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:
Manufacturer’s dosing: Oral: 25 mg 3 to 4 times daily as needed.
Nightly dosing: Oral: Due to its sedating properties, some experts recommend 25 to 50 mg once daily as needed at bedtime (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 (for new onset urticaria 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).
Uremic pruritus: Oral: 10 to 25 mg once or twice daily as needed (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (large Vd) (Ref):
Oral, IM: Administer 25 to 50% of usual dose (Ref).
Uremic pruritus: Oral: 10 to 25 mg once or twice daily as needed (Ref).
CRRT: Oral, IM: Administer 50% of usual dose (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral, IM: Administer 50% of usual dose (Ref).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Hydroxyzine is primarily metabolized in the liver to the active metabolite, cetirizine (Ref). Hydroxyzine elimination half-life is prolonged in patients with liver impairment, which may increase the likelihood of sedation; therefore, use with caution in patients with hepatic encephalopathy (Ref). There is insufficient data on the long-term use of hydroxyzine in patients with liver impairment (Ref).
Liver impairment prior to treatment initiation :
Initial or dose titration in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A to C: IM, Oral: Use minimum effective dose, not to exceed a total maximum daily dose of 25 mg/day (Ref).
Liver impairment developing in patients already receiving hydroxyzine:
Chronic disease progression (eg, outpatient):
Progression from baseline to Child-Turcotte-Pugh class A to C: IM, Oral: Use minimum effective dose, not to exceed a total maximum daily dose of 25 mg/day (Ref).
Acute worsening of liver function (eg, requiring hospitalization):
Child-Turcotte-Pugh class A to C: IM, O ral: Use minimum effective dose, not to exceed a total maximum daily dose of 25 mg/day; discontinue use if new or worsening hepatic encephalopathy (Ref).
Avoid use (Ref).
(For additional information see "Hydroxyzine: Pediatric drug information")
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, post-traumatic stress disorder); use has generally been replaced by newer, more effective agents (Ref). In adults, a lower daily dosing regimen of 37.5 to 75 mg/day in divided doses is recommended by experts (Ref).
Children <6 years: Oral: 12.5 mg 4 times daily (Ref); although FDA approved, expert guidelines do not recommend pharmacotherapy in patients <6 years of age (Ref).
Children ≥6 years and Adolescents: Oral: 12.5 to 25 mg 4 times daily (Ref).
Nausea and vomiting: 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.
Pruritus; associated with allergic conditions or chronic urticaria:
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:
Children and Adolescents:
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: Oral: 0.6 mg/kg/dose; maximum dose: 100 mg/dose.
IM: Infants, Children, and Adolescents: IM: 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.
Altered kidney function:
Note: There are no data on hydroxyzine pharmacokinetics in kidney impairment; however, based on adult data, 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 adult patients with chronic kidney insufficiency (Ref).
Children and Adolescents: Oral, IM:
Mild impairment: No dosage adjustment necessary (Ref).
Moderate to severe impairment: Administer ~50% of usual dose (Ref).
Hemodialysis, intermittent: Hydroxyzine is unlikely to be significantly dialyzed (due to large Vd (Ref)) and its metabolite (cetirizine) is <10% dialyzable (Ref).
There are no pediatric-specific recommendations; based on experience in adults with primary biliary cirrhosis, increasing length of dosing interval is recommended (Ref).
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%) (Ref), torsades de pointes (rare: <1%) (Ref)
Dermatologic: Acute generalized exanthematous pustulosis (rare: <1%) (Ref), pruritus, skin rash, urticaria
Hypersensitivity: Fixed drug eruption (Ref)
Nervous system: Cognitive dysfunction (Ref), 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.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as pamoate:
Vistaril: 25 mg [DSC], 50 mg [DSC]
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
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
Solution (hydrOXYzine HCl Intramuscular)
25 mg/mL (per mL): $35.11
50 mg/mL (per mL): $38.71
Syrup (hydrOXYzine HCl Oral)
10 mg/5 mL (per mL): $0.16 - $1.27
Tablets (hydrOXYzine HCl Oral)
10 mg (per each): $0.58 - $5.34
25 mg (per each): $0.10 - $0.85
50 mg (per each): $0.41 - $1.12
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
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 ([DSC])
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.
