Last reviewed: June 2020
Last updated: February  2020
12 Feb 2020

EMA's safety committee recommends restricting the use of ondansetron during the first trimester of pregnancy

The European Medicines Agency's (EMA's) pharmacovigilance risk assessment committee (PRAC) has recommended limiting the use of ondansetron during the first trimester of pregnancy.[19]

The PRAC review concluded that women who used ondansetron during the first trimester of pregnancy had an increased risk of birth defects, specifically cleft lip and/or palate. In one study, there were an additional 3 cases of orofacial cleft per 10,000 pregnancies exposed to ondansetron.[20] The available data on the risk of cardiac defects with ondansetron use show conflicting results.[20][21] However, the UK Teratology Information Service (UKTIS), in collaboration with the European Network of Teratology Information Services (ENTIS), issued a joint statement in response to the recommendations from the EMA PRAC regarding the use of ondansetron in the first trimester of pregnancy. UKTIS and ENTIS suggest ondansetron should still be considered an option for patients with severe vomiting in pregnancy in whom first-line treatments have failed, noting in their statement that there is much more information available about safety during pregnancy for ondansetron than for other antiemetic drugs, with data now available from over 168,000 women treated during the first trimester.[22] The UK Medicines and Healthcare products Regulatory Agency (MHRA) also issued a drug safety update for ondansetron that provides similar advice.[23]

This recommendation is in line with the current Royal College of Obstetricians and Gynaecologists (RCOG) recommendations that ondansetron should be reserved as a second-line agent for the treatment of nausea and vomiting in pregnancy, including hyperemesis gravidarum.[24] The drug should only be used during pregnancy if the benefits of treatment are considered to outweigh any potential fetal risks, and women must receive adequate counseling about both benefits and risks of treatment. 

See Management: approach

See Management: treatment algorithm

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History and exam

Key diagnostic factors

  • first trimester of pregnancy
  • weight loss of >5%

Other diagnostic factors

  • absence of thyroid enlargement/nodules
  • absence of central nervous system (CNS) signs
  • dry mucous membranes
  • postural dizziness
  • tachycardia
  • hypotension
  • ketotic breath

Risk factors

  • family history of hyperemesis gravidarum
  • previous history of NVP
  • multiple gestation or increased placental mass
  • gestational trophoblastic disease
  • other causes of increased placental mass
  • female fetus
  • history of motion sickness
  • history of migraine headache

Diagnostic investigations

1st investigations to order

  • complete blood count
  • basic metabolic panel
  • serum liver function tests
  • serum BUN and creatinine
  • serum thyroid-stimulating hormone (TSH) and free thyroxine (T4)
  • urinalysis
  • urine or serum ketones
  • fetal ultrasound with nuchal translucency
  • serum analytes
  • Helicobacter pylori breath test
More 1st investigations to order

Investigations to consider

  • urine culture
  • serum amylase and lipase
  • abdominal ultrasound
  • renal ultrasound
  • cranial CT or MRI
More investigations to consider

Treatment algorithm


Associate Professor

Family Medicine

Uniformed Services University of Health Sciences




JDQ declares that he has no competing interests.

Peer reviewersVIEW ALL

Faculty Physician

Family Medicine Residency

Naval Hospital Jacksonville



SJ declares that she has no competing interests.

Assistant Professor

Head of Department of Obstetrics and Gynecology

Mosul College of Medicine




YTJ declares that he has no competing interests.

Associate Director

Department of Obstetrics and Gynecology

Florida Hospital




DAH declares that he has no competing interests.

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