Key takeaways

The most effective oral antihistamines for allergy relief are Zyrtec, Claritin, and Allegra due to their low sedation and long-lasting effects.
First-generation antihistamines like Benadryl can cause drowsiness and impaired cognitive function, while second- and third-generation options are less likely to do so and are preferred for mild allergic rhinitis and hives.
Allegra is considered the least sedating among second-generation antihistamines, making it the most effective overall medication for allergies.
When choosing an antihistamine, factors such as specific symptoms, side effects, duration of relief, and individual health conditions should be considered, and consulting with a healthcare provider is advised.

Antihistamines are medications that help alleviate allergy symptoms such as hives, itchy eyes, sneezing, sinus congestion, runny nose, and watery eyes. Allergies are the sixth leading cause of chronic illness, with over 100 million Americans experiencing allergies yearly. According to a 2021 survey, 50% of adults with seasonal allergies in the United States reported they used over-the-counter (OTC) antihistamines to relieve their symptoms. Which one is best? It depends on a variety of factors—from the specific allergy symptoms to how long you need relief. Read on to learn more.

What is the best antihistamine?

Although their effectiveness can vary from person to person, the best oral antihistamines are Zyrtec (cetirizine), Claritin (loratadine), and Allegra (fexofenadine), says Don. J. Beasly, MD, an otolaryngologist at Boise ENT in Boise, Idaho. “These are generally considered the most effective for allergy relief due to their low sedation and long-lasting effects,” Dr. Beasly says.

Oral antihistamines for allergy symptoms can be broken down into the following groups:

First-generation antihistamines such as Benadryl (diphenhydramine) and Chlor-Trimeton (chlorpheniramine) are effective, but they can cause central nervous system (CNS) side effects like drowsiness and impaired cognitive function. That’s because they cross the blood-brain barrier, blocking histamine and cholinergic receptors.
Second- and third-generation antihistamines like Zyrtec (cetirizine), Claritin (loratadine), and Allegra (fexofenadine) don’t cross the blood-brain barrier, so they’re less likely to cause drowsiness. They have longer-lasting effects than first-generation antihistamines and are the recommended first-line of treatment for mild allergic rhinitis and urticaria (hives).

The most effective allergy medication overall is Allegra, says Lorneka Joseph, Pharm.D., a pharmacist and wellness coach based in Orlando, Florida. She says it’s the least sedating of the second-generation antihistamines.

When choosing the antihistamine that’s best for you, there are several considerations to keep in mind:

Symptoms: Dr. Beasly advises choosing an allergy medicine that targets the specific symptoms you are experiencing, such as nasal congestion, sneezing, or itching.
Side effects: Common side effects include dry mouth, dizziness, or drowsiness. If you need to stay alert, choose a non-drowsy option, says Dr. Joseph.
Duration: Some antihistamines work up to 24 hours, while others only provide relief for 4-6 hours, says Joyce Yu, MD, a pediatric allergist at Columbia Doctors Midtown in New York, New York.
Medical conditions and drug interactions: Consult with a healthcare provider if you have any underlying health issues or you’re taking any medications, says Dr. Beasly.

Antihistamine comparison chart
Medication	Type of antihistamine	Forms	Symptoms treated
Benadryl (diphenhydramine)	First-generation	Oral tablets Oral liqui-gels Oral chewable tablets Oral liquid suspension Topical cream, gel, spray, and stick	Runny nose Sneezing Itchy, watery eyes Itchy throat Itchy nose Itchy skin Hives Insomnia
Chlor-Trimeton (chlorpheniramine)	First-generation	Oral tablets Oral chewable tablets Oral long-acting tablets Oral liquid solution Oral long-acting capsules	Runny nose Sneezing Itchy, watery eyes Itchy nose Itchy throat Itchy skin Hives
Unisom (doxylamine)	First-generation	Oral tablets	Sneezing Runny nose Nasal congestion Itchy skin Hives Insomnia Nausea & vomiting during pregnancy
Allegra (fexofenadine)	Third-generation	Oral tablets Oral capsules Orally disintegrating tablets Oral liquid suspension Oral long-acting tablets	Runny nose Sneezing Itchy, watery eyes Itchy throat Itchy nose Itchy skin Hives
Zyrtec (cetirizine)	Second-generation	Oral tablets Oral capsules Orally disintegrating tablets Oral chewable tablets Oral liquid solution	Runny nose Sneezing Itchy, watery eyes Itchy nose Itchy throat Itchy skin Hives
Claritin (loratadine)	Second-generation	Oral tablets Oral capsules Orally disintegrating tablets Oral chewable tablets Oral liquid solution	Runny nose Sneezing Itchy, watery eyes Itchy nose Itchy throat Itchy skin Hives
Xyzal (levocetirizine)	Third-generation	Oral tablets Oral liquid solution	Runny nose Sneezing Itchy, watery eyes Itchy nose Itchy throat Itchy skin Hives

What is the difference between antihistamines?

