Can You Use Benadryl Cream With Xyzal?

Hi and thank you for your great question. I always appreciate when my patients ask me to double check that their OTC medications are safe together, especially if it’s two medications from the same class.

Levocetirizine (or by the brand Xyzal) is a “second or third generation” (depending on who is doing the classification) antihistamine. It works by binding to histamine receptors in the body so that histamine can’t bind to them. This helps to reduce the symptoms typically caused by allergies or histamine release. It is generally well tolerated and lasts about 24 hours.

Benadryl cream is a combination of diphenhydramine (an antihistamine) and zinc acetate. It is typically considered safe to use this with Xyzal or really any other antihistamine. Benadryl cream is usually not very well absorbed into the skin unless it is used over a very large area of the skin or applied directly on top of an open wound.

As long as your mosquito bites aren’t covering both of your legs completely, you shouldn’t absorb much of it, so it should be safe to use (i.e. won't interact with Xyzal).

You might want to reconsider using it though. There is very little evidence to show that topical diphenhydramine works well to treat bug bites.

In fact, I was not able to find any placebo controlled studies using topical diphenhydramine to treat bug bites. A topical steroid such as hydrocortisone (or under the brand Cortizone 10) is the usual recommended treatment for an uncomplicated bug bite and has a bit more evidence to support its use. Other products, like Sarna, are quite effective.

If you see good results with Benadryl cream, great! If not, you might want to try hydrocortisone or something like Sarna instead.

Thanks for reaching out to us and I hope this helps.