Is diphenhydramine (Benadryl) safe to use during pregnancy?

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Diphenhydramine (Benadryl) Safety During Pregnancy

Diphenhydramine (Benadryl) should be used with caution during pregnancy due to potential risks including association with cleft palate, and alternative second-generation antihistamines should be considered first if antihistamine treatment is necessary. 1

Safety Classification and Concerns

  • Diphenhydramine carries an FDA warning requiring pregnant women to "ask a healthcare professional before use," indicating safety concerns 2
  • The American Academy of Allergy, Asthma, and Immunology recommends using diphenhydramine with caution during pregnancy due to its association with potential risks, including cleft palate 1
  • Most antihistamines, including diphenhydramine, are classified as FDA Category B or C, indicating limited evidence of harm but incomplete safety data 1

Specific Risks and Considerations

  • First-generation antihistamines like diphenhydramine should generally be avoided during pregnancy when possible 3
  • Administration of diphenhydramine during pregnancy has been associated with the development of cleft palate, which is a significant concern 1
  • The National Institute of Child Health and Human Development recommends avoiding all antihistamines if possible during pregnancy, especially in the first trimester 1

Alternative Options

  • Second-generation antihistamines are preferable to first-generation antihistamines like diphenhydramine due to their better safety profile 1
  • Cetirizine and loratadine are the second-generation antihistamines of choice during pregnancy 3
  • Chlorpheniramine is often chosen by clinicians when antihistamine therapy is necessary during pregnancy because of its long safety record 1

Clinical Decision-Making Framework

  • Consider if antihistamine treatment is absolutely necessary, as avoiding medication during pregnancy is preferable when possible 1, 4
  • If treatment is necessary, use the lowest effective dose for the shortest duration possible 1
  • Always weigh the risk of untreated maternal conditions against the potential risks of medication 1
  • Great caution should be taken when prescribing any medication during pregnancy as no drug is entirely without side effects 5

Common Pitfalls and Caveats

  • Many pregnant women use over-the-counter medications including antihistamines without medical supervision, which can pose risks 6
  • There is limited research on the safety of over-the-counter medications during pregnancy despite their widespread use 6
  • Drug development specifically for pregnant women lags behind other population groups, leading to limited safety data 7
  • No antihistamine has been proven completely safe during pregnancy, and all should be used with caution 1

References

Guideline

Safety of Antihistamines During Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Allergy Medications During Pregnancy.

The American journal of the medical sciences, 2016

Research

Which drugs can be used during pregnancy?

Duodecim; laaketieteellinen aikakauskirja, 2016

Research

Drugs in pregnancy. Drugs to avoid.

Best practice & research. Clinical obstetrics & gynaecology, 2001

Research

Use of over-the-counter medications during pregnancy.

American journal of obstetrics and gynecology, 2005

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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