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Over-the-Counter Allergy Medication: Drugs to Treat Allergy

There are several over-the-counter (OTC) medications available to provide relief from allergies. These medications include antihistamines, decongestants, nasal sprays, and eye drops.

To people with sensitized immune systems, inhaled pollen (or dust, or animal dander or anything that triggers an inflammatory response) is an allergen – a normally harmless substance that your body attempts to reject. For most mild allergies, we recommend a second-generation antihistamine like Allegra, but because medication is a nuanced topic, your needs may vary.

This article also refers to relatively mild allergic reactions; antihistamines can help control some of the itchings that goes along with milder food allergies, but for more severe allergies you’re going to need to have an Epi-Pen nearby.

Picks, in brief

Allegra Adult Non-Drowsy Antihistamine Tablets, 24-Hour...
  • INCLUDES: One (1) 70-count bottle of Allegra Adult Non-Drowsy...
  • 24-HOUR RELIEF: One pill is all you need for round-the-clock relief...
  • FAST-ACTING: Allegra 24-Hour Allergy starts working in one hour for...
  • NON-DROWSY: Formulated with active ingredient fexofenadine, a...
  • INDOOR AND OUTDOOR ALLERGIES: Use Allegra tablets for indoor and...

Before we dive into theory and details, let’s cut to the chase: to keep your histamine receptors from surrendering to allergens on a regular basis, we recommend a second-generation antihistamine. Most are okay, but we’d start with Allegra because it’s faster-acting without the potential drowsiness of Zyrtec. Do consider Zyrtec if you are having skin reactions (which it is more effective on) and don’t mind some potential drowsiness.

We also recommend Benadryl and first-generation antihistamines for nighttime allergies if you need something to help you get to sleep.

We are also working on a guide to decongestants that will publish at a later date.

What causes allergies?

A seasonal allergy attack begins with sensitization, which is when your body meets an allergen for the first time.

A seasonal allergy attack begins with sensitization, which is when your body meets an allergen for the first time. Cells with special receptors for something called antigens (aka “antibody generators”) have the rather existential job of detecting the difference between proteins that are native to your body (“self”) and proteins that come from outside your body (“not-self”). “Not-self” proteins, which are not supposed to be in your body, send the immune system into full panic mode. These antigens signal a subset of white blood cells called T-helper cells (Th for short) to produce a signaling molecule called Interleukin-4 (Il-4 for short), which stimulates yet another type of white blood cell (B cells) to produce a specific antibody called immunoglobulin E (IgE).

The next time your body is exposed to the antigen, the IgE interacts with the allergen and specialized immune cells called mast cells to release a nitrogen compound called histamine. Histamine triggers many of the familiar symptoms of an allergy: runny nose, watery eyes, cough—all reactions designed to help your body get rid of that pesky allergen.

The whole system seems pretty Rube Goldberg-ish (which is often used as an argument against Creationism, since an all-powerful and all-knowing God would never design something so rinky-tink), but for our purposes, that’s good—all you need to do is interrupt the process at just about any point and your allergic reaction can be minimized.

How to determine which drug will help you the most

A quick note for the recommendations below: to figure out whether you’ve chosen the right treatment for you, consider keeping a symptom diary: write down how much congestion, runny nose, sneezing, coughing and itchy nose/eyes you have each day on a scale from 1 to 5. This is similar to how these drugs are tested in clinical studies and can give you an idea, after a week or so, if you’ve found a good option or if you should try something else.

More is not always better

Consider starting at low doses and increasing only as necessary to avoid subjecting your system to more than it needs.

It might be tempting to look at comparative drugs by picking the one with more active ingredient. That’s not really the best way to go about things. Consider starting at low doses and increasing only as necessary to avoid subjecting your system to more than it needs. Also watch dosage amount and frequency; some people may prefer higher amounts of drugs to be taken less frequently (i.e. Mucinex with 600 mg dextromethorphan once daily) whereas others might like smaller dosages taken throughout the day (i.e. Robitussin with 200 mg dextromethorphan every 4 hours as needed) so you don’t get more than you absolutely need. Either one will work out to the same amount of drug during the day. Again, if in doubt, talk to your doctor or pharmacist.

On generics vs. brand name drugs: go for generics

Anything we recommend below you can get in the generic version and be just fine. Matthew Sander, our resident biochemist who worked for years developing pharmaceutical products, says “I personally always prefer generics because in general the difference between brand name meds and generics is just marketing (and generics are cheaper).” Susan Elrod, our pharmacist, says “I’m a big proponent of generics, too.  They’re the same product, and you’re paying for the drug rather than marketing and development.”

Antihistamines: the first line of defense

As we mentioned above, we recommend a second-generation antihistamine to start with for seasonal allergies.  That’s because antihistamines start fighting off the results of your histamine receptors being affected and second-generations are safer than first (see below for all the gory details).

Allegra might be slightly better than the other second-generation options, and second-generation tend to be much better than first-gens.

