Hydroxyzine
Hydroxyzine is a first-generation antihistamine of the diphenylmethane and piperazine classes, first developed in 1956.1 Primarily prescribed for allergic conditions such as itchiness and urticaria,2 it also exhibits anxiolytic and sedative properties, making it useful for treating generalized anxiety disorder and insomnia.23 Hydroxyzine is additionally employed to reduce nausea4 and has been used to potentiate opioid analgesia while diminishing opioid-related side effects like itchiness.45
Contents
Dosage & Duration
Dosage
Duration
Subjective Effects
The experience is dominated by sedation, with subjective sleepiness closely tracking the degree of central histamine receptor blockade. Onset occurs within roughly 15 to 60 minutes and effects last around four to six hours, with the calming quality often described as a general settling rather than any distinct alteration of perception. Reported sedation is most pronounced on first exposure and diminishes markedly over the following five to seven days of repeated use. Anxiolysis and reduced nausea accompany the sedative state.
Physical
Deep sleepiness, dizziness, and reduced coordination are the principal physical effects, alongside dry mouth and headache. Overdose is characterised chiefly by extreme sedation.
Sedation
Uncomfortable
Cognitive
The overall character is calming and anxiety-reducing, though confusion has been reported, particularly at higher doses or alongside other sedating drugs. Hallucinations and cognitive decline are documented but uncommon, appearing mainly in overdose or when combined with other central nervous system depressants.
Impairment
Auditory
Multisensory
Reagent Testing
Loading reagent data
Pharmacology
Pharmacodynamics
Hydroxyzine is a potent and selective histamine H1 receptor inverse agonist, meaning it actively dampens receptor activity rather than simply blocking it.6 This inverse agonism underlies its antihistamine effects and sedative properties. Unlike many other first-generation antihistamines, hydroxyzine has lower affinity for muscarinic acetylcholine receptors, resulting in a reduced risk of anticholinergic side effects.7 Hydroxyzine also acts more weakly as an antagonist at serotonin 5-HT2A receptors, dopamine D2 receptors, and α1-adrenergic receptors. The comparably weak antiserotonergic activity likely contributes to its usefulness as an anxiolytic, as other antihistamines lacking such properties have not demonstrated efficacy for anxiety. Hydroxyzine readily crosses the blood-brain barrier; a positron emission tomography study found that a single 30 mg dose achieved 67.6% occupancy of brain H1 receptors, with subjective sleepiness correlating well with receptor occupancy.8 Hydroxyzine also functions as an inhibitor of acid sphingomyelinase.9
Pharmacokinetics
Hydroxyzine is rapidly absorbed from the gastrointestinal tract following oral administration, reaching peak plasma concentrations approximately 2 hours after dosing.6 The absolute bioavailability has not been determined due to the unavailability of intravenous formulations. Hydroxyzine is metabolized in the liver primarily by CYP3A4 and CYP3A5.6 The main metabolite, comprising approximately 45-60% of an oral dose, is the second-generation antihistamine cetirizine, formed through oxidation of the alcohol moiety to a carboxylic acid.6 Additional metabolites include an N-dealkylated metabolite (norchlorcyclizine) and an O-dealkylated metabolite with a plasma half-life of 59 hours.6 The elimination half-life averages approximately 20 hours in adults, 7.1 hours in children, and 29 hours in elderly patients.101112 Higher concentrations are found in the skin than in plasma.6 Approximately 70% of cetirizine is excreted unchanged in the urine.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Other antihistamine sleep aids, First-generation antihistamines
Harm Potential
Addiction & Dependence
Psychological
LowHydroxyzine has low abuse potential due to its lack of euphoric effects. It is not a controlled substance and is not typically associated with compulsive use patterns.
Physical
LowPhysical dependence is not commonly reported with hydroxyzine use. It does not produce significant withdrawal syndromes characteristic of other sedative classes.
Toxicity
Administration of large amounts during early pregnancy has been associated with fetal abnormalities in animal studies, including hypogonadism at doses significantly above human therapeutic ranges.
Psychosis Risk
Hallucinations and confusion have been observed in rare cases,17 attributed mostly to overdosage or in patients being treated for neuropsychological disorders.
Seizure Risk
Convulsions may occur in overdose situations17 but are not commonly associated with therapeutic use.
