Antiemetic: Note: Expert recommendations for postoperative nausea and vomiting (PONV) management do not suggest hydroxyzine as a therapeutic option; use has typically been replaced by newer agents with an improved safety profile (Ref). Infants, Children, and Adolescents: IM: 1.1 mg/kg/dose; maximum dose: 100 mg/dose.
Anxiety: Note: Although FDA approved for use in anxiety, data in pediatric patients are sparse; expert recommendations for pediatric patients do not consider hydroxyzine a therapeutic option for the management of anxiety disorders (eg, generalized anxiety disorder, separation anxiety, specific phobias, panic disorder, PTSD); use has generally been replaced by newer, more effective agents (Ref).
Children and Adolescents: Oral: 0.5 mg/kg/dose every 6 hours; maximum dose is age-dependent: Age <6 years: 12.5 mg/dose; age ≥6 years: 25 mg/dose (Ref). Note: In pediatric patients, some experts have recommended lower initial doses, although reported experience is lacking. In adults, experts suggest a lower daily dosing regimen of 37.5 to 75 mg/day in divided doses (Ref).
Pruritus; associated with allergic conditions or chronic urticaria: Children and Adolescents:
Age-directed dosing:
Children <6 years: Oral: 12.5 mg 3 to 4 times daily (Ref).
Children ≥6 years and Adolescents: Oral: 12.5 to 25 mg 3 to 4 times daily (Ref). Note: Based on pharmacokinetic studies, dosing once daily (at bedtime) or twice daily may be adequate due to the long half-life (Ref).
Weight-directed dosing:
Patient weight ≤40 kg: Oral: 2 mg/kg/day divided every 6 to 8 hours as needed; maximum dose: 25 mg/dose. Note: Based on pharmacokinetic studies, dosing once daily (at bedtime) or twice daily may be adequate due to the long half-life (Ref).
Patient weight >40 kg: Oral: 25 to 50 mg once daily at bedtime or twice daily (Ref).
Pruritus; associated with opioid use: Limited data available: Children and Adolescents: IM, Oral: 0.5 mg/kg/dose every 6 hours as needed; usual maximum dose: 50 mg/dose (Ref).
Sedation; pre-/postoperative, adjunctive therapy: Note: Although FDA approved, pre-/postoperative hydroxyzine use has largely been replaced by other agents.
Oral: Children and Adolescents: 0.6 mg/kg/dose; maximum dose: 100 mg/dose.
IM: Infants, Children, and Adolescents: 1.1 mg/kg/dose; maximum dose: 100 mg/dose.
Sedation; procedural, adjunctive therapy (eg, dental, echocardiography): Limited data available: Children 2 to 12 years: Oral: 1 mg/kg/dose as a single dose 30 to 45 minutes prior to procedure in combination with other sedatives (eg, midazolam, chloral hydrate) has been used in children prior to dental procedures or echocardiograms; maximum dose: 100 mg/dose (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; active metabolite (cetirizine) is renally eliminated (Ref); based on experience in adult patients, dosing adjustment suggested.
There are no pediatric-specific recommendations; based on experience in adults, dosing adjustment suggested.
(For additional information see "Hydroxyzine: Drug information")
Anxiety, monotherapy or adjunctive therapy (alternative agent):
Note: May be useful for insomnia associated with anxiety or for short-term immediate control of symptoms until maintenance therapy is effective (Ref).
Oral: Usual dosage range: 25 to 50 mg up to 4 times daily, as needed; may increase based on response and tolerability up to 400 mg/day; maximum single dose: 100 mg. For insomnia associated with anxiety, administer at bedtime (Ref).
Peripartum management, adjunct to opioids:
Note: May be used to potentiate opioid analgesia and decrease side effects (eg, nausea and vomiting).
IM: 25 to 50 mg as a single dose; may repeat after 4 hours if needed (Ref).
Pruritus: Oral: 10 to 25 mg 3 to 4 times daily as needed (Goddard 2020; manufacturer's labeling). Some experts may use single doses up to 50 mg (Ref).
