Hydroxyzine

Identification

Summary

Hydroxyzine is an antihistamine used to treat anxiety and tension associated with psychoneuroses, as well as allergic conditions such as pruritus and chronic urticaria.

Brand Names
Atarax, Vistaril
Generic Name
Hydroxyzine
DrugBank Accession Number
DB00557
Background

Hydroxyzine is a first-generation histamine H1-receptor antagonist of the dephenylmethane and piperazine classes that exhibits sedative, anxiolytic, and antiemetic properties.2,12 It was first developed in 1955,10 and has since remained a relatively common treatment for allergic conditions such as pruritus, urticaria, dermatoses, and histamine-mediated pruritus.18 The active metabolite of hydroxyzine, cetirizine, is also available as an active ingredient in allergic medications, and is responsible for much of its hydroxyzine's antihistaminic effect.13 Hydroxyzine is also used for generalized anxiety disorder, tension caused by psychoneurosis, and other conditions with manifestations of anxiety.18

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 374.904
Monoisotopic: 374.176105825
Chemical Formula
C21H27ClN2O2
Synonyms
  • Hidroxizina
  • Hychotine
  • Hydroksyzyny
  • Hydroxine
  • Hydroxizine
  • Hydroxizinum
  • Hydroxycine
  • Hydroxyzin
  • Hydroxyzine
  • Hydroxyzinum
  • Idrossizina
External IDs
  • U.C.B-4492

Pharmacology

Indication

Hydroxyzine is indicated for the symptomatic relief of anxiety and tension associated with psychoneuroses, and as an adjunct in organic disease states in which anxiety is manifested.18 It is also indicated in the treatment of histamine-mediated pruritus and pruritus due to allergic conditions such as chronic urticaria.18

Canadian labeling states that hydroxyzine is also indicated in adults and children as a premedication prior to medical procedures, such as dental surgery.15 It is also used in the control of nausea and vomiting, excluding nausea and vomiting of pregnancy.15

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Prevention ofAnxiety••••••••••••
Adjunct therapy in treatment ofAnxiety••••••••••••
Symptomatic treatment ofAnxiety••••••••••••
Symptomatic treatment ofNausea and vomiting••••••••••••
Treatment ofPruritus••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Hydroxyzine blocks the activity of histamine to relieve allergic symptoms such as pruritus.18 Activity at off-targets also allows for its use as a sedative anxiolytic and an antiemetic in certain disease states.15

Hydroxyzine is relatively fast-acting, with an onset of effect that occurs between 15 and 60 minutes and a duration of action between 4-6 hours.2 Hydroxyzine may potentiate the effects of central nervous system (CNS) depressants following general anesthesia - patients maintained on hydroxyzine should receive reduced doses of any CNS depressants required.18 Hydroxyzine is reported to prolong the QT/QTc interval based on postmarketing reports of rare events of Torsade de Pointes, cardiac arrest, and sudden death, and should be used with caution in patients with an increased baseline risk for QTc prolongation.15,10

Mechanism of action

The H1 histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H1 receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes.11

Hydroxyzine is a potent inverse agonist of histamine H1-receptors2 - inverse agonists are agents that are considered to have a "negative efficacy", so rather than simply blocking activity at a receptor they actively dampen its activity.14 Inverse agonism at these receptors is responsible for hydroxyzine's efficacy in the treatment of histaminic edema, flare, and pruritus.

Hydroxyzine is not a cortical depressant, so its sedative properties likely occur at the subcortical level of the CNS.18 These sedative properties allow activity as an anxiolytic. Antiemetic efficacy is likely secondary to activity at off-targets.13

TargetActionsOrganism
AHistamine H1 receptor
inverse agonist
Humans
UVoltage-gated inwardly rectifying potassium channel KCNH2
inhibitor
Humans
Absorption

The absolute bioavailability of hydroxyzine has not been ascertained, as intravenous formulations are unavailable due to a risk of hemolysis.2 Hydroxyzine is rapidly absorbed from the gastrointestinal tract upon oral administration,18 reaching its maximum plasma concentration (Tmax) approximately 2 hours following administration.9

Volume of distribution

The mean volume of distribution is 16.0 ± 3.0 L/kg. Higher concentrations are found in the skin than in the plasma.2

Protein binding

Hydroxyzine has been shown to bind to human albumin in vitro,8 but the extent of protein binding in plasma has not been evaluated.

