Commentary

Ondansetron: New and troubling data


 

Another recent development is the FDA’s announcement in May 2013 that an increased risk for serotonin syndrome in patients taking 5-HT3 receptor antagonists, including Zofran, has been identified as a "potential safety issue" in the FDA’s adverse event reporting database during the first quarter of 2013, and that the agency was investigating this possible association further.

Typically, serotonin syndrome occurs with the coadministration of two or more dugs that affect serotonin, usually selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase (MAO) inhibitors. Cases of possible or probable serotonin syndrome have been reported with the use of ondansetron, and because many pregnant women are treated with SSRIs during pregnancy, the potential for serotonin syndrome with an SSRI and ondansetron should be considered. Therefore, life-threatening serotonin syndrome – characterized by a triad of cognitive or behavioral changes, such as confusion or agitation; autonomic instability; and neuromuscular changes – should be kept in mind as another potential risk for pregnant women taking ondansetron.

Based on the available data, one therefore needs to be cautious with ondansetron, considering the potential risks of cardiac malformations and oral clefts with first-trimester exposure, which needs to be studied further, and the maternal risks of serotonin syndrome and cardiac arrhythmias.

For about 30 years, there was no drug labeled in the United States for morning sickness, after the unjustified removal of Bendectin (doxylamine-pyridoxine). Hence, ondansetron has been increasingly used off-label for this indication. But now that the FDA has approved Diclegis (doxylamine succinate and pyridoxine hydrochloride) for morning sickness – the doxylamine-pyridoxine combination that has been studied in hundreds of thousands of pregnant women and is a pregnancy category A drug – there is now a safer option for women with NVP. Therefore, ondansetron should be used cautiously in pregnant women, and only after drugs with a more established safety record – particularly doxylamine-pyridoxine – have been prescribed.

Dr. Koren is professor of pediatrics, pharmacology, pharmacy, medicine, and medical genetics at the University of Toronto. He heads the Research Leadership for Better Pharmacotherapy During Pregnancy and Lactation at the Hospital for Sick Children, Toronto, where he is director of the Motherisk Program. He also holds the Ivey Chair in Molecular Toxicology at the department of medicine, University of Western Ontario, London. Dr. Koren was a principal investigator in the U.S. study that resulted in the approval of Diclegis, marketed by Duchesnay USA, and he has served as a consultant to Duchesnay. E-mail him at obnews@frontlinemedcom.com.

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