Urticaria, new onset and chronic spontaneous (alternative agent):
Note: Second-generation H1-antihistamines are preferred due to less sedating and anticholinergic effects (Ref). May consider use in combination with a second-generation H1-antihistamine in patients in whom bedtime sedating effects may be beneficial, or as initial parenteral therapy in patients with new-onset urticaria in whom more rapid onset of action is desired; avoid use in patients with high-risk occupations (eg, pilots, bus drivers) or who may be more prone to anticholinergic effects (eg, older adults) (Ref).
Oral: Initial: 10 to 25 mg at bedtime. May increase in 10 to 25 mg increments at weekly intervals if needed based on response and tolerability; daily dose may be administered at bedtime or in 3 to 4 divided doses (Ref). Some experts administer daily doses >100 mg in divided doses; do not exceed 200 mg/day (Ref).
IM (off label; new onset only): 25 to 50 mg 3 to 4 times per day as needed (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: There are no data on hydroxyzine pharmacokinetics in kidney impairment; however, the active metabolite, cetirizine, is cleared by the kidney and may accumulate in patients with kidney impairment (Ref). Additionally, hydroxyzine was associated with QTc prolongation in a cohort of patients with chronic kidney insufficiency (Ref).
Altered kidney function:
Oral, IM:
CrCl ≥50 mL/minute: No dosage adjustment necessary (Ref).
CrCl 10 to <50 mL/minute: Administer ~50% of usual dose (Ref).
CrCl <10 mL/minute: Administer ~25% to 50% of usual dose (Ref).
Hemodialysis, intermittent (thrice weekly): Hydroxyzine is unlikely to be significantly dialyzed (large Vd (Ref)) and its metabolite (cetirizine) is <10% dialyzable (Ref):
Oral, IM: Administer 25 to 50% of usual dose (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (large Vd) (Ref):
Oral, IM: Administer 25 to 50% of usual dose (Ref).
CRRT: Oral, IM: Administer 50% of usual dose (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral, IM: Administer 50% of usual dose (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. In patients with primary biliary cirrhosis, change dosing interval to every 24 hours (Ref).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as pamoate:
Vistaril: 25 mg, 50 mg
Generic: 25 mg, 50 mg, 100 mg
Solution, Intramuscular, as hydrochloride:
Generic: 25 mg/mL (1 mL); 50 mg/mL (1 mL, 2 mL)
Syrup, Oral, as hydrochloride:
Generic: 10 mg/5 mL (25 mL, 118 mL, 473 mL)
Tablet, Oral, as hydrochloride:
Generic: 10 mg, 25 mg, 50 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 10 mg, 25 mg, 50 mg
Solution, Intramuscular, as hydrochloride:
Generic: 50 mg/mL (1 mL)
Syrup, Oral, as hydrochloride:
Atarax: 10 mg/5 mL (473 mL) [contains alcohol, usp, menthol, sodium benzoate]
Generic: 10 mg/5 mL (500 mL)
Oral: May be administered without regard to food
Parenteral: For IM use only. Subcutaneous, intra-arterial, and IV administration are contraindicated and not recommended under any circumstances; intravascular hemolysis, thrombosis, and digital gangrene can occur; extravasation can result in sterile abscess and marked tissue induration (Ref).
Administer IM deep in large muscle. For IM administration in children, injections should be made into the midlateral muscles of the thigh. In infants and children, the upper outer quadrant of the gluteal region should be used only when necessary (eg, burn patients) to minimize potential damage to the sciatic nerve. In adults, the upper outer quadrant of the buttock is considered the preferred injection site. In older children and adolescents, the deltoid region should be only used if well developed and with caution to avoid radial nerve injury. Injections should not be made in the lower or mid-third of the upper arm. Aspirate before injection to avoid inadvertent injection into a blood vessel.
In the very rare instance that IV administration may be necessary, slow IV injection through a central venous line has been used in pediatric oncology patients (Ref).
