Zofran (ondansetron hydrochloride), manufactured by GlaxoSmithKline (GSK), is approved for use alone, or in combination with other medications, for the prevention of nausea and vomiting associated with chemotherapy and radiation therapy, and is used to prevent these symptoms following surgery.
Though not approved for use during pregnancy, Zofran is often prescribed for the nausea and vomiting that up to 80 percent of women experience in pregnancy. About 15 percent of pregnant women need antiemetic medication, Medscape Multispecialty reports. Nausea and vomiting peak during the first trimester and this is when there is the greatest danger of teratogenic effects of medications (harmful effects on the development of the fetus). Data on the effects of ondansetron on the developing fetus are limited and conflicting but there are findings that suggest the need for caution in prescribing Zofran.
In 2004, research from Canada and Australia compared rates of miscarriage, stillbirth, and major birth defects among pregnant women taking ondansetron, other antiemetics, or no antiemetics (176 women in each group). All women who received ondansetron were in the first trimester. The researchers saw no significant differences among the groups for adverse pregnancy outcomes; however, this industry-sponsored study was powered to detect only a 3.5-fold or greater increased risk in major birth defects. A larger, case/control study associated ondansetron with a significantly increased risk for cleft palate. The odds of cleft palate were 2.4 times higher with exposure to ondansetron during the first trimester. Australian researchers compared 251 pregnant women exposed to ondansetron from 2002 to 2005 with 96,717 women who were not exposed found a 20 percent increased risk for a major birth defect among infants exposed to ondansetron during the first trimester was reported.
A Danish study, using the Medical Birth Registry and National Patient Register, evaluated the teratogenic effects of ondansetron exposure during the first trimester using 1997-2010 data. Of 897,018 births, prescription records suggested that 1248 women were exposed to ondansetron. The odds of fetal heart malformation were two times higher in infants of women exposed to ondansetron compared with women not exposed to the drug.
Swedish researchers looking at data from the Swedish Medical Birth Register and Swedish Register of Prescribed Drugs found 1349 women exposed to ondansetron in early pregnancy from1998 and 2012. While ondansetron exposure was not associated with an increased risk for severe birth defects, the odds of general heart defects were 1.6 times higher, and the odds of heart septum defects were 2.1 times higher.
Under current guidelines in the U.S. and Canada, Zofran is not recommended as the first-line option for treating nausea and vomiting in pregnancy, Medscape Multispecialty reports. Lifestyle and dietary modifications should be the first steps. If medication is required, doxylamine/pyridoxine (Diclegis) is FDA-approved for the treating nausea and vomiting in pregnancy. Given the current evidence, ondansetron should be avoided in the first trimester of pregnancy unless other treatments are ineffective.