There are no drug interaction between Benadryl (diphenhydramine) and Sudafed (pseudoephedrine). They are safe to take together. In fact, the combination of an antihistamine (like Benadryl) and a decongestant (like Sudafed) is a very common drug combination.


Other antihistamine-decongestant combinations include:

  • Claritin-D (loratadine with pseudoephedrine)
  • Zyrtec-D (cetirizine with pseudoephedrine)
  • Allegra-D (fexofenadine with pseudoephedrine)


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, 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.