Ondansetron / Zofran Safety – The Science Debate

We continue to get calls and questions about Zofran, known generically as Ondansetron. There is a lot of misinformation out there. Following are quotes taken directly from published articles which we believe are reputable.

Is ondansetron safe for use during pregnancy?

Question: While I usually prescribe doxylamine-pyridoxine for morning sickness, some of my patients with severe nausea and vomiting of pregnancy (NVP) receive ondansetron in hospital. I have read some new precautions recommended by the US Food and Drug Administration (FDA). Is ondansetron safe to use during pregnancy?

Answer: During the past decade ondansetron has been increasingly used in the United States for NVP, owing to the lack of an FDA-approved drug for this condition. While fetal safety data for doxylamine-pyridoxine are based on more than a quarter of a million pregnancies, the fetal safety data for ondansetron are based on fewer than 200 births. Moreover, a recent case-control study suggested there was an increased risk of cleft palate associated with ondansetron. Recently, the FDA issued a warning about potentially serious QT prolongation and torsade de pointes associated with ondansetron use; the warning included a list of precautions and tests that must be followed. The drug is not labeled for use in NVP in either the United States or Canada. Based on the data available today, ondansetron use cannot be assumed to be safe during pregnancy.

Importantly, a recent large control study by the Slone Epidemiology Center in Boston, Mass, and the Centers for Disease Control and Prevention in Atlanta, Ga, detected a 2-fold increased risk of cleft palate associated with ondansetron taken for NVP in the first trimester of pregnancy (odds ratio 2.37 [95% CI 1.28 to 4.76]). Can Fam Physician. 2012 Oct; 58(10): 1092–1093.

Research Article: Off-Label Use of Ondansetron in Pregnancy in Western Australia

This study could not conclude that ondansetron is safe to use in pregnancy, given the small but potentially clinically important increases in several measures of outcome investigated. After adjusting for potential confounders, we found an increased risk of a major birth defect (1.2; 0.6–2.2), preterm birth (1.4; 0.7–2.5), shorter birth length (1.4; 1.0–1.8), and maternal urinary tract infection (1.6; 0.9–2.7).

BioMed Research International
Volume 2013 (2013), Article ID 909860, 8 pages

Toronto Star Article:
The controversial use of ondansetron in pregnant women has been the subject of several studies in the last decade, with conflicting results and scientists from Toronto to Denmark saying more research is needed.

A 2011 study suggested the drug doubles the chance of babies being born with cleft palate.

Concerns about ondansetron’s safety were briefly placated after a study regarding the risk of adverse outcomes was published in the Feb. 28, 2013, issue of the prestigious New England Journal of Medicine.

The researchers tracked more than 600,000 Danish births using national birth and prescription registries, and found the drug was not associated with a significant increased risk of spontaneous abortion, stillbirth or defect.

But the same day the study was presented at a drug safety conference in Montreal, another group of Danish doctors introduced contradictory findings based on the same national registries.

Those researchers, looking at nearly 900,000 births, detected a two-fold increase in heart defects in babies whose mothers received ondansetron. They have since expanded the study to include more births and arrived at the same conclusion; they recently submitted their results to an academic journal, the lead researcher told the Star.

Medical practice guidelines, including those approved by the Society of Obstetricians and Gynaecologists of Canada, urge caution, saying ondansetron should be used only after exhausting other medications that have been tested in pregnant women and are approved to treat morning sickness.

The main point is that the drug maker responsible for the label, Glaxo Smith Kline, promoted this drug for off label use in pregnancy, and was fined for doing so. GSK knew that this drug is being prescribed off label. Yet the drug has never been tested for safety in pregnant women, and is not approved for use by pregnant women for nausea and vomiting (NVP).

We continue to get calls from parents whose kids were born with these problems. We believe they are entitled to compensation and will continue to advocate for them. It is NOT the Mom’s fault!

Zoll & Kranz, LLC can be reached toll-free at (888)841-9623 if you have any questions.