Like any expectant mother, Suzanne Altomare was excited about the imminent birth of her second child. But eight days after her due date in November 1995, the 34-year-old was informed by her obstetrician, Dr. Thomas Kahan, that he wanted to induce labor. There is typically no medical necessity to induce healthy moms until they are at least two weeks overdue, but Kahan considered it the safer course. Altomare trusted her doctor, and she went along with his recommendation.
To jump-start her labor, Altomare was given two doses of Cytotec, a drug known to soften the cervix and cause uterine contractions that are more frequent and powerful than normal labor. What Altomare did not know was that Cytotec has not been approved by the Food and Drug Administration (FDA) for use in pregnant women. The drug, made by G.D. Searle Corporation, is approved only for treating peptic ulcers. Its package insert explicitly warned that “Cytotec may cause the uterus to rupture (tear) during pregnancy if it is used to bring on (induce) labor.” Uterine rupture, the insert added, “may result in severe bleeding, hospitalization, surgery, infertility, or death.”
According to court records and sources familiar with the case, Altomare soon went into very active labor. But several hours later, a delivery nurse at the hospital in Salem, Oregon, was no longer able to detect a fetal heart tone or find the baby’s head on a vaginal exam. Altomare’s uterus had ruptured, causing internal bleeding in the mother and leaving the baby without oxygen. The nurses called Dr. Kahan, who was at home. By the time he arrived and mobilized an emergency cesarean section, the infant was brain-dead. Kahan then performed an emergency hysterectomy. When Altomare awoke, she learned that she would never again be able to bear a child. Her newborn daughter died three days later.
Since Cytotec was introduced in 1988, a growing number of obstetricians have embraced it as a “miracle” drug — in spite of data that leave serious doubts about its safety. Lacking FDA approval and scientific consensus on how to use it on pregnant women, doctors have taken it upon themselves to administer Cytotec to their patients — often without the women’s informed consent. This “off-label” use is legal, thanks to an FDA loophole: Once a drug is approved for one purpose, it can be used by physicians to treat anything. (Misoprostol, the generic name for Cytotec, is also used in combination with RU-486: The abortion drug ends the pregnancy; misoprostol causes the uterus to expel its contents.)
Clinical trials suggest that Cytotec is remarkably effective at softening the cervix, a precursor to inducing labor. In a recent survey of 44 studies of the drug, Dr. Luis Sanchez-Ramos, professor of obstetrics and gynecology at the University of Florida in Jacksonville, concluded that women given Cytotec are more likely to have a vaginal delivery within 24 hours — and no more likely to require cesarean sections — than women who receive no medication or another labor-inducing drug. Cytotec is now “the predominant agent of choice” for inducing labor, according to Dr. Charles Lockwood, chairman of obstetrical practices for the American College of Obstetricians and Gynecologists (ACOG).
The drug’s appeal is twofold. Cytotec is much cheaper to use than other drugs: A dose costs less than 25 cents, compared with hundreds of dollars for other labor-inducing agents. It has also enabled doctors to induce more labors than ever before: Over the past decade, the induction rate has doubled — 1 in 5 women now has her labor induced — as doctors increasingly opt for additional medical intervention in childbirth. Speeding delivery can be medically necessary when the mother is overdue or at risk because of high blood pressure or diabetes, but critics charge that doctors often rely on Cytotec for “convenience inductions,” using the drug to induce labor during office hours rather than letting nature take its course.
“Cytotec enables doctors to practice daylight obstetrics,” says Dr. Marsden Wagner, a neonatologist who served for 15 years as a director of women’s and children’s health in industrialized countries for the World Health Organization. “It means that as a doctor, I can come in at 9 a.m., give you the pill, and by 6 p.m. I’ve delivered a baby and am home having dinner.”
But studies highlight alarming risks associated with Cytotec. The Cochrane Collaboration, an international body of independent analysts and physicians that publishes widely respected assessments of drug efficacy, cites numerous reports of uterine rupture and fetal distress involving the drug. “It cannot be recommended for routine use at this stage,” the group concluded last year. After another study revealed a 28-fold increase in the risk of uterine rupture among women with prior cesarean sections, ACOG issued guidelines in 1999 discouraging the use of Cytotec in such cases. The organization continues to recommend Cytotec for use in routine cases, however, insisting the drug is safe at low doses.
