Hydroxyzine vs. Benadryl: 7 Differences Between These Antihistamines
Key takeaways:
Hydroxyzine (Vistaril) and Benadryl (diphenhydramine) are both antihistamines. They’re similar, but have some important differences to keep in mind when comparing them.
Benadryl is available over the counter, while hydroxyzine requires a prescription. They also have different recommended dosages and age groups on their labeling.
Hydroxyzine lasts longer in your body compared to Benadryl. This means side effects can last longer with hydroxyzine. You may also need to be careful with drug interactions for a few days after stopping hydroxyzine.
Hydroxyzine and Benadryl are available as brand-name medications. But you can also find them as lower-cost generics. GoodRx can help make your medication more affordable with a prescription from your healthcare provider.
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Table of contents
If you’ve ever experienced allergy symptoms, you may have taken an antihistamine. These medications are widely recommended by healthcare providers both over the counter (OTC) and with a prescription.
Hydroxyzine (Vistaril) and Benadryl (diphenhydramine) are two first-generation antihistamines that have been around for decades. While they can both help relieve allergy symptoms, there are several key differences between these two medications. We’ll review seven differences between hydroxyzine and Benadryl below.
Note: Hydroxyzine comes in two forms: hydroxyzine pamoate and hydroxyzine hydrochloride. Both work very similarly with few differences. In this article, when we discuss “hydroxyzine,” we’re referring to both forms of the medication.
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1. Benadryl is available over the counter, while hydroxyzine is available by prescription only
If you’re looking for an OTC antihistamine, you won’t find hydroxyzine on pharmacy shelves. Hydroxyzine is a prescription-only antihistamine. Benadryl, on the other hand, is readily available OTC.
This difference is likely because hydroxyzine lasts in the body much longer than Benadryl. It can also be prescribed to treat anxiety. More details on these two differences later.
2. Hydroxyzine and Benadryl work slightly differently
Both hydroxyzine and Benadryl block a natural chemical in your body called histamine. Histamine is responsible for allergy symptoms. In addition to histamine, older antihistamines are known to affect other chemicals in the body, such as acetylcholine. And this can contribute to side effects such as drowsiness. In fact, drowsiness happens so frequently that first-generation antihistamines are commonly taken for occasional sleep troubles.
Because their chemical structures are different, hydroxyzine and Benadryl act in distinct ways. Hydroxyzine is one of a few antihistamines that has a chemical structure called a piperazine ring. Medications with this ring can help relieve anxiety or nausea in addition to allergy symptoms. Benadryl doesn’t have this chemical property, so it doesn’t provide these extra effects.
3. Hydroxyzine lasts longer in your system than Benadryl
Compared to Benadryl, hydroxyzine lasts longer in your body. It can take up to 2 days for Benadryl to leave most people’s bodies. But it can take around 5 days for most people to clear hydroxyzine.
This means that hydroxyzine might provide intended effects longer than Benadryl. But it also means side effects may last longer. Notably, you may experience drowsiness or dizziness longer after taking hydroxyzine compared to Benadryl.
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If you’re taking other medications, this difference can also result in drug interactions. Hydroxyzine could interact with other medications for a few days after you’ve stopped taking it. Benadryl’s time frame for interactions is likely shorter. But it’s a good idea to have your healthcare provider or pharmacist double-check your medication list for interactions when taking either medication.
Good to know: If you have liver or kidney problems, these medications could last even longer in your body. It may also take longer for your body to clear them if you’re over 65.
4. Hydroxyzine can be prescribed for anxiety
Unlike Benadryl, hydroxyzine is sometimes prescribed for short periods to treat anxiety. However, it isn’t considered a first-choice treatment.
It’s not fully clear how hydroxyzine works for anxiety. Researchers think its anti-anxiety effects might be related to how it affects histamine and serotonin. These chemicals are thought to play a role in anxiety disorders.
Benadryl is not FDA approved for anxiety.
