Is diphenhydramine (Benadryl) safe to use during pregnancy?

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Last updated: June 7, 2025View editorial policy

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From the Guidelines

Diphenhydramine is generally considered safe to use during pregnancy, but it should be used with caution and only when necessary, as some studies suggest a potential association with cleft palate 1. When considering the use of diphenhydramine during pregnancy, it is essential to weigh the benefits against the potential risks. The available human data for first trimester use of antihistamines, including diphenhydramine, are generally reassuring, with no significant increase in congenital malformations 1. However, a case-control study suggesting an association with cleft palate has yet to be sufficiently refuted, prompting caution when using diphenhydramine during pregnancy.

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

  • Using the lowest effective dose for the shortest duration possible
  • Avoiding regular use for sleep or other non-essential purposes
  • Being aware of potential side effects, such as drowsiness, dry mouth, and constipation, which could be more problematic during pregnancy
  • Consulting with a healthcare provider before taking any medication during pregnancy to discuss individual risks and benefits

It is also important to note that non-drug alternatives, such as saline nasal sprays for congestion or lifestyle changes for sleep issues, should be considered first when possible 1. Ultimately, the decision to use diphenhydramine during pregnancy should be made in consultation with a healthcare provider, taking into account the individual's specific health situation and stage of pregnancy.

From the FDA Drug Label

If pregnant or breast-feeding, ask a healthcare professional before use The FDA drug label does not answer the question.

From the Research

Diphenhydramine Safety in Pregnancy

There are no research papers provided that directly address the safety of diphenhydramine (Benadryl) during pregnancy.

Available Information on Diphenhydramine

  • Diphenhydramine is an antihistamine with many side effects, including sedation and risk of toxicity in overdose, including cardiac toxicity 2.
  • Second-generation antihistamines are available and have fewer side effects compared to diphenhydramine 2, 3.
  • Diphenhydramine has a higher adverse side-effect profile among children and older adults 3.
  • There is a recommendation to restrict access to first-generation antihistamines like diphenhydramine due to their problematic therapeutic ratio 3.

Related Studies

  • A study on the safety concerns of maternal antiseizure medications exposure on perinatal and offspring outcomes does not mention diphenhydramine 4.
  • A case report on hypersensitivity to laminaria mentions the use of diphenhydramine as a treatment, but it is not related to pregnancy 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diphenhydramine: Time to Move on?

The journal of allergy and clinical immunology. In practice, 2022

Research

Diphenhydramine: It is time to say a final goodbye.

The World Allergy Organization journal, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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