The next chart up is a healthy 12-week pregnant woman with vomiting. Labs have already been ordered and are normal. You decide to forego the IV and give her a Zofran dissolvable tablet – saving her time, needle stick, and the pain of having to swallow a pill while nauseated (let’s be honest: no one uses the suppositories). You remember watching Matlock on your day off yesterday and seeing an ad for something about Zofran on TV. You decide it was probably nothing and remember how sharp Andy Griffith looked in a grey suit.
The FDA classifies Zofran as a pregnancy Category B drug – meaning its 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 associated with chemotherapy, but it’s frequently used off-label for morning sickness. Currently, there is only one FDA-approved medication for morning sickness: Diclegis.
Studies regarding Zofran’s safety during pregnancy are conflicting. In 2013, a retrospective study detected a two-fold increase in cardiac malformations with Zofran, leading to an overall 30% increased risk of major congenital malformations. To rule out confounding by indication, researchers also examined metoclopramide (Reglan) and found no increased teratogenic risk.
In 2016, ACOG updated its morning sickness guidelines and commented that “further studies are warranted” on Zofran use but concluded that evidence that the drug causes birth defects is still not definitive. “As with all medications, the potential risks and benefits should be weighed in each case.”
A 2016 study published in Reproductive Toxicology found no association between Zofran and birth defects. It actually found evidence suggesting that women who took Zofran were less likely to have a miscarriage or a stillbirth. Researchers found that five heart defects and one cleft palate were reported among 952 infants whose mothers took Zofran. Eight heart defects and two cleft palates were reported among the 1,286 infants born to women who did not take Zofran.
So what to do? The simple fact that a Google search reveals so much controversy should be enough of a red flag. Daytime television is filled with ads imploring pregnant women exposed to Zofran to contact lawyers. Even though the evidence is conflicting, is it worth the risk? If an infant happens to be born with congenital defects and you prescribed Zofran, a lawsuit is possible. That simple possibility is enough for me to choose an alternative drug.
Glaxo-Smith-Kline is the manufacturer of the drug. Where they got into trouble was promoting drugs for non-FDA-approved indications. 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 “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).” This admission of fault is central to most of the lawsuits against GSK.
Bottom line: in first trimester nausea/vomiting of pregnancy, prescribe Zofran at your own risk.