5. Hydroxyzine and Benadryl are approved for different age ranges
Benadryl and hydroxyzine are both FDA approved for use in children and adults. But the specific ages they’re approved for differ, particularly children under 6 years old.
The manufacturer of hydroxyzine includes dosage recommendations for children younger than 6 with no minimum age listed. This leaves it up to a healthcare provider to determine if hydroxyzine is appropriate for a child based on their symptoms and medical history.
The manufacturer of OTC children’s Benadryl (both tablets and liquid) recommends only giving it to children who are at least 6 years old. If your child is younger than this, you should check with their provider before giving it to them.
In some cases, your child’s provider might recommend Benadryl if your child is under 6. For example, it’s common for providers to recommend it if a young child is having a mild allergic reaction. If they feel your child needs Benadryl, they’ll give you specific dosing recommendations based on your child’s body weight.
6. Hydroxyzine and Benadryl have different recommended dosages
Hydroxyzine is available as tablets, capsules, and an oral solution. It also comes as an intramuscular (IM) injection that can be given in a healthcare setting. Depending on why you’re taking it, adults may take 25 mg to 100 mg of hydroxyzine up to 3 or 4 times a day, as needed. The maximum daily dosage also depends on why you’re taking it.
Benadryl comes in many different dosage forms, including oral capsules, tablets, and liquids. There’s also an injectable form that’s only used in hospital settings. The usual adult dosage is 25 mg to 50 mg by mouth every 4 to 6 hours as needed. You typically shouldn’t take more than 6 doses (300 mg) in 24 hours.
Good to know: Diphenhydramine (Benadryl’s active ingredient) is included in several other OTC medications. These include sleep aids, anti-itch creams, and cold and flu medications. Check with your pharmacist before taking Benadryl with any of these products. It’s easy to take too much diphenhydramine by accident. And this can cause serious side effects, such as hallucinations or coma.
7. Hydroxyzine has a warning about QT prolongation
After hydroxyzine was approved, case reports were published about the medication causing long QT syndrome. This is an abnormal heart rhythm that can lead to life-threatening arrhythmias. In many cases, this side effect happened when people were taking the medication as prescribed. This prompted manufacturers to add a warning about long QT syndrome to hydroxyzine’s labeling.
Most reported cases of this serious hydroxyzine side effect were from people who had a higher risk of long QT syndrome. Hydroxyzine may not be safe to take if you have a personal or family history of heart problems or if you’re taking other medications that can cause long QT syndrome. And you shouldn't take it if you currently have the condition.
There have been reports of long QT syndrome in people taking Benadryl, too. But it’s much rarer and seems to happen most often when people take more than the recommended dosages. Benadryl’s labeling doesn’t include a warning for long QT syndrome like hydroxyzine. Still, it’s a good idea to check with your healthcare provider before taking Benadryl if you have a history of heart problems.
How to save on hydroxyzine and Benadryl
There are many ways to save on hydroxyzine and Benadryl, which are available as both brand-name and generic medications. GoodRx can help you save over 60% off the average retail price of the generic versions. If you’re taking Benadryl, you can still use a GoodRx coupon by having your healthcare provider write a prescription for it.
Generic hydroxyzine pamoate's price at certain pharmacies is as low as $8.54 with a free GoodRx coupon. Generic hydroxyzine hydrochloride’s price may be as little as $5.41. And generic Benadryl's price is as low as $1.20.
The bottom line
Hydroxyzine (Vistaril) and Benadryl (diphenhydramine) are two first-generation antihistamines. Benadryl is readily available over the counter. Hydroxyzine is only available with a prescription. While both medications can treat allergy symptoms, hydroxyzine is also FDA approved for anxiety. Each medication has its own unique recommended dosages and age ranges.
If you have any health conditions, especially a history of heart rhythm problems, speak with your healthcare provider. They can help make sure it's safe for you to take hydroxyzine or Benadryl.
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