There is a moderate interaction between Benadryl (diphenhydramine) and Xanax (alprazolam). In most situations, Benadryl and Xanax should not be taken together due to the additive effects that may occur.
Xanax is classified as a benzodiazepine and is well known to cause sedation, central nervous depression and at high doses, respiratory depression.
Benadryl is classified as a sedating, first generation antihistamine. Like Xanax, it can cause sedation and central nervous system depression. It does not commonly cause respiratory depression but it has been rarely reported.
Due to the additive effects of both drugs, coadministration can potentiate the effects of both, potentially increasing the risk of adverse effects.
Both Benadryl and Xanax are relatively short acting so although you shouldn't take them together, you may be able to take them in the same day. The effects of Benadryl last anywhere from 4 to 8 hours per dose while Xanax can last from 8 to 12 hours per dose. Whenever combining new medications, it is important to let your doctor know.
Lastly, if you are simply looking for an effective antihistamine that can be safely taken with Xanax, you could try a second generation antihistamine such as Claritin or Allegra. These are non-drowsy and do not interact with Xanax.