Metabolism

Hydroxyzine is metabolized in the liver2 by CYP3A4 and CYP3A5.18 While the precise metabolic fate of hydroxyzine is unclear, its main and active metabolite (~45 to 60% of an orally administered dose),13 generated by oxidation of its alcohol moiety to a carboxylic acid, is the second-generation antihistamine cetirizine.2 Hydroxyzine is likely broken down into several other metabolites, though specific structures and pathways have not been elucidated in humans.7

Hover over products below to view reaction partners

Route of elimination

Approximately 70% of hydroxyzine's active metabolite, cetirizine, is excreted unchanged in the urine.3 The precise extent of renal and fecal excretion in humans has not been determined.18

Half-life

The half-life of hydroxyzine is reportedly 14-25 hours,2 and appears to be, on average, shorter in children (~7.1 hours) than in adults (~20 hours).6 Elimination half-life is prolonged in the elderly, averaging approximately 29 hours,3 and is likely to be similarly prolonged in patients with renal or hepatic impairment.15

Clearance

Clearance of hydroxyzine has been reported to be 31.1 ± 11.1 mL/min/kg in children and 9.8 ± 3.3 mL/min/kg in adults.6

Adverse Effects
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Toxicity

The oral LD50 is 840 mg/kg in rats and 400 mg/kg in mice.16

Overdose from hydroxyzine is most commonly characterized by hypersedation, but may also manifest as convulsions, stupor, nausea, and vomiting.18 In cases of overdose, consider the induction of vomiting and the use of gastric lavage. Other treatment should involve general symptomatic and supportive care. Hypotension may be controlled by intravenous fluids and pressors, and caffeine and sodium benzoate injection may be used to counteract any observed CNS depressant effects. Hemodialysis is unlikely to provide any benefit in the treatment hydroxyzine overdose.18

Pathways
PathwayCategory
Hydroxyzine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of 1,2-Benzodiazepine.
AbametapirThe serum concentration of Hydroxyzine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Hydroxyzine can be increased when combined with Abatacept.
AcalabrutinibThe metabolism of Hydroxyzine can be decreased when combined with Acalabrutinib.
AcebutololThe risk or severity of QTc prolongation can be increased when Acebutolol is combined with Hydroxyzine.
Food Interactions
  • Avoid alcohol. Co-administration with alcohol may potentiate the CNS adverse effects of hydroxyzine.
  • Avoid grapefruit products. Co-administration with grapefruit inhibits hydroxyzine metabolism and can result in elevated serum concentrations.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Hydroxyzine hydrochloride76755771U32192-20-3ANOMHKZSQFYSBR-UHFFFAOYSA-N
Hydroxyzine pamoateM20215MUFR10246-75-0ASDOKGIIKXGMNB-UHFFFAOYSA-N
Product Images
International/Other Brands
Hyzine (Hyrex) / Masmoran (Pfizer) / Rezine / Vistaject-50 / Vistazine
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AtaraxSyrup10 mg / 5 mLOralSearchlight Pharma Inc1956-12-31Not applicableCanada flag
AtaraxSyrup10 mg/5mLOralRoerig2006-06-202016-06-16US flag
AtaraxTablet25 mg/1OralRoerig2006-06-202016-06-16US flag
AtaraxTablet100 mg/1OralRoerig2006-06-202016-06-16US flag
AtaraxTablet10 mg/1OralRoerig2006-06-202016-06-16US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
HydroxyzineInjection, solution50 mg/1mLIntramuscularHenry Schein, Inc.2022-01-17Not applicableUS flag
HydroxyzineInjection, solution50 mg/1mLIntramuscularGeneral Injectables & Vaccines, Inc2010-03-012023-08-31US flag
HydroxyzineInjection, solution50 mg/1mLIntramuscularGeneral Injectables & Vaccines, Inc2010-03-01Not applicableUS flag
HydroxyzineTablet, film coated25 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs2007-03-20Not applicableUS flag
HydroxyzineSolution10 mg/5mLOralPreferred Pharmaceuticals Inc.2015-08-21Not applicableUS flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ซีนิซTablet10 mgOralบริษัท ไทยนครพัฒนา จำกัด2007-03-26Not applicableThailand flag
ดร็อกซิมTablet25 mgOralบริษัท บุคคโล เทรดดิ้ง จำกัด จำกัด2008-06-25Not applicableThailand flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ATARAX FILM TABLET, 30 ADETHydroxyzine (10 mg) + Hydroxyzine (25 mg)TabletOralUcb Pharma S.A.1997-03-05Not applicableTurkey flag
ATARAX FILM TABLET, 30 ADETHydroxyzine (10 mg) + Hydroxyzine (25 mg)TabletOralUcb Pharma S.A.1997-03-05Not applicableTurkey flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
MKH Dose PackHydroxyzine hydrochloride (10 mg/1) + Ketamine hydrochloride (25 mg/1) + Midazolam (3 mg/1)TrocheSublingualImprimis Njof, Llc2019-03-04Not applicableUS flag

