Can you take Xyzal (levocetirizine) and Benadryl (diphenhydramine) together?

Taking Xyzal and Benadryl Together

Taking Xyzal (levocetirizine) and Benadryl (diphenhydramine) together is generally not recommended due to the increased risk of sedation and anticholinergic side effects without significant additional therapeutic benefit.

Understanding the Medications

Xyzal (Levocetirizine)

• Second-generation antihistamine
• Less sedating than first-generation antihistamines
• Longer duration of action (half-life of 7-11 hours) 1
• Primarily treats allergic symptoms with minimal CNS effects

Benadryl (Diphenhydramine)

• First-generation antihistamine
• Highly sedating with significant anticholinergic effects
• Shorter duration of action (half-life of 2.6 hours) 1
• Can cause significant cognitive impairment even without subjective awareness of sedation

Risks of Combination Use

1. Enhanced Sedation

   • First-generation antihistamines like diphenhydramine cause significant sedation
   • This sedation can be enhanced when combined with other medications, even second-generation antihistamines 1
   • Sedative effects can persist even when taken at bedtime due to prolonged half-life 1

2. Anticholinergic Effects

   • Diphenhydramine has significant anticholinergic effects including:
     • Dry mouth and eyes
     • Constipation
     • Urinary retention
     • Risk of narrow-angle glaucoma 1

3. Performance Impairment

   • Diphenhydramine has been associated with impaired driving performance and increased automobile accidents 1
   • A 2016 study showed diphenhydramine impaired psychomotor performance in simulated car-driving tasks, while levocetirizine did not 2
   • The combination could potentially worsen these effects

Therapeutic Considerations

1. Limited Additional Benefit

   • No evidence suggests that combining these medications provides superior symptom control
   • The 2022 research indicates that diphenhydramine should be avoided when newer, more favorable antihistamine medications like levocetirizine are available 3

2. Special Populations at Higher Risk

   • Older adults are at increased risk for adverse effects due to:
     • Greater sensitivity to anticholinergic effects
     • Higher incidence of pre-existing conditions like prostatic hypertrophy
     • Potential for cognitive impairment 1

Alternative Approaches

If Xyzal alone is not providing adequate symptom relief:

1. Adjust Xyzal Dosing

   • Consider timing medication to ensure highest drug levels when symptoms are worst 4

2. Try a Different Second-Generation Antihistamine

   • Individual responses to antihistamines vary, and patients should be offered a choice of at least two non-sedating antihistamines 4

3. Consider Combination with Other Medications

   • Adding an H2 antihistamine may provide better control than an H1 antihistamine alone 4
   • For allergic rhinitis, consider adding a leukotriene receptor antagonist like montelukast 5 or intranasal corticosteroids 6

Bottom Line

While technically possible to take these medications together, the combination of Xyzal and Benadryl offers little therapeutic advantage while significantly increasing the risk of sedation and anticholinergic side effects. Modern treatment approaches favor using second-generation antihistamines like Xyzal alone or in combination with other non-sedating medications rather than adding first-generation antihistamines like Benadryl.