Vesicant; the manufacturer considers IV administration a contraindication; however, if IV administration is necessary ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.
IM: For IM use only. Aspirate before injection to avoid inadvertent injection into a blood vessel. Do NOT administer IV, SubQ, or intra-arterially (contraindicated). Administer IM deep in large muscle. The preferred site is the upper outer quadrant of the buttock or midlateral thigh. The upper outer quadrant of the gluteal region should be used only when necessary to minimize potential damage to the sciatic nerve. The deltoid region should be only used with caution to avoid radial nerve injury. Injections should not be made in the lower or mid-third of the upper arm.
Oral: Administer without regard to food. Shake suspension vigorously prior to use.
Capsules: Store <30°C (86°F). Protect from light.
Injection: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
Suspension, syrup, tablets: Store at 20°C to 25°C (68°F to 77°F). Protect from light; do not freeze.
Oral: Treatment of anxiety and pruritus; pre- and postoperative sedation (All indications: FDA approved in pediatric patients [age not specified] and adults)
Note: Although FDA approved for use in anxiety, data in pediatric patients is sparse; expert recommendations for pediatric patients do not consider hydroxyzine a therapeutic option for the management of anxiety disorders (eg, generalized anxiety disorder, separation anxiety, specific phobias, panic disorder, PTSD); use has generally been replaced by newer, more effective agents (AACAP [Connolly 2007]; Bushnell 2018; Gale 2016)
Parenteral: Perioperative adjunctive sedation and nausea and vomiting (FDA approved in infants, children, adolescents, and adults); treatment of anxiety and pre-/postpartum adjunctive for nausea/vomiting control, anxiety, and opioid dose reduction (FDA approved in adults). Note: Expert recommendations for postoperative nausea and vomiting (PONV) management do not suggest hydroxyzine as a therapeutic option; use has typically been replaced by newer agents with an improved safety profile (SAA [Gan 2014]).
HydrOXYzine may be confused with hydrALAZINE, hydroCHLOROthiazide, hydroxyurea
Atarax may be confused with Ativan
Vistaril may be confused with Restoril, Versed, Zestril
The Institute for Safe Medication Practices (ISMP) includes this medication (when used in early pregnancy) among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Beers Criteria: Hydroxyzine, a first-generation antihistamine, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its potent anticholinergic properties resulting in increased risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity; use should also be avoided due to reduced clearance with advanced age and tolerance associated with use as a hypnotic (Beers Criteria [AGS 2019]).
Pharmacy Quality Alliance (PQA): Hydroxyzine, as a single agent or as part of a combination (excludes OTC products), is identified as a high-risk medication in patients 65 years and older on the PQA’s Use of High-Risk Medications in the Elderly (HRM) performance measure, a safety measure used by the Centers for Medicare and Medicaid Services (CMS) for Medicare plans (PQA 2017).
Vistaril [US and Turkey] may be confused with Vastarel brand name for trimetazidine [multiple international markets]
Acute generalized exanthematous pustulosis (AGEP) has rarely been reported (Ref). Resolution generally occurs 2 weeks after drug discontinuation (Ref); although, with hydroxyzine, may occur within 3 days (Ref).
Mechanism: Non–dose-related; immunologic. AGEP is considered a T-cell mediated reaction (Ref).
Onset: Delayed: usually within 24 hours after drug initiation (Ref).
Risk factors:
• Cross-sensitivity: Not established; conflicting evidence regarding cross-reactivity between hydroxyzine, cetirizine, and levocetirizine (Ref)
Drowsiness and dizziness may occur, especially after initial doses. These effects may persist the next morning after bedtime dosing causing daytime drowsiness (Ref). Drowsiness is usually transient and subsides after a few consecutive days of therapy or after dose reduction (Ref). Cognitive dysfunction has been reported after morning and evening dosing, which may impair the ability to drive or operate machinery (Ref). At recommended doses, clinically significant respiratory depression has not been observed.