Categories

ATC Codes
N05BB01 — HydroxyzineN05BB51 — Hydroxyzine, combinations
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
N-alkylpiperazines / Chlorobenzenes / Aralkylamines / Aryl chlorides / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Primary alcohols / Organopnictogen compounds / Organochlorides
show 1 more
Substituents
1,4-diazinane / Alcohol / Amine / Aralkylamine / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Chlorobenzene / Dialkyl ether
show 17 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monochlorobenzenes, N-alkylpiperazine, hydroxyether (CHEBI:5818)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
30S50YM8OG
CAS number
68-88-2
InChI Key
ZQDWXGKKHFNSQK-UHFFFAOYSA-N
InChI
InChI=1S/C21H27ClN2O2/c22-20-8-6-19(7-9-20)21(18-4-2-1-3-5-18)24-12-10-23(11-13-24)14-16-26-17-15-25/h1-9,21,25H,10-17H2
IUPAC Name
2-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)ethan-1-ol
SMILES
OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1

References

Synthesis Reference

U.S. Patent 2,899,436.

General References
  1. Clark BG, Araki M, Brown HW: Hydroxyzine-associated tardive dyskinesia. Ann Neurol. 1982 Apr;11(4):435. [Article]
  2. Altamura AC, Moliterno D, Paletta S, Maffini M, Mauri MC, Bareggi S: Understanding the pharmacokinetics of anxiolytic drugs. Expert Opin Drug Metab Toxicol. 2013 Apr;9(4):423-40. doi: 10.1517/17425255.2013.759209. Epub 2013 Jan 21. [Article]
  3. Simons KJ, Watson WT, Chen XY, Simons FE: Pharmacokinetic and pharmacodynamic studies of the H1-receptor antagonist hydroxyzine in the elderly. Clin Pharmacol Ther. 1989 Jan;45(1):9-14. doi: 10.1038/clpt.1989.2. [Article]
  4. Lee BH, Lee SH, Chu D, Hyun JW, Choe H, Choi BH, Jo SH: Effects of the histamine H(1) receptor antagonist hydroxyzine on hERG K(+) channels and cardiac action potential duration. Acta Pharmacol Sin. 2011 Sep;32(9):1128-37. doi: 10.1038/aps.2011.66. [Article]
  5. Crowe A, Wright C: The impact of P-glycoprotein mediated efflux on absorption of 11 sedating and less-sedating antihistamines using Caco-2 monolayers. Xenobiotica. 2012 Jun;42(6):538-49. doi: 10.3109/00498254.2011.643256. Epub 2011 Dec 22. [Article]
  6. Paton DM, Webster DR: Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet. 1985 Nov-Dec;10(6):477-97. [Article]
  7. Fouda HG, Hobbs DC, Stambaugh JE: Sensitive assay for determination of hydroxyzine in plasma and its human pharmacokinetics. J Pharm Sci. 1979 Nov;68(11):1456-8. doi: 10.1002/jps.2600681134. [Article]
  8. Martinez-Gomez MA, Villanueva-Camanas RM, Sagrado S, Medina-Hernandez MJ: Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE. Electrophoresis. 2007 Aug;28(15):2635-43. doi: 10.1002/elps.200600742. [Article]
  9. Simons FE, Simons KJ, Frith EM: The pharmacokinetics and antihistaminic of the H1 receptor antagonist hydroxyzine. J Allergy Clin Immunol. 1984 Jan;73(1 Pt 1):69-75. doi: 10.1016/0091-6749(84)90486-x. [Article]
  10. Schlit AF, Delaunois A, Colomar A, Claudio B, Cariolato L, Boev R, Valentin JP, Peters C, Sloan VS, Bentz JWG: Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re-evaluation of an established drug. Pharmacol Res Perspect. 2017 Apr 21;5(3):e00309. doi: 10.1002/prp2.309. eCollection 2017 Jun. [Article]
  11. Devillier P, Roche N, Faisy C: Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and levocetirizine : a comparative review. Clin Pharmacokinet. 2008;47(4):217-30. [Article]
  12. Sawantdesai NS, Kale PP, Savai J: Evaluation of anxiolytic effects of aripiprazole and hydroxyzine as a combination in mice. J Basic Clin Pharm. 2016 Sep;7(4):97-104. doi: 10.4103/0976-0105.189429. [Article]
  13. Gengo FM, Dabronzo J, Yurchak A, Love S, Miller JK: The relative antihistaminic and psychomotor effects of hydroxyzine and cetirizine. Clin Pharmacol Ther. 1987 Sep;42(3):265-72. doi: 10.1038/clpt.1987.145. [Article]
  14. How drugs act: General principles. (2020). In Rang and Dale's Pharmacology (9th ed.). Edinburgh: Elsevier. [ISBN:9780702080609]
  15. Health Canada Product Monograph: Hydroxyzine HCl oral capsules [Link]
  16. CaymanChem: Hydroxyzine MSDS [Link]
  17. FDA Approved Drug Products: Hydroxyzine HCl oral tablets [Link]
  18. FDA Approved Drug Products: Vistaril (hydroxyzine pamoate) [Link]
  19. FDA Approved Drug Products: VISTARIL (hydroxyzine pamoate) capsules and suspension [Link]
  20. DailyMed: hydroxyzine hydrochloride injection [Link]
Human Metabolome Database
HMDB0014697
KEGG Drug
D08054
KEGG Compound
C07045
PubChem Compound
3658
PubChem Substance
46508556
ChemSpider
3531
BindingDB
22875
RxNav
5553
ChEBI
5818
ChEMBL
CHEMBL896
Therapeutic Targets Database
DAP000324
PharmGKB
PA449943
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Hydroxyzine

