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

Hydroxyzine in Pregnancy: Avoid Use

Hydroxyzine is specifically contraindicated in early pregnancy and should be avoided throughout gestation. 1, 2, 3

FDA Contraindication

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 This represents the strongest regulatory warning against use during pregnancy.

Guideline Consensus

Multiple international guidelines consistently identify hydroxyzine as the only antihistamine specifically contraindicated during pregnancy:

• British guidelines explicitly state that hydroxyzine is the only antihistamine specifically contraindicated during the early stages of pregnancy in its U.K. manufacturer's Summary of Product Characteristics. 2
• U.S. allergy guidelines list hydroxyzine among medications to avoid during pregnancy, particularly in the first trimester. 2, 3
• Recent consensus recommendations (2025) confirm hydroxyzine should be avoided based on animal data showing potential risks. 3

Safer Alternative Antihistamines

Instead of hydroxyzine, use these well-studied alternatives:

First-Line Options:

• Chlorpheniramine: Recommended as the first-choice first-generation antihistamine with a long safety record and no significant increase in congenital malformations during first trimester exposure. 3, 4
• Cetirizine: FDA Pregnancy Category B with extensive safety data from large birth registries, case-control studies, and cohort studies confirming no increased teratogenic risk. 3, 4, 5, 6
• Loratadine: FDA Pregnancy Category B with comparable safety profile to cetirizine. 2, 3, 4

Key Advantages of Alternatives:

• Cetirizine is actually the active metabolite of hydroxyzine, providing similar therapeutic benefit without the pregnancy contraindication. 5, 6
• Second-generation antihistamines (cetirizine, loratadine) offer less sedation than first-generation options while maintaining excellent safety profiles. 3, 4

Clinical Caveats

Renal impairment considerations: If hydroxyzine were to be considered (which it should not be in pregnancy), the dose would need to be halved in moderate renal impairment. 2 However, this is moot given the pregnancy contraindication.

Neonatal withdrawal: High-dose hydroxyzine (600 mg daily) has been associated with neonatal withdrawal syndrome, providing additional evidence against its use. 7

Combination therapy: When antihistamines alone are insufficient, combine cetirizine or loratadine with intranasal corticosteroids (particularly budesonide) rather than considering hydroxyzine. 4

Practical Algorithm

1. If patient is already taking hydroxyzine and discovers pregnancy: Discontinue immediately and switch to cetirizine (the active metabolite) or chlorpheniramine. 3, 5

2. For new antihistamine needs in pregnancy:

   • First trimester: Chlorpheniramine (longest safety record) or cetirizine (most data). 3, 4
   • Second/third trimester: Same options remain safest. 3
   • Use lowest effective dose for shortest duration. 3

3. Avoid combining with oral decongestants (phenylephrine, pseudoephedrine) during first trimester due to associations with gastroschisis and small intestinal atresia. 2, 3, 4