Is intramuscular (IM) diphenhydramine (Benadryl) safe during pregnancy?

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Last updated: April 21, 2025View editorial policy

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From the Guidelines

Benadryl given intramuscularly (IM) should be avoided during pregnancy unless the potential benefit clearly outweighs the risks. The safety of antihistamines during pregnancy has been evaluated in several studies, with a focus on the first trimester when organogenesis occurs 1. According to the available data, first-generation antihistamines like diphenhydramine (Benadryl) have been used by pregnant patients, and recent studies have not detected any increased risk for congenital malformations 1. However, there is still some concern over a case-control study suggesting an association with cleft palate that has yet to be sufficiently refuted 1.

When considering the use of Benadryl during pregnancy, it's essential to weigh the potential benefits against the risks. Key points to consider include:

  • The first trimester is the most critical period for concern about potential congenital malformations due to medication use 1.
  • First-generation antihistamines, including Benadryl, have excellent safety records and do not show a significant increase in congenital malformations when used during the first trimester 1.
  • Oral formulations of antihistamines are preferred over IM administration when possible, as they may have a better safety profile 1.
  • Medical supervision is crucial if antihistamine treatment is necessary during pregnancy, especially for severe allergic reactions where IM administration might be considered.

Given the potential risks and the availability of alternative routes of administration, oral Benadryl is preferred over IM administration during pregnancy. If you're experiencing a severe allergic reaction during pregnancy that might require Benadryl, it's crucial to seek immediate medical attention rather than self-administering, as healthcare providers can best weigh the risks and benefits in your specific situation and monitor both maternal and fetal responses to treatment 1.

From the Research

Safety of Benadryl in Pregnancy

  • Benadryl is a first-generation antihistamine, and its safety during pregnancy is a concern.
  • According to the study 2, first-generation antihistamines are listed as medications to avoid during pregnancy.
  • This suggests that Benadryl may not be safe to use during pregnancy due to potential risks to the fetus.
  • The study 2 recommends second-generation antihistamines, such as cetirizine and loratadine, as safer alternatives for use during pregnancy.
  • It is essential to consult a healthcare provider before taking any medication, including Benadryl, during pregnancy to discuss potential risks and benefits.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Allergy Medications During Pregnancy.

The American journal of the medical sciences, 2016

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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