Is diphenhydramine (Benadryl) safe to use during pregnancy?

Diphenhydramine Safety During Pregnancy

Diphenhydramine (Benadryl) should be used with caution during pregnancy, particularly in the first trimester, due to concerns about a possible association with cleft palate, although recent studies have not consistently confirmed this risk. 1

Safety Profile and Recommendations

First Trimester Considerations

• While diphenhydramine has been frequently used during pregnancy with generally good overall safety data, there remains some concern from older case-control studies suggesting a possible association with cleft palate that has not been sufficiently refuted 1
• The FDA drug label specifically states: "If pregnant or breast-feeding, ask a healthcare professional before use" 2
• The most critical time for concern about potential congenital malformations is the first trimester, when organogenesis is occurring 1

Alternative Antihistamine Options

• Second-generation antihistamines (like cetirizine or loratadine) may be preferable options during pregnancy as they have accumulated comparable safety data to first-generation antihistamines but with less sedation 1
• Chlorphenamine is often chosen by clinicians 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 there is no evidence of harm to the fetus during pregnancy 1

Risk-Benefit Assessment

• Both first-generation and second-generation antihistamines generally have excellent safety records and do not show a significant increase in congenital malformations when used during the first trimester 1
• However, diphenhydramine's sedating properties and potential risks make it less desirable as a first-choice agent 1
• A 2009 study examining associations between antihistamine use and birth defects found that of 364 associations investigated, 8 potentially concerning associations involved diphenhydramine, though the authors noted these findings should be interpreted cautiously given the number of associations investigated 3

Clinical Decision Algorithm

1. First-line approach: Consider non-pharmacological approaches or alternative medications if possible

2. If antihistamine treatment is necessary:

   • Preferred options: Second-generation antihistamines (cetirizine, loratadine) or chlorphenamine
   • Use diphenhydramine only if:
     • Previous good response to this specific medication
     • Benefits clearly outweigh potential risks
     • Other antihistamines are contraindicated or ineffective

3. If diphenhydramine is used:

   • Use the lowest effective dose for the shortest duration
   • Avoid use during the first trimester if possible
   • Monitor for maternal side effects (sedation, anticholinergic effects)

Important Considerations

• It is generally best to avoid all antihistamines in pregnancy if possible, especially during the first trimester 1
• When prescribing any medication during pregnancy, the principle of using drugs for which experience has accumulated about their use during pregnancy should be followed 4
• The developing fetus is uniquely responsive to drugs, and fetal adverse effects may not always be immediately apparent 5
• Diphenhydramine elixir formulations may contain alcohol (up to 15% in some preparations), which should be considered when prescribing 6

By carefully weighing the benefits against the potential risks and considering alternative options when appropriate, healthcare providers can make informed decisions about the use of diphenhydramine during pregnancy.