Which antiemetic is contraindicated in pregnancy? A guide to medication safety

October 10, 2025 •

5 min read

Over 70% of pregnant women experience nausea and vomiting, but selecting the right treatment requires careful consideration. Understanding which antiemetic is contraindicated in pregnancy is crucial for ensuring the safety of both the mother and fetus, especially during the critical first trimester of development.

Quick Summary

Several antiemetics are considered less safe or have conflicting data regarding use during pregnancy, particularly in the first trimester. Safer first-line options often involve doxylamine and pyridoxine. Consulting a healthcare provider is essential to weigh the benefits and risks of any treatment.

Key Points

Not all antiemetics are safe: While many are used safely, some antiemetics carry significant risks or have conflicting data regarding their use during pregnancy.
Conflicting data on Ondansetron (Zofran): This potent antiemetic is not a first-line therapy due to conflicting studies on its association with birth defects like cleft palate and potential cardiac issues, especially in the first trimester.
Bismuth Subsalicylate (Pepto-Bismol) is contraindicated: Due to its salicylate component, similar to aspirin, Pepto-Bismol should be avoided, particularly in the second and third trimesters.
Doxylamine and Pyridoxine (Diclegis) are first-line: This combination is the only FDA-approved medication specifically for treating nausea and vomiting of pregnancy and is generally considered safe and effective.
Always consult a healthcare provider: Due to the complexities and potential risks, all pregnant individuals should speak with their doctor before taking any medication, even over-the-counter options.
Consider non-pharmacological options first: For mild symptoms, dietary changes, ginger, and acupressure are often recommended as initial treatment options before resorting to medication.

Understanding Antiemetic Safety in Pregnancy

Nausea and vomiting of pregnancy (NVP), commonly known as morning sickness, can range from a mild inconvenience to a severe, debilitating condition known as hyperemesis gravidarum. When lifestyle modifications and dietary changes are insufficient, pharmacologic intervention may be necessary. However, the safety of any medication during pregnancy is a primary concern. The concept of a medication being 'contraindicated' in pregnancy means the risks clearly outweigh any potential benefits, and the drug should not be used. For antiemetics, a handful of drugs have conflicting or limited safety data, particularly concerning first-trimester exposure, making them either truly contraindicated or not the preferred choice.

Ondansetron (Zofran) and Pregnancy

Ondansetron (brand name Zofran) is a potent antiemetic often prescribed off-label for severe morning sickness. Originally approved for chemotherapy-induced nausea, its use in pregnancy has come under scrutiny due to conflicting data on its safety.

Conflicting Study Results: Several studies have investigated the link between first-trimester ondansetron exposure and birth defects. Some epidemiological studies have shown a small increased risk of oral clefts (cleft lip/palate) and potentially cardiac malformations, prompting regulatory bodies like the European Medicines Agency to recommend avoiding its use in the first trimester. Other studies have yielded inconsistent results or did not find an increase in adverse pregnancy outcomes.
Cardiovascular Risks: Ondansetron also carries a "black box warning" for the risk of developing a potentially fatal abnormal heart rhythm, which poses a risk to the mother.
Second-Line Treatment: Due to this conflicting data and potential risks, ondansetron is generally reserved as a second-line treatment, used only when other, safer medications have failed. A comprehensive discussion with an obstetric care provider is essential to weigh the benefits against the potential risks before use.

Other Anti-Nausea Medications to Approach with Caution

Several other antiemetic and related drugs are considered less than ideal for routine use in pregnancy, particularly during early gestation:

Bismuth Subsalicylate (Pepto-Bismol): This over-the-counter medication should be avoided during pregnancy, especially in the second and third trimesters, because it contains a salicylate component similar to aspirin. Salicylates carry risks during pregnancy.
Phenothiazines (e.g., Promethazine, Prochlorperazine): Promethazine (Phenergan) is a phenothiazine-derivative antihistamine used for nausea, but it is not a preferred first-line option in pregnancy due to the availability of safer alternatives. Promethazine is classified as Pregnancy Category C, and its use late in pregnancy may cause sedation in the newborn. Similarly, prochlorperazine (Compazine) is a dopamine antagonist that, while sometimes used, is also Pregnancy Category C with potential extrapyramidal symptoms.
Methylprednisolone: A corticosteroid sometimes used for refractory hyperemesis gravidarum. However, its use before 10 weeks' gestation is associated with an increased risk of cleft lip, and its effectiveness data is mixed.

First-Line and Preferred Treatments

For most cases of NVP, especially in the first trimester, healthcare providers recommend interventions with established safety records:

Pyridoxine (Vitamin B6) and Doxylamine: This combination is considered the first-line pharmacologic treatment and is the only FDA-approved drug specifically for NVP. It is available as a prescription medication (Diclegis, Bonjesta) or can be purchased over-the-counter as separate components (Unisom SleepTabs for doxylamine).
Metoclopramide (Reglan): A dopamine antagonist, metoclopramide is often a second-line option for NVP. It has a relatively well-established safety profile in pregnancy, though providers should be cautious about high dosages or extended treatment (over 12 weeks) due to the risk of tardive dyskinesia.
Antihistamines: Certain first-generation antihistamines like dimenhydrinate (Dramamine) and diphenhydramine (Benadryl) are often used for NVP with known safety profiles, though they can cause drowsiness. Second-generation antihistamines like cetirizine (Zyrtec) or loratadine (Claritin) are preferred for allergies during pregnancy.

