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Zyrtec vs Benadryl – Exploring Differences, Uses, and Side Effects

Last Updated: February 26, 2024

Reviewed by David Levin

Allergies have a knack for turning the joy of blooming flowers or a good plate of food into a rash, sneezing, itchy-eyed ordeal.

Data from the CDC’s National Center for Health Statistics revealed that in 2021, nearly 1 in 3 U.S. adults and more than 1 in 4 U.S. children experienced a seasonal allergy, eczema or food allergy, thus finding the right antihistamine to relieve allergy symptoms is crucial.

Most people rely on two over-the-counter (OTC) popular choices: Zyrtec and Benadryl. Read on to explore the differences between Zyrtec vs Benadryl and their uses and side effects to help you make an informed decision about your health.

What are Antihistamines?

Antihistamines are a class of medications that work to counteract the effects of histamine, a natural substance produced by the body during an allergic reaction.

Histamine is responsible for itching, sneezing, runny nose, and watery eyes. Antihistamines block histamine receptors, preventing or reducing these allergy symptoms. Zyrtec and Benadryl are popular OTCs indicated for the temporary relief of these symptoms.

Benadryl (Diphenhydramine)

Trade name: Benadryl®

Generic name: Diphenhydramine

Diphenhydramine is a first-generation antihistamine (developed in the 1940s and 1950s) that competes with histamine for binding to H1 receptors. By blocking these receptors, Benadryl prevents histamine from exerting its effects.

Benadryl is commonly used to relieve symptoms such as itching, sneezing, and runny nose due to allergic reactions or the common cold. Due to its short duration of action may cause drowsiness, making it suitable for nighttime use.

Zyrtec (Cetirizine)

Trade name: Zyrtec®

Generic name: Cetirizine

Cetirizine is a second-generation antihistamine (developed in the 1980s and 1990s) that also works by blocking H1 receptors. It has a more selective action on peripheral receptors, minimizing central nervous system (CNS) effects and drowsiness compared to first-generation antihistamines.

Zyrtec is commonly used to relieve allergy symptoms such as sneezing, itching, and runny nose. It is known for having a longer duration of action, providing 24-hour relief from allergy symptoms and is considered non-sedating, making it suitable for daytime use.

4 Clinical Differences between Zyrtec vs Benadryl

While both Benadryl and Zyrtec are antihistamines used to treat allergies, they differ in several critical clinical aspects:

Zyrtec and Benadryl Development Generation

Drug generation is pivotal in determining their pharmacological characteristics, biological targets, and clinical applications.

  • First-generation Benadryl: Developed in the mid-20th century, Benadryl is a first-generation antihistamine characterized by its ability to pass the blood-brain barrier, exhibiting antihistaminic effects and sedative properties.
  • Second generation Zyrtec: Refined in the late 20th century, drugs like Zyrtec (Cetirizine) aimed for selectivity, focusing primarily on peripheral H1 receptors and diminished ability to penetrate the central nervous system. This resulted in significantly reduced drowsiness and a more targeted approach to allergy relief.

Mechanism of Action Zyrtec vs Benadryl

Allergic reactions result from an exaggerated immune response to allergens.

The mechanism of action of Benadryl (diphenhydramine) and Zyrtec (cetirizine) focuses on modulating the excessive immune response characteristic of allergic reactions.

  • Benadryl mechanism of action: Benadryl blocks H1 receptors in various tissues, causing comprehensive histamine receptor blockade. Its non-selective nature extends to the central nervous system, causing allergy relief and inducing sedation as a side effect.
  • Zyrtec mechanism of action:  Zyrtec selectively targets peripheral H1 receptors, minimizing penetration of the blood-brain barrier. This focused action reduces sedation compared to first generation antihistamines like Benadryl.

Onset of Action Zyrtec vs Benadryl

The onset of action of antihistamines is a critical consideration in managing allergic reactions, particularly significant for acute food allergies.

Diphenhydramine is mainly chosen for acute food allergies. Benadryl acts within 15-60 minutes providing rapid relief but a shorter duration of action. Its sedating nature requires careful consideration in evaluating patients during acute allergic reactions.

Cetirizine has an onset of 20–60 minutes and an extended duration of action (≥24 hours). Zyrtec’s focus on peripheral H1 receptors causes a slightly delayed onset, allowing the medication to engage with these receptors throughout the body effectively. Zyrtec offers prolonged relief from allergic symptoms, administered in one daily dose.

