Is Phenergan (Promethazine) 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 doxylamine and pyridoxine as first-line pharmacologic treatment of hyperemesis gravidarum, but also notes that promethazine can be used as a second-line therapy. However, it's essential to weigh the potential benefits against the risks, and safer alternatives like vitamin B6 (pyridoxine), doxylamine, or ginger are typically tried first. If prescribed during pregnancy, it's usually at the lowest effective dose for the shortest duration possible. The main concerns with Phenergan during pregnancy include potential risks of birth defects when used in early pregnancy and possible effects on fetal development.

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

• The medication should be used at the lowest effective dose for the shortest duration possible
• Safer alternatives like vitamin B6 (pyridoxine), doxylamine, or ginger should be tried first
• The potential benefits of using Phenergan should be weighed against the risks
• The medication can cause respiratory depression in newborns when used near delivery
• Pregnant women should discuss the specific risks and benefits with their healthcare provider, as individual circumstances vary and medical guidance is essential for making appropriate treatment decisions.

It's also important to note that the AGA clinical practice update on pregnancy-related gastrointestinal and liver disease recommends a step-up approach for patients who do not respond to first-line therapy, and promethazine can be used as a second-line therapy 1. Furthermore, the Motherisk Pregnancy-Unique Quantification of Emesis score can be used to quantify the severity of vomiting during pregnancy, and diet and lifestyle modification are the initial steps in managing these symptoms in pregnancy 1.

From the FDA Drug Label

Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of promethazine HCl. 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

Phenergan (promethazine) use in pregnancy is not recommended without careful consideration of the potential risks and benefits.

• The drug label indicates that there are no adequate and well-controlled studies in pregnant women.
• Promethazine hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 2.
• It is essential to weigh the potential benefits against the potential risks to the fetus before using Phenergan in pregnancy.

From the Research

Phenergan Safety in Pregnancy

• Phenergan, also known as promethazine, is an antihistamine that can be used to treat nausea and vomiting in pregnancy 3.
• A study comparing pyridoxine-metoclopramide combination therapy to prochlorperazine and promethazine monotherapies found that combination therapy was superior to monotherapy in treating nausea and vomiting in pregnancy 4.
• Another study found that metoclopramide and promethazine were equally effective in reducing the incidence of nausea and vomiting after pethidine administration in labor, but metoclopramide had a better analgesic effect 5.
• However, a study investigating the effect of metoclopramide on the fetus found that women exposed to metoclopramide had a higher rate of premature births compared to the control group, although the rates of major malformations did not differ significantly 6.

Treatment Options for Nausea and Vomiting in Pregnancy

• Ginger, vitamin B6, antihistamines, and metoclopramide are associated with improved symptoms of nausea and vomiting in pregnancy compared to placebo 3.
• Pyridoxine-doxylamine, promethazine, and metoclopramide are associated with greater benefit than placebo for moderate symptoms of nausea and vomiting in pregnancy 3.
• Ondansetron is associated with improvement in symptoms for a range of severity, while corticosteroids may be associated with benefit in severe cases 3.

Safety Considerations

• The quality of evidence for the safety and efficacy of treatments for nausea and vomiting in pregnancy is generally low 3.
• Metoclopramide use during the first trimester of pregnancy does not appear to be associated with an increased risk of malformations, spontaneous abortions, or decreased birth weight, but larger studies are needed to confirm these observations 6.