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableHydroxyzine / Reflex, Oculocardiac / Sinus Bradycardia / Strabismus1somestatusstop reasonjust information to hide
Not AvailableCompletedBasic SciencePlacebo Drug Interaction / Placebo Effect1somestatusstop reasonjust information to hide
Not AvailableCompletedSupportive CareChloral Hydrate / Electroencephalography / Hydroxyzine / Melatonin / Sleep Deprivation1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentSubstance Related Disorders1somestatusstop reasonjust information to hide
Not AvailableUnknown StatusPreventionPreoperative Anxiety1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Altana inc
  • App pharmaceuticals llc
  • Hospira inc
  • Luitpold pharmaceuticals inc
  • Pharmafair inc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Solopak laboratories inc
  • Watson laboratories inc
  • Wyeth ayerst laboratories
  • Organon usa inc
  • Pfizer laboratories div pfizer inc
  • Roerig div pfizer inc
  • Actavis mid atlantic llc
  • Alpharma us pharmaceuticals division
  • Hi tech pharmacal co inc
  • Kv pharmaceutical co
  • Vintage pharmaceuticals inc
  • Wockhardt eu operations (swiss) ag
  • Pfizer inc
  • Able laboratories inc
  • Actavis totowa llc
  • Amneal pharmaceutical
  • Halsey drug co inc
  • Heritage pharmaceuticals inc
  • Hetero drugs ltd unit iii
  • Invagen pharmaceuticals inc
  • Ivax pharmaceuticals inc
  • Kvk tech inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Northstar healthcare holdings ltd
  • Pliva inc
  • Purepac pharmaceutical co
  • Quantum pharmics ltd
  • Sandoz inc
  • Sun pharmaceutical industries inc
  • Superpharm corp
  • Usl pharma inc
  • Vintage pharmaceuticals llc
  • Barr laboratories inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Par pharmaceutical inc
  • Vangard laboratories inc div midway medical co
  • Teva pharmaceuticals usa inc
Packagers
  • Advanced Pharmaceutical Services Inc.
  • American Regent
  • Amerisource Health Services Corp.
  • Anda Inc.
  • Apotheca Inc.
  • APP Pharmaceuticals
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Barr Pharmaceuticals
  • Blenheim Pharmacal
  • Bryant Ranch Prepack
  • C.O. Truxton Inc.
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Caremark LLC
  • Carlisle Laboratories Inc.
  • Central Texas Community Health Centers
  • Clint Pharmaceutical Inc.
  • Co Med Pharmaceuticals Inc.
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Darby Dental Supply Co. Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Direct Pharmaceuticals Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • Glenmark Generics Ltd.
  • Goldline Laboratories Inc.
  • H and H Laboratories
  • H.J. Harkins Co. Inc.
  • Harris Pharmaceutical Inc.
  • Heartland Repack Services LLC
  • Heritage Pharmaceuticals
  • Hi Tech Pharmacal Co. Inc.
  • Innoviant Pharmacy Inc.
