A recent article argues that physicians should avoid prescribing the anti-nausea drug ondansetron, also known by its trade name Zofran, to women suffering from nausea and vomiting of pregnancy, or NVP.

The article appeared in the December 2014 issue of American Journal of Obstetrics and Gynecology. Author Dr. Gideon Koren argues that the effect of ondansetron on the risk of fetal heart defects is at best unknown and possibly harmful. Dr. Koren cited a recent study of Danish birth registries that “detected a 2-fold increased risk of cardiac malformations with ondansetron … leading to an overall 30% increased risk of major congenital malformations.”

Dr. Koren’s article questions the validity of prior Zofran studies that found little or no increased risk of birth defects with ondansetron use. In a 2004 study that found no increase in risk, the sample size was too small to rule out an increased risk of less than five-fold. Another Zofran study in 2013 used a sample in which half the cases had been exposed to ondansetron only after 10 gestational weeks, at which point the birth defects that are the focus of Dr. Koren’s article could not have been produced.

Dr. Koren concludes that given the uncertain risk of cardiac malformation and other birth defects that could be associated with ondansetron, as well as the existence of an alternative medication recently approved by the FDA as a treatment for NVP, there is no reason for physicians to expose women to ondansetron as a treatment for NVP.

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 and Pregnancy Risk

Ondansetron is manufactured and marketed by the pharmaceutical company GlaxoSmithKline under the trade name Zofran. It is one of a class of anti-nausea drugs known as selective serotonin 5HT3 receptor antagonists. It works by inhibiting the effect of the neurotransmitter serotonin in parts of the nervous system that are related to nausea and vomiting.

The FDA approved Zofran in 1991 as a treatment for nausea related to chemotherapy and radiation treatments. Although Zofran has not been approved for treatment of any other type of nausea, physicians often prescribe it for NVP, colloquially known as “morning sickness.” It is increasingly common for physicians to make such “off-label” prescriptions for morning sickness: by the end of 2013, physicians were writing 110,000 Zofran prescriptions per month for NVP.

Far from discouraging this off-label use, GlaxoSmithKline created a marketing scheme that abetted Zofran for morning sickness. In 2012, a criminal prosecution by the U.S. Department of Justice led to a guilty plea by GlaxoSmithKline over its marketing practices.

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.

Zofran Birth Defect Lawsuits

Plaintiffs have begun their own Zofran birth defect lawsuits. They cite multiple Zofran birth defect studies conducted in recent years that show a connection between using Zofran during pregnancy and subsequent heart birth defects.

These Zofran lawsuits typically allege that GlaxoSmithKline unlawfully marketed Zofran for off-label treatment of NVP. They allege that GlaxoSmithKline knew about the unreasonable risks of fetal harm associated with Zofran use as early as 1992 when reports of such Zofran birth defects began arising. The plaintiffs allege GlaxoSmithKline failed to properly warn consumers or their physicians about Zofran birth defect risks.