Patient Suitability Zyrtec vs Benadryl

Patient suitability for administering Zyrtec or Benadryl involves considering factors such as:

Age Groups

  • Zyrtec: Generally suitable for adults and children. Zyrtec is commonly used for long-term allergy management in children due to its non-sedating nature.
  • Benadryl: While suitable for adults and children, Benadryl is not recommended for adults age 65 and older as its side effects can be exaggerated. Its sedative effects may limit its use in some cases.

Pregnancy & Breastfeeding

  • Zyrtec: Generally, Zyrtec is safe during pregnancy and breastfeeding. However, it’s advisable to consult with a healthcare professional before using any medication during pregnancy or breastfeeding.
  • Benadryl: Also generally considered safe during pregnancy and breastfeeding, particularly for short-term use. Again, consultation with a healthcare provider is recommended.

Certain Medical Conditions

  • Zyrtec: Generally well-tolerated in individuals with conditions like hypertension, but caution is advised in individuals with liver impairment.
  • Benadryl: Should be used cautiously in individuals with certain medical conditions, such as narrow-angle glaucoma, prostatic hypertrophy, and cardiovascular diseases due to its anticholinergic effects.

Similar Side Effects of Zyrtec and Benadryl

Some of the similar side effects of diphenhydramine and cetirizine include:

  • Severe: Anaphylaxis, bronchospasm, hemolytic anemia, seizures
  • Moderate: Blurred vision, constipation, dermatitis, euphoria, thrombocytopenia, urinary retention
  • Mild: Abdominal pain, appetite stimulation, asthenia, drowsiness, diarrhea, dizziness, dry mouth, dry eyes, fatigue, headache, hyperhidrosis, insomnia, increased urinary frequency, paresthesias, photosensitivity, rash, tinnitus, urticarial, vertigo, weakness, weight gain

Zyrtec vs Benadryl Drug Interactions

Both medications may interact with other drugs. Zyrtec tends to have fewer interactions than Benadryl, which may interact with medications affecting the central nervous system.

Zyrtec (Cetirizine) Drug Interactions

Zyrtec (Cetirizine) may cause increased drowsiness when used with:

  • Opioid pain relievers (codeine, hydrocodone)
  • Alcohol
  • Marijuana (cannabis)
  • Sleep/anxiety drugs (alprazolam, lorazepam, zolpidem)
  • Muscle relaxants (carisoprodol, cyclobenzaprine)
  • Other antihistamines (chlorpheniramine, diphenhydramine)

Benadryl (Diphenhydramine) Drug Interactions

Benadryl (Diphenhydramine) may interact with:

  • Monoamine oxidase inhibitors (MAOIs)
  • Over-the-counter cough, cold, allergy, or insomnia medications
  • Anxiety or sleep medicines, antidepressants
  • Medications causing drowsiness, sleepiness or relaxation
  • Anticholinergic drugs
  • Benadryl interacts with alcohol
  • Marijuana

Choosing Zyrtec vs Benadryl: The Right Antihistamine for You

In selecting between Zyrtec and Benadryl, consider your specific needs and lifestyle. Zyrtec is a convenient once-daily tablet offering non-sedating relief, suitable for day and long-term use, while Benadryl can be purchased in tablets and gel, effective for nighttime use and acute allergy reactions.

Natural remedies for mild allergy management are also a complementary option. Remember that Zyrtec and Benadryl shouldn’t be taken together. Consult a doctor to explore the full range of options for personalized allergy care!

People Also Ask

Which one is better Zyrtec or Benadryl?

Zyrtec is often preferred for long-term use due to its non-sedating nature and once-daily dosing. Benadryl is effective for acute situations but may cause sedation. The choice depends on the specific needs and circumstances.

Why is Zyrtec better?

Zyrtec is often considered better due to its non-sedating profile, longer duration of action (up to 24 hours), and once-daily dosing. It provides effective and sustained allergy relief with minimal impact on alertness.

What is stronger than Benadryl antihistamine?

Several antihistamines, like cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra), are considered equally effective or stronger than Benadryl without causing as much sedation.

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Retrieved on February 26, 2024.

Published on: June 5th, 2019

Updated on: February 26th, 2024

María José Petit-Rodríguez

About Author

María José Petit-Rodríguez

Medically Reviewed by

David Levin

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