Antihistamines are chemical compounds that provide relief from allergy, cold and flu symptoms.
There are currently three generations of antihistamines in use in scores of over-the-counter medications. Each successive generation provides more focused relief and produces fewer and less severe side effects.
That said, the number and variety of antihistamine-based products can be intimidating. To make your search a bit easier, we trained a critical eye on the market and determined that the following are the best antihistamines of 2021.
1. Xyzal Allergy
Whether you suffer outdoor or indoor allergies, Xyzal Allergy can help. It uses the third-generation antihistamine levocetirizine to relieve your runny nose, cool your burning eyes and reduce sneezing.
What we like: Xyzal does not waste any time getting to work. In most cases, you will start to feel better in about 30 minutes. The 24 hour relief is another big plus. And, because it does such a good job relieving symptoms, it doesn’t have to knock you out.
Flaws: Water retention can be an issue for some people.
2. Bausch + Lomb Alaway Antihistamine Eye Drops
Bausch + Lomb may make for an unlikely entry at #2 on our list. But the quality of their Alaway Eye Drops is undeniable. They use the second-generation antihistamine ketotifen to address all your seasonal allergy symptoms.
What we like: Alaway Eye Drops provide comprehensive relief for itchy, watery eyes due to hay fever, pet hair, and more. These drops offer fast, effective relief that lasts for up to 12 hours. Safe for the kids as well.
Flaws: They are not as widely available in brick and mortar pharmacies as some other antihistamines.
3. Benadryl Allergy Ultratabs
Sometimes you need an antihistamine that will not put you to sleep. And sometimes you need one that will. If you are in the latter camp, Benadryl Ultratabs are just what the doctor ordered. They tackle your insomnia just as well as they tackle your runny nose.
What we like: Benadryl addresses all your allergy symptoms and is non-habit forming. It also helps you get the restful sleep that can be so elusive during allergy season, or if you have a cold or flu. It also does a good job suppressing coughs.
Flaws: Benadryl uses the first-generation antihistamine diphenhydramine. So its main flaw is also its main strength: it makes you drowsy.
Claritin contains the second-generation antihistamine loratadine, also known as pseudoephedrine. Because of that, you will need to look behind the counter to find it at the drugstore. It is a potent antihistamine that should relieve all your common allergy symptoms.
What we like: Claritin is available in multiple forms and gets to work quickly. It provides a blanket defense against hundreds of allergens and can relieve your cold symptoms as well. In addition, it provides 24 hour relief.
Flaws: It is more expensive than some other alternatives.
5. Allegra Adult 24 Hour Allergy Relief
Allegra Adult 24 Hour provides fast, effective, non-drowsy relief by way of the second-generation antihistamine fexofenadine. It comes in tablets, gelcaps, and liquids and addresses eye, nose, and throat symptoms.
What we like: Like all second and third-generation antihistamines, Allegra provides all-day relief. It is also non-drowsy, non-addictive, and any side effects are typically mild. The gelcaps are also easy to swallow.
Flaws: It cost more than some others. You may also build an immunity to it if you take it too much.
6. Unisom SleepGels
Unisom SleepGels use the first-generation antihistamine diphenhydramine to alleviate your allergy symptoms. At the same time, they help you get the sleep you need. Just take one SleepGel right before bed.
What we like: If your allergies have you tossing and turning all night, Unisom will bring an end to that. It also does a good job tackling runny nose, itchy eyes, and more. Also, unlike most hard tablets, the softgels are easy to swallow.
Flaws: Older folks may feel a bit irritable or confused after using these. It does not last as long as second-generation antihistamines.
7. Zyrtec 24 Hour Allergy Relief Tablets
Zyrtec is an all-purpose second-generation antihistamine that tackles cold and flu symptoms as well as it handles your allergy symptoms. It can also address hives and a multitude of upper respiratory allergies.
What we like: You do not have to wait an hour for Zyrtec to kick in. Being a second-generation antihistamine, you also do not have to worry about drowsiness. You also have a choice of tablet, chewable, liqui-cap, or syrup.
Flaws: Being a second-gen antihistamine, the possibility of drowsiness is still there.
8. Kirkland Signature Aller-Fex
If you are tired of paying through your runny nose for allergy relief, consider Kirkland Signature Aller-Fex. Kirkland may not enjoy the market luster of better-known brand names, but it gets to work quickly and will not interfere at work.
