Are antihistamines (anti-histamine medications) safe to use during pregnancy?

Safety of Antihistamines During Pregnancy

While it is generally best to avoid all antihistamines during pregnancy when possible, especially during the first trimester, both first-generation and second-generation antihistamines have excellent safety records and do not show significant increases in congenital malformations when medically necessary. 1

Safety Profile of Different Antihistamines

First-Generation Antihistamines

• Chlorpheniramine is often chosen by clinicians when antihistamine therapy is necessary during pregnancy due to its long safety record 1
• Diphenhydramine is commonly used during pregnancy, though some caution exists due to an older case-control study suggesting an association with cleft palate that has not been sufficiently refuted 1
• Hydroxyzine should be used cautiously during the first trimester based on animal data and is specifically contraindicated during early pregnancy according to UK manufacturer guidelines 1

Second-Generation Antihistamines

• Loratadine and cetirizine are classified as FDA Pregnancy Category B drugs, implying no evidence of harm to the fetus, although well-controlled human studies are limited 1
• The safety of second-generation antihistamines during the first trimester has been confirmed through large birth registries, case-control studies, and cohort studies 1
• Limited data exists for desloratadine, azelastine, and levocetirizine during pregnancy 1

Timing Considerations

• The first trimester is the most critical period for potential congenital malformations due to medication use, as this is when organogenesis occurs 1
• If antihistamine therapy is necessary, it should be approached with particular caution during this period 1

Evidence from Recent Research

• A 2017 meta-analysis that included a large number of studies found that H1 antihistamines are not associated with an increased risk of major malformations or other adverse fetal outcomes 2
• A 2020 case-control study analyzing over 41,000 pregnancies found limited evidence to conclude that birth defects are associated with exposure to antihistamines during early pregnancy 3

Recommendations for Clinical Practice

When Antihistamines Are Necessary During Pregnancy:

1. First Choice Options:

   • Chlorpheniramine if a first-generation antihistamine is needed 1
   • Cetirizine or loratadine if a second-generation antihistamine is preferred 1, 4

2. Medications to Use with Caution:

   • Diphenhydramine (monitor for potential risks) 1
   • Fexofenadine (animal studies are negative for teratogenicity, but human pregnancy data is limited) 1

3. Medications to Avoid:

   • Hydroxyzine, especially during the first trimester 1
   • Intranasal antihistamines and first-generation antihistamines when alternatives are available 4

Important Considerations

• Always consult product labeling - both cetirizine and loratadine labels advise consulting a healthcare professional before use during pregnancy 5, 6
• Consider the risk-benefit ratio - treat only when the benefits to the mother outweigh potential risks to the fetus
• Use the lowest effective dose for the shortest duration possible
• Avoid combination products containing decongestants, especially during the first trimester 1

Common Pitfalls to Avoid

• Assuming all antihistamines have identical safety profiles during pregnancy
• Failing to distinguish between first and second-generation antihistamines when making treatment decisions
• Not considering the trimester of pregnancy when selecting an antihistamine
• Using combination products containing decongestants without recognizing the additional risks

When antihistamine therapy is necessary during pregnancy, the evidence supports using chlorpheniramine, cetirizine, or loratadine as relatively safer options, while being particularly cautious during the first trimester.