Taking Benadryl With Zyrtec

In our latest question and answer, we explore taking the combination of Benadryl and Zyrtec.


Can I take Benadryl (Diphenhydramine) and Zyrtec (Cetirizine) together?​​

Asked by Jolene On Sep 28, 2017

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Sep 28, 2017
Pink Benadryl Capsules With Text - Zyrtec


In general, it is NOT recommended that Benadryl (diphenhydramine) and Zyrtec (cetirizine) be taken together, although there are exceptions.

Both drugs are antihistamines, and they both work the same way mechanistically. They both block what is known as the 'histamine-1 receptor'. This prevents histamine from binding to it and producing the symptoms we are all very familiar with (runny nose etc...).[1]

Taking them together generally doesn't increase the antihistamine effect of both, and most likely will only increase the risk of side effects, such as:[2]

  • Sedation
  • Dry mouth
  • Dry eyes
  • Constipation

As an overall point, due to the duplicative and additive nature of using Zyrtec and Benadryl together, concurrent use is not recommended.

This precaution is more in regard to everyday use of both together. There are certainly cases where taking both the same day may be safe and even recommended by your doctor. I talk about this in the next section.


Benadryl and Zyrtec are both antihistamines and have the same mechanism of action. They generally are not recommended to be taken together due to the risk of additive side effects.

Combined Use?

The interaction we are worried about is the additive sedation, drowsiness, and related effects when both Benadryl and Zyrtec are taken together.

One situation where it may be OK to take both close to each other is in the event of an allergic reaction.

It is thought that Benadryl is slightly more effective than Zyrtec at stemming an anaphylactic reaction, such as the reaction some people have to bee stings. The second-generation antihistamines (which includes Zyrtec), while likely beneficial, aren't thought to be quite as effective in these situations.[3][4]

If you take Zyrtec on a daily basis for your seasonal allergies and were in a situation where you were having a serious allergic reaction, Benadryl may be an appropriate choice to add on before you make it to the hospital.

Another situation may be 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 for example.

Taking Zyrtec in the morning and Benadryl (or diphenhydramine) in the evening for a short amount of time most likely won't cause significant issues. Be sure to only do so under the direction of your doctor, however.

Benadryl Information

Benadryl is a first-generation antihistamine. The duration of action of the drug is typically 4-6 hours per dose (25 mg to 50 mg).[5]

The first-generation antihistamines are known for their sedative effects and CNS depressant effects. Many patients cannot tolerate this drug except if it is given at bedtime due to the sedation it causes. Even then, some people experience a hangover effect the next morning.

Zyrtec Information

Zyrtec is a second-generation antihistamine. Most second-generation antihistamines are not associated with sedation although Zyrtec does appear to cause some drowsiness in a small percentage of people (~10%).[6]

After dosing, the antihistamine effects occur quickly, within one hour. Each dose lasts around 24 hours.

Zyrtec is also available in combination with other drugs, like nasal decongestants (e.g. Zyrtec-D)

  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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Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor of Pharmacy degree in 2010. He has been featured in numerous publications including the Huffington Post as well as a variety of health and pharmacy-related blogs. Please feel free to reach out to him directly if you have any inquiries or want to connect! He's answered thousands of medication and pharmacy-related questions and he's ready to answer yours! Brian.Staiger@PharmacistAnswers.com Office: 716-389-3076

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