Zofran, generically known as ondansetron, is a powerful “antiemetic,” or anti-nausea drug. Approved by the US Food & Drug Administration on January 4, 1991, it was initially found a safe treatment for the nausea and vomiting associated with powerful cancer therapies and surgical anesthesia.
How Does Zofran Work?
Ondansetron is known as a “5-HT3 receptor agonist,” which is a lengthy way to say that it blocks a chemical from working in your body. In particular, Zofran blocks the activity of serotonin, a neurotransmitter that most researchers believe triggers nausea and vomiting. Block the chemical from meeting its receptor and you “short-circuit” the nausea before it can begin.
What Causes Nausea & Vomiting?
Generally, we feel sick to our stomachs and throw up because our body has detected toxins. It wants these toxins out because they’re dangerous, and vomiting is the way to do that. Feelings, like stress and anxiety, can also trigger nausea, but it’s likely that we feel sick to our stomachs at these times for a similar reason.
There are two basic ways that your body can detect toxins, and it turns out that serotonin plays a role in both.
Serotonin receptors are located in your brain’s medulla oblongota, a portion of the brainstem that receives signals from the rest of your body and transmits them to the brain’s main processing centers. Part of the medulla oblongata, the “area postrema,” is able to filter through your flowing blood, detect toxins and then send neural signals that force you to vomit. In this case, the “area postrema” has to send a signal to another part of the brainstem, and it does so using serotonin.
But more often than not, the serotonin receptors on your brainstem are triggered by serotonin from somewhere else in your body, and that causes nausea and vomiting. So where does that process usually begin?
In your intestines.
When the GI tract is irritated by a foreign substance, it releases lots of serotonin. In fact, researchers at the Mayo Clinic believe that 95% of your body’s serotonin begins in your gut. Serotonin travels through your body to the medulla oblongota, binds to those special receptors and then triggers nausea and vomiting. Anxiety has a similar effect: it pumps your GI tract full of hormones and, as a side-effect, your intestines start producing serotonin.
In both of these cases, Zofran blocks serotonin from reaching its goal, by getting there first and filling the receptor itself.
What Kinds Of Nausea Is Zofran Approved For?
Ondansetron is a strong medication. Among Zofran’s less-serious side effects are diarrhea, fatigue, fever and headache. Serious effects can include a slowed heart rate, anxiety and vision loss. So the FDA has only approved Zofran for two uses:
Chemotherapy & Irradiation
Cancer treatments like radiation and chemotherapy produce free radicals, molecules with unpaired electrons that are unstable and highly reactive. Free radicals “attack” cells in an attempt to steal their electrons and become more stable. But this attack can also destroy lipids, proteins and enzymes, the things that cells are made of, and that often results in cell death.
This process is essential to anticancer therapies, and good insofar as cancerous cells are the ones being attacked. But free radicals in the GI tract also result in the release of serotonin, triggering the vomiting center.
Multiple clinical trials have found treatment of chemotherapy-related nausea with ondansetron and Zofran superior to placebos. Foreign trials in pediatric cancer patients have shown similar results, and ondansetron was “well tolerated in these pediatric patients.”
Postoperative Nausea & Vomiting
Anesthesia often causes unpleasant nausea; anywhere from 25% to 30% of patients who receive it experience some level of nausea and vomiting. In some cases, severe vomiting can reverse the beneficial effects of surgery, so its treatment is a major concern.
Ondansetron has been used to treat this form of nausea since the early 90s, although there’s little clinical evidence suggesting when and how it should be used. Less than 30% of surgical patients get relief from any type of anti-nausea drug, let alone Zofran.
Is Zofran Approved For Morning Sickness?
The FDA has not approved Zofran, or any form of ondansetron, for the treatment of nausea and vomiting during pregnancy. Nor has GlaxoSmithKline ever tested the drug’s effects in pregnant women, which would be necessary before an approval.
But in the early 1990s, several factors aligned to make Zofran the most widely prescribed drug for morning sickness in America.
How Widely Used Is Zofran?
Boston University’s Slone Epidemiology Center has been conducting its “Birth Defects Study” for 39 years now. The study has interviewed over 44,000 women, both those whose children were born with birth defects and not. Between 2004 and 2008, 3% of the women interviewed by Slone reported being prescribed ondansetron for pregnancy-related nausea.
There are about 6.7 million pregnancies every year in America. 3% would represent 201,000 women, 201,000 women every year whose unborn babies may have been exposed to Zofran.
Is That Illegal?
The use of a medication to treat unapproved conditions is called “off-label” use. In the US, physicians are free to prescribe drugs for any use they believe medically appropriate.
