A common prescription for mothers-to-be is a powerful antiemetic (a nausea control agent) called Zofran. It has been putting corks in people's urges to vomit since 1991, and was hailed for many years as a "godsend." More recently, however, research has shown that Zofran use can have extremely harmful effects on a developing fetus.
Too bad its manufacturer took their sweet time before saying anything about that possibility.
Who Makes Zofran?
The pharmaceutical giant GlaxoSmithKline (GSK) has been circulating Zofran since 1991, when it was approved by the FDA for treating nausea in chemo- and radiation therapy patients. It was also approved to help control nausea after certain types of surgical procedures.
This drug was not approved for distribution to pregnant women, but it was quickly offered by GSK as a solution to the difficulties caused by being "in the family way." Nausea is nausea, right?
Any physician whose med school wasn't in the back of a van can tell you that various maladies are wired into a patient differently, and trying to treat what looks superficially like the same symptoms with the same methods can have problematic results.
To point out the most obvious and damning difference, chemotherapy also doesn't involve a developing baby that absorbs part of what its mother takes in. You're medicating for two--what you take to help yourself has to be good or at least consequence-free for a fetus, too.
Is It Just Zofran That's Affected?
Zofran has more or less been the king of the nausea hill since its release in the 90's. After its patent expired in the mid-2000's, generic ondansetron (the key ingredient of Zofran) entered the market as well, but brand-name Zofran is still the name of the game for the most part.
Two other medications designed in the same scope as Zofran (serotonin antagonists) are Kytril and Anzemet. While they can also be prescribed for the same reasons as Zofran, the focus primarily rests on ondansetron as the damaging drug. Kytril and Anzemet are based on other formulations (granisetron and dolasetron, respectively).
What Specifically Is the Issue with Zofran?
The allegations currently brought against GSK revolve around its failure to disclose the possibility that taking Zofran can cause a series of congenital defects in unborn children.
Research is still being conducted to determine exactly how many defects can be tied to Zofran; genetic history and other external influences have to be ruled out in each case to refine certainty that ondansetron is a, if not the, factor.
Among the common birth defects currently thought to be caused by Zofran are:
- Congenital Heart Defects, such as atrial/ventricular septal defects, ventricular hypertension, and tetralogy of fallot
- Kidney Malformations, such as hydronephrosis
- Facial Dysmorphic Conditions, such as Cleft Lip and/or Palate
- Talipes Equinovarus (Club Foot), a limb malformation that prevents a child from walking
- Inguinal (abdominal) Hernia
- Hearing Loss
- Syndactyly (webbed fingers/toes)
- Polydactyly (extra fingers/toes)
This is only a partial list.
It's important to note that Zofran is not guaranteed to be the direct, or proximate, cause when these defects appear. There is research that seems to indicate a connection, but other factors can also play a part. In instances where parents work around hazardous or toxic materials, or it can be shown that either parent has genetic markers for these conditions, GSK can mount defenses citing "confounders"--circumstances that introduce doubt as to the specific cause of the defect.
How Widespread is the Problem?
Adverse event reports began to show up across the country shortly after doctors began prescribing Zofran for morning sickness. By the year 2000, GSK had 32 reports on file about birth defects linked to the use of ondansetron. To date, over 200 reports exist from all across the country, yet GSK has not made efforts to adapt their labels to warn of these dangers.
Keep in mind that those 200 reports are only the ones filed with the company itself--complaints that were serious enough to get earmarked by their legal department. The FDA has also received thousands of adverse reaction reports, including several hundred about birth defects. The agency also admits that its reporting system is not comprehensive, suggesting that for every reported case, many others will likely go unknown.
To be clear, drug manufacturers are required by law to warn the public of potential consequences from taking their products. This is one of the mandatory conditions set forth by the FDA for drug approval. If a drug is prescribed for something, the hazards of taking it have to be weighed and announced, or a patient cannot be expected to give informed consent.
That concept merits another few words: The American legal system is built on a foundation of individual rights and entitlements, including a citizen's right to decide for herself how best to preserve her health. Informed consent is the idea that while physicians have the knowledge to best advise you on a course of action, their word is not law. While many of us have had experiences with condescending doctors, the medical world is not paternalistic enough to require you to do as you are told. It's a patient's right ultimately to decide how to proceed, and in order to make the best decision, they are entitled to information of the alternatives' known risks. Much of that obligation falls to the manufacturer, which is why warnings and information are printed on the product's box, label, and paper inserts.
What Can Be Done About It?
While this drug currently faces some harsh scrutiny, doctors continue to prescribe it for situations other than the ones it's approved to treat. It is unquestionably effective at suppressing nausea; the conflict is really in the cost of that benefit.
Alternative medications are currently being researched. As noted before, ondansetron isn't the only game in town, it's just one of the most effective.
