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Ondansetron – is it safe in pregnancy?

15th September, 2018, Dr Chee L Khoo

Nausea and vomiting affects up to 80% of pregnancies but severe nausea and vomiting in early pregnancy or hyperemesis gravidarum (HG) can affect up to 1% of pregnancy. As GPs, we are often the first port of call for these women. We know how debilitating it is to those women. There is also an significant economic impact not just because of many of these women ended up in hospital on more than one occasion before 20 weeks of gestation but many (and often their partners) can’t go to work during this period. It’s frustrating on our part because metoclopramide often doesn’t work.  In desperation we try all sorts of other agents. How effective and safe are these agents though?

Surprisingly, despite being a fairly common and debilitating condition, there are very few high quality and consistent studies looking at the efficacy and safety of the various intervention. Further, there is no consistency in the definition of HG. A Cochrane review in 2016 looked at 25 clinical trial involving 2052 women. There was insufficient evidence to identify clear differences between metoclopramide, ondansetron, promethazine, acupuncture or corticosteroids. Women on vitamin B6 had a slightly longer hospital stay compared with placebo.

Another systematic review in JAMA in October 2016 looked at 78 studies involving 8930 women with HG. It found that for mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. They did comment that the quality of evidence was low.

In a 2004 prospective study of 176 Australian women who took ondansetron, all during the first trimester of pregnancy, no increase in the rates of major malformations were found. There have been many similar studies done in UK, Sweden and Canada. They all reported no linkage to any birth defects. A United States case control study (N = 55 exposed pregnancies) in 2012 reported an increase in cleft palate defects but not in cleft lip, hypospadias, or neural-tube defects

The largest study came from data from the Danish Medical Birth Registry and National Patient Registry between 2004-2008. Out of 608,385 pregnancies, 1970 of them were exposed to ondansetron in the first 10 weeks of pregnancy. Ondansetron exposure was not associated with any significant increased risk of major adverse foetal outcomes.

A Western Australia study looked pregnancies between 2002-2005. Women who were prescribed ondansetron under the PBS were compared with other births. 251 women were exposed to ondansetron during this period and they did not detect any adverse outcomes but they could conclude that ondansetron was safe to use in pregnancy.

A most recent systematic review published in 2016 looked at 8 studies and concluded that “the overall risk of birth defects associated with ondansetron exposure appears to be low. There may be a small increase in the incidence of cardiac abnormalities in ondansetron-exposed neonates. Therefore, ondansetron use for nausea and vomiting of pregnancy should be reserved for those women whose symptoms have not been adequately controlled by other methods”.

Data from two large case–control studies, the National Birth Defects Prevention Study (1997–2011) and the Slone Birth Defects Study (1997–2014) in Boston, USA were examined recently to investigate associations between first-trimester ondansetron use and major birth defects. They found no increased risk of major birth defects associated with first-trimester use of ondansetron for treatment of nausea and vomiting of pregnancy compared with no treatment. Modest increases in risk were observed for cleft palate in the National Birth Defects Prevention Study and renal agenesis–dysgenesis in the Birth Defects Study, although these findings may be the result of chance.

MIMS categorise ondansetron as Category B1 in pregnancy which says:

“The safety of ondansetron for use in human pregnancy has not been established. Evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to the development of the embryo or fetus, the course of gestation, and perinatal and postnatal development. However, as animal studies are not always predictive of human response, the use of ondansetron in pregnancy is not recommended.”

It seems that pregnant women are increasingly being prescribed ondansetron these days. I must say, anecdotally, it works better than metoclopramide but how safe is it? Should we be discussing the potential adverse effects with the woman? I think so.

Access the abstract here.


Interventions for treating hyperemesis gravidarum. Boelig RC1, Barton SJ, Saccone G, Kelly AJ, Edwards SJ, Berghella V. Cochrane Database Syst Rev. 2016 May 11;(5)

Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G. The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study. BJOG 2004;111:940-943

Björn Pasternak, Henrik Svanström, Anders Hviid, Ondansetron in Pregnancy and Risk of Adverse Fetal Outcomes. N Engl J Med 2013; 368:814-823

Carstairs SD. Ondansetron Use in Pregnancy and Birth Defects: A Systematic Review. Obstet Gynecol. 2016 May;127(5):878-83. doi: 10.1097/AOG.0000000000001388. Review.

Samantha E. Parker; Carla Van Bennekom; Marlene Anderka; Allen A. Mitchell. Ondansetron for Treatment of Nausea and Vomiting of Pregnancy and the Risk of Specific Birth Defects. Obstetrics & Gynecology. 132(2):385–394, AUG 2018




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