What we like: Kirkland Aller-Fex provides hours of indoor and outdoor relief. The second-generation antihistamine fexofenadine produces few side effects and is both non-drowsy and non-habit forming.
Flaws: Not as long-lasting as some other 2nd generation antihistamine products.
9. Alka-Seltzer Plus Cold and Cough Liquid Gels
Alka-Seltzer Plus Cold and Cough is a medication that transcends its marketing. It says ‘cold and cough’, but it also does a bang-up job on allergy symptoms. Those who catch a cold while suffering through allergy season will appreciate its multi-symptom effectiveness.
What we like: We appreciate the effectiveness of the first-gen antihistamine chlorpheniramine. We love that it reduces symptoms across the board and helps you get to sleep. And that it works just as well for seasonal allergies as for colds.
Flaws: The size of the pills may be an issue for people with difficulty swallowing.
10. Zaditor Antihistamine Eye Drops
The makers of Zaditor focus on providing relief for burning, watery eyes due to allergies or environmental pollutants. There are no superfluous ingredients in this, the original prescription-strength formula that is now available OTC.
What we like: Zaditor uses the second-generation antihistamine ketotifen – and only ketotifen – to provide non-drowsy relief from outdoor and indoor allergy symptoms. One drop in each eye lasts up to 12 hours.
Flaws: Does not do much to relieve sneezing or respiratory symptoms.
Who Needs Antihistamines?
Antihistamines provide a wealth of benefits (as we will shortly see) to people who suffer seasonal allergies, pet allergies, fabric or material allergies, and those suffering from the common cold or seasonal flu. Antihistamines block the action of histamines that create the runny nose, watery eyes, itching, and sneezing we can all live without.
But that is not all. Antihistamines have shown themselves potentially useful in treating a number of other conditions, including stomach ulcers, insomnia, anaphylactic shock (1), certain types of anxiety, and even morning sickness (2). Second and third-generation antihistamines have also broken down the historical barriers between antihistamines and the elderly. Those barriers were a product of first-gen antihistamines producing sometimes profound drowsiness. Succeeding generations of antihistamines have virtually eliminated this phenomenon.
How We Ranked
Different people react differently to antihistamines and use them for different reasons. Most are trying to get a handle on their seasonal allergies, while some are more concerned with addressing their cold or flu symptoms. And, as we saw above, still others use them for reasons that have nothing to do with a runny nose. For our rankings, we focused on how effective the various antihistamines are at fulfilling their primary purpose: allergy relief.
To that end, we considered whether a particular antihistamine was first, second or third generation. That matters because there is a fundamental difference in side effects between the generations. First-gen antihistamines are well-known for producing drowsiness. Newer generations have solved this problem while still retaining their effectiveness. So higher marks for next-gen antihistamines.
We also considered the delivery format. Some antihistamine tablets can be difficult to swallow, while some liquids can make your taste buds recoil. So, products that were easier to take earned extra points. Also, if an antihistamine was lost in a forest of other ingredients it did not make our list. If you need a prescription to obtain it, it did not rank for our list. And if the product did not produce reasonably fast results (within 30 minutes), it did not rank for our list.
Finally, you may notice some first-generation antihistamines on our list (in products like Benadryl). It is not a mistake, and there is a good reason for their inclusion. While first-gen antihistamines are no longer considered leading-edge, they still have an important role to play in enabling people racked by allergy symptoms to get the sleep they need.
Antihistamines can relieve allergy symptoms. Antihistamines are a multi-billion dollar industry in the US alone (3). The primary reason people use antihistamines is to help them deal with their allergy symptoms. And they (the antihistamines) do a generally outstanding job of it. Whether you have a runny nose, watery eyes, sneezing, or nasal swelling, antihistamines can and do help.
Antihistamines can help you get to sleep. This is particularly true of first-generation antihistamines like diphenhydramine (4). Often found in allergy medicines like Benadryl, diphenhydramine is known for its ability to produce drowsiness. Many allergy medicines have moved away from first-gen antihistamines for just this reason. At the same time, though, Benadryl remains popular in part because of its ability to help allergy sufferers get to sleep.
Antihistamines relieve congestion. While they are not expressly designed to relieve congestion, antihistamines nonetheless do a pretty good job. They do not actually go after the congestion itself like a decongestant will, instead they work to prevent histamines from producing congestion (5) in the first place. A lot of people prefer this proactive approach to the decongestant approach of waiting until you are already stuffed up.