Mechanism : Dose related; related to the pharmacologic action (ie, competitive binding to histamine-1 receptors in the CNS) (Ref).
Onset: Rapid; occurs within the first few days of therapy initiation (Ref)
Risk factors:
• Dose (especially initiation) (Ref)
• Concurrent use of other CNS depressant medications
• Concurrent use of alcohol (Ref)
• Age >65 years (Ref)
Hydroxyzine is associated with a conditional risk of prolonged QT interval on ECG, defined as a QTc >500 msec (Ref). Hydroxyzine-related QT prolongation and torsades de pointes (TdP) have been described in case reports (Ref). QTc values return to normal within days to weeks after drug discontinuation (Ref).
Mechanism: Human ether-à-go-go (hERG) channel inhibition leading to prolongation of the cardiac action potential (Ref).
Onset: Rapid; typically occurs within 5 days after initial dose (Ref).
Risk factors:
Drug-induced QTc prolongation/TdP (in general):
• Females (Ref)
• Age >65 years (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)
• Genetic defects of cardiac ion channels (Ref)
• History of drug-induced TdP (Ref)
• Congenital long QT syndrome (Ref)
• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)
• Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) (Ref)
• Bradycardia (Ref)
• Hepatic impairment (Ref)
• Kidney impairment (Ref)
• Diuretic use (Ref)
• Sepsis (Ref)
• Concurrent administration of multiple medications (≥2) that prolong the QT interval or medications with drug interactions that increase serum concentrations of QT-prolonging medications (Ref)
Drug-specific:
• hERG gene mutation (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Gastrointestinal: Xerostomia
Nervous system: Drowsiness (transient)
Respiratory: Respiratory depression (high doses)
Postmarketing:
Cardiovascular: Prolonged QT interval on ECG (rare: <1%) (Schlit 2017; Vigne 2015), torsades de pointes (rare: <1%) (Ali 2021; Schlit 2017)
Dermatologic: Acute generalized exanthematous pustulosis (rare: <1%) (O’Toole 2014), pruritus, skin rash, urticaria
Hypersensitivity: Fixed drug eruption (Bhari 2017)
Nervous system: Cognitive dysfunction (Church 2010; Conen 2011), hallucination, headache, involuntary body movements, seizure (high doses)
Neuromuscular & skeletal: Tremor (high doses)
Hypersensitivity to hydroxyzine or any component of the formulation; early pregnancy; prolonged QT interval.
Additional contraindications:
Oral: Hypersensitivity to cetirizine or levocetirizine.
Injection: SUBQ, intra-arterial, or IV administration.
Canadian labeling: Additional contraindications (not in US labeling): Oral: Hypersensitivity to other piperazine derivatives, aminophylline or ethylenediamine; history of torsade de pointes, including congenital long QT syndromes; history of cardiac arrhythmias; significant electrolyte imbalance (eg, hypokalemia, hypomagnesemia); significant bradycardia; family history of sudden cardiac death; concomitant use with other QT/QTc-prolonging drugs or with CYP3A4/5 inhibitors; asthmatics who have previously experienced a serious anti-histamine induced adverse bronchopulmonary effect; porphyria; patients of childbearing potential.
Concerns related to adverse effects:
• QT prolongation/torsades de pointes: Oral hydroxyzine is contraindicated in patients with a prolonged QT interval.
Disease-related concerns:
• Glaucoma: Use with caution in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade. Screening is recommended.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.
• Respiratory disease: Use with caution in patients with asthma or chronic obstructive pulmonary disease (COPD).
Special populations:
Older adult: May cause over sedation in older adults; avoid use.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and/or sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Other warnings/precautions:
• Appropriate administration: Parenteral: For IM use only. Severe injection-site reactions have been reported with IM administration (eg, extensive tissue damage, necrosis, gangrene) requiring surgical intervention (including debridement, skin grafting, and amputation). SubQ, IV, and intra-arterial routes of administration are contraindicated. Intravascular hemolysis, thrombosis, and digital gangrene have been reported with IV or intra-arterial administration (Baumgartner 1979); SubQ administration may result in significant tissue damage. If inadvertent IV administration results in extravasation, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.
