Benadryl (Diphenhydramine) With Sudafed (Pseudoephedrine) Interaction
In our latest question and answer, the pharmacist discusses whether or not there is an interaction between Benadryl and Sudafed.

Question
Is it OK to take Benadryl and pseudoephedrine together? (I’m also on 20mg prednisone 2 x daily and Mucinex)

Answered by Dr. Brian Staiger, PharmD
Medical Content Reviewed By HelloPharmacist
Staff
Last updated May 10, 2025
Key points
- There is no drug interaction between Benadryl (diphenhydramine) and Sudafed (pseudoephedrine). They are safe to take together.
- There are several products on the market that contain both an antihistamine and nasal decongestant, such a Zyrtec-D and Claritin-D/
Answer
There is no drug interaction between Benadryl (diphenhydramine) and Sudafed (pseudoephedrine). They are safe to take together. In fact, the use of an antihistamine (like Benadryl) and a decongestant (like Sudafed) is a very common, and safe, combination.
Other antihistamine-decongestant combinations include:
- Claritin-D (loratadine with pseudoephedrine)
- Zyrtec-D (cetirizine with pseudoephedrine)
- Allegra-D (fexofenadine with pseudoephedrine)
I do want to mention here that while Benadryl is a good option to help with allergies, it has a very short duration of action (around 4 to 6 hours). If you are looking to treat seasonal allergies that happen to you on a daily basis, one of the above options may be more convenient as they last 24 hours per dose.
Additional Information
Benadryl and Sudafed are also safe to take with Mucinex and prednisone. The only potential issue is that prednisone can be stimulating in certain individuals. Sudafed can do the same. This additive effect will likely be mild if it happens at all but can certainly cause insomnia if taken too close to bedtime.
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Dr. Brian Staiger, PharmD
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