History & Culture
Hydroxyzine is a first-generation antihistamine of the diphenylmethane and piperazine classes. It was first developed in 195518 and subsequently manufactured by Union Chimique Belge in 1956.20 That same year, it was approved for sale in the…
Legality
By Country
References
Source Pages
Citations
- (n.d.). Hydroxyzine - LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. https://www.ncbi.nlm.nih.gov/books/NBK548128/1
- (n.d.). Hydroxyzine Hydrochloride Tablet — DailyMed Label. U.S. National Library of Medicine / DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8e5fce17-936e-46ea-a969-518c952c209112
- Llorca PM, Spadone C, Sol O, Danniau A, Bougerol T, Corruble E, Faruch M, Macher JP, Sermet E, & Servant D. (2002). Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study. Journal of Clinical Psychiatry, 63(11), 1020-7. https://pubmed.ncbi.nlm.nih.gov/12444816/1
- (n.d.). Hydroxyzine Hydrochloride Injection, USP - DailyMed (setid: 8af7e5ce-d9d9-44cc-9f2f-4ddbc89e758a). U.S. National Library of Medicine, DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8af7e5ce-d9d9-44cc-9f2f-4ddbc89e758a12
- Juneja MM, Ackerman WE 3rd, & Bellinger K. (1991). Epidural morphine pruritus reduction with hydroxyzine in parturients. Journal of the Kentucky Medical Association, 89(7), 319-21. https://pubmed.ncbi.nlm.nih.gov/1919305/1
- (2013). Atarax (Hydroxyzine Hydrochloride) Data Sheet. GlaxoSmithKline. https://www.e-lactancia.org/media/papers/Hydroxyzine-DS-Glaxo-SK2013.pdf123456
- (March 1987). Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay. Japanese Journal of Pharmacology, 43(3), 277–282. https://doi.org/10.1254/jjp.43.2771
- (October 2009). Dose dependency of brain histamine H(1) receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C]doxepin. Human Psychopharmacology, 24(7), 540–548. https://doi.org/10.1002/hup.10511
- (2011). Identification of Novel Functional Inhibitors of Acid Sphingomyelinase. https://pmc.ncbi.nlm.nih.gov/articles/PMC3166082/1
- (January 1984). The pharmacokinetics and antihistaminic of the H1 receptor antagonist hydroxyzine. The Journal of Allergy and Clinical Immunology, 73(1 Pt 1), 69–75. https://doi.org/10.1016/0091-6749(84)90486-x1
- (1985). Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clinical Pharmacokinetics, 10(6), 477–497. https://doi.org/10.2165/00003088-198510060-000021
- (January 1989). Pharmacokinetic and pharmacodynamic studies of the H1-receptor antagonist hydroxyzine in the elderly. Clinical Pharmacology and Therapeutics, 45(1), 9–14. https://doi.org/10.1038/clpt.1989.21
- (n.d.). Atarax (hydroxyzine hydrochloride) tablet and syrup — DailyMed (setid 7eaf5043-5c73-47af-904b-8e1fae02af2e). U.S. National Library of Medicine (DailyMed). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7eaf5043-5c73-47af-904b-8e1fae02af2e1234
- (1 September 1991). Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine. European Journal of Clinical Pharmacology, 41(5), 435–439. https://doi.org/10.1007/bf0062636512
- Richardson GS, Roehrs TA, Rosenthal L, Koshorek G, & Roth T. (2002). Tolerance to daytime sedative effects of H1 antihistamines. 22(5), 511-5. https://doi.org/10.1097/00004714-200210000-000121
- (March 2023). Efficacy and safety of hydroxyzine for sleep in adults: Systematic review. Human Psychopharmacology, 38(2). https://doi.org/10.1002/hup.28641
- (n.d.). Hydroxyzine Pamoate Capsules USP — DailyMed Label. U.S. National Library of Medicine / DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=53d3540a-667d-474e-9994-aed08b3b160412345
- (2017). Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re-evaluation of an established drug. https://pmc.ncbi.nlm.nih.gov/articles/PMC5415947/123
- (April 1982). Hydroxyzine-associated tardive dyskinesia. Annals of Neurology, 11(4), 435. https://doi.org/10.1002/ana.410110423123
- (n.d.). UCB Company History – Atarax Development. Companies History. https://www.companieshistory.com/ucb/1
- (n.d.). ATARAX: FDA-Approved Drugs – NDA 010392. DrugFuture (FDA data). https://www.drugfuture.com/fda/drugview/0103921
- (n.d.). Cetirizine – StatPearls. StatPearls Publishing / NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK549776/1
- (n.d.). Hydroxyzine Drug Usage Statistics, United States, 2014 - 2023. ClinCalc. https://clincalc.com/DrugStats/Drugs/Hydroxyzine1
- (n.d.). ATARAX — Drug Product Database, Health Canada (DIN 00024694). Health Canada. https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=31612
- (n.d.). HISTAN (Hydroxyzine HCl oral solution) — Thai FDA Drug Registration (1A 127/66). Thai Food and Drug Administration (อย.). https://pertento.fda.moph.go.th/FDA_SEARCH_DRUG/SEARCH_DRUG/pop-up_drug.aspx?Newcode_U=U1DR1A1022660012711C1
- (n.d.). ATARAX FILM TABLET 25 mg 30 tablet — ilacdata.com (Turkish pharmaceutical database). ilacdata.com. http://www.ilacdata.com/ilac.asp?ilac=103412
- (n.d.). Vistaril (hydroxyzine pamoate) capsules and oral suspension — DailyMed (setid c271f97f-040e-492b-9194-2c8b74675a95). U.S. National Library of Medicine (DailyMed). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c271f97f-040e-492b-9194-2c8b74675a9512
- (n.d.). Hydroxyzine Hydrochloride Tablets, USP — DailyMed (setid 9de2de56-614f-4294-8794-d30758cf5f70). U.S. National Library of Medicine (DailyMed). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9de2de56-614f-4294-8794-d30758cf5f701
Further Reading
Drugs.com: Hydroxyzine- Drugs.com: Hydroxyzine-Oxycodone Interaction
- Drugs.com: Hydroxyzine-Xanax Interaction
FDA: Vistaril (hydroxyzine pamoate) Label
GoodRx: Hydroxyzine Side Effects
Mayo Clinic: Hydroxyzine (Oral Route)
Medical News Today: Hydroxyzine Interactions
NCBI: Co-Administration of Subeffective Doses of Diazepam and Hydroxyzine- PubMed: Potentiation of Pain Relief with Hydroxyzine
Real Life Pharmacology: Hydroxyzine Pharmacology
ScienceDirect: Hydroxyzine Overview
Talkiatry: Hydroxyzine vs Xanax
WebMD: Hydroxyzine (Atarax, Vistaril)
Automated synthesisInformation aggregated and synthesized using an autonomous workflow built by Josie Kins.
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