Key takeaways
Zyrtec and Benadryl are both OTC medicines that treat allergy symptoms like sneezing and runny eyes.
Benadryl contains diphenhydramine, a first-generation antihistamine, and Zyrtec contains cetirizine, a second-generation antihistamine with fewer side effects than first-generation antihistamines.
Both medications effectively relieve allergy symptoms, although Zyrtec causes less drowsiness and lasts longer than Benadryl.
Zyrtec (cetirizine) and Benadryl (diphenhydramine) are two popular brand-name over-the-counter (OTC) allergy medicines that alleviate symptoms like sneezing and watery eyes. Although they’re both antihistamines, Benadryl is a first-generation antihistamine, which can cause sedation and drowsiness, as well as impair coordination and driving. Zyrtec (cetirizine) is a second-generation antihistamine that may cause less drowsiness and fewer side effects in general.
Compare Zyrtec vs. Benadryl key differences |
||
|---|---|---|
| Feature | 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, capsule
Also as Zyrtec-D (antihistamine + decongestant: cetirizine/pseudoephedrine) |
Capsules, chewable tablet, cream, gelcap, liquid, 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 |
| Who typically uses the medication? | Children and adults | Children and adults |
| How long does it last? | Up to 24 hours | About 4 to 6 hours |
| Risk of drowsiness | Lower; drowsiness may still occur, though | Higher; marked drowsiness may occur |
Zyrtec vs. Benadryl conditions treated
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 or 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.
Is Zyrtec or Benadryl more effective?
Both Zyrtec and Benadryl are effective. The main difference to consider is their risk of sedation and duration of action.
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).
Your pharmacist or healthcare provider can help choose based on symptom pattern, sedation risk, age, other medicines, and medical history.
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 Zyrtec costs about $27. A SingleCare card can bring the price down to about $9 if you have a prescription, which is required in order to process SingleCare discounts for OTC medicines.
A box of 30 tablets of 25 mg diphenhydramine (generic Benadryl) costs about $15. A SingleCare card can drop the cost to approximately $9 if you have a prescription from a healthcare provider.
Compare Zyrtec vs. Benadryl cost & coverage |
||
|---|---|---|
| Cost/coverage | Zyrtec | Benadryl |
| Typically covered by insurance? | No | No |
| Typically covered by Medicare Part D? | No | No |
| Average retail cost | $27 for 30, 10 mg tablets of brand Zyrtec | $9 for 24, 25 mg tablets of brand Benadryl |
| How to save | Get coupon | Get coupon |
Allergy Medicine Coupons & Resources
Common side effects of Zyrtec vs. Benadryl
Zyrtec and Benadryl have similar side effects, although Benadryl has a higher risk of sedation. The most common side effects are sleepiness or drowsiness, fatigue, dry mouth, dizziness, constipation, and headaches.
This is not a full list of side effects. Other adverse effects may occur. Consult your healthcare provider for professional medical advice.
Drug interactions of Zyrtec vs. Benadryl
You should not take Zyrtec or Benadryl with alcohol or sedating medications due to additive central nervous system effects. The combination could cause excess dizziness, drowsiness, and psychomotor impairment. As a result, a heightened risk of falls or motor vehicle accidents can be a concern.
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.
Compare Zyrtec vs. Benadryl drug interactions |
|||
|---|---|---|---|
| Drug or substance | Zyrtec | Benadryl | What to know |
| Alcohol | May interact | May interact | Alcohol can increase drowsiness and impairment with either antihistamine. |
| Sedatives and tranquilizers | May interact | May interact | Taking these with Zyrtec or Benadryl can increase drowsiness. |
| Other medications that cause drowsiness | Use caution | Use caution | Combining either antihistamine with other sedating medicines may increase sleepiness and impairment. |
| Other products containing diphenhydramine | Not applicable | Avoid | Do not combine Benadryl with another product containing diphenhydramine, including some sleep, cold, allergy, or topical products. |
| MAO inhibitors | — | May interact | MAO inhibitors may increase or prolong the anticholinergic effects of diphenhydramine. |
Who should avoid Zyrtec or Benadryl?
Zyrtec and Benadryl are safe for many people when used as directed, but they may not be appropriate for everyone. People with liver or kidney disease should ask a healthcare provider before taking Zyrtec, as they may need a different dose.
Benadryl may not be appropriate for people with certain conditions, including glaucoma, an enlarged prostate that causes difficulty urinating, or breathing problems such as emphysema or chronic bronchitis. Benadryl should not be combined with other products containing diphenhydramine and should never be used to make a child sleepy.
Both medications can cause drowsiness, although this is generally a greater concern with Benadryl. Avoid alcohol and use caution with sedatives or tranquilizers because they can increase drowsiness. People who are pregnant or breastfeeding should also check with a healthcare professional before using either medication.
RELATED: What are non-drowsy Benadryl options?
Frequently asked questions about Zyrtec vs. Benadryl
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.
Is Zyrtec or Benadryl better?
Both drugs are similarly effective, but Zyrtec may cause less drowsiness and is often the more practical choice for routine allergy symptoms since it lasts longer and causes less sedation than Benadryl. Your pharmacist or healthcare provider can help you select the right medication for you while considering any health conditions you have or other medications you may be taking.
Can I use Zyrtec or Benadryl while pregnant?
Small studies have examined the safety of Zyrtec in pregnancy and been reassuring. As a result, it is one of the preferred antihistamines in this setting. However, Zyrtec should only be used in pregnancy if clearly needed and with the guidance of a healthcare provider.
As for Benadryl, it’s also recommended that it be used during pregnancy only if benefits outweigh the risks. Consult your healthcare provider for guidance.
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.
The SingleCare prices in this article are the most accurate at the time of publishing in ZIP code 23666 as of Oct. 28, 2026. Prices vary by pharmacy. Visit our coupon page for updated drug prices at pharmacies near you.
- Zyrtec, FDA
- Benadryl, PDR
- Summary review (cetirizine), Center for Drug Evaluation and Research (2010)
- Antihistamines, Cleveland Clinic (2020)
- Comparison of cetirizine to diphenhydramine in the treatment of acute food allergic reactions, The Journal of Allergy and Clinical Immunology (2011)
- Diphenhydramine versus nonsedating antihistamines for acute allergic reactions: a literature review, Allergy and Asthma (2007)
- Evidence-based use of antihistamines for treatment of allergic conditions, Annals of Allergy, Asthma & Immunology (2023)
- Living with allergies, American College of Allergy, Asthma & Immunology
- Medically accurate: SingleCare’s Medical Review Board analyzes all of our content to confirm it’s in line with current medical advice.
- Evidence-based: Our content is sourced from reputable U.S.-based healthcare professionals and peer-reviewed research.
- Trustworthy: All of SingleCare’s content goes through a multi-phase review process by our writers, editors, and Medical Board in order to provide clear and credible information.