  • InvaGen Pharmaceuticals Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • KVK-Tech Inc.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Luitpold Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Martica Enterprises Inc.
  • Martin Surgical Supply
  • Medisca Inc.
  • Medvantx Inc.
  • Merit Pharmaceuticals
  • Merrell Pharmaceuticals Inc.
  • Monument Pharmaceutical Co. Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • National Pharmaceuticals
  • Nightingale Medical Of Indiana LLC
  • Northstar Rx LLC
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patheon Inc.
  • Patient First Corp.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacy Service Center
  • Pharmedix
  • Physicians Total Care Inc.
  • Piramal Healthcare
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescript Pharmaceuticals
  • Prescription Dispensing Service Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Sun Pharmaceutical Industries Ltd.
  • Talbert Medical Management Corp.
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Vangard Labs Inc.
  • Veratex Corp.
  • Vintage Pharmaceuticals Inc.
  • Watson Pharmaceuticals
  • Wockhardt Ltd.
Dosage Forms
FormRouteStrength
Capsule, liquid filledOral25 mg
Tablet, film coatedOral50 mg
TabletOral10.00 mg
Injection, solutionIntramuscular
SyrupOral
SyrupOral10 mg/5mL
TabletOral10 mg/1
TabletOral10.000 mg
TabletOral100 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, film coatedOral
SyrupOral200 ml
SolutionIntramuscular50 mg / mL
Tablet, film coatedOral30 mg
SyrupOral300 mg
TabletOral500 mg
TabletOral
Tablet, chewableBuccal25 mg
Tablet, coatedOral50 mg
SolutionIntramuscular100 mg
SolutionOral10 mg
SolutionOral250 mg
SyrupOral250 mg
SolutionOral0.25 g
TabletOral2500000 mg
SyrupOral0.25 g
CapsuleOral10 mg
CapsuleOral25 mg
CapsuleOral50 mg
Injection, solutionIntramuscular50 mg/1mL
SolutionOral10 mg/5mL
SyrupOral50 mg/25mL
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
LiquidIntramuscular50 mg / mL
Tablet, film coatedOral10.000 mg
Tablet, film coatedOral25.000 mg
CapsuleOral100 mg/1
CapsuleOral25 mg/1
CapsuleOral50 mg/1
Tablet, film coatedOral10 mg
TrocheSublingual
CapsuleOral10 mg / cap
CapsuleOral25 mg / cap
Injection, solutionIntramuscular25 mg/1mL
SyrupOral10 mg / 5 mL
Solution / dropsOral10 ml
Solution / dropsOral20 ml
SolutionIntramuscular50 mg/1mL
SuspensionOral25 mg/5mL
TabletOral25.000 mg
Tablet, coatedOral25 mg
TabletOral25 mg
TabletOral10 mg
Tablet, film coatedOral25 mg
Solution10 mg/5ml
Tablet, coatedOral10 mg
Prices
Unit descriptionCostUnit
Hydroxyzine Hcl 50 mg/ml4.42USD ml
Hydroxyzine 50 mg/ml vial3.96USD ml
Hydroxyzine 25 mg/ml vial3.6USD ml
Hydroxyzine hcl powder2.75USD g
Hydroxyzine pamoate powder2.14USD g
Vistaril 50 mg capsule2.03USD capsule
HydrOXYzine HCl 50 mg/ml vial1.78USD vial
Vistaril 25 mg capsule1.71USD capsule
Vistaril 100 mg capsule1.7USD capsule
Hydroxyzine hcl 50 mg tablet1.19USD tablet
Hydroxyzine hcl 10 mg tablet0.72USD tablet
Hydroxyzine hcl 25 mg tablet0.7USD tablet
HydrOXYzine Pamoate 100 mg capsule0.67USD capsule
Hydroxyzine pam 50 mg capsule0.64USD capsule
