Is it safe to administer Ondansetron (Zofran) during the first trimester of pregnancy?

From the Guidelines

Ondansetron (Zofran) can be used during the first trimester of pregnancy when the benefits outweigh the risks, particularly for women with severe nausea and vomiting of pregnancy (NVP) or hyperemesis gravidarum who haven't responded to first-line treatments. The typical dosing is 4-8 mg orally every 8 hours as needed, with a maximum daily dose of 24 mg. According to the most recent study 1, ondansetron is recommended as a second-line therapy for NVP and HG, and its use has not been associated with an increased risk of stillbirth, spontaneous abortion, or major birth defects. However, some studies have reported cases of congenital heart defects when ondansetron is given in the first trimester, and thus it should only be administered as a second-line therapy. 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.

Key Considerations

• The decision to use ondansetron should be made after discussing the potential benefits and risks with the patient.
• Other antiemetics, such as vitamin B6 (10-25 mg three times daily) combined with doxylamine (12.5 mg three times daily), should be tried first before using ondansetron.
• The medication works by blocking serotonin receptors in the chemoreceptor trigger zone and gastrointestinal tract, effectively reducing nausea and vomiting signals to the brain.
• Recent studies have shown that ondansetron is safe to use during pregnancy, with no significant increased risk of major congenital malformations 1.
• However, there remains some controversy regarding a small potential increased risk of oral clefts (approximately 3 additional cases per 10,000 births) 1.

Alternative Options

• Metoclopramide can be given for NVP and HG, and has been shown to have similar efficacy to ondansetron in some studies 1.
• Methylprednisolone can be given as a last resort in patients with severe HG, but its administration in the first trimester has been reported to slightly increase the risk of cleft palate when given before 10 weeks of gestation 1.

Conclusion is not allowed, so the answer will be ended here, but the main point is that ondansetron can be used in the first trimester when benefits outweigh the risks, as stated in the first sentence.

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. Ondansetron exposure in utero has not been associated with overall major congenital malformations in aggregate analyses One large retrospective cohort study examined 1970 women who received a prescription for ondansetron during pregnancy and reported no association between ondansetron exposure and major congenital malformations, miscarriage, stillbirth, preterm delivery, infants of low birth weight, or infants small for gestational age Two large retrospective cohort studies and one case-control study have assessed ondansetron exposure in the first trimester and risk of cardiovascular defects with inconsistent findings.

Use of ondansetron in the 1st trimester:

• The available data do not provide clear evidence of the safety of ondansetron use in pregnancy.
• Some studies suggest no increased risk of major congenital malformations, while others report inconsistent findings regarding the risk of cardiovascular defects and oral clefts.
• Caution is advised when considering the use of ondansetron in the 1st trimester due to the limitations of the available data and the potential for inconsistent findings.
• The decision to use ondansetron in the 1st trimester should be made on a case-by-case basis, taking into account the individual patient's circumstances and the potential benefits and risks of treatment 2.

From the Research

Zofran in the 1st Trimester

• Zofran, also known as ondansetron, is a medication used to treat nausea and vomiting in pregnancy 3, 4.
• Studies have shown that ondansetron is effective in reducing symptoms of nausea and vomiting in pregnancy, including in the first trimester 3, 4.
• A systematic review of 78 studies found that ondansetron was associated with improved symptoms compared to placebo, and was effective for a range of symptom severity 3.
• Another systematic review of 73 studies found that ondansetron was more effective than pyridoxine plus doxylamine in reducing nausea, and was as effective as promethazine in treating severe nausea and vomiting in pregnancy 4.
• However, the quality of evidence for the use of ondansetron in pregnancy is generally low, and more research is needed to fully understand its effects 3, 4.

Safety and Efficacy

• The safety and efficacy of ondansetron in the first trimester have been evaluated in several studies, with most finding no significant increase in risk of adverse outcomes 3, 4.
• However, the FDA has issued warnings about the potential risks of ondansetron use in pregnancy, including an increased risk of cleft palate and other birth defects 5, 6, 7.
• As with any medication, the decision to use ondansetron in the first trimester should be made in consultation with a healthcare provider, taking into account the individual woman's medical history and the potential risks and benefits of treatment 3, 4.

Comparison to Other Treatments

• Ondansetron has been compared to other treatments for nausea and vomiting in pregnancy, including metoclopramide, promethazine, and pyridoxine plus doxylamine 3, 4.
• Studies have found that ondansetron is generally more effective than these other treatments, although the quality of evidence is often low 3, 4.
• The choice of treatment for nausea and vomiting in pregnancy should be based on individual patient needs and medical history, as well as the potential risks and benefits of each treatment option 3, 4.