Is Unisom (doxylamine) safe to use during pregnancy?

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Last updated: September 12, 2025View editorial policy

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Safety of Unisom (Doxylamine) During Pregnancy

Doxylamine (Unisom) is considered safe to use during pregnancy and is often recommended for managing nausea and vomiting of pregnancy.

Evidence for Safety

Doxylamine has been extensively studied in pregnancy, particularly in combination with pyridoxine (vitamin B6) as the FDA-approved medication Diclegis® for nausea and vomiting of pregnancy (NVP). A randomized controlled trial demonstrated that doxylamine succinate is not associated with an increased rate of adverse events compared to placebo, including no increased risk of CNS depression, gastrointestinal or cardiovascular effects 1.

First-generation antihistamines like doxylamine have extensive safety data from long-term use during pregnancy 2. Unlike diphenhydramine, which has been associated with cleft palate development in some studies, doxylamine does not have this specific safety concern 3.

Dosing and Administration

  • Standard dosing for sleep: 25mg at bedtime
  • For nausea and vomiting of pregnancy: 10mg doxylamine (often combined with 10mg pyridoxine)
  • Maximum recommended daily dose: Up to 4 tablets daily has been shown to be safe and well-tolerated 1

Important Considerations

  • First trimester use: While all medications should be used with caution during the first trimester (period of organogenesis), doxylamine has not shown evidence of teratogenicity
  • Side effects: The main side effect is drowsiness, which can be beneficial when used as a sleep aid
  • Duration: Short-term use is preferable when possible, though longer-term use for persistent pregnancy symptoms has not shown adverse outcomes

Alternatives and Comparative Safety

When considering antihistamines during pregnancy:

  • First-generation antihistamines (like doxylamine and chlorpheniramine) have more extensive safety data but cause more sedation 2
  • Second-generation antihistamines with established pregnancy safety data include loratadine and cetirizine 2
  • For allergic rhinitis specifically, intranasal corticosteroids like budesonide (FDA Pregnancy Category B) may be preferred options 3

Clinical Algorithm for Use

  1. For insomnia during pregnancy:

    • First-line: Non-pharmacological approaches (sleep hygiene)
    • Second-line: Doxylamine 25mg at bedtime as needed
  2. For nausea and vomiting of pregnancy:

    • First-line: Dietary modifications and ginger
    • Second-line: Doxylamine (often combined with pyridoxine)
    • Third-line: Consider prescription medications if symptoms are severe

Conclusion

Doxylamine has a favorable safety profile during pregnancy based on extensive clinical experience and research data. It represents one of the safer medication options for treating both insomnia and nausea/vomiting during pregnancy, with minimal risk to the developing fetus when used as directed.

References

Guideline

Antihistamine Use During Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 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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