Zyrtec vs. Benadryl: Differences, similarities, and which is better for you

In this article:

• Zyrtec vs. Benadryl
• Conditions treated
• Efficacy
• Cost
• Side effects
• Interactions
• Warnings
• FAQs

In this article

• Zyrtec vs. Benadryl
• Conditions treated
• Efficacy
• Cost
• Side effects
• Interactions
• Warnings
• FAQs

Zyrtec and Benadryl are two popular brand-name over-the-counter (OTC) allergy medicines that alleviate symptoms like sneezing and watery eyes. Both medicines are approved by the United States Food and Drug Administration (FDA). Continue reading to learn more about Zyrtec and Benadryl. 

What are the main differences between Zyrtec and Benadryl?

Zyrtec contains the active ingredient cetirizine, while Benadryl contains diphenhydramine. Both products are available in brand and generic and in various formulations to suit multiple ages and patient preferences. 

Zyrtec and Benadryl are antihistamines, or H1 receptor blockers. They work by blocking histamine, a substance the body makes during an allergic reaction that causes those pesky symptoms. By blocking histamine, Zyrtec and Benadryl help relieve allergies.

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 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. 

	Zyrtec	Benadryl
Drug class	Second-generation antihistamine	First-generation antihistamine
Brand/generic status	Brand and generic	Brand and generic
What is the generic name?	Cetirizine hydrochloride	Diphenhydramine hydrochloride
What form(s) does the drug come in?	Tablet, syrup, chewable tablet, dissolving tablet, liquid gels Also as Zyrtec-D (antihistamine + decongestant: cetirizine/pseudoephedrine)	Capsules, chewable tablet, cream, gelcap, liquid, liquid gels, injection, spray, stick Also available in combination products such as Benadryl-D, Benadryl Allergy Plus Congestion
What is the standard dosage?	Adults: 10 mg by mouth once daily as needed Children: varies by age. Follow package instructions or consult a pediatrician	Adults: 25 to 50 mg by mouth every 4 to 6 hours as needed Children: varies by age. Follow package instructions or consult a pediatrician
How long is the typical treatment?	Varies	Varies
Who typically uses the medication?	Children and adults	Children and adults

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, and chronic urticaria. Zyrtec is available over-the-counter (since 2007). While those indications still apply, the packaging information states that Zyrtec is used to temporarily relieve 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 also treats runny noses and sneezing from the common cold.

Condition	Zyrtec	Benadryl
Seasonal allergies	Yes	Yes
Perennial allergies	Yes	Yes
Chronic urticaria (hives/itchy skin)	Yes	Off-label
Temporary relief of symptoms due to hay fever, allergies, or the common cold	Yes	Yes

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 found that Zyrtec was similar to Benadryl in terms of 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 nonsedating antihistamines concluded that all antihistamines were similarly effective, but newer antihistamines, like Zyrtec, caused less sedation. 

Experts often recommend second-generation antihistamines like Zyrtec, over first-generation antihistamines like Benadryl, because the second-generation antihistamines have been extensively studied and are well-established in safety and effectiveness, with less side effects than older antihistamines. Experts also frequently recommend nasal steroid sprays, such as Flonase (fluticasone). This does not mean that first-generation antihistamines should not be used, though, as first-generation antihistamines may be preferred in certain situations or patients.

Because 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 fewest side effects. Your healthcare provider or pharmacist can guide you with product selection as well. 

Coverage and cost comparison of Zyrtec vs. Benadryl

Because they are available OTC, 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 prescription—a prescription is required in order to process SingleCare discounts for OTC medicines.

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 healthcare provider.

	Zyrtec	Benadryl
Typically covered by insurance?	No	No
Typically covered by Medicare Part D?	No	No
Standard dosage	#30, 10 mg tablets	#24, 25 mg tablets
Typical Medicare copay	N/a	N/a
SingleCare cost	$5	$4

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. 

	Zyrtec		Benadryl
Side Effect	Applicable?	Frequency	Applicable?	Frequency
Somnolence (excess sleepiness) or drowsiness	Yes	13.7%	Yes	22%
Fatigue	Yes	5.9%	Yes	% not reported
Dry mouth	Yes	5%	Yes	5%
Dizziness	Yes	2%	Yes	2.5%
Headache	Yes	>2%	Yes	2.5%
Nausea	Yes	>2%	No
Constipation	Yes	% not reported	Yes	% not reported

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 and excess dizziness, drowsiness, and psychomotor 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.

Drug	Drug Class	Interacts with Zyrtec?	Interacts with Benadryl?
Alcohol	Alcohol	Yes	Yes
Carbamazepine Divalproex sodium Gabapentin Lamotrigine Levetiracetam Phenobarbital Phenytoin Pregabalin Topiramate	Anticonvulsants	Yes	Yes
Aripiprazole Olanzapine Quetiapine Risperidone Ziprasidone	Antipsychotics	Yes	Yes
Amitriptyline Citalopram Desvenlafaxine Duloxetine Escitalopram Fluoxetine Fluvoxamine Nortriptyline Paroxetine Phenelzine Rasagiline Sertraline Tranylcypromine Venlafaxine	Antidepressants	Yes	Yes
Codeine Hydrocodone Meperidine Methadone Morphine Oxycodone Tramadol	Opioid pain relievers	Yes	Yes
Alprazolam Clonazepam Diazepam Lorazepam Temazepam	Benzodiazepines	Yes	Yes
Baclofen Carisoprodol Cyclobenzaprine Metaxalone	Muscle relaxants	Yes	Yes
Potassium (solid dosage forms)	Potassium	No	Yes

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. 
• If you have an allergic reaction to Zyrtec or Benadryl, with symptoms like hives, trouble breathing or swelling of the lips, tongue, or throat, seek emergency medical treatment. 
• Keep medication out of the 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 adults. 

Frequently asked questions about Zyrtec vs. Benadryl

How common are allergies?

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.

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, 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 on pregnant 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 be used during pregnancy only if 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 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.

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.