Zyrtec vs. Benadryl: Which works better? (2024)

| Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Sneezing, runny eyes, feeling itchy all over—these are typical allergy symptoms that can make you feel miserable. If you suffer from allergy symptoms, you’re not alone. Over 50 million Americans experience allergies throughout the year. Allergies are the sixth leading cause of chronic illness every year.

There is no cure for allergies, but you’ll undoubtedly see plenty of allergy medications when visiting your local pharmacy. Zyrtec and Benadryl are two popular over-the-counter (OTC) medications used to alleviate allergy symptoms. Both medicines are approved by the United States Food and Drug Administration (FDA).

Zyrtec and Benadryl are antihistamines, or H1 receptor blockers. They work by blocking histamine. Histamine is a substance your body makes during an allergic reaction, causing those pesky symptoms. By blocking histamine, Zyrtec and Benadryl help relieve allergy symptoms.

Benadryl (diphenhydramine) is a first-generation antihistamine. First-generation antihistamines tend to cause more sedation and drowsiness and can impair coordination and driving. Zyrtec (cetirizine) is a second-generation antihistamine. Although Zyrtec (Zyrtec details) can still cause drowsiness and other side effects, the drug tends to cause less drowsiness and fewer side effects in general and is safer if you need to drive or operate machinery.

What are the main differences between Zyrtec and Benadryl?

Zyrtec and Benadryl are brand names for cetirizine and diphenhydramine, respectively. Zyrtec and Benadryl are both antihistamines that block histamine receptors and provide allergy relief. Both products are available in brand and generic and in various formulations to suit multiple ages and patient preferences.

Conditions treated by Zyrtec and Benadryl

When the FDA approved Zyrtec as a prescription product in 1995, it had three indications: to treat seasonal allergic rhinitis, perennial allergic rhinitis, or chronic urticaria. Zyrtec has been available over the counter since 2007. While those indications still apply, the packaging information states that Zyrtec is used for temporary relief of runny nose, sneezing, watery or itchy eyes, and itching of the nose/throat due to hay fever or other respiratory allergies.

Benadryl’s packaging information states that the medication can be used for temporary relief of allergy symptoms (runny nose, sneezing, itchy or watery eyes, itching of the nose and throat) caused by hay fever or other allergies. Benadryl is also used to treat runny noses and sneezing from the common cold.

Is Zyrtec or Benadryl more effective?

There is very little data comparing the oral forms of Zyrtec and Benadryl. One study compared the two medications for food allergies. The study concluded that Zyrtec was similar to Benadryl’s effectiveness and took the same amount of time to start working. Zyrtec also had a longer duration of action (lasted longer).

A literature review of Benadryl compared to non-sedating antihistamines concluded that all antihistamines were similarly effective, but that the newer antihistamines, like Zyrtec, caused less sedation.

The Canadian Society of Allergy and Clinical Immunology (CSACI) recommends that newer antihistamines like Zyrtec be used in favor of older antihistamines like Benadryl. The CSACI says that the newer antihistamines are safer, less-sedating, and more effective. They state that Benadryl is associated with significant side effects like sedation, poor sleep, and motor impairment, potentially leading to accidents and death, and should only be used as a last resort.

Because both Zyrtec and Benadryl are OTC, the most effective medication for you can be determined by trial and error to see which medication helps your symptoms while causing the least side effects. Your healthcare provider can guide you with product selection as well.

Coverage and cost comparison of Zyrtec vs. Benadryl

Because they are available over-the-counter, Zyrtec and Benadryl are not usually covered by insurance or Medicare Part D or Advantage plans. Some exceptions may apply.

A box of 30 tablets of 10 mg cetirizine (generic Zyrtec) costs about $12. A SingleCare card can bring the price down to about $5 if you have a doctor’s prescription.

A box of 24 tablets of 25 mg diphenhydramine (generic Benadryl) costs about $9. A SingleCare card can drop the cost to approximately $4 if you have a prescription from a doctor.

Get the SingleCare prescriptions discount card

Common side effects of Zyrtec vs. Benadryl

Zyrtec and Benadryl have similar side effects. The most common side effects are sleepiness or drowsiness, fatigue, dry mouth, dizziness, and headache.

This is not a full list of side effects. Other adverse effects may occur. Consult your healthcare provider for professional medical advice.

Source: FDA Label (Zyrtec), Prescribers’ Digital Reference (Benadryl)

Drug interactions of Zyrtec vs. Benadryl

You should not take Zyrtec or Benadryl with alcohol or sedating medications due to additive respiratory and/or central nervous system effects. The combination could cause slowed breathing as well as excess dizziness, drowsiness, and psychom*otor impairment. Benadryl also should not be taken with potassium products in solid dosage forms due to the risk of ulcerative lesions.

