What is the safety of Diphenhydramine (Antihistamine) and Dimenhydrinate (Antiemetic) during pregnancy?

From the Guidelines

Diphenhydramine and dimenhydrinate can be used during pregnancy, but with caution, due to potential risks and side effects, and only when benefits outweigh the risks, as suggested by the most recent study 1. When considering the use of diphenhydramine and dimenhydrinate during pregnancy, it is essential to weigh the potential benefits against the risks.

• The medications can be used to treat nausea, allergies, or insomnia, but non-medication approaches should be tried first.
• Diphenhydramine can be taken at 25-50 mg every 4-6 hours (not exceeding 300 mg daily), while dimenhydrinate dosing is typically 50-100 mg every 4-6 hours (not exceeding 400 mg daily).
• These medications should be used at the lowest effective dose for the shortest duration possible, as first-generation antihistamines like these can cause drowsiness.
• Pregnant women should avoid driving or operating machinery after taking them, and if symptoms persist or worsen, they should consult their healthcare provider rather than increasing the dose or duration of use. According to the study 1, both first-generation and second-generation antihistamines have excellent safety records and do not show a significant increase in congenital malformations when used during the first trimester.
• However, caution is still advised for a few antihistamines, including diphenhydramine, due to a case-control study suggesting an association with cleft palate that has yet to be sufficiently refuted. The more recent study 1 suggests that H1-receptor antagonists, such as doxylamine, promethazine, and dimenhydrinate, are considered safe first-line pharmacologic antiemetic therapies, if needed, and doxylamine is US Food and Drug Administration–approved and recommended by ACOG for persistent NVP refractory to non-pharmacologic therapy.
• Therefore, the use of diphenhydramine and dimenhydrinate during pregnancy should be carefully considered, and alternative treatments, such as doxylamine, should be explored first.

From the FDA Drug Label

Pregnancy Category B Reproduction studies have been performed in rats at doses up to 20 times the human dose, and in rabbits at doses up to 25 times the human dose (on a mg/kg basis), and have revealed no evidence of impaired fertility or harm to the fetus due to dimenhydrinate. There are no adequate and well-controlled studies in pregnant women However, clinical studies in pregnant women have not indicated that dimenhydrinate increases the risk of abnormalities when administered in any trimester of pregnancy.

It would appear that the possibility of fetal harm is remote when the drug is used during pregnancy Nevertheless, because the studies in humans cannot rule out the possibility of harm, dimenhydrinate should be used during pregnancy only if clearly needed.

Diphenhydramine and Dimenhydrinate Safety in Pregnancy: The safety of dimenhydrinate in pregnancy is classified as Pregnancy Category B.

• There are no adequate and well-controlled studies in pregnant women.
• However, clinical studies have not indicated that dimenhydrinate increases the risk of abnormalities when administered in any trimester of pregnancy.
• The possibility of fetal harm is considered remote when the drug is used during pregnancy.
• Dimenhydrinate should be used during pregnancy only if clearly needed.
• There is no direct information about diphenhydramine in the provided drug label 2.

From the Research

Diphenhydramine and Dimenhydrinate Safety in Pregnancy

• There is limited information available on the safety of diphenhydramine and dimenhydrinate in pregnancy from the provided studies.
• According to 3, metoclopramide and antihistamines, such as diphenhydramine, are first-line options for nausea and vomiting in pregnancy.
• However, there is no specific information available on dimenhydrinate in the provided studies.
• Another study 4 compared cetirizine and diphenhydramine in the prevention of chemotherapy-related hypersensitivity reactions, but it does not provide information on the safety of diphenhydramine in pregnancy.
• A third study 5 is unrelated to the topic of diphenhydramine and dimenhydrinate safety in pregnancy, as it discusses the use of cattle to protect sheep from bluetongue infection.
• Overall, while there is some information available on the use of antihistamines like diphenhydramine in pregnancy, more research is needed to fully understand the safety of diphenhydramine and dimenhydrinate in pregnant women, as the provided studies do not directly address this topic 3, 4.