ROCK & A HARD PLACE

Is This Anti-Nausea Pill Safe for Pregnant Women?

A new lawsuit alleges Zofran caused birth defects. It isn’t the first time a drug like this has come under fire—and it won’t be the last.

11.04.15 6:00 AM ET

Deana Brown believes that an anti-nausea drug she took in the first trimester of her pregnancy left her newborn deformed, and she wants GlaxoSmithKline (GSK), its manufacturer, to pay for it.

“GSK’s conduct was tantamount to using expectant mothers and their unborn children as human guinea pigs,” an attorney for Brown alleges in a new lawsuit, filed in October in a U.S. District Court in Idaho.

But is GSK’s drug Zofran actually causing birth defects, or is it just a convenient target in a recurring anxiety over the medications used for morning sickness? Without further research, the answers are still unclear but two things are certain: This isn’t the first time that a drug like Zofran has come under fire, and it won’t be the last.

Brown’s daughter was born with amniotic band constriction and teratologic clubfoot deformity, conditions that affect the development of a child’s limbs, hands, and feet. In her lawsuit, Brown’s attorney alleges that GSK, one of the world’s largest drug companies, concealed a known risk of harm related to Zofran, and that “her child would never [have] been injured” if she had been warned of the drug’s alleged side effects.

Brown isn’t alone in her mindset. By Courthouse News’s count, hers is the 193rd Zofran-related lawsuit filed this year alone. As of mid-October, cases like hers are now being consolidated into multidistrict litigation (MDL) in the District Court of Massachusetts, and law firms are rounding up plaintiffs.

But OB/GYNs tell The Daily Beast that the jury is still out on the link between birth defects and Zofran, and that widespread litigation could discourage drug manufacturers from developing necessary morning sickness medication for women who are left with few options.

The Food and Drug Administration (FDA) classifies Zofran as a Category B pregnancy drug, which means that the medication’s safety during pregnancy has been studied in animals but not in humans. The FDA advises, “Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.”

On-label, Zofran is used to treat nausea and vomiting resulting from chemotherapy, but doctors have long prescribed the drug off-label for severe morning sickness. At present, there is only one FDA-approved medication for morning sickness: Diclegis, recently seen on Kim Kardashian’s Instagram, where the reality star promoted the drug without noting its side effects and received an FDA warning as a result.

Although off-label prescription is a common medical practice, drug companies are not allowed to promote products for uses that are not indicated by the FDA. And it is here that GSK has gotten itself into hot water in the past.

In 2012, GSK “agreed to plead guilty and to pay $3 billion to resolve its criminal and civil liability arising from the company’s unlawful promotion of certain prescription drugs,” the Justice Department reported at the time. It was, they added, “the largest healthcare fraud settlement in U.S. history and the largest payment ever by a drug company.” In the settlement agreement, the U.S. claimed that GSK “knowingly promoted the sale and use of Zofran for a variety of conditions other than those for which its use was approved as safe and effective by the FDA (including hyperemesis or pregnancy-related nausea).” The guilty plea was related to other drugs, but this claim was the basis for a portion of the company’s civil liabilities in the settlement.

This allegation is central to Brown’s case, and to many other lawsuits pending against GSK. But the settlement does not necessarily mean that the drug has been proven to cause birth defects.

Dr. Jennifer Gunter, a Bay Area OB/GYN, told The Daily Beast that she herself took Zofran for severe nausea during pregnancy and her son was born with a heart defect, but she doesn’t blame the drug for the outcome.

In a blog post about Zofran litigation, Gunter reviewed the conflicting research on the drug and wrote,  “Medications should never be the first line for nausea and vomiting. There are other things to try first, but for some women, like me, these things will fail and then every woman has to decide her individual risk-benefit ratio.”

Gunter also fears the impact that litigation could have on the future of morning sickness medication: “[E]very time some personal injury lawyer decides a potential slight increased risk from a conflicting study means ‘let a jury decide,’ there is a direct negative effect on the willingness of companies to invest in studying morning sickness, and fewer doctors will be willing to prescribe anything except saltine crackers and sympathy.”

Dr. Amy Tuteur, an OB/GYN and author who blogs at The Skeptical OB, largely agreed with Gunter’s assessment, telling The Daily Beast that “Zofran can be a literal lifesaver,” and one that should “be available when other treatments fail.” Women who are “profoundly ill,” Tuteur says, cannot always tolerate Diclegis in treatment for hyperemesis gravidarum (severe vomiting during pregnancy), and might opt to use Zofran instead.

“The evidence linking Zofran to birth defects is limited,” she said. “Nonetheless it should be reserved for those who really need it, and there are some women who really need it.”

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Tuteur compared the current furor over Zofran to the widespread litigation around the drug Bendectin in the 1970s and 1980s.  The controversy around that drug played out in a strikingly familiar fashion: hundreds of birth defect cases were consolidated into MDL based on unclear evidence. In 1983, under an avalanche of over 300 lawsuits, manufacturer Merrell Dow voluntarily stopped making Bendectin, then the only FDA-approved morning sickness drug on the market.

Hospitalizations for nausea and vomiting during pregnancy (NVP) doubled after use of the drug stopped.

Then, in 1994, large-scale meta analysis later determined that there was no increased risk of birth defects related to Bendectin and now, its active ingredients are—“ironically,” as Tuteur notes—back on the market in the form of Diclegis.

In August of this year, the American College of Obstetricians and Gynecologists (ACOG) updated its morning sickness guidelines and noted that “further studies are warranted” on Zofran use but concluded that evidence that the drug causes birth defects is still not definitive.

“Thus, although some studies have shown an increased risk of birth defects with early ondansetron [Zofran] use, other studies have not and the absolute risk to any fetus is low,” the ACOG update concluded. “As with all medications, the potential risks and benefits should be weighed in each case.”

The FDA reaffirmed Zofran’s classification as a Category B drug in a letter published October 27th, a GSK spokesperson told The Daily Beast. This letter came just two days before Brown’s suit was filed.

“While we cannot comment on any individual case, we believe that the general allegations in the recently filed lawsuits involving Zofran are entirely unfounded,” the spokesperson said in a statement.

“GSK fully respects the right of doctors to assess the health care needs of their patients and apply their own knowledge, training, and experience in deciding whether the therapeutic benefits of a medicine outweigh the potential risks in each patient,” the statement continued.

Asked about the FDA classification of Zofran as a Category B drug, Aimee Wagstaff, an attorney for Brown, alleged that GSK had evidence from its own animal studies of “several concerning trends related to fertility and fetal development” tied to the use of Zofran but continued to “launch and market” the drug anyway.

“If GSK was truly concerned about providing an option for women with severe morning sickness, GSK should actually study the effects of its own drug on pregnant women rather than subjecting unborn children and their families to unknown and untested side effects,” Wagstaff said. “Certainly GSK has the resources to conduct proper clinical trials prior to launching its product, its decision makers just chose not to.”

Correction 11/4/15 8:oo PM: A previous version of this article incorrectly attributed a quote from a 2012 settlement agreement to GSK rather than the U.S. The settlement is now described in greater detail.