Long Shunned, Morning Sickness Drug May Be Staging a Comeback
A once wildly popular prescription treatment for morning sickness--driven off the market 17 years ago by hundreds of lawsuits claiming it caused birth defects--is poised to make a comeback.
The drug, Bendectin, first approved in 1956 and taken by at least 33 million women here and abroad, was removed by its manufacturer in 1983 because of the increasing financial burden of litigation initiated by women who believed that it had caused limb deformities--missing fingers and bones--in their children.
But numerous scientific studies prompted by the lawsuits since have produced a solid case supporting the drug’s safety--and the Food and Drug Administration is prepared to approve its return.
To that end, the FDA has been working with a drug company in Canada--where a generic version of the drug continues to be sold--to bring Bendectin back to the U.S. market.
It is extremely rare for a drug that has been reviled and forced off the market earlier to be exonerated and returned for its original purpose. But in this case, time and science have proved that the panic was misguided.
“It’s unusual for drugs to come back--very unusual,” said Dr. Robert Temple, associate director for medical policy in the FDA’s center for drug evaluation and research. “They have such a lot of baggage to overcome.”
But the case of Bendectin is different.
The FDA never believed that the drug was harmful and the agency was not involved in its removal--as it typically is when a drug appears problematic. Rather, Bendectin’s manufacturer, Merrell Dow Pharmaceuticals, decided on its own to quit making the drug and cut its losses in the wake of growing product liability actions.
The rehabilitation of Bendectin once again has focused attention on the long-simmering debate over the risks and benefits of taking drugs while pregnant--and how these medical decisions are made.
And it has also revived the still-thorny dilemma of how to promote research on medicine use during pregnancy while reconciling the conflicting ethical and legal issues involved.
In the aftermath of Bendectin--and drugs such as Thalidomide, which caused horrific birth defects in West Germany, England and Canada four decades ago but has since been approved here to treat a side effect of Hansen’s disease (leprosy)--drug companies have resisted developing drugs for pregnancy-related conditions. In fact, they do not like to test any drugs in pregnant women.
This is a problem because many pregnant women routinely take over-the-counter drugs, such as pain relievers, as well as prescription medicines, such as asthma drugs and antibiotics.
“I don’t think there is any problem with the ethics of trying to treat illnesses that are serious during pregnancy, but we’ve not found a way to make [researchers] take those risks on,” Temple said. “The result is that [pregnant women] take drugs without adequate studies.”
Some have suggested creation of nongovernment-sponsored registries that will track what pregnant women take and the outcomes of their pregnancies. The concept is eventually to include such information on the drugs’ labels. “There has been some talk about the usefulness of such registries,” the FDA’s Temple said.
Dr. Ray Woosley, chairman of Georgetown University’s department of pharmacology, has proposed creation of an independent drug safety board--modeled after the National Transportation Safety Board--which would be a neutral assessor of drugs’ safety.
“Sometimes people are harmed by drugs coming off the market,” Woosley said. “We need a real spokesperson for the public, a drug safety board, that would have said: ‘You should have left Bendectin on the market in the first place.’ ”
One animal study conducted in Germany had shown that rats given the drug developed holes in their diaphragms, a defect that could be life-threatening in humans. But the flurry of lawsuits filed against Bendectin all were related to limb deformities.
“We never believed, nor do we now believe, that there was evidence the drug caused these limb defects,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group, which raised questions about the drug’s safety after the rat study.
Wolfe dismissed most of the litigation responsible for the manufacturer’s withdrawal of the drug as “frivolous.”
Many of the lawsuits were decided in favor of plaintiffs, then later reversed. Some were settled with the company for small amounts. The Bendectin litigation became the cornerstone of judicial arguments against the introduction of so-called junk science, because studies proving the drug’s harmful effect were not substantiated. Ultimately, the U.S. Supreme Court raised the standard for the use of expert witnesses in a way that made future Bendectin-type lawsuits unlikely.
Most experts now believe that the rate of birth defects occurring among babies born to women who took Bendectin was not statistically higher than among those who did not take the drug.
About 4% of all babies are born with birth defects, according to Dr. T. Murphy Goodwin, USC’s maternal-fetal chief of medicine. “And if you’re taking a drug, you’re going to remember that association--and that was the engine that drove a lot of the litigation.” Morning sickness afflicts up to 90% of all pregnant women and its cause is unknown. Many believe it is related to human chorionic gonadotropin (HCG), one of the fundamental hormones produced in large amounts by the developing placenta during pregnancy.
Experts believe that the effect of morning sickness should not be seen as trivial. “For a lot of women, it really affects their lives--they can’t work well and it affects their family lives,” Goodwin said.
And about 1% suffer an extreme form, hyperemesis gravidarum, which can be dangerous to the fetus. It can produce weight loss, dehydration and electrolyte imbalances, sometimes requiring hospitalization.
The FDA took another look at the drug’s safety data last year and once again called it safe. In August 1999, the agency published a Federal Register notice amounting to an invitation for interested companies to apply to once again market the drug.
This opened the way for a Quebec company, Duchesnay Inc., to seek approval here for its generic Bendectin, sold in Canada under the name Diclectin. FDA’s major requirement is that the company demonstrate that its version is chemically the same as Bendectin. The company says that it is in the process of doing so.
Bendectin’s main ingredients, vitamin B6 and the antihistamine doxylamine, are already sold here over the counter, and some physicians are trying to mix the right dose for their patients, “but it isn’t quite the same thing, since Bendectin had a timed-release formula,” Goodwin said.
