Pregnancy and Nausea: Which medications are safe and effective to use?

Up to 80% of women have nausea during pregnancy, most often in the first trimester. For most, it is unpleasant but manageable. For some, it is severe enough to affect eating, drinking, work and daily life. Early, effective and safe treatment matters for both the mother and the baby. Because the first trimester is when the baby's organs are forming, many women and their healthcare providers are understandably cautious about medications. This article explains which treatments are recommended, what the evidence says about their safety and how your genes can affect some anti-nausea medications.

When is nausea in pregnancy serious?

Nausea and vomiting usually start around 6 weeks of pregnancy and improve by 16 to 20 weeks. About 1 in 100 women develop a severe form called hyperemesis gravidarum, with constant vomiting, weight loss and dehydration. It can be distressing and isolating and needs medical care. Contact your healthcare provider right away if you cannot keep fluids down, notice very dark urine, feel dizzy or are losing weight.

What are the first treatments for nausea in pregnancy?

The Society of Obstetricians and Gynaecologists of Canada (SOGC) recommends starting with simple steps and the medications with the most safety data:

• Diet and lifestyle. Eat small, frequent meals, avoid an empty stomach and avoid smells or foods that trigger nausea. Switching from a prenatal vitamin to folic acid alone for a while can help some women.
• Ginger and vitamin B6 can help mild symptoms.
• Doxylamine-pyridoxine (Diclectin) is the first-line medication in Canada. It combines an antihistamine with vitamin B6 and has been used by millions of pregnant women, with a strong safety record.
• Other options, if needed, include antihistamines such as dimenhydrinate, and metoclopramide. Your healthcare provider will choose based on your symptoms.

Cannabis products, including nabilone (a synthetic form of THC), are not recommended for nausea in pregnancy.

Are antihistamines safe for nausea in pregnancy?

Some antihistamines help with nausea and are among the most studied medications in pregnancy. Doxylamine (in Diclectin) and dimenhydrinate (Gravol) are commonly used for morning sickness. They can cause drowsiness, so avoid driving if they make you sleepy. Non-drowsy allergy antihistamines, such as cetirizine (Reactine), do not help with nausea. Learn more about how antihistamines differ and how your genes affect them. Check with your healthcare provider or pharmacist before taking any antihistamine during pregnancy.

Is ondansetron safe during pregnancy?

Ondansetron (Zofran) is mainly used to prevent nausea from chemotherapy and surgery, but it has also been used for nausea in pregnancy. The largest study, of 1.8 million pregnancies in the United States, found that ondansetron in the first trimester was not linked to more heart defects or more birth defects overall. It was linked to a small increase in the risk of oral clefts (cleft lip or palate): about 14 per 10,000 births with ondansetron, compared with about 11 per 10,000 without it, or roughly 3 extra cases per 10,000 births.

Based on this signal, Health Canada advises that ondansetron is not recommended for use during pregnancy. If your symptoms are severe and other treatments have not worked, talk to your healthcare provider about the benefits and risks of each option.

Other medications in the same class, such as granisetron, palonosetron and dolasetron, are used mainly for chemotherapy and have much less information about their use in pregnancy.

How does CYP2D6 affect anti-nausea medications?

Ondansetron and tropisetron are broken down by the CYP2D6 liver enzyme. According to the Clinical Pharmacogenetics Implementation Consortium (CPIC), people who are CYP2D6 ultrarapid metabolizers clear these medications quickly and may get less relief from them. CPIC suggests considering an alternative that is not mainly broken down by CYP2D6, such as granisetron. CYP2D6 plays a smaller role for palonosetron and dolasetron. For poor and intermediate metabolizers, CPIC recommends no change.

Some antidepressants and other medications strongly block CYP2D6 and can change how these medications are processed, so your full medication list should be reviewed together with your genetic results.

Which medications should be avoided while breastfeeding?

Codeine and tramadol are turned into stronger opioids by CYP2D6. In mothers who are CYP2D6 ultrarapid metabolizers, much more of the active opioid can pass into breast milk, and infant deaths have been reported. Health Canada and the US Food and Drug Administration advise against using codeine and tramadol while breastfeeding. Ask your healthcare provider about safer pain relief options after delivery.

What about depression during and after pregnancy?

Many women experience depression or anxiety during pregnancy or after the baby is born. Treatment is important for both mother and baby, and it may include psychotherapy and, when needed, antidepressants. Many antidepressants are affected by CYP2D6 and CYP2C19, so genetic testing can help guide the choice and dose.

How can a pharmacogenetic test help?

A Pillcheck test uses a simple cheek swab to show how your genes, including CYP2D6, CYP2C19 and CYP3A4, affect anti-nausea medications, pain relievers, antidepressants and many other medications used during pregnancy, after delivery and beyond. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. A Pillcheck pharmacist reviews your results together with all your medications and gives recommendations to discuss with your healthcare provider. Your results last a lifetime, so testing before or early in pregnancy can guide decisions at every stage.

Summary

• Up to 80% of pregnant women have nausea. Severe, persistent vomiting (hyperemesis gravidarum) needs medical care.
• Diet changes, ginger, vitamin B6 and doxylamine-pyridoxine (Diclectin) are the first-line treatments in Canada.
• Ondansetron was not linked to heart defects or birth defects overall but was linked to a small increase in oral clefts. Health Canada does not recommend it in pregnancy.
• CYP2D6 ultrarapid metabolizers may get less relief from ondansetron.
• Codeine and tramadol should be avoided while breastfeeding, especially in CYP2D6 ultrarapid metabolizers.

Frequently asked questions

What is the safest medication for nausea in pregnancy?

In Canada, doxylamine-pyridoxine (Diclectin) is the first-line medication, with a long safety record. Talk to your healthcare provider before taking any medication in pregnancy.

I took ondansetron early in pregnancy. Should I be worried?

The overall risk is small. In the largest study, ondansetron was linked to about 3 extra cases of oral clefts per 10,000 births and no increase in heart defects or birth defects overall. Talk to your healthcare provider, who can discuss your situation.

Can a genetic test tell me which anti-nausea medication will work?

It can show whether you are likely to clear ondansetron quickly because of your CYP2D6 genes, which can help your healthcare provider choose an alternative. It cannot predict every response.

Is it safe to take a pharmacogenetic test during pregnancy?

Yes. The test uses a cheek swab and poses no risk to you or your baby.

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.

Moore C, Bourque MS, Halman A, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of 5-HT3 Receptor Antagonists: 2026 Update. Clin Pharmacol Ther. 2026;120(2):387-393.

Bell GC, Caudle KE, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and use of ondansetron and tropisetron. Clin Pharmacol Ther. 2017;102(2):213-218.

Campbell K, Rowe H, Azzam H, Lane CA. The Management of Nausea and Vomiting of Pregnancy. J Obstet Gynaecol Can. 2016;38(12):1127-1137.

Health Canada. Health Product InfoWatch, November 2020: ondansetron.