Is Promethazine (Phenergan) safe during pregnancy?

From the Guidelines

Phenergan (promethazine) is considered compatible with pregnancy, including the first trimester, according to the most recent guidelines. The European Association for the Study of the Liver Clinical Practice Guidelines on the management of liver diseases in pregnancy, published in 2023 1, list promethazine as a compatible medication during pregnancy, including the first trimester. Additionally, the American Gastroenterological Association (AGA) clinical practice update on pregnancy-related gastrointestinal and liver disease, published in 2024 1, recommends a step-up approach for managing nausea and vomiting in pregnancy, with promethazine considered a viable option. However, it's essential to note that the use of promethazine during pregnancy should be carefully evaluated, and safer alternatives like vitamin B6, doxylamine, or other medications with better safety profiles should be considered first.

Some key points to consider when using Phenergan during pregnancy include:

• The medication should only be used under close medical supervision
• The potential benefits of using Phenergan should clearly outweigh the risks
• Safer alternatives should be considered first
• The medication's potential effects on the developing nervous system and possible risks of birth defects should be carefully evaluated

It's crucial to consult with a healthcare provider to determine the most appropriate treatment approach for individual cases of nausea and vomiting during pregnancy. They will weigh the specific situation, symptom severity, and gestational age to make an informed decision.

From the FDA Drug Label

Pregnancy Teratogenic Effects-Pregnancy Category C Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of promethazine HCl. These doses are from approximately 2.1 to 4. 2 times the maximum recommended total daily dose of promethazine for a 50-kg subject, depending upon the indication for which the drug is prescribed. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats There are no adequate and well-controlled studies of promethazine hydrochloride tablets in pregnant women. Promethazine hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

Promethazine is not entirely safe for pregnancy.

• The drug is classified as Pregnancy Category C, indicating that teratogenic effects have not been demonstrated in animal studies, but there are no adequate and well-controlled studies in pregnant women.
• Potential risks to the fetus exist, and the drug should only be used during pregnancy if the potential benefit justifies the potential risk.
• Fetal mortality has been observed in rats at high doses of promethazine.
• The effect of promethazine on later growth and development of the newborn is unknown 2.

From the Research

Phernergan Safety in Pregnancy

• There is limited information available on the safety of Phernergan (promethazine) in pregnancy, but some studies provide insight into the use of antiemetics during pregnancy 3, 4.
• A study published in 2021 found that ondansetron and metoclopramide were used as second-line antiemetics in women with nausea and vomiting in pregnancy, but the study did not progress beyond the pilot phase due to slow recruitment 3.
• Another study from 2013 identified promethazine as one of the most commonly used prescription medication components in the first trimester of pregnancy, but noted that there were insufficient data available to fully characterize the fetal risk 4.
• Other studies have compared the efficacy of ondansetron and metoclopramide in preventing nausea and vomiting, but these studies were not specifically focused on pregnancy 5, 6, 7.
• It is essential to consult with a healthcare provider to determine the safest and most effective treatment options for nausea and vomiting during pregnancy.

Antiemetic Use in Pregnancy

• Antiemetics such as ondansetron and metoclopramide are commonly used to treat nausea and vomiting in pregnancy, but their safety and efficacy must be carefully evaluated 3, 4.
• The choice of antiemetic medication during pregnancy should be based on the individual patient's needs and medical history, as well as the potential risks and benefits of each medication.
• Healthcare providers should be aware of the latest research and guidelines on antiemetic use in pregnancy to provide the best possible care for their patients.

Research Gaps

• There is a need for further research on the safety and efficacy of antiemetic medications, including Phernergan, in pregnancy 4.
• Studies should aim to fill the knowledge gaps in understanding fetal risk and provide evidence-based guidance for healthcare providers to make informed decisions about antiemetic use in pregnancy.