Ondansetron in Pregnancy: Is It Safe?

Ondansetron (Zofran) is one of the most effective anti-sickness medications available - it was originally developed for chemotherapy patients. When first-line pregnancy anti-sickness drugs haven't worked, ondansetron is often the next step. But with its power comes questions about safety. Here's an honest, evidence-based look at ondansetron in pregnancy.

Table of Contents

1. What Is Ondansetron?
2. When It's Prescribed in Pregnancy
3. Is It Safe? The Evidence
4. The Cleft Palate Question
5. Dosage
6. Side Effects
7. Weighing Up the Decision
8. FAQ

What Is Ondansetron?

Key Facts

• Drug class: 5-HT3 receptor antagonist
• Brand name: Zofran
• Availability: Prescription only
• Forms: Tablets (4mg, 8mg), dissolvable tablets (ondispers), IV (hospital), suppositories
• Effectiveness: Often highly effective when antihistamines haven't worked

When It's Prescribed in Pregnancy

First-Line Hasn't Worked

• Cyclizine, promethazine, or prochlorperazine haven't controlled symptoms
• You're still vomiting despite first-line medication
• Your GP is escalating treatment

Hyperemesis Gravidarum

• You have HG and need stronger medication
• You've been admitted to hospital
• You need IV medication (ondansetron can be given IV)

Combination Therapy

• Ondansetron is often combined with other medications (e.g., cyclizine) for HG
• Combination therapy is more effective than any single drug

Why Not First-Line?

Ondansetron is effective but has slightly less pregnancy safety data than the older antihistamine medications. For this reason, GPs usually try antihistamines first and reserve ondansetron for when they don't work. However, for severe HG, ondansetron may be prescribed from the start.

Is It Safe? The Evidence

The Reassuring Evidence

• Multiple large studies involving hundreds of thousands of women have found no increased risk of major birth defects with ondansetron use in pregnancy.
• No evidence of increased miscarriage risk.
• No evidence of increased risk of preterm birth or low birth weight.
• The vast majority of studies show ondansetron is safe in pregnancy.

The Concerns

• A few smaller studies have suggested a possible very small increased risk of cleft palate (see below).
• Some studies have found a slightly increased risk of cardiac defects, but other large studies have not confirmed this.
• The overall risk, even in studies that found an association, is very small.

The Consensus

Major medical bodies, including the UK's RCOG and the American College of Obstetricians and Gynecologists (ACOG), consider ondansetron safe to use in pregnancy when clinically indicated. The benefits of treating severe nausea and vomiting (preventing dehydration, malnutrition, and hospitalisation) outweigh the very small potential risks.

The Cleft Palate Question

What the Studies Found

• Some studies (notably a 2013 Danish study) found a very small increased risk of cleft palate in babies whose mothers took ondansetron in the first trimester.
• The absolute risk is very low: cleft palate occurs in about 1 in 1,000 babies normally. The studies suggesting an increase put the risk at about 1 in 900-1,000 - a tiny increase if it exists at all.
• Other large studies have found no increased risk of cleft palate with ondansetron.

The Interpretation

• The evidence is mixed and inconsistent
• Any increased risk, if it exists, is very small
• The risk must be weighed against the risks of untreated severe vomiting (dehydration, malnutrition, hospitalisation, which can harm both mother and baby)

What This Means for You

• If your GP recommends ondansetron, it's because they believe the benefits outweigh the very small potential risk
• You can ask about the cleft palate studies if you're concerned
• You can request a detailed anomaly scan at 18-20 weeks (standard on the NHS) which will check for cleft palate
• Untreated HG is more dangerous than the medication

Dosage

Starting Dose

• 4mg twice daily initially
• Increase if needed
• Take the first dose in the morning

Forms Available

• Standard tablets: Swallowed whole
• Ondispers (dissolvable): Dissolve on the tongue - ideal if you can't keep tablets down
• IV: In hospital for severe HG
• Suppositories: If you can't keep anything oral down

How to Take

• Can be taken with or without food
• Dissolvable tablets: Place on the tongue and let them dissolve - don't swallow whole
• Regular timing: Take at consistent intervals (set alarms)
• Don't stop suddenly if you feel better

If You Vomit After Taking It

• Dissolvable tablets are less likely to be vomited as they absorb through the tongue
• Standard tablets: If you vomit within 30 minutes, take another dose
• Consistently vomiting doses: Ask about IV or suppository options

Side Effects

Less Common Side Effects

• Diarrhoea
• Dry mouth
• Blurred vision
• Serotonin syndrome (rare, more likely if taking other serotonergic drugs)

Managing Side Effects

• Headache: Paracetamol is safe in pregnancy; stay hydrated
• Constipation: This is a significant issue with ondansetron. Drink plenty of water, eat high-fibre foods, and ask your GP about pregnancy-safe laxatives.
• Drowsiness: Time doses to allow rest

When to Contact Your GP

• Severe headache that doesn't respond to paracetamol
• Severe constipation
• Allergic reaction (rash, swelling, breathing difficulty)
• Symptoms not improving after 72 hours
• Any unusual symptoms

Weighing Up the Decision

The Balance

Risks of taking ondansetron:

• Very small potential risk of cleft palate (evidence mixed)
• Possible side effects (headache, constipation)

Risks of not treating severe nausea/vomiting:

• Dehydration (can require hospital admission)
• Weight loss and malnutrition
• Electrolyte imbalances (can be dangerous)
• Impact on mental health
• Inability to work or care for family

For most women with severe symptoms, the risks of not treating are greater than the very small risks of the medication.

If You're Still Unsure

• Ask for a second opinion (a different GP or a specialist)
• Contact Pregnancy Sickness Support for advice
• Consider a private consultation with an obstetrician
• Don't refuse treatment without understanding the full picture

Frequently Asked Questions

The overall evidence suggests ondansetron is safe in pregnancy. Multiple large studies have found no increased risk of major birth defects. A few studies have suggested a very small increased risk of cleft palate, but other studies have not confirmed this. The consensus is that benefits outweigh risks when clinically indicated.

Does ondansetron cause birth defects?

The majority of studies have found no increased risk of birth defects with ondansetron. A small number of studies have suggested a very slight increase in cleft palate risk, but the absolute risk remains very low (about 1 in 900-1,000). Your 20-week anomaly scan will check for this.

When is ondansetron prescribed in pregnancy?

Ondansetron is usually prescribed when first-line anti-sickness medications (cyclizine, promethazine, prochlorperazine) haven't worked. It may be prescribed from the start for severe hyperemesis gravidarum. It can be given alone or in combination with other medications.

Will ondansetron make me constipated?

Yes, constipation is a common side effect of ondansetron. It slows the digestive tract. Drink plenty of water, eat high-fibre foods, and ask your GP about pregnancy-safe laxatives if needed.

Can I take ondansetron throughout my pregnancy?

Most women only need anti-sickness medication for the first trimester. However, some women with HG need medication throughout pregnancy. Your GP will review your medication regularly and reduce it when appropriate.

Further reading:

• NHS — Common pregnancy symptoms

This article is for informational purposes only and does not constitute medical advice. Always consult your GP or midwife with any concerns about your pregnancy.

Last reviewed: June 2026

Related articles:

• Cyclizine in Pregnancy
• Anti-Sickness Medication in Pregnancy
• HG Treatment Options in UK
• Hyperemesis Gravidarum Guide