Can You Take Xyzal After Benadryl?
In our latest question and answer, the pharmacist discusses when Xyzal can safely be taken after Benadryl.

Question
I took 2 Benadryl today at 10 am, would it be safe to take a Xyzal this evening? I'm suffering from a bad case of hay fever. Thank you.

Answered by Dr. Brian Staiger, PharmD
Medical Content Reviewed By HelloPharmacist
Staff
Last updated Apr 10, 2025
Key points
- Benadryl (diphenhydramine) and Xyzal (levocetirizine) generally shouldn't be taken at the same time as they are in the same drug class (antihistamines). Combining both may result in additive side effects.
- Benadryl only lasts around 4 to 6 hours per dose, and Xyzal can safely taken after this period of time.
Answer
While Benadryl and Xyzal generally should not be taken at the same time, it is safe to take Xyzal around 4 to 6 hours after your last dose of Benadryl, as the effects of the drug will have worn off by then for most individuals. Per your question, if you took Benadryl at 10 AM, it is safe to take Xyzal later that night.
On the other hand, if you take Xyzal first, you should generally wait 24 hours before taking Benadryl to avoid additive side effects such as sedation, dry mouth, and general drowsiness as Xyzal has a duration of action of around 24 hours.
Benadryl (Diphenhydramine) Information
Benadryl, a first-generation antihistamine, has a duration of action of around 4 to 6 hours, although this can be extended in certain individuals such as in the elderly. One of the main side effects of Benadryl is sedation and is commonly added to over-the-counter sleep products such as ZzzQuil.
Xyzal (Levocetirizine) Information
Xyzal, a third-generation antihistamine, has a duration of action of around 24 hours, and is, therefore, able to be dosed just once a day. Although not classified as "non-drowsy", it does have a lower incidence of sedation and drowsiness than first-generation antihistamines such as Benadryl.
Taking Benadryl And Xyzal Together
As mentioned above, it generally isn't recommended to use antihistamines together. There is a risk of additive antihistamine side effects such as:
- Dry mouth
- Dry eyes
- Drowsiness
- Constipation
However, Benadryl only has a duration of action of 4 to 6 hours. If you take Benadryl first, you can safely take Xyzal 4 to 6 hours later. If you take Xyzal first, you should wait around 24 hours before dosing with Benadryl.
One exception to this could potentially be if you need to use Benadryl to stem an allergic reaction. Out of all the antihistamines, many studies show that Benadryl tends to be the most effective for slowing down the allergic reaction to bee stings, poisonous plants, etc... Just be aware of the additive sedative and other side effects if you do take Benadryl within 24 hours of your Xyzal dose.
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Dr. Brian Staiger, PharmD
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