Oral: May be administered without regard to food.
Parenteral: For IM use only. SUBQ, 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 only be 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.
Oral:
Anxiety: Symptomatic relief of anxiety.
Pruritus: Management of pruritus due to allergic conditions (eg, atopic and contact dermatoses) and histamine-mediated pruritus.
Urticaria, new onset and chronic spontaneous: Management of urticaria.
IM:
Peripartum management, adjunct to opioids: As prepartum and postpartum adjunctive medication to permit reduction in opioid dosage, allay anxiety, and control emesis.
Urticaria, new onset: Management of urticaria.
HydrOXYzine may be confused with hydrALAZINE, hydroCHLOROthiazide, HYDROmorphone, 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 among its list of drugs (contraindicated in early pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
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. Exposure to concurrent anticholinergic drugs also increases risk of falls, delirium, and dementia; consider total anticholinergic burden when conducting medication reviews (Beers Criteria [AGS 2023]).
Hydroxyzine is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) due to an increased risk of falls in patients with recurrent falls. Use is not recommended for the treatment of insomnia, as first-line treatment of allergy or pruritus, or in patients with delirium or dementia (O’Mahony 2023).
Vistaril [US and Turkey] may be confused with Vastarel brand name for trimetazidine [multiple international markets]
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor
Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amantadine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Amezinium: Antihistamines may increase stimulatory effects of Amezinium. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor
Benzylpenicilloyl Polylysine: Coadministration of Antihistamines and Benzylpenicilloyl Polylysine may alter diagnostic results. 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: Antihistamines may decrease therapeutic effects of Betahistine. Betahistine may decrease therapeutic effects of Antihistamines. Risk C: Monitor
Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects 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
Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects 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
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Certoparin: Antihistamines may increase therapeutic effects of Certoparin. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects 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 increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid
CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects 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 increase CNS depressant effects 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 increase CNS depressant effects 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
Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects 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
Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid
DroPERidol: May increase CNS depressant effects 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: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects 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): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid
Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor
Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Hyaluronidase: Antihistamines may decrease therapeutic effects of Hyaluronidase. Risk C: Monitor
Ipratropium (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects 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
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects 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
Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists 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
Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor
OxyCODONE: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pitolisant: Antihistamines may decrease therapeutic effects of Pitolisant. Risk X: Avoid
Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects 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
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor
Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
QT-prolonging Agents (Highest Risk): HydrOXYzine may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk C: Monitor
QuiNIDine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider Therapy Modification
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects 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 increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects 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
Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid
Suvorexant: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of Thalidomide. Risk X: Avoid
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid
Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor
Tranylcypromine: May increase anticholinergic effects of Antihistamines, First Generation. Risk X: Avoid
Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor
Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects 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
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Hydroxyzine crosses the placenta (Prenner 1977; Serreau 2005).
Based on data from animal reproduction studies, the use of hydroxyzine in early pregnancy is contraindicated. Outcome data following maternal use of hydroxyzine in humans during pregnancy are available (Etwel 2017; Hansen 2020; Heinonen 1977; Kocatürk 2022). 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, agents other than hydroxyzine are recommended for the treatment of nausea and vomiting of pregnancy (ACOG 189 2018).
Algorithms are available for the treatment of urticaria. First-generation oral antihistamines are generally not recommended for use in pregnant patients due to side effects (EAACI [Zuberbier 2022]).
It is not known if hydroxyzine is present in breast milk.
Drowsiness and irritability have been reported in breastfed infants exposed to antihistamines (Ito 1993). Sedation has been reported in breastfed infants exposed to hydroxyzine (Soussan 2014). In general, if a breastfed infant is exposed to a first-generation antihistamine via breast milk, they should be monitored for irritability or drowsiness (Butler 2014).
Antihistamines may decrease maternal serum prolactin concentrations when administered prior to the establishment of lactation (Messinis 1985).
Use of a second-generation antihistamine is preferred when an oral antihistamine is needed in lactating patients (EAACI [Zuberbier 2022], Butler 2014).
Relief of symptoms, mental status and alertness, BP, rash (including worsening of pre-existing skin reactions), signs/symptoms of hypersensitivity reaction.
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).