Hydroxyzine pam 100 mg capsule0.63USD capsule
Hydroxyzine pam 25 mg capsule0.46USD capsule
Vistaril 25 mg/5ml Suspension0.45USD ml
HydrOXYzine Pamoate 25 mg capsule0.3USD capsule
HydrOXYzine Pamoate 50 mg capsule0.23USD capsule
Apo-Hydroxyzine 50 mg Capsule0.22USD capsule
Novo-Hydroxyzin 50 mg Capsule0.22USD capsule
Apo-Hydroxyzine 25 mg Capsule0.15USD capsule
Novo-Hydroxyzin 25 mg Capsule0.15USD capsule
HydrOXYzine HCl 10 mg/5ml Syrup0.13USD ml
Apo-Hydroxyzine 10 mg Capsule0.12USD capsule
Novo-Hydroxyzin 10 mg Capsule0.12USD capsule
Atarax 2 mg/ml Syrup0.06USD ml
Pms-Hydroxyzine 2 mg/ml Syrup0.04USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)200CCanadian Label
Predicted Properties
PropertyValueSource
Water Solubility0.0914 mg/mLALOGPS
logP3.43ALOGPS
logP3.41Chemaxon
logS-3.6ALOGPS
pKa (Strongest Acidic)15.12Chemaxon
pKa (Strongest Basic)7.45Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area35.94 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity107.07 m3·mol-1Chemaxon
Polarizability41.99 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.8623
Blood Brain Barrier+0.9516
Caco-2 permeable-0.5565
P-glycoprotein substrateSubstrate0.7447
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.6394
Renal organic cation transporterInhibitor0.592
CYP450 2C9 substrateNon-substrate0.8352
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7193
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9111
CYP450 2D6 inhibitorInhibitor0.8535
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9623
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7615
Ames testNon AMES toxic0.7558
CarcinogenicityNon-carcinogens0.9102
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6612 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5929
hERG inhibition (predictor II)Inhibitor0.7898
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0udj-4291000000-5750700bc5e75e581102
GC-MS Spectrum - EI-BGC-MSsplash10-0udi-6491000000-95c46c16c2b29900f4d9
Mass Spectrum (Electron Ionization)MSsplash10-0uxr-4591000000-d2e3424c44feae8a5d9c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0593000000-f20d2328497a3a80239b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-ea8e9386af034db2f970
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-4009000000-82a93759c53ebe3a9537
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0zfr-0096000000-4e9aa5e0b6000400dc11
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03kc-9028000000-ad990344a3859f84c00e
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ufr-5692000000-b6a27399e087ae28b29c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-9181000000-2983d1840355019c9e57
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-201.4104609
predicted
DarkChem Lite v0.1.0
[M-H]-185.55614
predicted
DeepCCS 1.0 (2019)
[M+H]+201.0609609
predicted
DarkChem Lite v0.1.0
[M+H]+187.91415
predicted
DeepCCS 1.0 (2019)
[M+Na]+201.2974609
predicted
DarkChem Lite v0.1.0
[M+Na]+194.821
predicted
DeepCCS 1.0 (2019)