• Long-term use: The effectiveness of hydroxyzine for long-term use (>4 months) has not been assessed; periodically reassess use.
Neonatal withdrawal symptoms, including seizures, have been reported following long-term maternal use or the use of large doses near term (Serreau 2005).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Benzylpenicilloyl Polylysine: Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects. Risk D: Consider therapy modification
Betahistine: May diminish the therapeutic effect of Antihistamines. Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
CNS Depressants: HydrOXYzine may enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): HydrOXYzine may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Hydroxyzine crosses the placenta. Possible withdrawal symptoms have been observed in neonates following chronic maternal use of hydroxyzine during pregnancy (Prenner 1977; Serreau 2005).
Hydroxyzine is approved for pre- and postpartum adjunctive therapy to control emesis, reduce opioid dosage, and treat anxiety. However, use in early pregnancy is contraindicated by the manufacturer and other agents are recommended for the treatment of nausea and vomiting of pregnancy (ACOG 189 2018). Hydroxyzine may be used as an antipruritic if systemic therapy is needed (use caution late in pregnancy) (Murase 2014); although other agents may be preferred (BSACI [Powell 2015]; Zuberbier 2018).
Mental status, blood pressure
Competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract (Simons 1994). Possesses skeletal muscle relaxing, bronchodilator, antihistamine, antiemetic, and analgesic properties. Activity at muscarinic, serotonergic (5HT2), and dopaminergic receptors in the hippocampus, cerebral cortices, and whole brain may produce anxiolytic effects (Guaiana 2010; Sawantdesai 2016).
Onset of action: Oral: 15 to 30 minutes; IM: Rapid.
Duration: Decreased histamine-induced wheal and flare areas: 2 to ≥36 hours; Suppression of pruritus: 1 to 12 hours (Simons 1984a).
Absorption: Oral: Rapid.
Distribution: Children and Adolescents 1 to 14 years: 18.5 ± 8.6 L/kg (Simons 1984b); Adults: Vd: 16 ± 3 L/kg (Simons 1984a); Elderly: ~23 L/kg (Simons 1989b); Hepatic dysfunction: ~23 L/kg (Simons 1989a).
Metabolism: Hepatic to multiple metabolites, including cetirizine (active) (Simons 1989a).
Half-life elimination:
Children and Adolescents 1 to 14 years (mean age: 6.1 ± 4.6 years): 7.1 ± 2.3 hours; Note: Half-life increased with increasing age and was 4 hours in patients 1 year of age and 11 hours in a 14-year-old patient (Simons 1984b).
Adults: ~20 hours (Simons 1984a); Elderly: ~29 hours (Simons 1989b); Hepatic dysfunction: ~37 hours (Simons 1989a).
Time to peak: Oral administration: Serum: ~2 hours; Peak suppression of antihistamine-induced wheal and flare: 4 to 12 hours (Simons 1984a).
Excretion: Urine; active metabolite (cetirizine) is renally eliminated (Simons 1994).
Capsules (hydrOXYzine Pamoate Oral)
25 mg (per each): $0.21 - $0.57
50 mg (per each): $0.22 - $0.61
100 mg (per each): $1.19
Capsules (Vistaril Oral)
25 mg (per each): $0.22
50 mg (per each): $3.65
Solution (hydrOXYzine HCl Intramuscular)
25 mg/mL (per mL): $27.86
50 mg/mL (per mL): $30.73
Syrup (hydrOXYzine HCl Oral)
10 mg/5 mL (per mL): $0.16 - $1.27
Tablets (hydrOXYzine HCl Oral)
10 mg (per each): $0.62 - $0.65
25 mg (per each): $0.30 - $0.92
50 mg (per each): $0.41 - $1.12
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