Is hydroxyzine (an antihistamine) safe to use during pregnancy for anxiety management?

Hydroxyzine Safety in Pregnancy

Hydroxyzine is contraindicated in early pregnancy and should not be used; cetirizine (its active metabolite) is a safer alternative with an established safety record. 1, 2

FDA Contraindication and Regulatory Position

• The FDA drug label explicitly states that hydroxyzine is contraindicated in early pregnancy because it induced fetal abnormalities in rats and mice at doses substantially above the human therapeutic range, and clinical data in humans are inadequate to establish safety. 1
• British guidelines specifically identify hydroxyzine as the only antihistamine contraindicated during the early stages of pregnancy based on animal data showing potential risks. 2
• U.S. allergy guidelines list hydroxyzine among medications to avoid during pregnancy, particularly in the first trimester. 2

Neonatal Risks Beyond First Trimester

• Neonatal withdrawal syndrome has been documented with hydroxyzine use later in pregnancy, with withdrawal signs including tremors, irritability, and hyperactivity lasting up to 5 weeks requiring treatment. 2
• This risk persists even if the medication is used after the first trimester, making it problematic throughout pregnancy. 2

Safer Alternative Antihistamines

Cetirizine is the preferred alternative as it is the active metabolite of hydroxyzine but has a long safety record with no significant increase in congenital malformations during first trimester exposure. 2

First-Line Options for Pregnancy:

• Chlorpheniramine has been specifically recommended as a first-choice agent during pregnancy with sufficient human observational data demonstrating no significant increase in congenital malformations when used during the first trimester. 2
• Cetirizine and loratadine are confirmed safe through large birth registries, case-control studies, and cohort studies, offering the advantage of less sedation compared to first-generation antihistamines. 2

Clinical Considerations for Anxiety Management

• For anxiety management specifically during pregnancy, non-pharmacological treatments such as cognitive behavioral therapy should be employed whenever possible before considering medication. 3
• If medication is required for anxiety, hydroxyzine should be avoided entirely and alternative anxiolytics or antidepressants with better pregnancy safety profiles should be considered after careful risk-benefit assessment. 3
• The lowest effective dose for the shortest possible time should be used to minimize fetal exposure with any medication. 2

Important Caveats

• Avoid combining any antihistamine with oral decongestants (phenylephrine, pseudoephedrine) during the first trimester, as these combinations are associated with gastroschisis and small intestinal atresia. 2
• The risk of malformations increases when decongestants are combined with acetaminophen or salicylates. 2
• Dose adjustments are necessary for cetirizine in moderate renal impairment (halve the dose) and it should be avoided in severe renal impairment. 2

Contradictory Evidence Note

While one prospective controlled study from 1997 found no increased teratogenic risk with hydroxyzine use during pregnancy 4, this single observational study cannot override the FDA contraindication based on animal data and inadequate human safety data. 1 The regulatory position and guideline consensus take precedence, particularly given the availability of safer alternatives with more robust safety data. 2, 1