Is diphenhydramine (Benadryl) safe to use during the third trimester of pregnancy?

Safety of Diphenhydramine in the Third Trimester of Pregnancy

Diphenhydramine (Benadryl) can be used with caution during the third trimester of pregnancy, but patients should consult their healthcare provider before use. 1, 2

Safety Profile

• The FDA drug label for diphenhydramine indicates that pregnant women should "ask a healthcare professional before use," suggesting caution rather than absolute contraindication 2
• While most safety concerns about antihistamines focus on first trimester use when organogenesis occurs, diphenhydramine has been used in pregnant patients with relatively good safety records in later pregnancy 1
• Recent studies have not detected significant increased risks for congenital malformations with diphenhydramine use during pregnancy, though historical concerns about a possible association with cleft palate exist primarily for first trimester exposure 1

Third Trimester Considerations

• Unlike NSAIDs which are specifically contraindicated in the third trimester due to risks of oligohydramnios and premature closure of ductus arteriosus, diphenhydramine does not carry these specific third-trimester warnings 3
• Diphenhydramine has been studied for treatment of insomnia during the third trimester of pregnancy and was found to improve sleep quality without causing adverse pregnancy outcomes 4
• The primary concerns with diphenhydramine in the third trimester relate to its sedative properties rather than teratogenicity 1

Alternative Options

• If antihistamine treatment is necessary during pregnancy, chlorpheniramine has been recommended as a first-choice agent due to its longer safety record 1
• Second-generation antihistamines like cetirizine and loratadine (FDA Pregnancy Category B) have accumulated substantial safety data and may be preferred options with less sedation 1

Practical Recommendations

• If diphenhydramine is needed in the third trimester:
  • Use the lowest effective dose for the shortest duration necessary 1
  • Be aware of potential sedative effects and avoid combining with other sedatives or alcohol 2
  • Monitor for any unusual symptoms and maintain regular prenatal care 1
• Over-the-counter medications, including antihistamines, are commonly used during pregnancy, with acetaminophen, ibuprofen, and pseudoephedrine being among the most frequently used 5

Important Precautions

• Marked drowsiness may occur with diphenhydramine use, which could affect maternal well-being 2
• Avoid combining diphenhydramine with other products containing the same active ingredient to prevent overdose 2
• Exercise caution when driving or operating machinery while taking diphenhydramine due to its sedative effects 2

Clinical Decision-Making

• The benefit of symptom relief must be weighed against potential risks when prescribing any medication during pregnancy 6
• For severe allergic symptoms requiring treatment in the third trimester, diphenhydramine appears to have an acceptable safety profile when other options are not suitable or effective 1, 4