How antihistamines work

The histamine molecule fits like a key into four different types of receptors (called, obviously, H1, H2, H3, and H4). H1, found in smooth muscle cells and in the central nervous system, is primarily responsible for causing allergy symptoms such as itching, cough and tightness of breath. H2, found in vascular tissues like veins, arteries and capillaries, is also in on the act, increasing blood flow to the inflamed area as a way to bring more antibodies and white blood cells to where the allergens are. Antihistamines act by filling the H-receptors in the “off” position of the receptor, so that the histamine ‘key’ can no longer turn an open H-receptor ‘lock’. Antihistamines literally shut down your allergy symptoms.

Second-generation antihistamines (Zyrtec, Allegra, Claritin)

First Line of Defense

Allegra Adult Non-Drowsy Antihistamine Tablets, 24-Hour Allergy Relief, 180 mg, 70 Count
Allegra Adult Non-Drowsy Antihistamine Tablets, 24-Hour Allergy Relief, 180 mg, 70 Count
NON-DROWSY: Formulated with active ingredient fexofenadine, a non-drowsy antihistamine

Allegra works the fastest and is generally the best choice for second-generation antihistamines. It works best against symptoms associated with seasonal allergies.

The history of second-generation antihistamines: around 1980, researchers saw the drawbacks of first-gen antihistamines (discussed below) and began to develop drugs that are selective to just H1 histamine receptors, without classic side effects like unwanted heavy sedation. (First-gen antihistamines still have their place—more on that later—but we think second-generations are the first thing to consider because they have fewer side effects.)

Symptoms treated:

  • runny nose
  • itchy eyes
  • sneezing
  • rash
  • general allergy symptoms

The three over-the-counter second-generation antihistamines are

  1. fexofenadine (Allegra)
  2. cetirizine (Zyrtec)
  3. loratadine (Claritin)

Zyrtec, Allegra and Claritin are all second-generation antihistamines, and though all are really similar there’s evidence that Allegra and Zyrtec might work faster than Claritin (about one hour compared to up to 3) according to a review article by Slater, et al. (Slater, et al. Drugs 1999 Jan;57(1):31-47,

All these drugs are taken just once a day because they continue to work for hours after absorption. Again, the review paper by Slater, et al. shows all three second-generation antihistamines have a half-life (the time it takes for the amount of drug to decrease by half, commonly used to determine duration) of around 10-12 hours, meaning they keep working throughout the day.

Best for Itchy Skin

Zyrtec might make you a bit drowsy but will help you deal with skin reactions better than the others.

As mentioned above, Allegra might be the best option of the three, since it works more quickly than Claritin and doesn’t cause the drowsiness sometimes seen with Zyrtec (which is still less common than with first-generation antihistamines). One caveat with Allegra: fruit juices such as apple, orange and grapefruit inhibit the GI transporter responsible for absorbing Allegra, so if you drink those you’ll want avoid them for 4 hours before your dose or 2 hours after it.  However, if you get a rash with your allergies, Zyrtec’s a better option; it has better distribution to the skin and consistently shows superior benefit against rash. A review paper from the College of Pharmacy at Oregon State University noted: “[f]or urticaria [i.e. allergic rash], cetirizine [Zyrtec ] . . . demonstrates superior suppression . . . at the dosages recommended by the manufacturer”.  Again, though, drowsiness is more common with Zyrtec, so be careful there.

Allegra is dosed as 60 mg twice a day or 180 mg once daily. Clever readers will realize that 60 mg twice a day is only 120 mg total, which may be enough when spaced out throughout the day. This is just a personal preference as to whether you’d prefer to take no higher dose than necessary or would rather take just one pill.

Some studies have found 5 mg daily (i.e. half a tablet) Zyrtec to be effective, so it’s possible you might only need half a dose. So if you’d like a more cost-effective option, start with 5 mg and go to 10 mg if you need more relief.

Keeping that symptom diary mentioned at the beginning of the article can help you pick the best treatment for you.

Precautions for second-generation antihistamines

None of these drugs have significant drug interactions or side effects with the exception of possible sedation with Zyrtec and fruit juice interaction with Allegra.

Combination drugs with second-generation antihistamines plus decongestants

Zyrtec, Claritin and Allegra are all available by themselves and in combination with pseudoephedrine (Sudafed) behind the counter.  In these cases, the suffix ‘D’ (Zyrtec-D, Claritin-D, Allegra-D) indicates pseudoephedrine.  So if you look at your symptom diary and decide you need an extra decongestant and don’t want to take another pill, you can brave the rigamarole of buying these behind the counter.

First-Generation Antihistamines (Benadryl, Allerest, Dimetapp)

Symptoms treated:

  • runny nose
  • itchy eyes
  • sneezing
  • rash
  • other general allergy symptoms

The early antihistamines include:

  1. diphenhydramine (Benadryl),
  2. chlorpheniramine (Allerest and lots of others; this one’s been around forever)
  3. brompheniramine (Dimetapp)

These antihistamines are all still available over the counter. Why aren’t they as good as the modern antihistamines we mentioned first? Well, while they all definitely do their job by turning off the H1 receptor, they don’t know when to quit. They can block other histamine receptors and even wreak havoc on non-histamine receptor cells.

Best for Nighttime Allergies

Benadryl is best to take at night. It makes you drowsy so you can sleep soundly.

