Hydroxyzine pamoate vs. HCl: What’s the difference?

In this article:

• Key differences
• Conditions treated
• Which is better for anxiety or sleep?
• Which is better for itching?
• Side effects
• Drug interactions and warnings
• Insurance coverage and cost
• FAQs

In this article

• Key differences
• Conditions treated
• Which is better for anxiety or sleep?
• Which is better for itching?
• Side effects
• Drug interactions and warnings
• Insurance coverage and cost
• FAQs

Hydroxyzine, a common anti-anxiety and antihistamine prescription medication, comes in two forms: hydrochloride (HCl) and pamoate. They both contain the same active drug, but they have different salt forms (pamoate vs. hydrochloride).  There are virtually no other established differences between hydroxyzine pamoate versus. HCl, but recent studies suggest pamoate may provide an extra boost for treating itchy skin.

Key differences 

Hydroxyzine HCl and hydroxyzine pamoate contain the same active ingredient and are used to treat the same conditions. The main difference is the salt form of the drug.

Hydroxyzine is a chemical compound that contains carbon, hydrogen, chloride, nitrogen, and oxygen atoms.

To make a drug, hydroxyzine is combined with other compounds to form a salt.

• When hydroxyzine bonds with hydrogen chloride (HCl), it’s called hydroxyzine HCl. You may also see this referred to as hydroxyzine dihydrochloride.
• When hydroxyzine bonds with pamoic acid, it’s called hydroxyzine pamoate. Some publications call it hydroxyzine embonate.

So, hydroxyzine HCl and hydroxyzine pamoate have different salt forms, but they deliver the same active ingredient: hydroxyzine.

Why does the chemical structure matter?

Because hydroxyzine HCl and hydroxyzine pamoate have different salt forms, there may be minor differences in how the medications are absorbed in the body. However, these differences are not considered clinically significant, and the two medications are equally effective.

“Studies indicate that the blood concentration of hydroxyzine HCl peaks much earlier, and the absorption curve of hydroxyzine pamoate is much slower and sustained,” says Raymond Douglas, MD, a California-based oculoplastic and reconstructive surgeon. “I sometimes refer to HCl as a sprinter and pamoate as a marathon runner.”

That said, the prescribing labels for both types of hydroxyzine say they can start working in 15 to 30 minutes.

“Since the active drug is the same, both drugs will be equally effective when they enter your bloodstream,” Dr. Douglas says.

James Lyons, MD, clinical adviser at Epiphany Wellness, says the different chemical structures also affect the way patients can take hydroxyzine. Because hydroxyzine HCl dissolves in water, it comes not only in an oral tablet, but also as an injection and oral liquid.

“Hydroxyzine HCl comes in a variety of formulations and has a greater number of applications beyond oral administration, so it’s used much more frequently,” Dr. Lyons says. “However, the salt designation (HCl vs. pamoate) is not nearly as important as the dosage level when thinking about the effectiveness of the drug.”

Is hydroxyzine salt?

Both types of hydroxyzine are called “salts,” but this doesn’t mean they’re related to table salt.

Hydroxyzine is a weak base. When it reacts with an acid (like hydrochloric acid or pamoic acid), chemists call the resulting product (hydroxyzine HCl or hydroxyzine pamoate) a salt.

Do hydroxyzine salts have different brand names? 

In the U.S., all name-brand versions of hydroxyzine HCl have been discontinued due to the widespread availability of the more affordable generic. Hydroxyzine pamoate is still available under the brand name Vistaril.