“Antihistamines work by blocking the action site of a chemical in the body called histamine,” says Dr. Joseph. The immune system releases histamine in response to unfamiliar proteins (allergens), including pollen, mold, dust mites, and pet dander. Then, the chemical binds to histamine receptors on the surface of cells, causing allergy symptoms.

In severe cases, the histamine release can cause anaphylaxis, a severe and possibly fatal reaction causing airways to swell and blood pressure to drop. This type of reaction is more common with food allergies, such as peanuts and shellfish. But depending on the allergen and the specific person, histamine release leads to skin reactions such as itching, hives, redness, or swelling. Other people may experience typical symptoms of allergic rhinitis such as:

Runny nose
Stuffy nose
Sneezing
Coughing
Itchy, watery eyes
Itchy throat

The primary mechanism of antihistamines is not to block histamine release, says Dr. Yu. Instead, the medications block histamine receptors so that histamine can’t interact with them—preventing an allergic response.

There are two types of histamine receptors, H1 and H2. Similarly, there are two main classes of antihistamines: H1-receptor blockers and H2-receptor blockers. H1-receptor blockers prevent H1 receptor activity involved in allergic reactions, while H2-receptor blockers stop H2 receptor activity involved in triggering stomach acid production, says Dr. Yu.

“H-2 blockers are typically used for heartburn and acid reflux, not allergies,” says Dr. Beasly.

When most people refer to antihistamines, they mean H1-receptor blockers, adds Dr. Yu. H1-receptor blockers are broken down further into first-, second-, and third-generation antihistamines.

Compare types of antihistamines
Type of antihistamine	Examples of brand names	Indications	Common side effects
First generation antihistamines	Benadryl, Unisom, Dramamine	Allergy symptoms, motion sickness	Drowsiness Dry mouth Dry eyes Blurred or double vision Dizziness Headache Low blood pressure Rapid heart rate Difficulty urinating Constipation
Second and third generation antihistamines	Zyrtec, Claritin, Allegra, Xyzal	Allergy symptoms	Drowsiness Headache Cough Nausea Upset stomach

How quickly do antihistamines work?

Though the onset of action for different antihistamines varies, these meds typically work within 30 minutes to two hours, says Dr. Joseph. A person with mild symptoms may notice their symptoms subsiding in about 30 minutes, says Dr. Yu. For seasonal allergies (also known as hay fever), it may help to take antihistamines as a preventive measure, starting a daily antihistamine about two weeks before exposure to known triggers.

Dr. Beasly says the duration of relief varies; some last 4-6 hours (first-generation), while others can provide relief for 24 hours (second-generation). For daily use, second-generation antihistamines like cetirizine, loratadine, or fexofenadine are generally preferred due to their lower sedation potential, says Dr. Beasly. He says first-generation antihistamines like diphenhydramine may provide more immediate relief but are more likely to cause drowsiness.

How quickly do antihistamines work?
Antihistamine	How quickly does it take to work?	Duration of action	How often should it be taken?
Zyrtec	20 to 60 minutes	24 hours	Once daily
Claritin	1 to 3 hours	24 hours	Once daily
Allegra	1 hour	12-24 hours	Once daily
Benadryl	15 to 30 minutes	4 to 6 hours	Every 4 to 6 hours
Xyzal	1 hour	24 hours	Once daily
Chlor-trimeton	30 minutes to 1 hour	4 to 6 hours	Every 4 to 8 hours

Who can take antihistamines?

Most adults and older children can use antihistamines, says Dr. Beasly. However, it’s essential to consult a healthcare provider, especially if you have underlying medical conditions or are taking other medications.

Antihistamines can cause central nervous system (CNS) depression, especially when combined with other sedating drugs, says Dr. Joseph. Caution is advised in patients with:

Diabetes
Enlarged prostate or difficulty passing urine
Epilepsy
Heart disease
High blood pressure
Glaucoma (increased pressure in the eye)
Overactive thyroid

According to Dr. Beasly, children younger than 2 should not use most antihistamines. Pregnant or breastfeeding women and seniors should consult with their providers before using them.

