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Zyrtec vs. Benadryl

Compare OTC Allergy Medications: Zyrtec vs. Benadryl

Zyrtec (cetirizine) and Benadryl (diphenhydramine) are two popular over-the-counter medications used to treat allergies. These medications work in different ways, so read on to learn more about these medications and which one may work best at relieving those pesky seasonal allergy symptoms.

Check out the Claritin vs. Zyrtec blog as well.

How do they work?
Both Zyrtec and Benadryl work by blocking histamine, a natural substance that your body makes during an allergic reaction. Histamine is responsible for allergy symptoms like sneezing, runny nose, itchy or watery eyes, and itchy nose or throat. By binding to histamine receptors in your body, Zyrtec and Benadryl prevent histamine from attaching to your cells and causing allergy symptoms.

Benadryl is a first-generation antihistamine and differs from Zyrtec because it causes marked sedation, or drowsiness. Zyrtec is considered a second-generation antihistamine and is much less likely to cause drowsiness, although may still cause some mild sleepiness in some patients.

What type of allergic conditions do they treat?
Benadryl is approved by the FDA for the treatment of seasonal allergies in patients 6 years of age and older, use in addition to epinephrine for anaphylaxis, occasional insomnia, prevention or treatment of motion sickness, and the management of symptoms such as shaking caused by other medications (sometimes known as parkinsonism or dystonia). Although not approved by the FDA, it is sometimes also used for the treatment of nausea and vomiting in pregnancy, hives, and vertigo.

Zyrtec is approved to treat seasonal allergies in anyone 2 years of age or older. It is also approved to treat hives, which may be caused by an allergic reaction. Although not approved by the FDA, Zyrtec has also been used off-label to treat skin-related symptoms of severe allergic reactions.

Which is more effective?
Both Zyrtec and Benadryl are very effective at relieving allergy symptoms. If your allergy symptoms are more skin related, Benadryl may be more effective for you. Benadryl is very likely to cause sedation, but Zyrtec may also cause some drowsiness. If you drink alcohol or are taking any other medications that affect your CNS such as sedatives or anxiety medications, you should not take Benadryl or Zyrtec without talking to your doctor first.

Zyrtec should treat your allergy symptoms for at least 24 hours with just one dose, while Benadryl needs to be taken every 4-6 hours to continue relieving symptoms. The duration of action for Benadryl can also vary drastically from patient to patient depending on age – if you are 65 years of age or older, you should be especially careful when taking Benadryl.

How much do they cost?
Benadryl is often less expensive than Zyrtec but does need to be taken more often to control allergy symptoms all day. Because they are available over-the-counter, your insurance is not likely to pay for either of these medications. They are both available as generics, which are often less expensive than brand-name versions.

What are some common side effects?
Benadryl may cause some serious, dose-dependent side effects called anticholinergic side effects. These side effects are more likely to affect older patients and may include:

  • Blurred vision
  • Dry mouth
  • Urinary retention
  • Rapid heart beat
  • Nausea or constipation
  • CNS effects (such as agitation, confusion, delirium, or sedation)

Zyrtec’s side effects are generally milder but may include:

  • Dry mouth
  • Headache
  • Mild drowsiness
  • Fatigue

Zyrtec is a first-line over-the-counter treatment for allergy symptoms such as sneezing, runny nose, and itchy, watery eyes. In some people, Zyrtec may cause slight drowsiness. Benadryl is best used for allergic skin reactions or at the specific direction of your doctor because of the potential for serious side effects, including significant sedation.

  1. Kuna, P., Jurkiewicz, D., Czarnecka-Operacz, M. M., Pawliczak, R., Woroń, J., Moniuszko, M., & Emeryk, A. (2017). The role and choice criteria of antihistamines in allergy management–Expert opinion. Alergologia Polska-Polish Journal of Allergology, 4(1), 7-19.
  2. Marion, DW. Cetirizine. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2021.
  3. Marion, DW. Diphenhydramine. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2021.

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Dr. Joanna L. Hodder

Dr. Joanna L. Hodder is a transitions of care pharmacist for a large hospital system in Denver, Colorado. She received her BA in English Literature from Iowa State University and PharmD from University of Minnesota College of Pharmacy. Dr. Hodder completed a post-graduate year 1 (PGY-1) residency at Northeast Iowa Family Practice Center, where she delivered quality patient care in both hospital and primary care settings. She is passionate about empowering patients to take charge of their health through evidence-based education and improving access to medications. When she isn’t working closely with patients, Dr. Hodder enjoys gardening, hiking with her dog, and yoga.




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