This chart is not a full list of drug interactions. Other drug interactions may occur. Consult your healthcare provider for a complete list of drug interactions.

Warnings of Zyrtec and Benadryl

• Do not use Zyrtec or Benadryl if you have ever had an allergic reaction to either product.
• Do not use Zyrtec if you have ever had an allergic reaction to an antihistamine called hydroxyzine.
• Consult your healthcare provider before using Zyrtec or Benadryl if you have liver or kidney problems.
• Consult your healthcare provider before using Zyrtec or Benadryl if you take any sedating medications.
• Zyrtec or Benadryl may cause drowsiness.
• Avoid alcohol.
• Alcohol or sedative medications may increase drowsiness.
• Use caution when driving or operating machinery until you know how the medicine affects you.
• Stop using Zyrtec or Benadryl and contact your doctor if you have an allergic reaction such as hives. If you have severe anaphylaxis (trouble breathing, swelling of the lips, tongue, or throat), seek emergency medical treatment.
• Keep out of reach of children.
• Consult your healthcare provider before using Zyrtec or Benadryl if you are pregnant or breastfeeding.

Additional warnings of Benadryl:

• Do not use Benadryl to make a child fall asleep.
• Do not use Benadryl with any other product that contains diphenhydramine (including sleep products, combination cold/allergy medications, or topical creams).
• Consult your healthcare provider before using if you have glaucoma, an enlarged prostate/trouble urinating, or a breathing problem like emphysema or chronic bronchitis.
• Benadryl may cause excessive drowsiness, which is increased by alcohol and sedatives.
• Excitability may occur, which is more common in children than in adults.

Frequently asked questions about Zyrtec vs. Benadryl

What is Zyrtec?

Zyrtec is a second-generation antihistamine. It contains the ingredient cetirizine. It is available OTC in brand and generic form.

What is Benadryl?

Benadryl is a first-generation antihistamine, containing the ingredient diphenhydramine. You can purchase Benadryl over-the-counter in brand or generic form.

Are Zyrtec and Benadryl the same?

Zyrtec and Benadryl are both antihistamines that help relieve allergy symptoms. Benadryl is a first-generation antihistamine and tends to cause more side effects. Zyrtec is a second-generation antihistamine and causes fewer side effects.

Other common newer antihistamines you may see on the shelf include Claritin (loratadine), Allegra (fexofenadine), and Xyzal (levocetirizine).

Is Zyrtec or Benadryl better?

Both drugs are similarly effective, but Zyrtec may cause less drowsiness. Zyrtec still can cause drowsiness as well, though. Since both medications are available OTC, you can try one to see how it improves your symptoms. Your pharmacist can help you select an appropriate product. Be sure to inform your pharmacist of any medical conditions you have and any medications you take.

Can I use Zyrtec or Benadryl while pregnant?

In animal studies, Zyrtec did not cause congenital anomalies. However, there are no adequate studies performed in women. Therefore, Zyrtec should only be used in pregnancy if clearly needed. Your healthcare provider can guide you in this situation.

As for Benadryl, it’s also recommended that it should be used in pregnancy only if clearly needed. Consult your healthcare provider for guidance.

Can I use Zyrtec or Benadryl with alcohol?

No. You should avoid alcohol while taking these allergy medications. The combination can increase the risk of respiratory depression (slowed breathing, not getting enough oxygen), which can be dangerous. It can also cause additive effects, worsening the side effects of the medication, and causing impairment.

If you drink alcohol and want to treat your allergies, a nasal spray is a better option. Your pharmacist can help you find an appropriate nasal spray.

Which antihistamine is best?

The best antihistamine depends on each individual. Some people swear by Allegra, while others love Xyzal. It’s really a matter of trial and error, based on how effective the medicine is for you and what kind of side effects you experience. Your healthcare provider can help you select an antihistamine to try.

Will Zyrtec help with an allergic reaction?

Yes. Zyrtec can help with an allergic reaction. If you are having a mild allergic reaction, like hives or itching, you can take Zyrtec. However, if you are having trouble breathing or if you have swelling around the face or mouth, you should seek emergency medical treatment.

Do antihistamines weaken the immune system?

Antihistamines do not weaken the immune system. Drugs that weaken or suppress the immune system include oral or inhaled steroids, medications used to prevent rejection after an organ transplant, and certain medicines used for autoimmune conditions.