Benadryl (Diphenhydramine) With Zyrtec-D (Cetirizine; Pseudoephedrine)

Benadryl and Zyrtec-D generally shouldn't be taken together as they both contain antihistamines.

Nov 06, 2018

Victoria asked

Is it safe to take Benadryl after taking Zyrtec-D 12 hours apart?

At a glance

  • Taking two antihistamines at the same time generally won't result in better effects and may increase the risk of side effects. However, Benadryl may be recommended for you to take if you are having an allergic reaction.
  • Benadryl and Zytec-D both contain antihistamines and generally should not be used together.


Benadryl (diphenhydramine) and Zyrtec-D (cetirizine; pseudoephedrine) generally should not be taken at the same time as they both contain an antihistamine.

The active ingredient in Benadryl is diphenhydramine, a 'first-generation' antihistamine, while the active ingredients in Zyrtec-D are cetirizine, a 'second-generation' antihistamine, and pseudoephedrine (nasal decongestant).

Taking both Zyrtec-D and Benadryl at the same time would be considered a therapeutic duplication, potentially increasing the risk of side effects.

However, as per your question, you could safely take Benadryl first, then take Zyrtec-D 12 hours apart.

Benadryl has a short duration of action, around four to six hours for most individuals. 12 hours after taking Benadryl would typically be enough time for the effects of the drug to wear off, making it safe to take Zyrtec-D.

About Zyrtec

Zyrtec (cetirizine) is a 'second-generation' antihistamine, indicated for the treatment and prevention of perennial allergies, seasonal allergies and hives.

'Second-generation' antihistamines include:

  • Zyrtec
  • Allergra (fexofenadine)
  • Claritin (loratadine)

'Second-generation' antihistamines differentiate themselves from 'first-generation' antihistamines in a few key areas, including duration of action and sedative side effects. One dose will typically last around 24 hours and have a low incidence of sedation.

However, at indicated doses (5mg and 10mg), Zyrtec has a higher incidence of sedation than other second-generation antihistamines, such as Allegra (fexofenadine) and Claritin (loratadine).

Nevertheless, it still causes less sedation than older, 'first-generation antihistamines' such as Benadryl.

Zyrtec is taken once daily, with an onset of action around one hour.

About Benadryl

Benadryl (diphenhydramine) is a 'first-generation', sedating antihistamine (H1-blocker) of the ethanolamine class.

Due to the sedative properties of Benadryl, it is a common ingredient in over the counter sleep aid products, like ZzzQuil.

It also has potent "drying" effects in many, which is why it causes dry mouth, dry eyes, and constipation.

The onset of action of Benadryl is around 15-30 minutes after taking by mouth, with peak effects occurring 1 to 3 hours later.

The duration of action is around 4 to 6 hours, with this being prolonged in the elderly and in those with liver disease.

  1. ClinicalKey: Lithium Monograph. ClinicalKey (Subscription Required)
  2. Time-dependent inhibition of histamine-induced cutaneous responses by oral and intramuscular diphenhydramine and oral fexofenadine. PubMed
  3. Zyrtec-D Monograph. ClinicalKey (Subscription Required)

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