Antihistamines stop your runny nose. A runny nose is one of the most unpleasant aspects of seasonal allergies. Antihistamines, as their name implies, block the action of histamines. Histamines are released by mast cells (6) as a function of the body’s immune response. Once released, they produce a variety of visible effects, including watery eyes and a runny nose. By blocking histamine release, antihistamines prevent a runny nose.
Antihistamines side effects are typically mild. Antihistamines are not side effect free, but those side effects are usually mild. They may include a dry mouth, moodiness, or dizziness. And, as we mentioned, first-generation antihistamines are known to cause drowsiness. On rare occasions, people may experience more severe side effects such as confusion or urinary retention that should be reported to a doctor.
Antihistamines reduce red, itchy eyes. Those same histamines that cause a runny nose also cause the red, itchy eyes you experience during an allergy attack. It is all part of the body’s natural immune response. But knowing that does not make it any easier to take. Antihistamines shut down histamine activity and restore normal eye function.
Antihistamines no longer cause urinary retention. One of the most common side effects of first-generation antihistamines was (and is) water retention. Because they prevent histamines from enabling cell permeability, the body would be fooled into thinking it was short of fluids. As a result, it would stop passing fluid by way of urination. Today’s antihistamines allow for a higher degree of permeability, which prevents urinary retention.
Antihistamines allow you to enjoy the great outdoors. One of the worst aspects of seasonal allergies is feeling like you have to stay indoors all the time. Antihistamines can provide a defensive wall pollen will not be able to penetrate, enabling you to re-engage with your favorite outdoor activities.
Antihistamines are affordable healthcare. It is estimated that OTC medicines, including over the counter antihistamines, save US citizens nearly $150 billion a year by preventing unneeded doctor visits, lab tests, and hospitalizations (7). Before the advent of modern antihistamines, people either suffered in silence or were forced to seek professional help that, frankly, was not always that helpful. Today, they have a cheap and easy way to get relief.
Antihistamines do not require a prescription. ’Over the counter’ means no prescription is necessary. That fact not only negates the need for an expensive visit to the doctor, it also saves you time. There is no need to take an afternoon off from work to see the doctor. You can simply buy your preferred antihistamine online in your spare time and have it delivered to your door.
Antihistamines are proven safe and effective. Antihistamines are a safe and effective form of medication taken by millions of people every day. They only become problematic if taken in large quantities, or when a person who is drowsy from antihistamine use tries to operate heavy equipment or some type of vehicle (8). But again, when taken as directed, antihistamines are a safe and effective means of obtaining relief.
Antihistamines no longer make you drowsy. First generation antihistamines like diphenhydramine were and are generally effective. However, that effectiveness comes at a price. They tend to make a lot of people drowsy. A major incentive for the creation of second and third-generation antihistamines was to find a way to avoid the drowsiness. And, fortunately, most new antihistamine products no longer produce drowsiness.
Antihistamines can help your children deal with allergies. First generation antihistamines provide effective relief for many adults but were (and are) considered inappropriate for children due to the threat of overdosing. Today’s second and third-generation antihistamines largely negate that threat and are considered both safe and effective for kids (9).
Antihistamines can be administered in a variety of ways. Not everyone is comfortable, or even able, to take medicine the same way. Antihistamines are available in different forms to accommodate people’s differing needs. Hard tablets, gel caps, liquids, and nasal sprays are the most popular methods of administering OTC antihistamines. Sometimes a doctor may prescribe intravenous antihistamines (10). But such occasions are rare.
Antihistamines are safer than ever for seniors. Falls are a significant health concern for the elderly (11). As such, anything that increases the potential for a fall is a potential problem. For this reason, the elderly were, and are, discouraged from using first-generation antihistamines that often cause drowsiness. Fortunately, the new generation of antihistamines do not cause drowsiness, which enables seniors to enjoy safe and effective allergy relief.
Antihistamines can be used to treat flu symptoms. Contrary to popular belief, antihistamines are not just for allergy symptoms. If you suffer from a runny nose or watery eyes due to a cold or flu, it is likely antihistamines can help. They may also reduce sneezing and itching associated with a cold or flu. So if your current cold medicine is not working, ask your doctor if you should try antihistamines.
