How safe and effective is ondansetron for nausea and vomiting in pregnancy?
EVIDENCE-BASED ANSWER:
Oral ondansetron is more effective than a combination of pyridoxine and doxylamine for outpatient treatment of nausea and vomiting in pregnancy (strength of recommendation [SOR]: B, randomized controlled trial [RCT]).
For moderate to severe nausea and vomiting, intravenous (IV) ondansetron is at least as effective as IV metoclopramide and may cause fewer adverse reactions (SOR: B, RCTs).
Disease registry, case-control, and cohort studies report a slight increase in the risk of cardiac defects with ondansetron use in first-trimester pregnancies, but no major or other birth defects are associated with ondansetron exposure (SOR: B, a systematic review of observational trials and a single retrospective cohort study).
A specialty society guideline recommends weighing the risks and benefits of ondansetron use before 10 weeks’ gestational age and suggests reserving ondansetron for patients who have persistent nausea and vomiting unresponsive to first- and second-line treatments (SOR: C, expert opinion).
No study demonstrated an increased rate of major malformations associated with ondansetron exposure except for 2 disease registry studies with nearly 2.4 million patients that reported a slight increase in the risk of cardiac defects (odds ratio [OR] = 2; 95% CI, 1.3-3.1; OR = 1.6, 95% CI, 1-2.1). Comparisons of other birth defect rates associated with ondansetron exposure were inconsistent, with studies showing small increases, decreases, or no difference in rates between exposed and nonexposed women.
Exposure vs nonexposure: No difference in adverse outcomes
A 2013 retrospective cohort study looked at 608,385 pregnancies among women in Denmark, of whom 1970 (0.3%) had been exposed to ondansetron.5 The study found that exposure to ondansetron compared with nonexposure was associated with a lower risk for spontaneous abortion between 7 and 12 weeks’ gestation (1.1% vs 3.7%; hazard ratio [HR] = 0.5; 95% CI, 0.3-0.9).
No significant differences between ondansetron exposure and nonexposure were found for the following adverse outcomes: spontaneous abortion between 13 and 22 weeks’ gestation (1% vs 2.1%; HR = 0.6; 95% CI, 0.3-1.2); stillbirth (0.3% vs 0.4%; HR = 0.4; 95% CI, 0.1-1.7); any major birth defect (2.9% in both exposed and nonexposed women; OR = 1.12; 95% CI, 0.69-1.82); preterm delivery (6.2% vs 5.2%; OR = 0.9; 95% CI, 0.7-1.3), low birth weight infant (4.1% vs 3.7%; OR = 0.8; 95% CI, 0.5-1.1); and small-for-gestational-age infant (10.4% vs 9.2%; OR = 1.1; 95% CI, 0.9-1.4).
RECOMMENDATIONS
The American College of Obstetricians and Gynecologists (ACOG) states that insufficient data exist regarding the safety of ondansetron for the fetus.6 ACOG recommends individualizing the use of ondansetron before 10 weeks of pregnancy after weighing the risks and benefits. ACOG also recommends adding ondansetron as third-line treatment for nausea and vomiting unresponsive to first- and second-line treatments.
EDITOR'S TAKEAWAY
Higher-quality studies showed ondansetron to be an effective treatment for hyperemesis gravidarum. Lower-quality studies raised some concerns about adverse fetal effects. Although the adverse effects were rare and the quality of the evidence was lower, the cautionary principle suggests that ondansetron should be a second-line option.
