about the risk of rare infections.
Mifeprex is approved to end a pregnancy up to 49 days after the start of a woman's last menstrual cycle. It is a two-part treatment _ one drug blocks a hormone required to sustain a pregnancy and the other, taken days later, ends the pregnancy.
The FDA calls for both pills to be swallowed, but the agency says it is aware that many abortion clinics and doctors recommend that the second pill be inserted vaginally based on studies that have shown its effectiveness in ending a pregnancy.
Dr. Vanessa Cullins, vice president of medical affairs at Planned Parenthood Federation of America, said she believes vaginal insertion is safe. Abortion clinics counsel women on making sure their hands are clean before they insert the pill to avoid infection, Cullins said.
Federal drug regulators are unsure whether this so-called ``off-label use'' might have contributed to the deaths, but it is one of the areas being investigated.
Health investigators also will do tests to make sure the pills weren't contaminated. Two of the infections were caused by a common bacterium called Clostridium sordelli, which can cause nausea and diarrhea, but is rarely fatal. Investigators will study whether the germ might have mutated and become more lethal.
Authorities can't rule out simple math as one explanation for the group of deaths in California: Perhaps more women of child-bearing age are using the abortion pill in the nation's most populous state. There's also the possibility that California doctors may be more inclined to file the voluntary reports of adverse effects.
Monty Patterson, whose 18-year-old daughter Holly died of septic shock after taking Mifeprex to end an unplanned pregnancy in 2003, said the pill should be pulled from the market.
Patterson has been lobbying to halt sale of the pill since Holly's death, which was the first of the four California cases to be reported to the FDA.
``This drug is not safe,'' said Patterson, who lives in Livermore. ``Holly never thought she would take a drug that would kill her. She wouldn't have done it.''
Patterson sued Danco last year for an unspecified amount, claiming wrongful death and product liability.
The other U.S. death associated with Mifeprex was a case of a ruptured tubal pregnancy in 2001. Health officials have warned that the pill should not be used in women with suspected or confirmed ectopic pregnancies.