A drug that’s frequently prescribed for morning sickness has been linked to an increased occurrence of severe birth defects. The drug is Zofran, also known by its generic name ondansetron. It’s been on the market since the FDA first approved it in 1991.

Currently, Zofran is approved by the FDA as a treatment for nausea and vomiting associated with recovery from surgery and with chemotherapy or radiation treatment for cancer. Zofran is actually not FDA-approved as a treatment for morning sickness and it never has been.

Nevertheless, some physicians have been prescribing Zofran to treat nausea associated with pregnancy for years. By one measure, prescriptions for Zofran for morning sickness increased from 50,000 in 2008 to 110,000 in 2013.

This sort of “off-label” use of a drug is generally permissible when it’s done by an individual physician on a case-by-case basis. At the same time, a few studies have raised the possibility of a connection between Zofran use early in pregnancy and the later development of severe birth defects.

Zofran Studies Point to Risk of Birth Defects

A study of thousands of Danish birth records from 1997 to 2010 revealed that babies who were exposed to ondansetron during pregnancy were more than twice as likely to be born with severe cardiac defects, such as atrial or ventricular septal defects. Overall, the records showed a 30 percent increase in risk for major congenital malformations.

Those results were consistent with results from a 2014 study published in the Reproductive Technology journal, which showed an increase in the incidence of cardiac septal defects and other cardiovascular defects. A third study found the risk of developing cleft palate more than doubled in mothers who took ondansetron during pregnancy.

Other studies revealed that Zofran use during the first trimester co-occurred with an increased likelihood of premature birth and shorter birth length.

Despite these findings, the U.S. Food and Drug Administration recently rejected a petition to change Zofran’s drug category, saying in an October 2015 statement that these studies “do not support a determination that there is an increased risk of fetal adverse outcomes.”

Zofran Misbranding

Doctors have the power to write a prescription for a particular medication for whatever use they deem appropriate on a case-by-case basis. What’s against the law, however, is for a pharmaceutical company to promote a particular drug for any use other than those approved by the FDA.

The Food, Drug and Cosmetic Act requires pharmaceutical companies to specify all proposed uses for a particular drug when they apply to the FDA for approval. Once the FDA approves a drug for particular uses, those are the only uses for which the company may promote the drug. Any promotion for any other so-called “off-label” uses – like promoting Zofran for morning sickness – is unlawful. Such promotion renders the drug “misbranded.”

GlaxoSmithKline, the maker of Zofran, has been taken to task for allegedly doing that with Zofran. In 2012, GSK settled a federal, civil false claim lawsuit alleging GSK had promoted Zofran for the treatment of morning sickness in pregnant women despite being approved only for post-operative nausea, and that GSK had paid doctors kickbacks for prescribing Zofran. In 2012, GSK settled that lawsuit along with three similar lawsuits regarding other GSK products for $1.043 billion.

Part of that agreement was meant to address allegations that GlaxoSmithKline unlawfully promoted Zofran for use as a morning sickness medication, even though it has never been approved for that use by the FDA. The agreement also covered many other allegations not related to Zofran, including false price reporting practices and failure to report safety information.