Antihistamines: Types, Side Effects, and Safe OTC Use Guidelines

When your nose starts running, your eyes itch, or you can’t stop sneezing, you probably reach for an antihistamine. These are among the most common over-the-counter medications in the UK and US, used by millions every year. But not all antihistamines are the same. Some knock you out. Others barely make you blink. And if you pick the wrong one, you could end up dizzy at work, groggy behind the wheel, or worse.

What Antihistamines Actually Do

Antihistamines block histamine, a chemical your body releases when it thinks it’s under attack - like from pollen, pet dander, or dust mites. Histamine triggers sneezing, runny nose, itchy skin, and watery eyes. By stopping histamine from binding to receptors, antihistamines calm these symptoms.

There are two main types: H1 and H2. H1 antihistamines are what you buy for allergies. H2 ones, like ranitidine, target stomach acid and aren’t used for sneezing. This guide focuses on H1 antihistamines - the kind you find on pharmacy shelves.

First-Generation vs. Second- and Third-Generation: The Big Difference

Not all antihistamines are created equal. The biggest split is between older, sedating versions and newer, non-sedating ones.

First-generation antihistamines - like diphenhydramine (Benadryl), chlorpheniramine (Chlor-Trimeton), and doxylamine (Unisom) - were developed in the 1940s. They’re cheap and work fast. But they cross the blood-brain barrier easily. That means they affect your brain, not just your nose. About half of people who take them feel drowsy. Some studies show they impair driving as much as a 0.10% blood alcohol level - legally drunk in most places.

Second- and third-generation antihistamines - like cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra) - were designed to avoid the brain. They’re less likely to cause drowsiness. They last 24 hours, so you take them once a day. And they’re now all available over-the-counter in the UK and US.

Here’s the catch: even among the non-sedating ones, some still make people sleepy. Cetirizine (Zyrtec) causes drowsiness in about 14% of users. Fexofenadine (Allegra)? Only 6%. That’s not a small difference - it’s the difference between getting through your day or needing a nap after lunch.

Which One Works Best for You?

There’s no single best antihistamine. It depends on your body, your lifestyle, and your symptoms.

• Fexofenadine (Allegra) is the least likely to make you tired. It’s the top pick for truck drivers, surgeons, or anyone who can’t afford to zone out. It starts working in 1-2 hours and lasts all day. It’s also the only OTC antihistamine with FDA approval specifically for hives, though all of them work for itching.
• Loratadine (Claritin) is the most popular. It’s gentle, reliable, and has a 4.4/5 rating on Amazon from over 28,000 reviews. Most users say it works without drowsiness. It’s a safe starting point if you’ve never tried an antihistamine before.
• Cetirizine (Zyrtec) works fast - often within an hour. But it’s the most likely of the non-sedating group to cause sleepiness. If you’re fine taking it at night or you don’t mind a little grogginess, it’s very effective. Just don’t take it before driving or operating machinery.
• Levocetirizine (Xyzal) is the active ingredient in Zyrtec, but purified. It’s slightly less sedating than Zyrtec, but still more likely than Allegra or Claritin to cause drowsiness. Importantly, its OTC label doesn’t include dosing instructions for people over 65 - a red flag for older adults.

Real people on Reddit and Amazon say it plainly: Allegra users report ‘zero drowsiness even at double doses.’ Zyrtec users say, ‘It works, but I’m useless by 3 p.m.’ Claritin gets called ‘the quiet achiever.’

Side Effects You Should Know

Non-sedating antihistamines are generally safe. But they’re not harmless.

• Drowsiness - Even the ‘non-sedating’ ones can cause it in some people. If you feel sleepy, don’t drive. Period.
• Headache - Common with Zyrtec and Xyzal.
• Dry mouth - Happens with all antihistamines, but less with fexofenadine.
• Stomach upset - Rare, but possible. Take with food if it bothers you.
• Heart issues - High doses of cetirizine have been linked to rare heart rhythm changes. Stick to the recommended dose.

First-generation antihistamines carry bigger risks: confusion, memory problems, urinary retention (especially in older men), and increased fall risk in seniors. The American Academy of Pediatrics says they shouldn’t be given to children under 6.

How to Use Them Safely

Here’s how to avoid common mistakes:

1. Start early - Don’t wait until you’re sneezing nonstop. Begin taking your antihistamine 1-2 weeks before allergy season hits. It’s preventive, not just reactive.
2. Don’t mix with alcohol - Even non-sedating antihistamines can make alcohol’s effects worse. You’ll feel more tired, dizzy, or uncoordinated.
3. Avoid grapefruit juice - It can raise blood levels of some antihistamines by up to 37%, increasing side effects. Stick to water.
4. Check the label for age limits - Xyzal doesn’t list adult doses over 65. That’s because older adults are more sensitive. If you’re over 65, talk to your pharmacist before using it.
5. Don’t take more than directed - More isn’t better. Doubling your dose won’t make allergies go away faster - it just raises your risk of side effects.

Who Should Avoid Antihistamines?

Not everyone should use them without a doctor’s advice:

• People with glaucoma - Antihistamines can increase eye pressure.
• Those with prostate problems - They can make urination harder.
• People with liver or kidney disease - Your body may not clear the drug properly.
• Pregnant or breastfeeding women - Talk to your doctor. Some are considered safe, but not all.
• Anyone taking other sedatives, sleep aids, or antidepressants - They can add up and cause dangerous drowsiness.

What About Long-Term Use?

Can you take antihistamines every day for months or years?

Yes - for most people, second-generation ones are safe for daily use. Studies tracking users for over a decade show no major safety issues. The American College of Allergy, Asthma, and Immunology considers them a cornerstone of long-term allergy control.

But there’s one concern: a 2022 JAMA study looked at older adults (over 75) who took first-generation antihistamines daily for years. They saw a slight increase in dementia risk. The same wasn’t found with second-generation drugs. So if you’re older and still using Benadryl every night - stop. Switch to Claritin or Allegra.

What’s New in 2025?

Things are changing. In 2023, the FDA approved a new version of Allegra-D - combining fexofenadine with an extended-release decongestant. It gives 24-hour allergy relief plus 12-hour nasal congestion control in one pill.

Sanofi is launching a nasal spray version of rupatadine in 2024. It delivers the drug right where it’s needed - in the nose - with fewer systemic side effects.

The market is shifting fast. Eighty-seven percent of allergy meds sold in the US are now OTC. Second-generation antihistamines make up 78% of that market. People are choosing safety over speed. They’re choosing clarity over sleepiness.

Bottom Line: What to Choose

If you want to feel normal - not dazed - pick fexofenadine (Allegra). It’s the least sedating, works just as well as the others, and has the best safety record for daily use.

If you need fast relief and don’t mind a little sleepiness, cetirizine (Zyrtec) is strong and fast.

If you want the most trusted, widely used option with minimal side effects, loratadine (Claritin) is your go-to.

Avoid first-generation antihistamines unless it’s an emergency - like a sudden allergic reaction. They’re not meant for daily life.

And if you’re unsure? Talk to your pharmacist. They see hundreds of people every week choosing antihistamines. They know what works - and what doesn’t.

If you're managing allergies year-round, the right antihistamine can change your life. It’s not about picking the most popular one. It’s about picking the one that lets you live without being sleepy, foggy, or stuck on the couch. Start with Allegra if you’re unsure. It’s the quietest, safest option - and it works.