Letter to Editor: The controversy over the safety of ondansetron in pregnancy-why does it continue?

Motherisk Int J 2020;1:14

 

I read with great interest your article “The controversy over the safety of ondansetron in pregnancy-why does it continue?” (1).  I have recently thought the problem with widely conflicting safety evidence might be due to a dose-response relationship. In the US some OB/GYNs use a company that put ondansetron in an insulin pump to administer the drug continuously subcutaneous at high daily doses over weeks at a time. No reliable evidence exits to support the practice but it is highly profitable.

In your article you addressed dose but not duration and I think this also plays a potentially confounding role in the existing evidence.

Let me know if you have given this any thought and would be willing to share them.

Jim Reichmann
MPH student
Georgia State University
Atlanta, Ga USA

 

Response

We thank Mr. Reichmann for his interest in our article. Indeed, the dose-response of ondansetron- fetal malformation is an important facet in trying to explain why different studies arrived at different results. We have identified 3 such studies, 2 claiming a dose-response relation (2-3) whereas a third one did not (4). Dose intensity is a combination of the dose and the length of therapy, but the existing studies were not very clear about these 2 components We agree that this point should be better addressed in future studies.

 

References:

  1. Koren G, Kaplan YC. The controversy over the safety of ondansetron in pregnancy-why does it continue? Motherisk Int J 2020;1:10
  2. Lemon LS, Bodnar LM, Garrard W, Venkataramanan R, Platt RW, Marroquin OC, Caritis SN. Ondansetron use in the first trimester of pregnancy and the risk of neonatal ventricular septal defectS. Int J Epidemiol. 2019 Dec 20. pii: dyz255. doi: 10.1093/ije/dyz255.
  3. Zambelli-Weiner A, Via C, Yuen M, Weiner DJ, Kirby RS. First trimester ondansetron exposure and risk of structural birth defects.Reprod Toxicol. 2019 Jan;83:14-20.
  4. Huybrechts KF, Hernandez-Diaz S, Straub L, Gray KJ, Zhu Y, Mogun H, Bateman Intravenous Ondansetron in Pregnancy and Risk of Congenital Malformations. JAMA. 2019 Nov 15. doi: 10.1001/jama.2019.18587. [Epub ahead of print]