Is diphenhydramine (Benadryl) safe to use during pregnancy?

Safety of Diphenhydramine (Benadryl) During Pregnancy

Diphenhydramine (Benadryl) should be used with caution during pregnancy and only after consulting with a healthcare professional, as it has been associated with potential risks including cleft palate development. 1

Risk Assessment

• According to the FDA drug label, pregnant women should consult a healthcare professional before using diphenhydramine 2
• The Joint Task Force on Practice Parameters for Allergy and Immunology notes that while diphenhydramine is frequently used during pregnancy with generally good overall safety data, its administration has been associated with the development of cleft palate 1
• First-generation antihistamines like diphenhydramine have more sedating effects and impaired performance characteristics, making them less desirable choices than second-generation antihistamines during pregnancy 1

Safer Alternatives for Allergic Symptoms

First-line options:

• Second-generation antihistamines are preferred over first-generation antihistamines like diphenhydramine:

  • Loratadine has the most safety data (studied in over 2,000 pregnant women) with no increased risk of major congenital malformations 3, 4
  • The accumulated safety data for second-generation antihistamines during pregnancy are comparable to first-generation antihistamines 1

• Intranasal corticosteroids are considered first-line treatments for allergic rhinitis during pregnancy:

  • They have minimal systemic absorption and have not been associated with increased congenital malformations 3
  • Beclomethasone, budesonide (Pregnancy Category B), and fluticasone propionate have more accumulated safety data than other intranasal corticosteroids 1

Important considerations:

• Benefit-risk assessment must be performed for each patient
• Non-pharmacological approaches should be tried first when possible
• For mild symptoms, intranasal sodium cromoglycate (cromolyn sodium) is considered low-risk 3

Clinical Decision Algorithm

1. Assess severity and necessity:

   • Is medication absolutely necessary? Can non-pharmacological approaches be used?
   • How severe are the symptoms?

2. If medication is needed:

   • For mild to moderate symptoms: Consider second-generation antihistamines (loratadine preferred) or intranasal corticosteroids
   • For allergic rhinitis: Intranasal corticosteroids (preferably budesonide - Pregnancy Category B) are most effective with minimal systemic effects
   • Use diphenhydramine only if:
     • Benefits clearly outweigh risks
     • Other safer alternatives have failed
     • Under healthcare professional supervision
     • At lowest effective dose for shortest duration

3. Monitor for adverse effects:

   • Marked drowsiness may occur with diphenhydramine
   • Avoid alcohol and other sedatives/tranquilizers which may increase drowsiness
   • Be cautious when driving or operating machinery

Important Caveats

• Meta-analyses examining H1-antihistamines in pregnancy (including first-generation antihistamines) have not shown increased teratogenic risk overall 4
• However, specific concerns about diphenhydramine and cleft palate warrant caution 1
• The FDA pregnancy risk categories have been replaced with more descriptive labeling, but diphenhydramine specifically requires healthcare professional consultation before use 2
• Avoid using multiple medications containing diphenhydramine simultaneously 2

Remember that while antihistamines as a class are generally considered to have acceptable safety profiles in pregnancy, diphenhydramine specifically carries additional concerns that make second-generation antihistamines or intranasal corticosteroids preferable first-line options.