Side Effects of Zofran for Morning Sickness Linked to Reports of Birth Defects

Concerns have emerged about the potential pregnancy risks associated with Zofran use for morning sickness, following reports that suggest some women may have subsequently given birth to children with developmental defects or malformations. 

An investigation last year by the Toronto Star indicated a number of women who were given Zofran to treat nausea during pregnancy and later reported complications, including infant deaths and children born with birth defects. The investigation gleaned the reports from the FDA’s adverse event reporting system.

The story has since sparked concerns about the potential side effects of Zofran when used off-label for treatment of morning sickness among pregnant women, raising questions about why that country’s health agency, Health Canada, has not issued a warning.

The investigation found at least 20 reports of pregnant Canadian women in 2012, whose children may have suffered complications after exposure to Zofran morning sickness treatments before birth. In two of the cases, the infants died. In others, they suffered heart and kidney malformations.

Zofran (ondansetron), which is manufactured by GlaxoSmithKline, is a member of a class of drugs known as 5-HT3 receptor antagonists, which works by blocking the actions of serotonin. It is commonly used for treatment of nausea caused by cancer treatments, but it has been widely prescribed off-label for pregnant women suffering from morning sickness, even though the FDA has not approved it for that use.

About 10% of pregnant women suffer from nausea severe enough that doctors recommend they take anti-nausea medication. However, at least one study has raised concerns that Zofran could cross the placenta and adversely affect their child’s development or health. The study suggested that the Zofran side effects among pregnant women could increase the risk of oral cleft birth defects, such as cleft palate and cleft lip, but those findings were not confirmed by this latest study.

Another study published by the New England Journal of Medicine in 2013, however, found no link between Zofran and birth defects.

Known side effects of Zofran have also been linked to a risk of a type of irregular heart rhythm problems among users, known as QT interval prolongation.  This may predispose patients to develop Torsades de Pointes, which may lead to sudden death if proper treatment is not received.

In December 2012, the FDA announced a partial Zofran recall because of the heart rhythm problems associated with the drug. The recall only affects the 32 mg, single intravenous (IV) dose, which is usually used to prevent chemotherapy-induced nausea and vomiting.

The most recently updated label and medication guide (PDF) for the oral tablet version of Zofran, manufactured by GlaxoSmithKline, claims that testing on rats and rabbits revealed harm to fetuses following Zofran use. However, the label also notes that there are “no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.”

The manufacturers of Zofran reportedly told the Toronto Star that use of the medication by pregnant women was not recommended and not approved by the FDA.