Can You Take Benadryl With Zyrtec?

In our latest question and answer, our pharmacist discusses whether or not Benadryl and Zyrtec can be taken together.

Can You Take Benadryl With Zyrtec?
Sep 28, 2017

Jolene asked

Can I take Benadryl and Zyrtec together?​​ I find that only taking Zyrtec hasn't been helpful enough and want to add something else on to make my allergy symptoms go away.

At a glance

  • Although Benadryl is a first-generation antihistamine and Zyrtec is a second-generation antihistamine, they both work the same way (by blocking histamine receptors).
  • Taking Benadryl and Zyrtec together likely will increase the risk of side effects (e.g. tiredness, dry mouth etc...) but there are situations where both can be used the same day.
  • Examples of these situations include when Benadryl is being used as a short-term sleep aid or used to help stem the effects of an allergic reaction.


Benadryl Bottle On Blue Background With Text- Can You Take Benadryl And Zyrtec Together

Benadryl (diphenhydramine) and Zyrtec (cetirizine) are both antihistamines and it generally isn't recommended to take drugs together that are in the same class and work the same way. Having said that, there certainly are occasions where both can be used together safely and may be even recommended by your doctor.

There are two main concerns with taking multiple drugs that work the same way (Zyrtec and Benadryl in this case):

  • There is the risk of additive side effects. Both Zyrtec and Benadryl will cause you to be tired for example. The use of both together will only increase the chance of this happening, and to a more severe degree.
  • You likely won't experience much added benefit. Taking two antihistamines won't make them work twice as well. I discuss this in more detail in the following paragraph.

As mentioned, both Benadryl and Zyrtec are antihistamines, and they both work the same way mechanistically. Specifically, they both block what is known as the 'histamine-1 receptor'. This prevents histamine from binding to these receptors and producing the symptoms we are all very familiar with (runny nose, sneezing, itching etc...).

Now, both do a pretty good job of blocking histamine receptors on their own. Taking both Benadryl and Zyrtec will simply cause them to compete for the same receptors. Once a receptor is blocked, it's blocked. In other words, if Benadryl is already bound to a histamine receptor, Zyrtec won't be able to act on it. This is why there isn't much of a cumulative effect in using two antihistamines at the same time.

So, the overall point here is that taking Benadryl and Zyrtec together doesn't increase the antihistamine effect of both, but will likely only increase the risk of side effects. These side effects include:

  • Sedation (i.e. tiredness)
  • Dry mouth
  • Dry eyes
  • Constipation

I said at the beginning of this answer that there are occasions where these drugs could be used together. These situations include:

  • If you are experiencing an allergic reaction.
  • You are using Benadryl as a sleep aid.
  • You take Benadryl and Zyrtec the same day, but separated by appropriate amount of time.

Situations Where You May Use Benadryl And Zyrtec Together

In many cases, Benadryl and Zyrtec shouldn't be taken together, and certainly not every day. However, the following sections detail situations where it may be beneficial to do so.

Allergic Reaction

Although studies are conflicting, some show that Benadryl is slightly more effective than Zyrtec at stemming an allergic reaction, such as the reaction some people have to bee stings. This may be because Benadryl has stronger 'anticholinergic' effects than Zyrtec.

The anticholinergic actions of Benadryl are responsible for many of the side effects, like sedation, but they also help to reduce itching and swelling. Zyrtec has been shown in studies to help reduce itching, but again, Benadryl may have the upper hand here. In fact, it is Benadryl, not Zyrtec, that is recommended in the guidelines for managing vaccine reactions for reducing hives and itching due to an adverse immunization reactions.

Let's say you take Zyrtec on a daily basis for your seasonal allergies and you found yourself in a situation where you were having a allergic reaction. Benadryl may be an appropriate choice to add-on since it may help provide you with some additional Relief.

Sleep Aid

Another situation where the combination may be okay is if your doctor recommends taking Benadryl as a short-term treatment for insomnia. The active ingredient in Benadryl is diphenhydramine, which is used in many over the counter sleep aids. It is the active ingredient in ZzzQuil and also the sleep aid used in Tylenol PM for example.

Your doctor may recommend taking Zyrtec in the morning, every day, to manage your allergy symptoms and Benadryl in the evening as needed. While this may make you slightly more tired than using Benadryl alone to sleep, this shouldn't be much of an issue because, after all, you are trying to go to bed.

Separate Administration Time

Benadryl is a short-acting, first-generation antihistamine. Each dose only lasts around four to six hours. Therefore, if you took Benadryl first, and then Zyrtec four to six hours later, Benadryl will have worn off by that point so there is no interaction to be concerned about.

Zyrtec on the other hand, is a long-acting, second-generation antihistamine. Each dose last around 24 hours (the adult dose at least, which is 10mg) so you really can't avoid having both in your system on the same day if you took Zyrtec first, and Benadryl second. Nevertheless, as I just wrote about above, there are times where this is okay.

Final Words

You mentioned that in your question that Zyrtec wasn't helping enough for you. Adding on Benadryl, in my opinion, is not the best option for optimal allergy relief.

If Zyrtec isn't working, you may want to try a different over the counter antihistamine, like Allegra (fexofenadine) and Xyzal (levocetirizine). Additionally, you could add on a nasal steroid, like Flonase (fluticasone) or Nasonex (mometasone). Nasal steroids are very effective at treating as well as preventing allergy symptoms and you use them at the same time as antihistamines.

At the very least, be sure to discuss your concerns with your doctor. They can help you find the best therapy for your situation.

  1. Elsevier ClinicalKey: Drug Interaction Report. ClinicalKey (Subscription Required)
  2. Pharmacology of Antihistamines. PubMed
  3. Guideline for acute therapy and management of anaphylaxis. PubMed
  4. Oral antihistamines for insect bites. PubMed
  5. Elsevier ClinicalKey: Benadryl Monograph. ClinicalKey (Subscription Required)
  6. Elsevier ClinicalKey: Zyrtec Monograph. ClinicalKey (Subscription Required)

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