Hydroxyzine During First Trimester
Hydroxyzine is contraindicated during the first trimester of pregnancy and should be avoided. 1
FDA Drug Label 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
Guideline Recommendations
Major allergy guidelines consistently recommend against hydroxyzine use during the first trimester:
The American Academy of Allergy, Asthma, and Immunology specifically advises that hydroxyzine should be used cautiously during the first trimester based on animal data showing teratogenic effects. 2
British guidelines explicitly state that hydroxyzine is the only antihistamine specifically contraindicated during the early stages of pregnancy. 3
This contraindication is based on animal reproductive toxicology studies, though human data remain limited. 2
Safer Alternative Antihistamines
If antihistamine therapy is necessary during the first trimester, choose from these well-studied alternatives:
Cetirizine (the active metabolite of hydroxyzine) is FDA Pregnancy Category B with extensive human safety data showing no increased risk of congenital malformations during first trimester exposure. 4, 5
Loratadine is also FDA Pregnancy Category B with robust observational data confirming safety across all trimesters. 5
Chlorphenamine (chlorpheniramine) is a first-generation antihistamine with a long safety record and no significant increase in congenital malformations when used during the first trimester, though it causes more sedation. 3, 5
Evidence Quality Considerations
While one prospective controlled study from 1997 found no increased teratogenic risk with hydroxyzine exposure during pregnancy 6, this single observational study is insufficient to override the FDA contraindication and consistent guideline recommendations against first trimester use. 1, 2, 3 The animal data showing fetal abnormalities, combined with inadequate human safety data, justifies the cautious approach. 1
Treatment Algorithm for First Trimester
When treating allergic symptoms during the first trimester:
First-line: Intranasal corticosteroids (budesonide preferred) have the best safety and efficacy profile with minimal systemic absorption. 5
Second-line: Add cetirizine or loratadine if additional symptom control is needed. 5
Alternative: Chlorphenamine if patient prefers a first-generation antihistamine with long safety record, accepting sedation. 3
Avoid completely: Hydroxyzine, oral decongestants (phenylephrine, pseudoephedrine), and newer antihistamines with limited human pregnancy data (levocetirizine, desloratadine, fexofenadine). 2, 4, 5
Critical Pitfalls to Avoid
Do not assume hydroxyzine is safe simply because cetirizine (its metabolite) has good safety data—the parent compound has specific contraindications. 1, 3
Do not combine any antihistamine with oral decongestants during the first trimester, as decongestants are associated with gastroschisis and small intestinal atresia, with risk increasing when combined with acetaminophen or salicylates. 2, 5
Do not continue hydroxyzine if pregnancy is discovered—switch immediately to cetirizine or another safer alternative. 3, 5