Is it safe to administer ondansetron (Zofran) to a female at 8 weeks gestation?

From the Guidelines

Ondansetron (Zofran) can be administered to a female at 8 weeks gestation, but only after weighing the benefits against potential risks and under the guidance of a healthcare provider. The American College of Obstetricians and Gynecologists (ACOG) recommends using ondansetron on a case-by-case basis in patients with persistent symptoms before 10 weeks of pregnancy 1. While some studies have reported a small increased risk of congenital heart defects and cleft palate when ondansetron is given in the first trimester, the absolute risk is still relatively low, with an increase from 11 cases per 10,000 births to 14 cases per 10,000 births 1.

Key considerations for the use of ondansetron in pregnancy include:

• The severity of nausea and vomiting
• The presence of other underlying medical conditions
• The potential risks and benefits of treatment
• Alternative treatment options, such as non-medication approaches or other anti-emetic medications

The European Association for the Study of the Liver Clinical Practice Guidelines recommend doxylamine and pyridoxine as first-line pharmacologic treatment of hyperemesis gravidarum, with metoclopramide and ondansetron as second-line therapies 1. The decision to use ondansetron should be made on a case-by-case basis, taking into account the individual patient's circumstances and the potential risks and benefits of treatment.

In terms of dosage, the typical dose of ondansetron is 4-8 mg orally every 8 hours as needed. However, the dosage and duration of treatment should be determined by a healthcare provider, based on the individual patient's needs and medical history. It is essential for the pregnant woman to discuss her specific situation with her obstetrician or healthcare provider rather than taking Zofran without medical supervision.

From the FDA Drug Label

Available data on ondansetron use in pregnant women from several published epidemiological studies preclude an assessment of a drug-associated risk of adverse fetal outcomes due to important methodological limitations, including the uncertainty of whether women who filled a prescription actually took the medication, the concomitant use of other medications or treatments, recall bias, and other unadjusted confounders. Reproductive studies in rats and rabbits did not show evidence of harm to the fetus when ondansetron was administered during organogenesis at approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, based on body surface area (BSA), respectively

The administration of ondansetron to a female at 8 weeks gestation may be considered. However, due to the inconsistent findings and methodological limitations of the available studies, caution is advised. The decision to administer ondansetron should be made on a case-by-case basis, taking into account the individual patient's situation and the potential benefits and risks of the medication 2. Key considerations include:

• The available data do not provide clear evidence of a drug-associated risk of adverse fetal outcomes
• Reproductive studies in animals have not shown evidence of harm to the fetus
• The patient's individual situation and the potential benefits and risks of the medication should be carefully evaluated.

From the Research

Safety of Ondansetron Administration

• The administration of ondansetron to a female at 8 weeks gestation has been studied in several research papers 3, 4, 5.
• According to a study published in 2017, there are large reassuring studies on the fetal safety of ondansetron, but they are contrasted by some studies claiming increased fetal risk 3.
• A 2014 study states that ondansetron is an option for pharmacologic management of nausea and vomiting in pregnancy, along with other medications such as antihistamines and metoclopramide 4.
• A systematic review published in 2016 found that ondansetron was associated with improved symptoms compared to placebo for moderate symptoms of nausea and vomiting in pregnancy 5.
• However, the same review notes that the quality of evidence was low, and more studies are needed to quantify fetal risks 5.
• Another study published in 1998 suggests that antiemetics, including ondansetron, are not usually prescribed before 12 weeks gestation, except for women with hyperemesis, due to concerns about teratogenic effects 6.
• A 2007 study reviews the safety of different classes of antiemetics used to treat nausea and vomiting in pregnancy and discusses that some have better safety profiles than others, but most appear to be safe to use in pregnancy 7.