Physicians usually prescribe ondansetron to pregnant women only for cases of hyperemesis gravidarum, the most severe form of morning sickness. Florida Hospital estimates that between 0.3% and 2% of expectant mothers are affected by its symptoms, which include:
- severe nausea
- weight loss
- electrolyte balance
In criminal and civil cases filed by the US Department of Justice (DOJ), federal authorities alleged that GlaxoSmithKline never gave physicians that opportunity.
How Did Zofran Become America’s “Morning Sickness” Drug?
According to pediatrician Gideon Koren, ondansetron’s “off-label” use exploded because the last drug approved by the FDA for morning sickness was taken off the market 30 years ago. At its peak, this drug, Bendectin, was used by as many as 25% of pregnant women in the US.
Bendectin was voluntarily pulled from the market after a firestorm of controversy over its potential teratogenic effects, ones that are able to disturb the growth and development of an embryo or fetus. During this time, the manufacturer of Bendectin saw its insurance premiums rise to an annual $10 million. Compared to $13 million in yearly revenue for the sales of Bendectin itself, treating nausea during pregnancy didn’t seem worth it.
Did GlaxoSmithKline Find Its New Market?
For the next 30 years, there was no FDA approved drug for morning sickness. But there was a lot of nausea and vomiting.
Morning sickness is extremely common during pregnancy; up to 80% or 90% of women experience it during their first trimester. It’s estimated that 10% to 15% of pregnant women need some form of drug treatment to relieve their symptoms.
Claims made by the Department of Justice might be interpreted to suggest that GlaxoSmithKline could not resist exploiting this new market. According to federal allegations, GSK began promoting Zofran as an off-label treatment for morning sickness, without the foundation of any clinical research as to its safety during pregnancy.
Whether or not GlaxoSmithKline illegally marketed Zofran, sales of the anti-nausea drug took off. In 2003, GSK recorded sales from Zofran alone as over $463 million. In 2004, sales grew to more than $495 million. By 2006, Zofran was making GlaxoSmithKline more than $645 million.
Don’t You Think That This Should Be Stopped?
We believe that this is not an acceptable practice. And thankfully, the DOJ brought a lawsuit against GlaxoSmithKline to halt the practice of promoting Zofran for these off-label uses.
Again, Zofran was never approved to treat morning sickness in pregnant women. And while physicians are legally allowed to prescribe drugs “off label,” without any evidence that they are safe for expectant mothers or their developing babies, if GlaxoSmithKline marketed Zofran for unapproved purposes they were breaking the law.
In 2012, GlaxoSmithKline settled with the DOJ, in a historic case involving multiple counts of fraudulent marketing. Zofran was publicly named as one of the drugs illegally advertised for unapproved purposes, and while GSK never admitted liability, the company agreed to pay a settlement of $3 billion.
For perspective, compare that settlement to GlaxoSmithKline’s recorded profit of almost $11 billion in 2013.
Is Zofran Dangerous For Pregnant Women Or Their Babies?
A series of new clinical developments has raised concerns over ondansetron’s safety.
Zofran has been found to alter the heart’s electrical activity, leading to fatal arrhythmias and a rare disorder called Torsade de Pointes. It can also increase the risk of serotonin syndrome, an uncommon accumulation of neurotransmitters than can be fatal as well.
In all, the FDA has notified GlaxoSmithKline to change Zofran’s warning label 19 times.
But Zofran’s most devastating effects have yet to be confronted by the FDA. In multiple independent research studies, ondansetron has been linked to severe birth defects, including cleft lip, cleft palate and congenital heart malformations.
Crucially, nausea and vomiting manifest during early pregnancy, surfacing between 3 to 8 weeks and peaking between 7 and 12 weeks. This is the time when a fetus is most susceptible to a drug’s teratogenic effects, and the time at which Zofran prescription is most likely.
Is There A Safe Alternative?
Bendectin’s “dangers” were never clinically demonstrated, and on April 8, 2013, the FDA approved Diclegis, a new formulation of the same active ingredients, for the treatment of nausea and vomiting in pregnant women.
Can Women & Children Sue GlaxoSmithKline?
Recent allegations have surfaced that GlaxoSmithKline was aware of ondansetron’s damaging effects, but hid test results from the FDA and doctors nationwide. If these claims prove true, GlaxoSmithKline may be fully liable for any and all damages that occurred as a result of its failure to warn the public.
Women who took Zofran, and then delivered children with birth defects, may be owed significant financial compensation from GlaxoSmithKline. By filing personal injury lawsuits, families are seeking compensation for damages, alleging that GlaxoSmithKline’s negligent pursuit of profit has caused harm to their child.
To learn more, visit our guide on Zofran Lawsuits.