With many doctors still regularly using Cytotec to induce labor, the toll on pregnant women and their babies is mounting. Mother Jones has learned through a Freedom of Information Act request to the FDA that in the last three years alone, the agency has received reports of 30 cases of uterine rupture in connection with the use of Cytotec, and eight cases in which the fetus died in utero.
Cytotec’s impact has now become the subject of lawsuits. In Oregon, Suzanne Altomare sued her doctor and won $2 million in a confidential settlement last year. In Texas, Lauren Carroll was awarded $1 million in 1999 after she suffered a uterine tear, lost her newborn son, and underwent an emergency hysterectomy. In Connecticut, a mother died at Yale-New Haven Hospital in 1998 after being given Cytotec. Doctors delivered a severely impaired boy from her lifeless body, but the boy died last year.
“For the drug company, off-label use allows for potentially massive sales of the drug without making any warranties for its efficacy or safety,” says Michael Koskoff, an attorney representing the Connecticut woman’s husband. “It is equally advantageous for medical professionals, since it allows them to use a drug in essentially an unregulated manner.”
Searle, the maker of Cytotec, was recently named as a defendant for the first time in a lawsuit brought by a man in Portland, Oregon, whose wife died in childbirth after being induced with the drug. Last August, Searle sent a letter to 200,000 health care providers warning them that “Cytotec administration by any route is contraindicated in women who are pregnant because it can cause abortion.” The company noted that the off-label use of Cytotec has resulted in reports of uterine rupture, hysterectomy, and the death of mothers and infants.
Rather than heed Searle’s warning, however, many obstetricians reacted angrily to the letter. “I think it’s a great setback to women’s health,” fumes Dr. Steven Clark, a professor of obstetrics and gynecology at the University of Utah School of Medicine. “What this letter means is that if anything bad should happen during labor and delivery, this is going to be blown up in great big huge letters in front of the jury. Do doctors want to take the risk of using a drug that is expressly forbidden for this use by the manufacturer?”
But experts say such legal consequences are inherent in off-label use. If doctors insist on prescribing a drug for a nonapproved use, observes former FDA Commissioner David Kessler, “they are going to have to make sure that it is the standard of care. Otherwise they face great risks.”
According to one informal poll, at least one-third of hospitals have restricted the use of Cytotec in response to the Searle letter. “It has certainly had a chilling effect on the use of this drug,” says Lockwood, the ACOG committee chairman. But many physicians say they are disregarding the warning. “It hasn’t impacted us at all,” says Sanchez-Ramos of the University of Florida, who insists Cytotec is safe.
Whatever the drug’s dangers, most women who receive it have no idea that it is not approved for use during pregnancy. Alicia Balassa-Clark, a 35-year-old artist in Vancouver, Washington, planned to have her baby in a birthing center where she could be attended by midwives. But her insurance covered only births attended by a physician, and she was referred to a local obstetrician. To help induce labor, Balassa-Clark recalls, the doctor inserted Cytotec into her vagina, assuring her that she would have “a completely natural labor.”
After 14 hours of labor, Balassa-Clark says, the doctor told her that she was “almost there.” Suddenly, a nurse said that she could not detect fetal heart sounds. “My doctor’s face went ashen as the monitor readings registered that my baby was in fetal distress,” Balassa-Clark recalls. (The doctor did not respond to requests for comment.) An emergency cesarean section was performed, but the baby was not breathing when she was born. Twenty-four hours later, Balassa-Clark and her husband made the agonizing decision to remove the small girl they had named Isabella Marie from life support. “I held her in my arms as she took a few tiny little breaths and then passed away,” she recounts.
Without informed consent, say some medical experts, patients are being treated as little more than human guinea pigs. Wagner, the former official with the World Health Organization, notes that Cytotec is not used to induce labor in Europe, and chides American obstetricians for what he calls “vigilante obstetrics.”
“Vigilante justice is: We’re not gonna wait for the judge, we’re gonna just hang ’em,” he says. Using Cytotec on women “is saying we’re not gonna wait for the judge — the FDA and scientists — we’re gonna just go ahead and use it.”