Overview

Ondansetron is a 5-HT3 receptor antagonist indicated for the prevention of nausea and vomiting induced by chemotherapy and radiotherapy. It is also indicated for prevention and treatment of postoperative nausea and vomiting.

Currently, there are 14 ondansetron-containing products (as tablet and injection formulations) registered in Malaysia.

Background of the safety issue

The National Pharmaceutical Regulatory Agency (NPRA) received information from the product innovator on the risk of birth defects associated with ondansetron. This safety issue has been previously communicated to healthcare professionals in Malaysia on 26^th February 2020 via the NPRA Safety Alerts. To view this safety alert, click here.

More recently, three (3) new epidemiological studies related to the use of ondansetron in pregnancy, were published in four (4) publications by Parker et al. (2018), Lemon et al. (2019) and Huybrechts et al. (2018, 2020). These studies showed that there is an increased risk of orofacial clefts observed in the infants of women administered with ondansetron during the first trimester of pregnancy.^1,2 However, there were conflicting results for cardiac malformations.^1-4

Adverse Drug Reaction (ADR) Reports

To date, NPRA has received 32 ADR reports with 47 adverse events suspected to be related to ondansetron use. However, no event related to birth defects has been reported.⁵

Advice for Healthcare Professionals

• The use of ondansetron during pregnancy is not recommended.
• Ondansetron is not indicated for the treatment of nausea and vomiting in pregnancy.
• Always consider the risk of birth defects associated with ondansetron use before prescribing ondansetron to patients.
• Advise women of childbearing potential to use contraception while taking ondansetron and for two (2) days after stopping it. Inform the patient on the potential risk of birth defects associated with ondansetron use in pregnancy.
• Please report all suspected adverse events associated with ondansetron to the NPRA.

NPRA has completed a review of this safety issue and has approved a Direct Healthcare Professional Communication (DHPC) letter issued by Novartis (Malaysia) Sdn. Bhd. on 13^th August 2020 to highlight the review of this safety issue with the summaries of the publications. For further information, please contact your local sales person for a copy of the DHPC.

The package insert and consumer medication information leaflet (Risalah Maklumat Ubat untuk Pengguna) of ondasetron products will be updated to reflect this risk.

A directive [Ruj. Kami: NPRA.600-1/9/13 (15)] also has been issued for all registration holders of ondansetron products to update the local package inserts and consumer medication information leaflet (Risalah Maklumat Ubat untuk Pengguna) to reflect this safety information.

References:

1. Huybrechts KF et al. (2018): Association of maternal first-trimester ondansetron use with cardiac malformations and oral clefts in offspring.  JAMA 320(23): 2429-2437.
2. Parker SE et al. (2018): National birth defects prevention study.  Ondansetron for treatment of nausea and vomiting of pregnancy and the risk of specific birth defects. Obstet Gynecol 132(2): 385-394.
3. Lemon LS et al. (2019): Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defect.  International Journal of Epidemiology DOI: 10.1093/ije/dyz255.
4. Huybrechts KF et al (2020): Intravenous ondansetron in pregnancy and risk of congenital malformations. JAMA DOI: 10.1001/jama.2019.18587.
5. The Malaysian Adverse Drug Reaction database, NPRA [Accessed: 3^rd September 2020]

DISCLAIMER

This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.