Ondansetron in pregnancy - risk of oral clefts (cleft palate)

Outside of its authorised indications, ondansetron is used second line for treating women with hyperemesis gravidarum - a severe and potentially life-threatening condition

• if a physician considers, based on their professional judgement, the available evidence and the risks for mother and baby of malnutrition in early pregnancy, that a licensed treatment (for example doxylamine/pyridoxine) is not suitable or not sufficient alone to control severe nausea and vomiting in pregnancy, and there is a special clinical need to use ondansetron, then this decision should be made in consultation with the patient after she has been fully informed of the potential benefits and risks of the different treatment options (1)
  
  
• study evidence reveals a small increased risk of orofacial malformations in babies born to women who used ondansetron in early pregnancy
  • an observational study of 1.8 million pregnancies in the USA of which 88,467 (4.9%) were exposed to oral ondansetron during the first trimester of pregnancy (2)
    • study reported that ondansetron use was associated with an additional 3 oral clefts per 10,000 births (14 cases per 10,000 births versus 11 cases per 10,000 births in the unexposed population)

Prescribers should refer to clinical guidance if treatment with ondansetron is considered for severe nausea and vomiting in pregnancy (3).

Reference:

• MHRA (28/1/2020). Ondansetron: small increased risk of oral clefts following use in the first 12 weeks of pregnancy. Drug Safety Update volume 13, issue 6: January 2020: 2.
• Huybrechts KF, et al. Association of maternal first-trimester ondansetron use with cardiac malformations and oral clefts in offspring. JAMA 2018; 320: 2429-37.
• Royal College of Obstetrics and Gynaecology. The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum. Green-top Guideline No. 69. June 2016.