In most cases, it is NOT be recommended to take Benadryl (diphenhydramine) and Xyzal (levocetirizine) together as they are in the same class of medication. There are however, some exceptions which we will discuss below.


Both Benadryl and Xyzal are antihistamine medications and have the same mechanism of action. They work by blocking the histamine-1 receptor, preventing histamine from binding to it and producing the allergy symptoms we are all familiar with (runny nose, stuffy nose, post-nasal drip etc...).


Benadryl is classified as a first generation antihistamine. The duration of action of the drug is typically 4-6 hours per dose (25 mg to 50 mg). The first generation antihistamines are known for their sedative effects and CNS depressant effects. Many patients cannot tolerate Benadryl unless if it is given at bedtime due to the sedation it causes. Even then, some people experience a hangover effect the next morning. Due to this, Benadryl (diphenhydramine) is a common ingredient in many night time cold formulations and sleep aides. 


Xyzal (levocetirizine) is known as a second generation antihistamine. Most second generation antihistamines are not associated with sedation. However, Xyzal is associated with a very minor sedative effect and isn't generally considered 'non-drowsy' like Claritin or Allegra are.


Due to the duplicative nature of Benadryl and Xyzal, concurrent use of both is not recommended.


The interaction we are worried about is the additive drowsiness when both are taken together. Although Xyzal (levocetirizine) is only very mildly sedative, combining it with another antihistamine like Benadryl could cause additive effects of the two. In addition, you most likely would not get any additional benefit from taking the two together. Each drug on their own does a good of blocking the histamine receptor and taking the two together would not produce any appreciate difference from one alone.


Having said that, there are cases when both are used together.


One situation where it may be OK to take both close to each other is during an allergic reaction. It is thought that Benadryl (diphenhydramine) is slightly more effective at stemming an anaphylactic reactions such as the reaction some people have to bee stings. The second generation antihistamines, while possibly beneficial, aren't thought to be quite as effective in these situations. If you take Xyzal (levocetirizine) on a daily basis for your seasonal allergies and were in a situation where you were having a serious allergic reaction, Benadryl (diphenhydramine) may be an appropriate choice to add on before you seek medical attention.