More data indicating that ondansetron is not associated with an increase in most birth defects when taken for nausea and vomiting during the first trimester of pregnancy have emerged from an analysis of two large studies.
"Ondansetron...is approved by the [US Food and Drug Administration] only for the treatment of nausea and vomiting related to chemotherapy, radiation therapy, and surgery. Although not approved for nausea and vomiting of pregnancy, ondansetron has become the most commonly used [off-label] prescription antiemetic for this condition in the United States," note Samantha E. Parker, PhD, from the Massachusetts Center for Birth Defects Research and Prevention, Boston, and colleagues, in their paper, published in Obstetrics & Gynecology.
Although a few prior studies have indicated a low risk for birth defects with such off-label use of ondansetron, the drug is not recommended as a first-line treatment for morning sickness.
Still, use of ondansetron for this purpose increased in the 15 years studied, from less than 1% before 2000 to 13% of antiemetic use during 2013 to 2014, the researchers write.
Large Data Sets Able to Study Many Birth Defects
The researchers analyzed data from two large case control studies of birth defects: the National Birth Defects Prevention Study, conducted during 1997 to 2011, and the Slone Birth Defects Study, conducted during 1997 to 2014.
This included 6751 control mothers (who gave birth to infants with no defects) and 14,667 case mothers (who gave birth to infants with major birth defects) from the National Birth Defects Prevention Study, and 5873 controls and 8533 cases from the Slone Birth Defects Study. All the mothers experienced first-trimester nausea and vomiting.
In terms of antiemetic use, the researchers classified the women into three groups: those who took off-label ondansetron with or without other prescription antiemetics, those who received other prescription antiemetics or intravenous fluids only, and those who received no treatment for nausea and vomiting (the reference group).
The investigators studied 51 birth defects including neural tube defects, cleft lip with or without cleft palate, cleft palate, hypospadias, septal defects, and renal collecting system anomalies.
First-trimester ondansetron use was not linked to an increased risk for most of the birth defects studied compared with the reference group of women, who had untreated first-trimester nausea and vomiting of pregnancy. This was also the case after adjustment for potential confounders including maternal age, maternal education, periconceptual folic acid use, and study year.
"Two exceptions were cleft palate in the National Birth Defects Prevention Study and renal agenesis–dysgenesis in the Birth Defects Study," note the researchers. "The cleft palate finding was not replicated in the Slone Birth Defects Study analysis, and renal agenesis–dysgenesis has not previously been considered."
The risk for cleft palate was modestly elevated among women who took ondansetron in the National Birth Defects Prevention Study compared with the reference group who had no treatment for morning sickness (adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 - 2.3).
The risk for renal agenesis-dysgenesis was modestly increased among women taking ondansetron in the Slone Birth Defects Study compared with the reference group (adjusted OR, 1.8; 95% CI, 1.1 - 3.0).
A strength of the study is that it used two data sets that provided sample sizes large enough to study many specific birth defects, the researchers stress.
In addition, they note they used maternal interviews to obtain information on nausea and vomiting during pregnancy, as opposed to prescriptions issued or filled but not used, to represent reported use and gestational timing.
Still, "the number of exposed cases for many specific birth defects was small, leading to imprecise estimates," they write, noting that the association of ondansetron use with cleft palate and renal agenesis-dysgenesis could simply be because of chance.
"For the majority of specific birth defects investigated, there was no increased risk associated with first-trimester use of ondansetron for treatment of nausea and vomiting of pregnancy compared with no treatment," they observe.
Data Will Inform for Ondansetron Use in the Future
Although the researchers reiterate the use of ondansetron as a first-line treatment for first-trimester nausea and vomiting is inconsistent with current clinical guidelines, they acknowledge that it is being widely used nevertheless, and so this new study "contributes to the accruing body of literature regarding the safety of this medication."
It is also possible that approvals of new antiemetics for morning sickness could "affect patterns of ondansetron use and other prescription antiemetics," going forward, they conclude.
In 2013, the US Food and Drug Administration sanctioned the first new antiemetic for nausea and vomiting of pregnancy for 15 years in the United States, doxylamine and pyridoxine (Diclegis), "a rebranded formulation of Bendectin," and in 2016, the agency approved a fixed-dose combination of doxylamine succinate and pyridoxine HCI (Bonjesta, Duchesnay) for the same indication.
One author reports serving on the Tecfidera Pregnancy Registry Advisory Committee supported by Biogen. The remaining authors have disclosed no relevant financial relationships.
Obstet Gynecol. Published online July 7, 2018. Abstract
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Cite this: More Data Indicate Ondansetron Is Safe for Morning Sickness - Medscape - Jul 20, 2018.