Pregnancy & breastfeeding
Ondansetron (Zofran) in pregnancy and breastfeeding
5-HT3 receptor antagonist (antiemetic) · Nausea and vomiting; used off-label for nausea and vomiting of pregnancy
Pregnancy
Reasonable second-line optionLarge cohort studies do not show an increase in major birth defects overall, miscarriage or stillbirth with ondansetron. One large U.S. study found a small increase in oral clefts with first-trimester use, about 3 extra cases per 10,000 exposed pregnancies. ACOG places it after first-line doxylamine-pyridoxine when nausea and vomiting are not controlled.[1, 2]
- First trimester
- Major malformations overall were not increased in Danish, U.S. Medicaid and multinational cohorts. Oral clefts: adjusted RR 1.24 (absolute increase 2.7 per 10,000) in the Medicaid cohort.[3, 1, 4]
- Later pregnancy
- No signal for preterm birth, low birth weight or stillbirth in the Danish cohort.[3]
Breastfeeding
Compatible with breastfeedingCommonly given around cesarean delivery without effects on breastfeeding or reported infant harm. Amounts in milk are small compared with doses given directly to infants, and ondansetron is labeled for infants from 1 month of age.
Written for clinicians. If you are pregnant or breastfeeding, talk to your clinician before you start, stop or change any medicine.
Ask EvidencePulse about ondansetron
Get a cited answer from the newest studies, for your patient's trimester or your question.
What the human data show
Ondansetron is one of the most studied antiemetics in pregnancy. The questions have been oral clefts and cardiac defects after first-trimester use.
Propensity-matched national cohort · Denmark · 2013
608,385 pregnancies; 1,233 to 1,915 exposed women per outcome, matched 1:4 to unexposed women.
No increase in miscarriage, stillbirth, any major birth defect, preterm birth or small-for-gestational-age infants.[3]
Major birth defects 2.9% vs 2.9% (POR 1.12, 95% CI 0.69-1.82). Stillbirth 0.3% vs 0.4% (HR 0.42, 0.10-1.73).
Medicaid cohort with propensity score stratification · United States · 2018
1,816,414 pregnancies; 88,467 (4.9%) exposed in the first trimester.
No increase in cardiac malformations or malformations overall; a small increase in oral clefts.[1]
Cardiac malformations adjusted RR 0.99 (0.93-1.06). Oral clefts 14.0 vs 11.1 per 10,000; adjusted RR 1.24 (1.03-1.48), risk difference 2.7 per 10,000 (0.2-5.2).
Multinational cohort vs other antiemetics · Canada, US, UK · 2021
456,963 pregnancies; ondansetron compared with other antiemetics to limit confounding by nausea severity.
No increase in fetal death, miscarriage, stillbirth or major malformations.[4]
Fetal death aHR 0.91 (0.67-1.23). Major malformations OR 1.06 (0.91-1.22).
Meta-analysis of 12 studies · International · 2020
Cohort and case-control studies of first-trimester exposure.
Small pooled increases in ventricular septal defects and oral clefts; no increase in major malformations or cardiac malformations overall.[5]
VSD OR 1.11 (1.00-1.23). Oral clefts OR 1.22 (1.00-1.49).
For scale: about 3 in 100 U.S. births have a major birth defect, and oral clefts affect roughly 1 in 1,000. Observational studies cannot fully separate the drug from the severity of nausea it treats.
The FDA label, summarized
Current-format labels say published studies on ondansetron and major birth defects are inconsistent and have important limitations (uncertain whether filled prescriptions were taken, other medicines, recall bias), so they do not support firm conclusions either way. Postmarketing data have not identified a drug-associated risk of miscarriage or maternal harm, and animal studies at multiples of the human dose showed no fetal harm.
Ondansetron is not FDA-approved for nausea and vomiting of pregnancy; that use is off-label. Older generic labels still carry the retired Category B wording.
- Label
- Ondansetron Hydrochloride (Chartwell RX, LLC.), effective Jan 2, 2026 · Full label on DailyMed
- Former FDA letter category
- B (the FDA retired letter categories in 2015; labels now describe the data instead)
LactMed: infant exposure and effects
LactMed considers ondansetron acceptable during breastfeeding with no special precautions. Most data come from intravenous use around cesarean delivery; longer outpatient use has been studied less.
Milk levels
In a pharmacokinetic study of 78 women given 4 to 8 mg IV after delivery, the estimated relative infant dose was about 3 to 4% of the weight-adjusted maternal dose, under 2% of a standard infant dose.
Effects in breastfed infants
No adverse effects were reported in breastfed infants in that study or after use around cesarean section.
Effects on milk supply
Ondansetron around cesarean delivery did not delay the first breastfeed or milk production in controlled comparisons.
- Source
- LactMed® record “Ondansetron”, revised Jun 15, 2025 · Open the record
Alternatives to consider
- Doxylamine-pyridoxine
First-line pharmacologic treatment for nausea and vomiting of pregnancy in ACOG guidance, with decades of reassuring safety data.[2]
- Metoclopramide
Large cohorts are reassuring for birth defects; limit duration because of tardive dyskinesia risk.
- Promethazine
Antihistamine antiemetic often used when first-line therapy fails; sedation is common.
Non-drug measures (small frequent meals, ginger) and the patient's own weighting of symptoms come first. Hyperemesis gravidarum may need IV fluids and thiamine as well as antiemetics.
2MM+
New pregnancy and lactation studies, the day they publish
2MM+ members read every 2 Minute Medicine summary in full, with unlimited EvidencePulse questions and the NPI Lookup member tools.
Questions clinicians ask
Is ondansetron safe in the first trimester?
The largest studies show no increase in major birth defects overall, miscarriage or stillbirth. A U.S. Medicaid study found a small increase in oral clefts, about 3 extra cases per 10,000 exposed pregnancies. For most patients the absolute risk is small; many clinicians try doxylamine-pyridoxine first and use ondansetron when symptoms persist.[1, 4]
Does ondansetron cause heart defects?
The largest cohort, with 88,467 exposed pregnancies, found no increase in cardiac malformations after adjustment (RR 0.99). A 2020 meta-analysis found a small pooled increase in ventricular septal defects (OR 1.11) that is uncertain.[1, 5]
What was Zofran's pregnancy category?
Ondansetron was Category B before the FDA retired letter categories in 2015. Labels now describe the human and animal data instead of a letter.
Can I take ondansetron while breastfeeding?
Yes. Amounts in milk are small, no infant harm has been reported, and the drug is used directly in infants from 1 month of age.
References
- Huybrechts KF, Hernández-Díaz S, Straub L, et al. Association of maternal first-trimester ondansetron use with cardiac malformations and oral clefts in offspring. JAMA. 2018;320(23):2429-2437. PubMed · DOI
- ACOG Practice Bulletin No. 189: Nausea and vomiting of pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed · DOI
- Pasternak B, Svanström H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med. 2013;368(9):814-823. PubMed · DOI
- Dormuth CR, Winquist B, Fisher A, et al. Comparison of pregnancy outcomes of patients treated with ondansetron vs alternative antiemetic medications in a multinational, population-based cohort. JAMA Netw Open. 2021;4(4):e215329. PubMed · DOI
- Picot C, Berard A, Grenet G, et al. Risk of malformation after ondansetron in pregnancy: an updated systematic review and meta-analysis. Birth Defects Res. 2020;112(13):996-1013. PubMed · DOI
The free Daily Brief
Doctor-written summaries of the day's most important studies, in your inbox every morning.
Your subscription opens securely in a new tab. No spam.
Get the app