Display options
Cite
Damkier P, Kaplan YC, Shechtman S, et al. Ondansetron in pregnancy revisited: Assessment and pregnancy labelling by the European Medicines Agency (EMA) & Pharmacovigilance Risk Assessment Committee (PRAC). Basic Clin Pharmacol Toxicol. 2020;128(4):579-582doi: 10.1111/bcpt.13541.
Damkier, P., Kaplan, Y. C., Shechtman, S., Diav-Citrin, O., Cassina, M., & Weber-Schoendorfer, C. (2021). Ondansetron in pregnancy revisited: Assessment and pregnancy labelling by the European Medicines Agency (EMA) & Pharmacovigilance Risk Assessment Committee (PRAC). Basic & clinical pharmacology & toxicology, 128(4), 579-582. https://doi.org/10.1111/bcpt.13541
Damkier, Per, et al. "Ondansetron in pregnancy revisited: Assessment and pregnancy labelling by the European Medicines Agency (EMA) & Pharmacovigilance Risk Assessment Committee (PRAC)." Basic & clinical pharmacology & toxicology vol. 128,4 (2021): 579-582. doi: https://doi.org/10.1111/bcpt.13541
Damkier P, Kaplan YC, Shechtman S, Diav-Citrin O, Cassina M, Weber-Schoendorfer C. Ondansetron in pregnancy revisited: Assessment and pregnancy labelling by the European Medicines Agency (EMA) & Pharmacovigilance Risk Assessment Committee (PRAC). Basic Clin Pharmacol Toxicol. 2021 Apr;128(4):579-582. doi: 10.1111/bcpt.13541. Epub 2020 Dec 16. PMID: 33275828.
Copy Download .nbib Format: NLM
Share it on

Basic Clin Pharmacol Toxicol. 2021 Apr;128(4):579-582. doi: 10.1111/bcpt.13541. Epub 2020 Dec 16.

Ondansetron in pregnancy revisited: Assessment and pregnancy labelling by the European Medicines Agency (EMA) & Pharmacovigilance Risk Assessment Committee (PRAC).

Basic & clinical pharmacology & toxicology

Per Damkier, Yusuf Cem Kaplan, Svetlana Shechtman, Orna Diav-Citrin, Matteo Cassina, Corinna Weber-Schoendorfer

Affiliations

  1. Department of Clinical Biochemistry & Pharmacology, Odense University Hospital, Odense, Denmark.
  2. Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
  3. Terafar - Izmir Katip Celebi University Teratology Information, Training and Research Center, Izmir, Turkey.
  4. The Israeli Teratology Information Service, Ministry of Health, Jerusalem, Israel.
  5. The Israeli Teratology Information Service, Ministry of Health, and the Hebrew University Hadassah Medical School, Jerusalem, Israel.
  6. Clinical Genetics Unit, Department of Women's and Children's Health, University of Padua, Padua, Italy.
  7. Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Pharmacovigilance Institute for Embryotoxicology, Institute of Clinical Pharmacology and Toxicology, Berlin, Germany.

PMID: 33275828 DOI: 10.1111/bcpt.13541

Abstract

Ondansetron is an effective antiemetic that is being widely used as a second-line treatment option for severe nausea and vomiting of pregnancy in accordance with clinical guidelines. The safety of ondansetron during pregnancy has-following publication of controversial and seemingly contradictory results-been subject to considerable academic turmoil, specifically with respect to the risk of congenital cardiac malformations and oral cleft. In July 2019, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) released an updated, comprehensive assessment report on the use of ondansetron in the first trimester. The ensuing Summary of Product Characteristics (SmPC) was updated in November 2019 with important changes to section on "Fertility, pregnancy and lactation." The SmPC now states that ondansetron should not be used in the first trimester of pregnancy. ENTIS, The European Network of Teratology Information Services, believes that the implementation of this regulatory step-which has important clinical consequences-is insufficiently substantiated and is not serving the interest of pregnant women with severe nausea and vomiting. Herein, we discuss the underlying evidence and argue the case against the EMA decision.

© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Keywords: congenital malformations; nausea; ondansetron; pregnancy; vomiting

References

  1. The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69) [Internet]. Royal College of Obstetricians & Gynaecologists. [cited 2020 Feb 25]. Available from: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg69/ - PubMed
  2. Fiaschi L, Nelson-Piercy C, Deb S, King R, Tata LJ. Clinical management of nausea and vomiting in pregnancy and hyperemesis gravidarum across primary and secondary care: a population-based study. BJOG Int J Obstet Gynaecol. 2019;126:1201-1211. - PubMed
  3. Taylor LG, Bird ST, Sahin L, et al. Antiemetic use among pregnant women in the United States: the escalating use of ondansetron. Pharmacoepidemiol Drug Saf. 2017;26:592-596. - PubMed
  4. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131:e15-30. - PubMed
  5. Updated Signal assessment report on birth defects following in-utero exposure during the first trimester of pregnancy arising from recent publications with ondansetron [Internet]. 2019 [cited 2020 Feb 25]. Available from: https://www.ema.europa.eu/en/documents/prac-recommendation/updated-signal-assessment-report-birth-defects-following-utero-exposure-during-first-trimester_en.pdf - PubMed
  6. Ondansetron 4 mg film-coated tablets - Summary of Product Characteristics (SmPC) - (emc) [Internet]. [cited 2020 Feb 25]. Available from: https://www.medicines.org.uk/emc/product/5222/smpc#PREGNANCY - PubMed
  7. Kaplan YC, Richardson JL, Keskin-Arslan E, Erol-Coskun H, Kennedy D. Use of ondansetron during pregnancy and the risk of major congenital malformations: A systematic review and meta-analysis. Reprod Toxicol. 2019;86:1-13. - PubMed
  8. Huybrechts KF, Hernández-Díaz S, Straub L, et al. Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring. JAMA. 2018;18(320):2429-2437. - PubMed
  9. Zambelli-Weiner A, Via C, Yuen M, Weiner DJ, Kirby RS. First trimester ondansetron exposure and risk of structural birth defects. Reprod Toxicol Elmsford N. 2019;83:14-20. - PubMed
  10. Scholz T, Reinking B. Congenital Heart Disease. In: Gleason A, Juul SE, eds. Avery’s Diseases of the Newborn. 10th ed. Philadelphia, PA: Elsevier; 2018. - PubMed
  11. Affidavit of April Zambelli-Weiner, January 9, 2019 (Doc. No. 1272). Available from: https://www.govinfo.gov/content/pkg/USCOURTS-mad-1_15-md-02657/pdf/USCOURTS-mad-1_15-md-02657-16.pdf Accessed august 18, 2020 - PubMed
  12. Huybrechts KF, Hernandez-Diaz S, Straub L, et al. Intravenous ondansetron in pregnancy and risk of congenital malformations. JAMA. 2019;323:372-374. - PubMed
  13. Lemon LS, Bodnar LM, Garrard W, et al. Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defect. Int J Epidemiol. 2020;49:648-656. - PubMed
  14. Källén B. Lumping or Splitting? In: Drugs During Pregnancy: Methodological Aspects. 1st ed. Cham: Springer; 2016:89-91. - PubMed
  15. Huybrechts KF, Hernandez-Diaz S, Bateman BT. Contextualizing potential risks of medication in pregnancy for the newborn-the case of ondansetron. JAMA Pediatrics. 2020;174(8):747-748. - PubMed

Publication Types