How Long After Zyrtec Can You Take Benadryl?

In our latest question and answer, the pharmacist discusses how long after taking Zyrtec you can safely take Benadryl.


I’m having an allergic reaction from going through musty files from last night for 2.5 hours. My nose wouldn't stop running all day today. I took a dissolvable Zyrtec at 5:30 PM, can I now take a Benadryl tonight at 11:30 PM?

Asked by Patti On Oct 05, 2021

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Oct 05, 2021
Last updated Jun 14, 2024

Key points

  • Benadryl (diphenhydramine) and Zyrtec (cetirizine) are both antihistamines, and generally should not be taken together.
  • Taking both together could increase the risk of side effects such as dizziness and constipation.
  • Since Zyrtec lasts around 24 hours per dose, you ideally want to separate it from Benadryl for that period of time.
  • There are some situations where it may be safe to take both Benadryl and Zyrtec on the same day, it just shouldn't be done on a consistent basis.


Taking Zyrtec (cetirizine) and Benadryl (diphenhydramine) at the same time should only be done with caution due to the risk of increased adverse events.

If you are looking to take Benadryl after a dose of Zyrtec, you ideally want to wait 24 hours (as that is the length of time Zyrtec works), but there are situations where your doctor may recommend taking it soon.

Potential Side Effects Of Taking Both Together

Both Benadryl and Zyrtec are antihistamines and they work the same way. Taking them together greatly increases the risk of side effects such as:

  • Drowsiness
  • Dry mouth
  • Dizziness
  • Constipation
  • Dry eyes

Can You Take Benadryl After Zyrtec?

Zyrtec is a "second-generation" antihistamine, with a duration of action of around 24 hours while Benadryl is a "first-generation" antihistamine, and lasts only four to six hours per dose.

Since Zyrtec lasts around 24 hours, to best avoid additive side effects, Benadryl should ideally be taken 24 hours after your last Zyrtec dose.

One situation where taking both within a 24 window may be recommended, however, is if you are experiencing a mild allergic reaction.

Although data from studies are mixed, Benadryl may be slightly better at stemming the symptoms of an allergic reaction (e.g. inflammation, itching) than newer, second-generation antihistamines, like Zyrtec and Allegra.

It doesn't seem as though Benadryl is markedly better than the newer antihistamines in this regard, but some people do tend to respond better to it.

While you may be at an increased risk of certain side effects (such as drowsiness) from taking Benadryl and Zyrtec close together, they typically are mild in severity, and the benefits of taking Benadryl to lessen the effects of an allergic reaction could outweigh the risk of the mild side effects in most people.

In addition, your doctor may recommend you take Benadryl for allergy symptoms that are severe, and don't seem to lessen after taking your Zyrtec.

In general, they just shouldn't be taken together on a daily basis, only as needed intermittently.

Lastly, it's not uncommon to use Benadryl to help sleep at night, even if you are taking a daily antihistamine. Again, it shouldn't be a daily occurrence but is generally considered safe for most when done intermittently.

Final Words

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  • Diphenhydramine Monograph, PubChem
  • Cetirizine Monograph, PubChem
  • Time-dependent inhibition of histamine-induced cutaneous responses by oral and intramuscular diphenhydramine and oral fexofenadine, PubMed

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at [email protected]! You can also connect with Dr. Brian Staiger on LinkedIn.

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