Compare hydroxyzine pamoate vs. hydroxyzine HCl key differences
Feature	Hydroxyzine pamoate	Hydroxyzine HCl
Drug class	Antihistamine / anxiolytic	Antihistamine / anxiolytic
Brand/generic status	Brand and generic	Generic only
Generic name	Hydroxyzine pamoate	Hydroxyzine HCl
Dosage forms	Capsule	Tablet, solution, intramuscular injection
Available strengths	25 mg, 50 mg capsules	10 mg, 25 mg, 50 mg tablets
Typical treatment duration	As needed	As needed
Who typically uses it	Adults and children with anxiety or allergic itching	Adults and children with anxiety or allergic itching
Requires prescription?	Yes	Yes
Controlled substance?	No	No

Conditions treated

Hydroxyzine HCl and hydroxyzine pamoate have been approved by the U.S. Food and Drug Administration (FDA) for the same indications:

• Relieving anxiety and tension
• Soothing itchy skin caused by allergic conditions like atopic dermatitis
• Causing sedation before or after general anesthesia

Some healthcare professionals also prescribe hydroxyzine to improve sleep (an off-label use) or treat nausea and vomiting. Hydroxyzine’s sedative effects may also enhance the pain-relieving effects of opioid medications, so healthcare providers sometimes prescribe hydroxyzine as an add-on treatment to opioids.

Healthcare professionals may inject hydroxyzine HCl to offer quick anxiety relief or sedation when oral medication isn’t available. For example, it may be used to calm someone who feels stressed about visiting the dentist.

Compare hydroxyzine pamoate vs. hydroxyzine HCl conditions treated
Condition/use	Hydroxyzine pamoate	Hydroxyzine HCl
Anxiety and tension	Yes	Yes
Pruritus (itching) from allergic conditions	Yes	Yes
Pre- and post-operative sedation	Yes	Yes
Acute anxiety/nausea (injection)	No	Yes
Insomnia (sleep)	Yes	Yes
Nausea (non-surgical)	Yes	Yes

Which is better for anxiety or sleep?

There are currently no head-to-head studies or clinical trials comparing hydroxyzine pamoate versus HCl for anxiety or sleep.

However, the different absorption rate suggests that HCl might be the better option for faster sleep onset. “You may feel sleepy more quickly with HCl because it’s more quickly absorbed into your system,” Dr. Douglas says. “Pamoate gently leads you into sleepiness, but over a longer period of time.”

If you need rapid anxiety relief or sedation before a procedure, a healthcare provider may inject you with hydroxyzine HCl. Hydroxyzine pamoate isn’t available as an injection.

Read more: Hydroxyzine for anxiety: Does it work?

Which is better for itching?

There’s no definitive evidence that one form of hydroxyzine is better than the other for itching, but emerging research has found that pamoate may have additional activity that can benefit itching. It isn’t known whether this can provide more symptom relief than hydroxyzine HCl. .

In a 2010 report, a professor of pharmacology at the University of Michigan noted that pamoate has been shown to activate a certain receptor in the body called GPR35. GPR35 may play a role in immune responses and inflammation.

In 2023, a group of researchers found that pamoate improves itching and skin inflammation through a GPR35-related pathway.

It’s unclear whether hydrochloride (HCl) offers similar benefits.

Side effects

Both forms of hydroxyzine carry the same risk of side effects, which may include:

• Dry mouth
• Drowsiness
• Headache
• Allergic reaction
• A heart rhythm abnormality called QT prolongation

In rare cases, hydroxyzine can cause tremors or convulsions, a severe skin reaction called acute generalized exanthematous pustulosis (AGEP). Some people also hallucinate while taking hydroxyzine. “Blurred vision, constipation, and urinary retention can also occur,” Dr. Lyons says.

After receiving an injection of hydroxyzine HCl, a severe injection site reaction can occur in which the tissue becomes damaged, infected, and dies. This may require surgery.

It’s possible to take too much hydroxyzine. A hydroxyzine overdose can look like extreme sedation, convulsions, nausea, vomiting, and stupor.

“You also need to be careful about taking either form of hydroxyzine with other sedatives, such as pain medications, as they can also make you breathe slower than you should,” says Dr. Douglas.

Talk to a healthcare professional or pharmacist for a full list of potential hydroxyzine side effects.