In 2012, GSK was slammed with a $3 billion fine when the government investigated their collusion with health professionals. There's sometimes a feedback loop in the health care system where doctors earn "under the table" money from drug companies for prescribing their specific product (these kickbacks are spectacularly illegal, which is why GSK was fined such a steep amount). The bribery then prompts the doctors to give the drug to more patients, going so far as to prescribe it for uses other than its FDA-approved purpose; this is called "off-label" prescription.
The families of newborns and even late-term fetuses who have been diagnosed with defects are signing up to pursue damages against GlaxoSmithKline. While the company was heavily penalized by the federal government, that money didn't go to the individual citizens that suffered injuries. Personal injury litigation is going to be necessary to get any financial restitution to those parents and their damaged children.
Progress was made in June of 2015, when a new "final rule" from the FDA was enacted. The new policy requires the manufacturers of many drugs, including Zofran, to include a series of new items on their labels:
- A summary of the risks of using the drug during pregnancy
- An outline of the data supporting that summary
- Information to help health care providers counsel pregnant women about the use of the drug. This "pregnancy section" will have helpful information such as:
- Proper dosing and potential risks to the developing fetus
- Any available registry of data on pregnant women affected by the drug.
- The data that serve as the basis for any risk statements
This is a major step for the protection of pregnant women and their unborn children, as medicine labels will include greater transparency and information for doctors and patients. The FDA had been suggesting these measures to many firms, including GlaxoSmithKline, for years. Re-labeling is expensive, though, and the suggestions went largely unheeded. Fortunately, these requirements are now mandatory.
It's clear that GSK and groups like it needed this kick in the pants. Take a look at this excerpt from the prescribing information they sent to health care providers in 2014:
We learn two unsettling things from this short blurb (which is the only mention of effects on pregnant women in the whole document):
- As of 2014, with hundreds of adverse event reports on file, no solid studies had been performed to measure Zofran's effects on pregnant human women. Zofran became the number one medication for morning sickness in the U.S without even being approved to treat it, and without ever being double-checked to make sure it was safe to use that way.
- Explicit: "This drug should be used during pregnancy only if clearly needed."
Implicit: "But if you hand it out like M&M's to pregnant women, we'll grease your palm so hard you won't be able to grip your brand-new golf clubs."
To reiterate: Zofran was and is the most popular, most-prescribed morning sickness drug on the market. You don't get to that level if you're reserved for dire emergencies.
What Does All This Mean?
Really what we're looking at here--the reason this is serious, above and beyond the immediate issues it causes for pre- and neonatal health--is the involved indictment of modern pharmaceutical practice.
For civil lawsuits, we examine the claim for signs of negligence. In an attempt to find it, we can assume one of a few things about GlaxoSmithKline based on these allegations:
- GSK didn't know birth defects would be a problem if pregnant women took Zofran, because they didn't do any trials or research before encouraging doctors to prescribe it off-label. They didn't question a mistaken assumption that all nausea can be treated the same way.
- They knew or even just suspected that ondansetron could cause fetal damages, but ran some numbers and decided the likelihood was so statistically minimal that they could get away with it.
- They actually ran the numbers and found that there was a significant chance of danger to an infant, but ignored their findings and moved forward.
All three of these options, oversimplified as they are, are . GSK has an implicit agreement with the consuming public that they will produce drugs designed to promote individual health, either in curative or palliative fashion. That same inherent understanding, coupled with their legal obligations from the FDA, also says they must warn the public of potential dangers from taking the product.
Their warning information is fairly comprehensive with respect to complications in non-pregnant adults using the drugs as they are intended. By providing these warnings, GSK builds an effective defense against claims that the drug caused damages to these end-users. It is implied that because the warning information was available to the consumer, their use of the medication qualifies as informed consent, and a defense based on assumption of risk can logically be posited.
Nauseous pregnant women enjoyed no such transparency from GSK. They took Zofran/ondansetron in good faith after receiving prescriptions from their doctors. While their nausea was likely suppressed, the medication insidiously worked its way to their babies, affecting and inhibiting development.
They believe that GSK is responsible for these injuries, and science is starting to agree with (some of) them. If the courts determine they are correct, that $3 billion payout to the government may look like change between the couch cushions.
It's certainly heartbreaking when we see a baby born with serious health problems it didn't have to have. Its parents aren't to blame; how could they have known? And for all my talk of dirty doctors above, many family physicians and health care providers are just trying to do their jobs, and prescribed Zofran in earnest because it's highly effective. As you saw, the prescription information they got from GSK was underwhelming to say the least, so many of them wouldn't be aware of the risks.
That doesn't mean GSK gets away with its negligence, though. Parents around the country are fighting back and going after the pharmaceutical giant to hold it accountable for the damage done to their children. If you've used Zofran and your child was born with major health issues, there is a path to justice.