Targets

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Details
1. Histamine H1 receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inverse agonist
General Function
G-protein-coupled receptor for histamine, a biogenic amine that functions as an immune modulator and a neurotransmitter (PubMed:33828102, PubMed:8280179). Through the H1 receptor, histamine mediates the contraction of smooth muscles and increases capillary permeability due to contraction of terminal venules. Also mediates neurotransmission in the central nervous system and thereby regulates circadian rhythms, emotional and locomotor activities as well as cognitive functions (By similarity)
Specific Function
G protein-coupled serotonin receptor activity
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Spahr L, Coeytaux A, Giostra E, Hadengue A, Annoni JM: Histamine H1 blocker hydroxyzine improves sleep in patients with cirrhosis and minimal hepatic encephalopathy: a randomized controlled pilot trial. Am J Gastroenterol. 2007 Apr;102(4):744-53. Epub 2007 Jan 11. [Article]
  2. Altamura AC, Moliterno D, Paletta S, Maffini M, Mauri MC, Bareggi S: Understanding the pharmacokinetics of anxiolytic drugs. Expert Opin Drug Metab Toxicol. 2013 Apr;9(4):423-40. doi: 10.1517/17425255.2013.759209. Epub 2013 Jan 21. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)
Specific Function
delayed rectifier potassium channel activity
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Voltage-gated inwardly rectifying potassium channel KCNH2
Molecular Weight
126653.52 Da
References
  1. Lee BH, Lee SH, Chu D, Hyun JW, Choe H, Choi BH, Jo SH: Effects of the histamine H(1) receptor antagonist hydroxyzine on hERG K(+) channels and cardiac action potential duration. Acta Pharmacol Sin. 2011 Sep;32(9):1128-37. doi: 10.1038/aps.2011.66. [Article]
  2. Sakaguchi T, Itoh H, Ding WG, Tsuji K, Nagaoka I, Oka Y, Ashihara T, Ito M, Yumoto Y, Zenda N, Higashi Y, Takeyama Y, Matsuura H, Horie M: Hydroxyzine, a first generation H(1)-receptor antagonist, inhibits human ether-a-go-go-related gene (HERG) current and causes syncope in a patient with the HERG mutation. J Pharmacol Sci. 2008 Dec;108(4):462-71. Epub 2008 Dec 5. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Health Canada Product Monograph: Hydroxyzine HCl oral capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
Specific Function
aromatase activity
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Health Canada Product Monograph: Hydroxyzine HCl oral capsules [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Hamelin BA, Bouayad A, Drolet B, Gravel A, Turgeon J: In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists. Drug Metab Dispos. 1998 Jun;26(6):536-9. [Article]
  2. Flockhart Table of Drug Interactions [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Regulator
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
References
  1. Martinez-Gomez MA, Villanueva-Camanas RM, Sagrado S, Medina-Hernandez MJ: Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE. Electrophoresis. 2007 Aug;28(15):2635-43. doi: 10.1002/elps.200600742. [Article]
  2. Martinez-Gomez MA, Carril-Aviles MM, Sagrado S, Villanueva-Camanas RM, Medina-Hernandez MJ: Characterization of antihistamine-human serum protein interactions by capillary electrophoresis. J Chromatogr A. 2007 Apr 20;1147(2):261-9. doi: 10.1016/j.chroma.2007.02.054. Epub 2007 Feb 22. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
References
  1. Crowe A, Wright C: The impact of P-glycoprotein mediated efflux on absorption of 11 sedating and less-sedating antihistamines using Caco-2 monolayers. Xenobiotica. 2012 Jun;42(6):538-49. doi: 10.3109/00498254.2011.643256. Epub 2011 Dec 22. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 30, 2024 23:02