Zofran, a prescription drug manufactured by GlaxoSmithKline, is FDA approved for the prevention of severe forms of nausea and vomiting that often accompany chemotherapy, radiotherapy and surgical anesthesia.
The drug’s active ingredient is called ondansetron, and as many as 32 separate companies produce generic equivalents.
Zofran’s safety during pregnancy, or efficacy as a treatment for morning sickness, have never been studied. Neither the FDA, nor GlaxoSmithKline, have ever conducted clinical trials (studies using human subjects) to determine that the drug is free of harmful effects on fetal development.
Thus, it is not approved as a treatment for nausea and vomiting of pregnancy.
Why Was Zofran Prescribed To Pregnant Women?
But America’s last drug to be FDA approved as a morning sickness treatment, Bendectin, was pulled from the market entirely in 1983. Bendectin’s recall, voluntarily issued by its manufacturer, came after numerous civil lawsuits alleged an association between Bendectin and birth defects. This recall left a large vacuum: around 6.7 million women become pregnant every year in the US, and upwards of 80% to 90% will experience morning sickness during the first trimester.
Morning sickness, especially in its most severe form, hyperemisis gravidarum, can be debilitating. And with few other options, physicians across the world began prescribing pregnant women Zofran to alleviate their symptoms of nausea and vomiting.
The practice of prescribing drugs for unapproved purposes, known as “off-label” prescription, is not regulated by the FDA, and physicians are free to prescribe any drugs they feel medically appropriate. But drug manufacturers are prohibited from marketing their products for any purposes other than those for which the FDA has found them “safe and effective.”
Department Of Justice Claims That GlaxoSmithKline Fraudulently Marketed Zofran
On July 2, 2012, the Department of Justice announced that GlaxoSmithKline had agreed to pay a settlement totaling $3 billion, in the largest single case of alleged health care fraud in US history.
Among the federal government’s claims were three criminal charges, including two counts of “introducing misbranded products […] into interstate commerce” and one count of “failing to report safety data […] to the Food and Drug Administration.” GlaxoSmithKline pled guilty to those three charges and paid a criminal fine of $1 billion.
But the DOJ’s allegations also included a number of civil violations. Two of the government’s claims involved Zofran:
- The DOJ alleged that GlaxoSmithKline had “promoted certain forms of Zofran, approved only for post-operative nausea, for the treatment of morning sickness in pregnant women.”
- The government also claimed that GlaxoSmithKline “paid kickbacks to health care professionals to induce them to promote and prescribe” Zofran.
While GSK continues to deny these allegations, the company agreed to pay $2 billion to resolve its civil liabilities.
Studies Begin To Establish Association Between Zofran & Birth Defects
At the same time, several large-scale research studies have come to troubling conclusions. In three major studies, scientific teams from around the world have found an increased risk of birth defects, including cleft palate, in babies born to women prescribed Zofran during the first trimester.
Zofran’s Possible Link To Orofacial Clefts
Researchers at Harvard University and Boston University, funded in part by a grant from the US Centers for Disease Control & Prevention, reviewed the medical records of 10,383 women.
More than 67% of these women reported experiencing morning sickness, while 15.4% were prescribed a prescription drug for their symptoms. Comparing those women who had been prescribed Zofran or a generic equivalent to those who had not, the team found that babies exposed to ondansetron during early development were 2.37 times more likely to be born with cleft palate.
You can find an abstract of the study here.
Zofran’s Potential Association With Congenital Heart Defects
Danish researchers reviewed every birth record filed in Denmark between the years of 1997 and 2010. Despite an unprecedented sample size of 903,207 births, they found that only 1,368 pregnant women had been prescribed ondansetron for morning sickness during that period.
Even so, the researchers concluded that there was “an increase in the prevalence of major congenital heart defects in children whose mothers redeemed a prescription of ondansetron” during their first trimester. In particular, they found that expectant mothers who took ondansetron were 4.8 times more likely to deliver babies with atrioventricular septal defects, a congenital defect in which the heart’s four chambers fail to separate from one another.
Swedish researchers found a lower, but statistically significant, increase in heart defects as well. Including every birth record filed in Sweden from 1998 to 2012, they found that women prescribed ondansetron were 1.62 times more likely to give birth to children with “cardiac septum defects,” a category of conditions that involve holes in walls of the heart.
Families Have Begun To File Lawsuits Against GlaxoSmithKline
Now, at least six parents have filed private civil lawsuits against GlaxoSmithKline. In their complaints, these mothers and fathers claim that the company was aware of Zofran’s potential dangers during fetal development, but marketed the drug to pregnant women for an unapproved purpose anyway.
Six Parents Allege That Zofran Led To Child Birth Defects
Each plaintiff alleges that they were prescribed Zofran after experiencing morning sickness during early pregnancy, when the risk of a fetus developing congenital abnormalities is highest.
In case number 2:15-cv-00709-PD, a mother residing in Minnesota claims that her two daughters were both diagnosed with cardiac defects shortly after birth. Plaintiff also alleges that her children have experienced severe developmental delays.
A mother from Massachusetts claims that her daughter was born with a number of congenital heart defects, including an atrial septal defect, as well as “facial dysmorphia,” hearing loss and webbed toes. This second Zofran-related lawsuit was filed under case number 1:15-cv-10429.
Two additional lawsuits have been filed in California. The first, filed under case number R615761042, was brought by a mother who lives in Oakland. She claims that after taking Zofran she gave birth to a son who was diagnosed with a heart defect known as supraventricular tachycardia.
Parents in San Francisco filed suit against GlaxoSmithKline on March 5, 2015. They allege that their son was born with a rare heart defect, bicuspid aorta stenosis, after his mother was prescribed Zofran during the first trimester. Their complaint is registered as case number CGC-15-544524.
A family from Montana filed the nation’s fifth Zofran birth defect lawsuit on April 4, 2015, under case number 1:15-cv-00026-SPW-CSO. Plaintiffs claim that their daughter was born with a cleft lip and palate after her mother took Zofran as a morning sickness treatment during early pregnancy.
On April 17, 2015, a family from Texarkana, Texas brought the most recent legal claim against GlaxoSmithKline, alleging that first trimester exposure to Zofran caused their child’s “numerous congenital defects.” According to court documents, plaintiff’s child has been diagnosed with a heart murmur, fluid on the brain, abnormally thick arteries and developmental delays. Their claim was filed as case number 5:15-34.
Claims That GlaxoSmithKline Was Aware Of Zofran’s Potential To Cause Fetal Harm
These six complaints share many of the same allegations. Perhaps most important are claims that GlaxoSmithKline received evidence of Zofran’s potential dangers as early as the late 1980s.
After reiterating the Department of Justice’s allegations of fraudulent marketing, each complaint claims that GlaxoSmithKline perfomed a series of Zofran studies in pregnant rats and rabbits during the 80s.
According to court documents, these animal studies:
“revealed evidence of toxicity, intrauterine deaths and malformities in offspring, and further showed that Zofran’s active ingredient transferred through the placental barrier of pregnant mammals to fetuses.”
The complaints continue to allege that “GSK did not disclose this information to pregnant women or their physicians.”
The lawsuits also claim that GlaxoSmithKline has received multiple reports of “birth defects associated with Zofran.” They allege that GSK has received at least 200 such reports to date, but has failed to disclose this information to the public.