Compare hydroxyzine pamoate vs. hydroxyzine HCl side effects
Side effect	Hydroxyzine pamoate	Hydroxyzine HCl
Drowsiness/sedation	Common	Common
Dry mouth	Possible	Possible
Headache	Possible	Possible
Tremors, convulsions	Serious, rare	Serious, rare
QT prolongation (serious, rare)	Serious, rare	Serious, rare
Allergic reaction or rash	Serious, rare	Serious, rare
Injection site reaction	N/A	Can be severe, rare

Drug interactions and warnings

Hydroxyzine HCl and pamoate have identical drug interactions and warnings.

Tell your prescriber about all other medications and supplements you’re taking so they can check for potential drug interactions. It shouldn’t be taken by people who have a prolonged QT interval or who have previously been sensitive to hydroxyzine, cetirizine, or levocetirizine.

You should also tell your prescriber if you’re pregnant or planning to become pregnant. Hydroxyzine should not be taken in early pregnancy or while breastfeeding.

Your prescriber may need to adjust the dose of any opioids you take while taking hydroxyzine. Hydroxyzine increases the sedative effects of opioid medications. Note that hydroxyzine isn’t addictive, but its sedating effects can lead to misuse.

Insurance coverage and cost

Because hydroxyzine is a generic and low-cost medication, insurance companies tend to cover it without issue. You can double-check insurance coverage by contacting your insurance provider, healthcare provider, or pharmacist.

If you need to pay out of pocket, you’ll find both forms of hydroxyzine tend to be affordable.

• Generic hydroxyzine HCl costs an average of $33 for 30, 25 mg tablets without insurance or discounts.
• Generic hydroxyzine pamoate costs an average of $24 for 30, 25 mg capsules without insurance or discounts.

Note: Because hydroxyzine is usually taken as needed up to four times per day, thirty tablets or capsules could last one week or longer.

A free SingleCare coupon can lower the cost of hydroxyzine even more.

• Generic hydroxyzine HCl costs as low as $5 for 30, 25 mg tablets with a SingleCare coupon.
• Generic hydroxyzine pamoate costs as low as $5 for 30, 35 mg capsules with a SingleCare coupon.

SingleCare discounts can’t be combined with insurance, so they won’t count toward your deductible. The final price may vary based on form, quantity, and pharmacy.

Compare hydroxyzine pamoate vs. hydroxyzine HCl coverage and cost
Coverage and cost	Hydroxyzine pamoate	Hydroxyzine HCl
Typically covered by insurance?	Yes	Yes
Typically covered by Medicare Part D?	Yes	Yes
Typically covered by Medicaid?	Varies by state	Varies by state
Brand available?	Yes (Vistaril)	No (Discontinued)
Generic available?	Yes	Yes
SingleCare price	$5.47 for 30, 25 mg capsules at Kroger	$4.95 for 30, 25 mg tablets at Walmart
Get coupon	Get coupon	Get coupon

Bottom line

Hydroxyzine HCl and hydroxyzine pamoate are equally effective. You shouldn’t notice a difference in side effects or overall performance. Hydroxyzine HCl is also the only version that can be taken as a syrup or intramuscular injection, so it may work better for people who struggle to take pills or capsules.

A healthcare provider can recommend the right version of hydroxyzine for you. If you can’t take this medication due to hypersensitivity or a contraindication, ask your healthcare provider about hydroxyzine alternatives.

Frequently asked questions

Is hydroxyzine pamoate the same as hydroxyzine HCl?

Hydroxyzine pamoate and hydroxyzine HCl contain the same active ingredient (hydroxyzine), but they are different salt forms. They’re extremely similar, but hydroxyzine HCl is water-soluble and hydroxyzine pamoate isn’t.

Is Atarax a controlled substance?

No, Atarax (a brand name for hydroxyzine HCl that has been discontinued) is not a controlled substance.

Is hydroxyzine over the counter? 

No, hydroxyzine is not available over the counter. It requires a prescription.