They’ll also mess with your sleep, often making you drowsy, and they’ll cause stomach pain or other GI issues. They also don’t last as long as the second-generations, needing to be taken every 4 to 6 hours to continue being effective throughout the day.

The first examples of these types of antihistamine were developed in 1937, but they were too toxic for general use. The first antihistamine deemed safe enough to use in patients was pyrilamine, which was first used in 1944.  It’s still available OTC, though oddly enough it’s not used as an antihistamine so much anymore as a diuretic in products like Midol.

More on the downsides of first-generation antihistamines

The most common side effect of first-generation antihistamines is sleepiness.

Again, the most common side effect of first-generation antihistamines is sleepiness. But there are other, lesser-known symptoms we should explain.

Since these drugs are lipophilic, or fat-soluble, they easily cross the blood-brain barrier (BBB), which protects the brain from stuff in the blood that maybe shouldn’t get into the brain. The BBB is also made up of lipophilic cells, so lipophilic compounds like those first-gen antihistamines are welcomed in like long-lost family. Unfortunately, once in the brain, they become the black sheep of that family.

Histamine is used in the brain to regulate the body’s sleep/wake cycle, and first-gen antihistamines really do a number on this. They can induce drowsiness and sometimes even lead to wakefulness at the wrong times.

And because they can affect other parts of the brain, these drugs can cause increased appetite, blurred vision, tinnitus, dizziness, tremor, dry mouth, upset stomach and dry cough.

The reason first-generation antihistamines can cause stomach pain and other problems is that your GI system has H1 receptors, too, and the first-generation drugs can’t tell the difference between those and the ones in your lungs.  That means they can cause stomach pain, constipation, and other GI problems.

Oh, one more thing: Lots of products marketed for sleep contain Benadryl or other first-generation antihistamines, so make sure you read the labels to avoid doubling up on a drug.  In fact, in a fun bit of completely-legal-but-absolutely-insane business practices, you know the Tylenol product “Simply Sleep”?  It’s marketed as Tylenol PM if you only need to sleep rather than help with pain.  Guess what it is: Tylenol PM without the Tylenol.  It’s nothing but Benadryl.

There’s also something known as a paradoxical reaction, where certain patients (often children and the elderly) become agitated from first-generation meds rather than sedated.  It’s rare, and we’re not quite clear why it happens.

Though all these side effects can make one wonder how first-generation antihistamines ever made it out of the lab, they do work. But again, if you need a daily antihistamine you might be better off with a second-generation one.

Decongestants, cough relief, and combination medicine

Some more serious allergic reactions might require a dedicated decongestant or cough medicine. We’ll address those in a future guide.


What is the best over the counter medicine for allergies?

The first line of defense for congestion, runny nose and sneezing is to take one of the newer, less sedating antihistamines: Cetirizine (Zyrtec), fexofenadine (Allegra) and loratadine (Claritin or Alavert).

Is Claritin or Zyrtec better?

The difference is Zyrtec is more likely to cause sedation than ClaritinZyrtec also has a quicker onset of action (one hour vs up to three hours for Claritin) but both last for 24 hours. Zyrtec is a brand name for the drug cetirizine and Claritin is a brand name for the drug loratadine.

What can I take for severe allergies?

They include: Oral antihistamines. Antihistamines can help relieve sneezing, itching, a runny nose and watery eyes. Examples of oral antihistamines include loratadine (Claritin, Alavert), cetirizine (Zyrtec Allergy) and fexofenadine (Allegra Allergy).

Which is better Allegra or Zyrtec?

Allegra works within two hours and Zyrtec works within one hour. Several studies have found cetirizine (Zyrtec) to be more effective than fexofenadine (Allegra) at relieving symptoms of allergic rhinitis and urticaria, and it appears to have a longer duration of action. Zyrtec has no reported food interactions.

What is the strongest antihistamine over the counter?

Zyrtec and Claritin are effective for about 24 hours. A person should only take one dose per day. The body absorbs both antihistamines quickly, but Zyrtec seems to work faster for some people. A 2014 study found that both drugs were absorbed into the bloodstream within 1–2 hours of taking the medication

How do you stop allergies immediately?

6 Ways to Prevent or Treat Them
  1. Clean out your nose.
  2. Try an over-the-counter allergy medicine.
  3. Consider a prescription nasal spray or eye drops.
  4. Decongestants may also help relieve nasal congestion.
  5. Close your windows, and turn on the air conditioning.
  6. If things get bad, try allergy shots, also known as allergy immunotherapy.

Is Zyrtec or Claritin better for post nasal drip?

Thin postnasal drip secretions caused by allergies may be treated with antihistamines. Second-generation antihistamines such as Zyrtec and Claritin may offer better relief than older-type antihistamines such as promethazine (older antihistamines tend to thicken postnasal secretions)

What is the best natural antihistamine?

  1. Stinging nettle. A common herb in natural medicine, stinging nettle, may also be a natural antihistamine.
  2. Quercetin. Quercetin is an antioxidant found naturally in onions, apples, and other produce.
  3. Bromelain.
  4. Butterbur.