Comparison Table: Antiemetics in Pregnancy


Medication (Examples)	Class	Primary Use in Pregnancy	Safety Profile	Considerations
Doxylamine / Pyridoxine (Diclegis, Bonjesta)	Antihistamine / Vitamin B6	First-line NVP	FDA-approved and considered safe	Can cause drowsiness; available OTC in separate components
Ondansetron (Zofran)	Serotonin (5-HT3) Antagonist	Severe NVP (second-line)	Conflicting data on first-trimester risks (cleft lip/palate, cardiac defects)	Use with caution, especially in the first trimester; discuss with provider
Promethazine (Phenergan)	Phenothiazine / Antihistamine	NVP (second-line)	Generally compatible, but less preferred due to safer alternatives	May cause sedation in newborns if used near delivery
Metoclopramide (Reglan)	Dopamine Antagonist	NVP (second-line)	Generally considered safe, though side effects possible with long-term/high-dose use	Avoid high doses or prolonged use (>12 weeks) due to tardive dyskinesia risk
Bismuth Subsalicylate (Pepto-Bismol)	Salicylate derivative	Not Recommended	Should be avoided, especially in later pregnancy	Contains salicylate, which poses risks similar to aspirin
Methylprednisolone	Corticosteroid	Refractory Hyperemesis	Increased risk of cleft lip if used before 10 weeks	Only for extreme cases, requires careful risk-benefit analysis

The Crucial Role of Non-Pharmacological Interventions

Before resorting to medication, most healthcare providers will recommend trying lifestyle and dietary changes, especially for mild to moderate NVP. These can include:

Dietary Adjustments: Eating smaller, more frequent meals; avoiding greasy, fatty, or spicy foods; and consuming bland foods like crackers, bananas, and rice.
Ginger: Taking ginger in capsules, candies, or tea can help relieve nausea for some individuals.
Acupressure: Using acupressure wristbands may provide relief for some, though studies have yielded mixed results.
Managing Triggers: Avoiding smells or triggers that exacerbate nausea is important. This may involve using a fan while cooking or having someone else empty the trash.

Conclusion

When considering which antiemetic is contraindicated in pregnancy, it's clear that the decision is not always black and white. While some medications like bismuth subsalicylate are universally advised against, others like ondansetron carry conflicting evidence and potential risks, particularly in the critical first trimester. Therefore, these are typically reserved for more severe, refractory cases. The safest first-line pharmacological treatments, backed by strong evidence, include the combination of doxylamine and pyridoxine. Ultimately, the best course of action is to start with non-pharmacological interventions and always consult with a qualified healthcare provider before starting any medication. A doctor can help weigh the potential benefits of symptom relief against the potential risks to the pregnancy, ensuring a safe and healthy outcome for both mother and baby.

For more detailed guidelines, the American College of Obstetricians and Gynecologists (ACOG) provides valuable resources on managing morning sickness.

Sources

Frequently Asked Questions

Ondansetron is not considered a first-line treatment for nausea and vomiting of pregnancy due to conflicting study results regarding potential risks, including oral clefts and heart defects, especially with first-trimester use. It is reserved for severe cases where other, safer options have failed, and its use should be discussed carefully with a healthcare provider.

The combination of doxylamine and pyridoxine (Vitamin B6) is considered the safest and most effective first-line medication for morning sickness. It is the only FDA-approved drug for this purpose and is available by prescription (Diclegis) or as separate over-the-counter products.

No, you should avoid taking Pepto-Bismol during pregnancy. It contains bismuth subsalicylate, a component similar to aspirin, which is associated with risks during pregnancy, particularly in later stages.

Promethazine is not a preferred first-line choice because safer alternatives exist. While generally compatible, its use, especially near delivery, can cause sedation in the newborn. It is classified as Pregnancy Category C and should only be used after a thorough discussion of risks and benefits with a doctor.

Yes, several non-pharmacological options can help manage morning sickness. These include consuming ginger in various forms, eating smaller and more frequent meals, avoiding triggers like strong smells, and using acupressure wristbands.

If you have severe nausea and vomiting (hyperemesis gravidarum) and cannot keep down food or fluids, you may require more aggressive interventions. This can include hospitalization, receiving fluids intravenously to treat dehydration, and potentially needing prescription antiemetics that are carefully considered by your doctor.

Some over-the-counter sleep aids contain doxylamine, which is an ingredient in the FDA-approved combination therapy for morning sickness (Diclegis). However, it's important to consult with your doctor for proper dosing or to use the specific combination with Vitamin B6.