Antihistamines are safe for long term use. Because seasonal allergies can last for months at a time, and recur year after year, the safety of long term antihistamine use often comes up. That is understandable since most medicines are not intended to be used for months or years at a time. Fortunately, today’s antihistamines are considered safe when used over long periods, with the main concern being the potential for increased user tolerance (12).
Antihistamines improve your quality of life. There can be little doubt about this fact. For most people, antihistamines relieve the worst symptoms of allergies. In many cases, this enables the person to re-engage with life in ways they may have avoided for years. They become more productive, more upbeat, and see nature as less of an adversary. Their loved ones also benefit from this improved outlook.
Q: What is an antihistamine?
A: Histamines (13) are chemicals released by your immune system to deal with perceived threats. They bind to receptors on certain cells and enable those cells to work as immune system conduits for channeling defensive agents to fight intruders. Side effects of all this histamine-driven chemistry include a runny nose, watery eyes, sneezing, and more. Antihistamines block the action of histamines and prevent those side effects.
Q: What are the different types of antihistamines?
A: Antihistamines are available in a variety of forms, so there is bound to be one that will agree with you. Some take tablet form, others take the form of easy-to-swallow gelcaps. Some are available as liquids or nasal sprays, and still others are suspended in eyedrops. Most can be purchased over the counter. Although more potent antihistamines will require a doctor’s prescription.
Q: What is a second-generation antihistamine?
A: While first-generation antihistamines (like those in Benadryl) were and are very effective, they also produced some unwanted side effects, like drowsiness. Years of research and refinement resulted in second, and then third, generation antihistamines that were, and are, less general in nature and more purpose-oriented. These address specific aspects of histamine activity and cause less drowsiness.
Q: Do second-generation antihistamines have other advantages?
A: In addition to producing less drowsiness in users, second and third-generation antihistamines also eliminate urinary retention. In addition, there are few instances of dry mouth and constipation associated with these newer antihistamines. They also tend to last longer. So you do not need to take more every few hours like you often have to with first-gen antihistamines.
Q: Do antihistamines have any side effects?
A: They do. But those side effects tend to differ significantly in character and intensity depending on whether an antihistamine is first, second or third generation. First-gen antihistamines may cause drowsiness, mental confusion, water retention, moodiness, and blurred vision. While second and third-gen antihistamine side effects tend to be limited in character and short-lived.
Q: What are some of the uses for antihistamines?
A: By far, the most popular reason people use antihistamines is to deal with allergy symptoms. In most cases, that means seasonal allergies, or what is commonly known as ‘hay fever’ (14). But in other cases, it might mean pet allergies, allergic reactions to bee stings, hives (15), and more. Antihistamines also have applications beyond treating allergy symptoms. They are sometimes used to treat motion sickness, vertigo (16), and even insomnia.
Q: Why do some antihistamines make me drowsy?
A: First generation antihistamines were (and are) known for creating drowsy feelings in the people that use them. (In some cases people use them for precisely that reason.) How they cause drowsiness is an extremely complicated matter. In a nutshell, drowsiness occurs when the antihistamines cross the blood-brain barrier (17) which regulates the movement of microscopic compounds and cells between blood vessels and the brain.
Q: How come some antihistamines don’t make me drowsy?
A: Second and third-generation antihistamines have been deliberately engineered not to cross the blood-brain barrier. As a result, they do not produce the same type of drowsiness first-generation antihistamines do. There are exceptions to every rule, though. And in some cases, their ability to refrain from crossing the barrier is not complete. As a result, they may produce a mild sense of drowsiness in some. But nothing like their predecessors.
Q: How fast do antihistamines work?
A: In most cases, oral antihistamines take about 30 minutes to produce noticeable relief. But it depends, in part, on your metabolism as well. A person with a faster metabolism might start seeing relief in 15 or 20 minutes. Antihistamine nasal sprays tend to get to work faster. Sometimes in just a few minutes. But they are not for everyone. Some people do not like the way it feels to spray the medication directly into the nose.
Q: What are the long term health effects of antihistamines?
A: Because they are often used for months, or even years at a time, people have concerns about potential long term health consequences of antihistamines. However, research indicates antihistamines – regardless of generation – pose little long term threat to overall health (18). In some cases, mild liver damage has been observed. But it seems very limited and is not considered a serious health concern.
Q: Can I use an antihistamine for my cold?
