Benadryl Vs. Zyrtec: What Is The Difference?

Benadryl and Zyrtec are 'antihistamines' but there are significant differences between them!

Benadryl Vs. Zyrtec: What Is The Difference?
Aug 10, 2018

Sami asked

Can you let me know how Benadryl and Zyrtec are different? What characteristics separate them?

At a glance

  • There are several differences between Zyrtec and Benadryl, even though they are both antihistamines.
  • Most notably, Benadryl is a 'first-generation' antihistamine, which are known to cause sedation. Zyrtec is a 'second-generation' antihistamine and has a lower risk of sedative effects.
  • Additional differences between the two include how long they last per dose and what they can be used for.


Zyrtec Vs Benadryl

While Benadryl (diphenhydramine) and Zyrtec (cetirizine) are both classified as antihistamines, there are significant differences between them, including:

  • Classification
  • Dosing
  • Indications
  • Effectiveness
  • Side Effects

Below, we discuss each of these differences in detail and provide information to help you decide which will be best for you in a given situation.

Benadryl Vs. Zyrtec: Classification

Antihistamines are grouped largely by their 'generation' in regard to the time in which they were developed and made commercially available.

Benadryl is a 'first-generation' antihistamine in the ethanolamine class of drugs. 'First-generation' antihistamines are typically associated with:

  • A relatively short duration of action (around 4-12 hours).
  • Significant sedative and anticholinergic effects.

Zyrtec is a "second-generation" antihistamine in the piperazine class of drugs. They are structurally related to ethanolamines but have a:

  • Longer duration of action (12-24 hours).
  • Low to moderate sedative and anticholinergic effects.

Benadryl Vs. Zyrtec: Dosing

How each is dosed shows significant differences in the duration of action of each.


Benadryl has a duration of action of around 4 to 6 hours, although this can be prolonged in those with liver disease or in the certain populations like the elderly. In addition, some individuals can be 'slow-metabolizers' or 'fast-metabolizers' of Benadryl, which alters how long the effects last for.

Benadryl is typically dosed at 25 to 50 mg at 4 to 6 hour intervals.


Zyrtec has a duration of action of 24 hours, which is the claim to fame of most 'second-generation' antihistamines. This long duration of action allows it to be dosed only once a day, which is ideal for treating perennial and seasonal allergy symptoms.

The most common dose of Zyrtec is 10 mg once daily, although low doses of Zyrtec twice daily can be used in young children for certain indications, like atopic dermatitis (i.e. eczema).

Benadryl Vs. Zyrtec: Indications

Both Benadryl and Zyrtec can be used to treat allergy symptoms. When it comes to seasonal or perennial allergies, Zyrtec is more often preferred due to its longer duration of action.

Other than your run-of-the-mill allergy symptoms, both can be effective for:

  • Runny nose
  • Watery eyes
  • Urticaria (hives)
  • Itching
  • Dermatitis

In addition to the above, Benadryl is commonly used as an over the counter sleep aid, due to its sedative effects and short duration of action. In fact, diphenhydramine is an active ingredient in many over the counter products marketed for sleep including ZzzQuil.

Lastly, it comes to allergic reactions (e.g. drug induced), there is some controversy in regard to which is more effective.

This is discussed in the next section but it should be noted that Benadryl still hold preferential treatment for most allergic reactions.

This is best exemplified by the ACIP (Advisory Committee on Immunization Practices) recommendations to use diphenhydramine (active ingredient in Benadryl) for vaccine induce anaphylaxis, although the specific recommendation is injectable diphenhydramine.

Benadryl Vs. Zyrtec: Effectiveness

Both Benadryl and Zyrtec have shown comparable activity and efficacy when it comes to the treatment of allergic symptoms, and choice of either is typicality based on patient preference and desired characteristics (e.g. duration of action) .

It is commonly thought that 'first-generation' antihistamines like Benadryl are more effective for allergic reactions (e.g. bee stings, drug related, food related) than newer agents, but a variety of studies have reported that Zyrtec not only has similar efficacy, but it also works just as fast.

A popular and informative way antihistamines are tested is by inducing a 'wheal and flare' reaction in an individual via an injection of histamine and measuring response to a given drug in terms of relief of inflammation, redness and itching. Zyrtec consistently produces results comparable to Benadryl.

For the treatment of atopic dermatitis (i.e. eczema), results from studies are mixed. Efficacy is similar between Zyrtec and Benadryl but Benadryl certainly has more published evidence.

It is important to note that Zyrtec is used 'off-label' for atopic dermatitis while Benadryl is FDA approved for the symptomatic treatment of it.

Benadryl Vs Zyrtec: Side Effects

Perhaps the biggest difference between Benadryl and Zyrtec is the side effect profile of each.

Benadryl is well known to cause both sedation and somnolence. Zyrtec on the other hand, being a 'second-generation' antihistamine, is less associated with sedation. While most second-generation antihistamines (e.g. Claritin) are in fact 'non-drowsy', Zyrtec is not labeled as such, but produces far less sedation than Benadryl.

Multiple studies have reported that Benadryl, when compared to antihistamines like Zyrtec, is more strongly associated with:

  • Sedation
  • Drowsiness
  • Decreased mental performance
  • Decrease motor performance
  • Decreased ability to concentrate

Per the prescribing information for Zyrtec, the overall incidence of sedation and somnolence is around 10-15%. Benadryl causes sedation in more than 20-30% of individuals. The doses of Benadryl used for sleep (50 mg) cause an even higher incidence.

Lastly, due to stronger anticholinergic effects, Benadryl is also associated with a slightly higher incidence of:

  • Dry mouth
  • Dry eyes
  • Constipation
  • Heart palpitations (high doses)
  • Respiratory depression (high doses)

Final Words

Choosing between Benadryl and Zyrtec depends on what you are looking for in either drug.

For consistent allergy symptoms, Zyrtec is likely the better choice due to its long duration of action and lower incidence of sedation. For the treatment of insomnia, Benadryl is likely more effective due to its strong sedating effects.

For allergic reactions to food and drugs, evidence is mixed. Zyrtec may be just as beneficial as Benadryl and offer a lower risk of side effects. This is a more commonly accepted use of Benadryl however and it is the recommended agent of choice for vaccine induced allergic reactions (via IM injection).

Let us know which antihistamine you prefer and your experiences with them in the comment section below!

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