There are no reported interactions between Benadryl and Excedrin. They are considered safe to take together.


Excedrin is a combination drug product, which contains the following active ingredients:

  • Acetaminophen
  • Caffeine
  • Aspirin

Excedrin is an over the counter pain reliever that is often used to treat minor pains like migraines or other body aches. While the aspirin and acetaminophen components in Excedrin are responsbile for the relief of pain, the caffeine works by boosting the effects that these drugs exert on the body. Various studies have reported that caffeine can improve symptom relief by up to 40% compared to when either of these medications are used alone.


Benadryl is a 1st generation antihistamine that works by blocking the release of histamine. Histamine release is commonly associated with symptoms like itching, watery eyes, runny nose and inflammation. Antihistamines, like Benadryl, are most commonly used for the treatment of cold like symptoms or seasonal allergy symptoms. 

Benadryl is also used as a sleep aid, due to its sedative effects.


  • Benadryl and Excedrin are considered safe to take together.