Hydroxyzine Safety in Pregnancy
Direct Answer
Hydroxyzine is contraindicated in early pregnancy and should not be used in women who are trying to conceive. 1, 2
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 Consensus
- British guidelines explicitly state that hydroxyzine is the only antihistamine specifically contraindicated during the early stages of pregnancy. 2
- U.S. allergy guidelines list hydroxyzine among medications to avoid during pregnancy, particularly in the first trimester. 2
- The first trimester is the most critical period for concern about medication-induced congenital malformations due to organogenesis. 2
Safer Alternative for Anxiety in Women Trying to Conceive
Cetirizine (the active metabolite of hydroxyzine) is recommended as a safer alternative with a long safety record and no significant increase in congenital malformations during first trimester exposure. 2
Evidence Supporting Cetirizine Safety:
- A prospective controlled study of 39 women exposed to cetirizine during organogenesis found no significant differences in pregnancy outcomes, rates of major or minor anomalies, mean birth weight, or neonatal distress compared to controls. 3
- Cetirizine has been confirmed safe through large birth registries, case-control studies, and cohort studies. 2
Additional Safe Antihistamine Options
If antihistamine therapy is necessary for anxiety-related symptoms:
- 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
- Loratadine is also confirmed safe through large birth registries and offers the advantage of less sedation. 2
Clinical Neonatal Withdrawal Concerns
While hydroxyzine is contraindicated for teratogenic concerns, there is also evidence of neonatal withdrawal syndrome when used later in pregnancy. Documented withdrawal signs include tremors, irritability, hyperactivity, jitteriness, shrill cry, myoclonic jerks, hypotonia, increased respiratory and heart rates, feeding problems, and clonic movements, with symptoms lasting up to 5 weeks with treatment. 4
Common Pitfall to Avoid
Do not combine 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 increases further when decongestants are combined with acetaminophen or salicylates. 2
Treatment Algorithm for Anxiety in Women Trying to Conceive
- Discontinue hydroxyzine immediately if currently prescribed. 1, 2
- Switch to cetirizine if antihistamine properties are desired for anxiety management, using the lowest effective dose. 2, 3
- Consider non-antihistamine anxiolytics with better pregnancy safety profiles if anxiety is the primary concern rather than allergic symptoms.
- Avoid all oral decongestant combinations during attempts to conceive and throughout the first trimester. 2