Child vs. adult antihistamine dosage
Antihistamine	Age restrictions	Child dosage	Adult dosage
Benadryl (diphenhydramine)	Do not use in children younger than 6 unless your pediatrician tells you to; not for use in children younger than 2	Dosage (by weight, not age) is every 4-6 hours for children older than 2 years old: 20-24 lbs: 4 ml of 12.5 mg/5ml oral suspension or 25-37 lbs: 5 ml of 12.5 mg/5ml oral suspension or one 12.5g mg tablet 38-49 lbs: 7.5 ml of 12.5 mg/5ml oral suspension or one and one-half 12.5 mg tablets (18.75 mg) 50-99 lbs: 10 ml of 12.5 mg/5ml oral suspension or two 12.5 mg tablets (25 mg) 100 lbs or more: 2-4, 12.5 mg tablets (25-50 mg)	25-50 mg every 4-6 hours
Claritin (loratadine)	Do not use in children younger than 6 unless your healthcare provider advise it; not for use in children younger than 2	Ages 2-5: 2.5 ml of 5 mg/5 ml oral suspension Ages 6-11: 5 ml of 5 mg/5 ml oral suspension, or one 5 mg chewable tablet Ages 12+: 10 ml of 5 mg/5 ml oral suspension, two 5 mg chewable tablets, or one 10 mg tablet	10 mg every 24 hours
Allegra (fexofenadine)	Do not use in children younger than 6 months	Ages 6 months to 2 years: 2.5 ml of 30 mg/5 ml oral suspension twice a day for hives, other uses not recommended Ages 2 to 11 years: 5 ml of 30 mg/5 ml oral suspension twice daily for hives or allergic rhinitis Ages 12+: 10 ml of 30 mg/5 ml oral suspension twice daily	60 mg twice daily, or 180 mg once daily
Zyrtec (cetirizine)	Do not use in children younger than 6 months; ask your provider before giving Zyrtec to children younger than 2	Ages 2-6: 2.5 ml of 5 mg/5 ml solution once a day Ages 6+: 5 or 10 ml of 5 mg/5 ml solution or one 5 or 10 mg tablet, not to exceed 10 mg daily	5 or10 mg taken once daily
Chlor-Trimeton (chlorpheniramine)	Do not use in children younger than 4	Dosage every 4-8 hours for children over 2 years old is by weight, not age: 22-32 lbs: 2.5 ml of 2 mg/5 ml oral suspension 33-43 lbs: 4 ml of 2 mg/5 ml oral suspension 44-54 lbs: 5 ml of 2 mg/5 ml oral suspension or one-half 4 mg tablet 55-65 lbs: 5 ml of 2 mg/5 ml oral suspension or one-half 4 mg tablet 66-76 lbs: 7.5 ml of 2 mg/5 ml oral suspension or one-half 4 mg tablet 77-87 lbs: 7.5 ml of 2 mg/5 ml oral suspension or one 4 mg tablet 88 lb+: 10 ml of 2 mg/5 ml oral suspension or one 4 mg tablet	4 mg every 4-6 hours
Xyzal (levocetirizine)	Do not use in children younger than 2	Ages 2-5: 2.5 ml of 2.5 mg/5 ml solution at night every 24 hours Ages 6-11: 5 ml of 2.5 mg/5 ml solution at night every 24 hours Ages 12+: 5 or 10 ml of 2.5 mg/5 ml solution once daily	2.5-5 mg once daily

Alternatives to antihistamines

“Some individuals may not respond well to antihistamines and may need other allergy treatments,” says Dr. Beasly. He adds that some people might prefer natural remedies or have concerns about antihistamines’ side effects. In some cases, a healthcare provider may recommend a combination of medications.

Other treatments that may be recommended include:

Allergy shots, or immunotherapy
Eye drops, such as Pataday (olopatadine)
Nasal sprays, such as Flonase (fluticasone propionate) and Astepro (azelastine)
Mast cell stabilizers, like Singulair (montelukast)
Decongestants like Sudafed (pseudoephedrine)
Oral steroids like prednisone
Corticosteroid creams or ointments

Additionally, the following home remedies and lifestyle changes may help reduce allergy symptoms:

Use a neti pot to rinse your nasal passages.
Take a shower when you get home to wash off allergens.
Drink extra fluids to loosen congestion.
Stay indoors during allergy season when pollen levels are high.
Vacuum once or twice a week.
Keep your doors and windows closed.
Invest in a high-efficiency particulate air (HEPA) filter.

Choosing an antihistamine

When choosing the best antihistamine, keep in mind your symptoms, whether or not side effects like drowsiness are an issue, how long you want the medication to last, and any health conditions or medications that may be problematic when combined with an antihistamine.

It’s best to seek medical advice from a healthcare professional to determine your best choice. Dr. Beasly urges discussing new medications with a healthcare provider to check for potential contraindications or interactions.

What’s the best antihistamine?