This is not just a story about pregnancy woes….it really has to do with the way the American court of opinion can influence the regulation of medication. Many of you will remember the medication Bendectin, which was prescribed years ago to help control gestational nausea and pregnancy. (I took it along with 25 percent of all pregnant women! )
Bendectin was voluntarily withdrawn from the US market by the manufacturer 30 years ago. Nausea and vomiting occurs in 80% of all pregnant women between 6 and12 weeks of gestation. Roughly 1/3 of women who have nausea and vomiting of pregnancy have symptoms that are so severe that the quality of their lives and their pregnancy suffers tremendously. And 1% of pregnant women progress to a condition called hyperemesis gravidrum. Their persistent vomiting causes them to lose more than 5% of their body weight, develop an electrolyte imbalance and severe dehydration. The condition requires hospitalization, IV fluids and significant medication to stop the vomiting.
Bendectin was a medication that combined doxalamine succinate (an antihistamine) and peridoxine hydrochloride (vitamin B6) in one tablet. Between the late 1960s into the 1970s the medical journals began publishing letters reporting an association between Benedictin use and birth defects. (Well actually, at that time a general increase in reports of birth defects appeared as researches published the data that hospitals and medical organizations were releasing as they paid more attention to and recorded birth defects.) Lawsuits claiming that this product was a teratogen causing birth defects first appeared in 1980. And by the time the product was withdrawn in 1983 there were more than 300 pending lawsuits. However, as pointed out in an article in the section ” Prospective” in this week’s New England Journal of Medicine, “Courtroom testimony claiming that Bendectin was a human teratogen was markedly devoid of evidence-based corroboration”. As a result of all these lawsuits, Merrill Dow, the company that made Bendectin, withdrew the product … not because of safety issues, but because of financial concerns. The company’s insurance premiums had risen to $10 million per year which was only 3 million less than their total income from Bendectin sales.
So was Bendectin really a teratogen? In 1979 the FDA issued a talk paper stating that studies in animals as well as several large epidemiologic studies had provided no adequate evidence linking Bendectin to an increase risk of birth defects. Another review of 13 epidemiological studies found no association between Bendectin and elevated risk of birth defects. Data maintained by the birth defect monitoring programs of the CDC found that during the period from 1985 to 1987, (which was after the product was withdrawn) the incidence of birth defects was the same as that seen during the peak time of Bendectin use. There was actually an increase in the number of hospitalizations in the United States for nausea and vomiting of pregnancy in those years. It rose from 7 per 1000 live births to 16 per 1000 live births during the period from 1981 to 1987. So to make a long story short, pregnant women suffered and were more likely to be hospitalized once they did not have access to this drug.
So here’s the good news… Recently, the FDA approved Diclegis. Aside from the fact that it’s very difficult to pronounce or spell, this is a product that has the same combination of doxylamine and pyridoxine that had been marketed as Bendectin. I’m not writing this website as an advertisement for the new drug; I’m simply intrigued by the fact that the story of Bendectin demonstrates how important it is to make clinical decisions on the basis of scientific evidence and not on lawsuits. The FDA’s approval of the “new Bendectin” was based on efficacy and safety data from randomized, placebo-controlled clinical trials and took into account extensive data showing that this product is not teratogenic. Attorney-instigated lawsuits and the fear that they generate for manufacturers, physicians and patients was, in this case, finally superseded.
There are appropriate avenues to assess drugs and then there are litigious-inspired negative headlines. As physicians and patients we should prefer the former.