Is Benadryl (diphenhydramine) safe to use during pregnancy?

Safety of Benadryl (Diphenhydramine) During Pregnancy

Diphenhydramine (Benadryl) should be used with caution during pregnancy due to its association with potential risks, including cleft palate, though it has generally good overall safety data. 1

Safety Classification and Risk Assessment

• Diphenhydramine is frequently used during pregnancy and has accumulated safety data, but it is not classified as completely safe for use during pregnancy 1
• According to FDA pregnancy risk categories, most antihistamines fall under Category B or C, indicating limited evidence of harm but incomplete safety data 1
• The general recommendation is to avoid all antihistamines if possible during pregnancy, especially in the first trimester 1

Specific Concerns with Diphenhydramine

• Administration of diphenhydramine during pregnancy has been associated with the development of cleft palate, which is a significant concern 1
• While diphenhydramine has good overall safety data from historical use, this specific risk must be considered when evaluating treatment options 1
• A study examining associations between antihistamine use and birth defects found that diphenhydramine was involved in 8 of 24 associations with birth defects, suggesting a potential pattern worth consideration 2

Alternative Antihistamine Options

• Second-generation antihistamines may be preferable to first-generation antihistamines like diphenhydramine due to their safety profile 1
• Chlorphenamine (chlorpheniramine) is often chosen by clinicians in the UK when antihistamine therapy is necessary during pregnancy because of its long safety record 1
• 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

Clinical Decision-Making Framework

1. First-line approach: Consider if antihistamine treatment is absolutely necessary, as avoiding medication during pregnancy is preferable when possible 1, 3

2. If treatment is necessary:

   • Consider second-generation antihistamines before first-generation options like diphenhydramine 1
   • Chlorphenamine may be a better first-generation option if needed 1
   • Use the lowest effective dose for the shortest duration possible 3

3. Timing considerations:

   • Exercise particular caution during the first trimester when organogenesis occurs 1, 3
   • Risk/benefit assessment should be more favorable for use later in pregnancy 1

Important Caveats

• No antihistamine has been proven completely safe during pregnancy, and all should be used with caution 1, 4
• The overall risk of congenital abnormalities caused by medications accounts for less than 1% of total congenital abnormalities 5
• Self-reported use of over-the-counter medications like diphenhydramine during pregnancy is common, highlighting the importance of proper counseling 6
• Always consider the risk of untreated maternal conditions against the potential risks of medication 1