Taking Benadryl With Excedrin PM

In our latest question and answer, the pharmacist discusses whether or not there is a drug interaction between Benadryl and Excedrin PM.

Taking Benadryl With Excedrin PM
Apr 27, 2018

Jamie asked

Excedrin PM doesn't work well enough at night. Is it safe to take Benadryl with it?


Excedrin PMExcedrin PM and Benadryl should not be used together. Excedrin PM contains diphenhydramine, the same active ingredient in Benadryl. Using these medications together will result in additive effects and an increased risk of side effects.

Excedrin PM

Excedrin PM is a night time pain reliever that contains:

  • Acetaminophen
  • Diphenhydramine
  • Aspirin

Diphenhydramine is used in Excedrin PM for its sedative effects. Excedrin PM will generally begin working in 30 minutes to 1 hour and will last around 6 to 8 hours per dose.


Benadryl (diphenhydramine) is a first-generation antihistamine, commonly used to treat allergic reactions, hives and motion sickness. As Benadryl is sedating for most individuals, it is a common ingredient in night time sleep aids, like Excedrin PM

Taking Benadryl With Excedrin PM

As Benadryl and Excedrin PM both contain diphenhydramine, they should not be used together. Doing so will increase the risk of side effects such as:

  • Sedation
  • Confusion
  • Dry mouth
  • Dry eyes
  • Rapid hear beat
  • Respiratory depression

If both Excedrin PM and Benadryl are to be taken the same day, they should be separated by at least 6 hours.

Ready for a more personal experience with your meds?