A: Yes, you can use an antihistamine to address cold and flu symptoms. And millions of people do. Colds and allergies share many symptoms, including runny nose and itchy, watery eyes. And these symptoms are brought on by the activity of histamines. So antihistamines can and usually will provide some measure of relief. Just remember that the antihistamine is not going to cure your cold or flu just as it does not cure you of allergies.
Q: Why do I have allergies and others do not?
A: The fact is, no one is quite sure why some people develop allergies, and others do not. There are plenty of theories out there, but precious little agreement. Genetics is a popular theory (19). But in truth, just blaming mom and dad is a bit of cop out, because it does not address why they had allergies. The bottom line is: we know how allergies happen, and we know we can control them with antihistamines. But we do not really know why they happen.
Q: Are there some people who should not use antihistamines?
A: While most people can safely take antihistamines for their allergy or cold symptoms, some should not use them. These include people with epilepsy (20)(21), those with high blood pressure, people with kidney or liver disease, pregnant women, diabetics, and those with asthma. Also, children should never be given first-generation antihistamines.
Q: Can I have a few beers while taking antihistamines?
A: One of the primary side effects of first-generation antihistamines is drowsiness. That also happens to be one of the primary side effects of alcohol consumption. As such, the two should never be used together (22). That extra level of drowsiness presents a very real danger to life and limb by increasing the odds of an accident. It does not have to be an auto accident. It could be falling down stairs or drowning in a swimming pool.
Q: Do I have allergies or just a cold?
A: It can sometimes be difficult to determine whether sniffles and watery eyes are the result of allergies or a cold. There are a couple of pretty reliable ways to distinguish between the two. If the symptoms persist for weeks, it is likely allergies. If you have aches and pains along with the runny nose and watery eyes, it is likely a cold. In the end, it does not matter too much because antihistamines will address your symptoms, regardless of their source.
Q: Do antihistamines interact with other medications?
A: Antihistamines and alcohol should not be used together. But what about other drugs? Antihistamines are generally considered safe when used as directed. However, those taking the antipsychotic medicine Clozapine (23), or medications to treat Gaucher disease (24) should avoid antihistamines. Also, those taking Tamoxifen for breast cancer should avoid antihistamines. If you have any questions about interactions, consult your doctor.
Q: Can I take antihistamines every day indefinitely?
A: Antihistamines are not like a daily multivitamin supplement. They are not supposed to be part of your everyday routine. They are intended to be used only when the situation calls for it. This way, you minimize the risk of interactions with other medications, minimize your experience of side effects and reduce the chance that you could build a tolerance to them (25), which can be an issue if they are overused.
Q: Why are some antihistamines now kept behind the counter?
A: In 2006 Congress passed the Combat Methamphetamine Epidemic Act (CEMA). Part of this legislation dealt with restricting access to OTC medicines that contained pseudoephedrine (26). At the time (2006), pseudoephedrine was a popular ingredient in many allergy medications. After the passage of CEMA, many drug companies stopped using it. Others moved their products behind the counter where they could not be easily accessed.
Q: If histamines are good for you why do they make you feel bad?
A: It might help to think of histamines like firefighters. If your house is on fire, a firefighter may need to break down doors and walls to get to you. They work with the big picture in mind: the doors and walls can be replaced. You cannot. Same with histamines. Sure, they make you uncomfortable today, but their job is to make sure you live to see tomorrow. And while pollen is not a threat to life and limb, histamines do not know that. They treat all invaders the same.
Q: Will using antihistamines prolong a cold?
A: This is a good question. Logic would seem to dictate that if you block the beneficial activity of histamines that you would just be prolonging the time it takes to recover from a cold or flu. But there is virtually no agreement on whether that is actually true. Some argue that even if it is true, four days spent feeling not-so-bad is better than three days spent feeling awful. So the debate rages on.
Antihistamines help those beset by allergy symptoms regain a level of control over their lives. They reduce runny noses, itchy, watery eyes, sneezing, congestion, and more and allow people to re-engage with the outdoors in ways they could not previously imagine.
While they are not without their side effects, those side effects tend to be quite manageable as long as the antihistamines are used as directed. Second and third-generation antihistamines tend to produce fewer and milder side effects than their first-generation cousins. Most notably, they all but eliminate drowsiness.
Over the counter antihistamines are available today as tablets, gel-caps, liquids, nasal spray and eye drops. Use the above information to help you determine which type is right for you.
For cpoe.org’s #1 recommended antihistamine, click here.