Taking Benadryl With Primatene (Ephedrine)

In our latest question and answer, the pharmacist discusses whether or not there is an interaction between Primatene (ephedrine) and Benadryl (diphenhydramine).

May 09, 2018

Richard asked

Instead of my albuterol inhaler, I'll use over the counter Primatene Mist and Benadryl. Wanted to make sure that was considered okay.


Primatene and Benadryl do not have any known drug interaction. However, they do have opposing effects of sedation and stimulation. Taking them together may reduce the sedation from Benadryl or the stimulation from Primatene.


Primatene is a combination product that includes ephedrine and guaifenesin. It is most commonly used to treat mild asthma symptoms. The ephedrine causes a change in the vessels in the lungs to allow for patients to take deeper breaths while the guaifenesin works by breaking up the mucus found in the lungs to aid in allowing the body to expel the congestion.

Ephedrine is considered a stimulant and can cause an increase in blood pressure and heart rate, so it should be used cautiously in patients who have underlying heart conditions. Further this medication should only be used in patients who have a diagnosis of asthma. Patients should notify their physician if asthma symptoms become worse during the use of Primatene.


Benadryl is an antihistamine, used to treat allergic reactions and also commonly used as a sleep aid. This medication works by blocking the binding of histamine to its receptors in the body. histamine is a molecule that causes the symptoms of allergic reactions, like a runny nose, rash, and itching.

The most common side effects seen with the use of Benadryl is:

  • Sedation
  • Confusion
  • Constipation
  • Urinary retention

Benadryl has been placed on the Beer’s list because of the sedation that is commonly seen. Taking Benadryl places patients over the age of 65 years of age at greater risk of falling and developing delirium. 

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