Benadryl (Diphenhydramine) Interaction With Prozac (Fluoxetine)

In our latest question and answer, our pharmacist discusses whether or not there is an interaction between Benadryl & Prozac.


Can I take diphenhydramine while taking Prozac?

Asked by Mena On Oct 05, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Oct 05, 2022
Last updated Jun 03, 2023

Key points

  • Taking Benadryl and Prozac together could increase the risk of side effects, such as dizziness and sedation.


There is a minor interaction between Prozac (fluoxetine) and Benadryl (diphenhydramine).

Although they are generally considered safe to use together, it is important to keep in mind that both medications can cause sedation and dizziness.

More Detail

Benadryl is well known to cause sedation and is often used as a nighttime sleep aid. Prozac can cause sedation in certain people, especially when you first begin therapy. If Prozac is new to you, it generally is recommended to take it in the evening until you know how it may affect you.

Additionally, Prozac can inhibit a metabolizing enzyme responsible for breaking down Benadryl (CYP2D6). Co-administration can increase levels of Benadryl in our body, potentially increasing the risk of side effects, such as sedation.

Again, this interaction is considered relatively minor, and these drugs are often used together. Just be aware of the potential increase in sedative effects and aside from the possible additive sedative effect, you should not have any problems taking both Prozac and Benadryl together.

Final Words

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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! You can also connect with Dr. Brian Staiger on LinkedIn.

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