Zofran, GlaxoSmithKline’s incredibly popular anti-nausea medication, is commonly prescribed to pregnant women who suffer from severe morning sickness.
But the US Food & Drug Administration never approved Zofran, or its active ingredient ondansetron, for use during pregnancy. According to allegations made by the US Department of Justice, the pharmaceutical giant illegally marketed Zofran explicitly for this “off-label” purpose since 1991.
Now, recent research has linked Zofran to severe birth defects, including cleft palate and congenital heart defects. Seven lawsuits have already been filed by mothers who were prescribed Zofran, and then delivered children with severe birth defects. They claim that GlaxoSmithKline was aware of these dangers, but failed to examine the drug’s effects on pregnant women or their unborn babies.
Zofran & FDA Safety Regulations
Allegations in these lawsuits suggest that GlaxoSmithKline may have failed to warn the public of Zofran’s adverse effects out of sheer corporate greed.
Studies that found an increased risk of developmental abnormalities in pregnant animals were conducted as early as 1993. Six mothers who gave birth to children with severe congenital defects, and one who was forced to terminate her pregnancy, claim that GSK hid those results, as well as over 200 reports of birth defects in human babies.
Throughout, plaintiffs allege that GSK has continued to sell Zofran as a treatment for morning sickness in pregnant women, without having approval for its use for this purpose. The lack of testing of Zofran for use during pregnancy may be potentially endangering tens of thousands of developing fetuses.
Has Zofran Ever Been Tested In Pregnant Women?
To date, no clinical study involving pregnant women has been conducted. Instead, Zofran’s warning label makes note only of animal studies:
“Reproduction studies have been performed in pregnant rats and rabbits at daily oral doses up to 15 and 30 mg/kg/day, respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to ondansetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.”
The label has read similarly since 1993, despite the release of at least three studies finding an association between ondansetron and congenital birth defects. At a minimum, GSK should have begun investigating Zofran’s effects on pregnant humans when concerns were first raised. But they didn’t, and don’t seem to plan on it in the future.
While it’s true that an “association” is not the same as saying ondansetron causes birth defects, the FDA’s requirements clearly state that drug manufacturers must revise their labeling “to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.”
Plaintiffs claim that three recent studies have clearly shown such an association, but GSK has failed to warn expectant mothers of the risk.
What Happened In Animal Studies?
According to the new Zofran lawsuits, GSK’s claim that animal studies have “revealed no evidence” of maternal or fetal harm may be a lie altogether.
In the late 1980s, GSK conducted four studies to measure the effects of ondansetron on pregnant rats and rabbits. Each study revealed signs of toxicity: abnormal postures and lethargy in the pregnant animals and developmental retardation (most notably impaired bone growth) in the babies after they were born.
These were tests explicitly designed to root out ondansetron’s teratological effects, the adverse changes it may cause in a developing embryo or fetus. And while many of the animals experienced serious “pregnancy complications,” GSK chose not to define the effects of Zofran as teratological.
Animal studies are never assumed to show that similar effects will be suffered in humans. So even if ondansetron does have teratological effects in rats and rabbits, we can’t assume that human fetuses will develop abnormally as well. But that’s precisely the point. If allegations made by the US Department of Justice are true, GSK took this evidence of fetal harm and began marketing Zofran to pregnant women anyway, in clear violation of both scientific methods and public interest.
Zofran & The FDA’s Pregnancy Categories
After the animal studies, the FDA labeled Zofran with “Pregnancy Category B,” which indicates that no risk has been identified in non-human studies. The label currently reads:
“Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.”
In Zofran’s case, we know that “B” can only mean the former, because no human studies have been conducted.
But research has been published, revealing an increased association between Zofran and birth defects. Under the FDA’s regulations, if a drug shows “positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans,” it should be classified in Pregnancy Category D.
Zofran seems to fit this definition, but GSK has not sought approval for use in pregnant women for morning sickness and thus has no label warnings for these associated birth defect risks.
FDA Warnings & Results
While the FDA has yet to weigh in on Zofran’s potential to cause serious birth defects, the drug has come under fire for causing other serious health risks.
Abnormal Heart Rhythms
After multiple reports of fatal heart disturbances, the FDA announced an ongoing safety review of ondansetron on September 15, 2011. Citing an increased incidence of the rare abnormal heart rhythm known as Torsade de Pointes, the FDA instructed GlaxoSmithKline to conduct a study investigating Zofran’s effects on the heart.
In the meantime, the FDA strengthened the drug’s warning label, adding instructions to avoid use in patients with existing heart conditions caused by abnormal electrical activity.
On June 29, 2012, GlaxoSmithKline released the results of its study.
Examining patients that received a single, 32 milligram intravenous dose of ondansetron, GSK found an increased risk of QT interval prolongation. The “QT interval” is a measurement of the amount of time the heart takes to initiate and complete one beat. When this interval is “prolonged,” a second beat is begun before the first can properly finish, leading to an increased heart rate. This condition, known as tachycardia, increases the risk of ventricular fibrillation and sudden death.
As a result, GlaxoSmithKline pulled its 32 milligram dose from the market, and amended Zofran’s warning label to notify physicians of this danger.
Zofran’s most recent label revision came on September 18, 2014. Reviewing adverse event reports submitted by healthcare professionals, patients and pharmaceutical manufacturers, FDA analysts noticed a striking number of Zofran patients who suffered from a strange form of poisoning: serotonin syndrome, a complication of using more than one medication that affects certain neurotransmitters in the human body.
Serotonin syndrome is potentially fatal, and symptoms are extremely severe. It may also be more common in pregnant women who take Zofran.
Women are often prescribed antidepressants during pregnancy, and these drugs increase the body’s supply of serotonin. Serotonin syndrome has also been linked to electrolyte imbalances, which pregnant women often experience as a result of frequent vomiting. In conjunction with ondansetron, either of these contributing factors may lead to the deadly condition.
Can GlaxoSmithKline Be Held Accountable?
In 2012, GSK settled a case that involved multiple counts of illegal drug marketing. Brought by the US Department of Justice (DOJ) itself, the charges included Zofran explicitly. The DOJ claimed that GlaxoSmithKline had unlawfully advertised Zofran as a “safe” remedy for morning sickness, despite the fact that it had never been approved for this purpose. In the end, GSK never admitted deceit, but settled the lawsuit for a record setting $3 billion.
None of that money is intended for the tens of thousands of women and children now suffering birth defects that occurred after having used Zofran, despite the allegations of GSK’s improper actions. That money settled only the claims of the US Government, and therefore claims for personal injury are now being filed individually.
Injured women and children are eligible to file personal injury lawsuits, demanding significant financial compensation. Seven women have already filed lawsuits, claiming that GlaxoSmithKline’s fraudulent marketing resulted in their children’s congenital heart defects and cleft palate.
If you or your baby suffered any complications after taking Zofran, contact the personal injury lawyers at Monheit Law for a free consultation today. Speak with one of our experienced attorneys and learn more about your legal options. There’s no charge, and no obligation, just the answers you deserve.