Is it safe to take Claritin (loratadine) in the morning and Benadryl (diphenhydramine) at night?

Taking Claritin in the Morning and Benadryl at Night: Not Recommended

Taking Claritin (loratadine) in the morning and Benadryl (diphenhydramine) at night is not recommended due to potential safety concerns including next-day impairment and performance issues even when the first-generation antihistamine is taken only at bedtime. 1

Why This Combination Is Problematic

• First-generation antihistamines like diphenhydramine (Benadryl) have prolonged plasma half-lives and their effects persist longer than plasma levels of the parent compound, leading to next-day drowsiness and impairment even when taken only at bedtime 1
• The AM/PM dosing regimen (second-generation antihistamine in morning, first-generation at night) is specifically identified as "not a preferred strategy" in clinical guidelines 1
• PET imaging studies have demonstrated that diphenhydramine taken at night (11:00 PM) still shows significant H₁ receptor occupancy (44.7%) in the brain the following morning (11:00 AM), confirming residual sedative effects 2
• Drivers taking first-generation antihistamines are 1.5 times more likely to be responsible for fatal automobile accidents 1

Specific Concerns with Diphenhydramine (Benadryl)

• Performance impairment can exist without subjective awareness of drowsiness, meaning you may feel fine but still have impaired function 1
• The FDA drug label for diphenhydramine specifically warns that "marked drowsiness may occur" and to "be careful when driving a motor vehicle or operating machinery" 3
• Diphenhydramine can cause anticholinergic effects including dry mouth, dry eyes, constipation, urinary retention, and increased risk of narrow-angle glaucoma 1
• Taking diphenhydramine with other sedatives (including alcohol) may increase drowsiness 3

Safety Profile of Loratadine (Claritin)

• Loratadine is a second-generation antihistamine that does not cause sedation at recommended doses 1
• The FDA drug label for loratadine only warns against taking more than directed, which "may cause drowsiness" 4
• In comparative studies, subjects treated with loratadine performed as well as those given placebo on tests of divided attention, working memory, vigilance, and speed 5

Better Alternatives

• Use a single second-generation antihistamine consistently throughout the day 1
• Options include:
  • Fexofenadine (Allegra): Has no sedative properties even at higher than FDA-approved doses 1
  • Loratadine (Claritin): Non-sedating at recommended doses 1
  • Desloratadine (Clarinex): Non-sedating at recommended doses 1

Special Considerations

• Older adults are particularly sensitive to the psychomotor impairment from first-generation antihistamines and are at increased risk for falls and other complications 1
• If nighttime symptoms are problematic, consider:
  • Increasing the dose of the second-generation antihistamine (under medical supervision) 1
  • Adding a topical anticholinergic agent for persistent rhinorrhea rather than a systemic agent with anticholinergic properties 1
  • Using an intranasal corticosteroid in addition to the antihistamine for better symptom control 1

When Diphenhydramine Might Be Considered

• Only when a soporific (sleep-inducing) effect is specifically desired 1
• When anticholinergic properties are advantageous for specific symptoms 1
• With clear understanding that next-day impairment is likely, even without feeling drowsy 1, 2

Remember that even though diphenhydramine is available over-the-counter, it carries significant risks that should not be underestimated, particularly when combined with other medications that affect the central nervous system.