Hydroxyzine (Atarax): Clinical Overview

Indications

Hydroxyzine is FDA-approved for anxiety management and pruritus control, but its use is increasingly restricted to short-term nighttime adjunctive therapy due to significant sedation (80% rate) and performance impairment risks. 1, 2

Primary Approved Uses:

Anxiety disorders: Generalized anxiety disorder with demonstrated efficacy over 3-month periods 3
Pruritus: Dermatological conditions including urticaria, atopic dermatitis, and medication-related rash 2, 4
Anxiolysis in pediatric procedures: Short-term use for medical imaging and procedures 1

Off-Label Applications:

Rhinorrhea control in nonallergic rhinitis (though inadequate data exists for firm recommendations) 1
Adjunctive therapy for steroid-refractory pruritus in immune checkpoint inhibitor toxicity (10-25 mg QID or at bedtime) 2

Standard Dosing Regimens

Adults - Anxiety:

Standard dose: 50 mg/day in divided doses 3, 5
Alternative: 25 mg four times daily 1
Efficacy demonstrated within first week of treatment 5

Adults - Pruritus/Urticaria:

Preferred regimen: 25-50 mg at bedtime as adjunct to non-sedating antihistamine during the day 2, 4
Alternative: 10-50 mg at bedtime for dermatological conditions 2
Mild symptoms: 10 mg every 6 hours as needed 2
Bedtime dosing minimizes daytime sedation while providing sustained effects due to long half-life (20 ± 4.1 hours) 1, 2

Pediatric - Pruritus:

Optimal dose: 0.7 mg/kg three times daily (as effective as higher doses with significantly less sedation) 6
Higher dose: 1.4 mg/kg three times daily causes more sedation without additional benefit 6
Peak serum concentration occurs at 2.0 ± 0.9 hours with elimination half-life of 7.1 ± 2.3 hours in children 6

Pediatric - Anxiolysis for Procedures:

Dosing per institutional protocols for medical imaging procedures 1
Must be administered by authorized personnel according to hospital regulations 1

Critical Dose Adjustments

Renal Impairment:

Moderate impairment (CrCl 10-20 mL/min): Reduce dose by 50% 2, 4
Severe impairment (CrCl <10 mL/min): Avoid completely 4

Hepatic Impairment:

Severe liver disease: Avoid due to enhanced sedative effects 2, 4

Elderly Patients:

Start at low end of dosing range due to decreased hepatic, renal, and cardiac function 7
Consider avoiding entirely due to high risk of sedation, anticholinergic effects, cognitive impairment, and falls 2, 4
Hydroxyzine is specifically listed as a medication to deprescribe in older adults due to fall risk 2
Elderly patients with prostatic hypertrophy, elevated intraocular pressure, or cognitive impairment are at particularly high risk 1, 2

Absolute Contraindications

Hydroxyzine is contraindicated in the following situations per FDA labeling: 7

Prolonged QT interval (any cause) 7
Early pregnancy (teratogenic in animal studies at supratherapeutic doses) 2, 4, 7
Known hypersensitivity to hydroxyzine, cetirizine, or levocetirizine (cross-sensitivity risk) 7

Critical Safety Warnings

QT Prolongation and Cardiac Risk:

Post-marketing reports of QT prolongation and Torsade de Pointes, particularly in patients with pre-existing heart disease, electrolyte imbalances, or concomitant arrhythmogenic drugs 7
Use with extreme caution in patients with congenital long QT syndrome, family history of long QT syndrome, recent myocardial infarction, uncompensated heart failure, or bradyarrhythmias 7
Avoid concomitant use with Class 1A antiarrhythmics (quinidine, procainamide), Class III antiarrhythmics (amiodarone, sotalol), certain antipsychotics (ziprasidone, quetiapine, chlorpromazine), certain antidepressants (citalopram, fluoxetine), macrolide antibiotics (azithromycin, erythromycin), fluoroquinolones (moxifloxacin), and methadone 7

Sedation and Performance Impairment:

Hydroxyzine causes 80% sedation rates compared to 50% with diphenhydramine and 60-73% with promethazine 1, 2
Performance impairment occurs even without subjective drowsiness, affecting school performance, work, and driving 1, 2
Drivers taking hydroxyzine are 1.5 times more likely to be responsible for fatal automobile accidents 2
Impairment persists with bedtime-only dosing due to prolonged half-life and active metabolites 1, 2
Tolerance to sedation may not develop 2

CNS Depression:

Reduce dosage of concomitant CNS depressants (narcotics, non-narcotic analgesics, barbiturates, alcohol, sedatives) when used with hydroxyzine 7
Concomitant use dramatically enhances performance impairment 2, 7

Anticholinergic Effects:

Dry mouth, dry eyes, constipation, urinary retention, narrow-angle glaucoma provocation 1
Particular risk in elderly patients with prostatic hypertrophy, elevated intraocular pressure, or cognitive impairment 1, 2, 7
Better control of rhinorrhea compared to second-generation antihistamines due to anticholinergic properties 1, 2

Acute Generalized Exanthematous Pustulosis (AGEP):

Rare but serious skin reaction characterized by fever and numerous small, sterile pustules on edematous erythema 7
Discontinue immediately at first appearance of skin rash or worsening of pre-existing skin reactions 7
Do not resume if AGEP suspected; avoid cetirizine and levocetirizine due to cross-sensitivity 7

Clinical Algorithm for Use

Step 1: Assess Appropriateness

Exclude contraindications: QT prolongation, early pregnancy, hypersensitivity 7
Evaluate risk factors: Elderly age, cardiac disease, renal/hepatic impairment, cognitive impairment, prostatic hypertrophy, glaucoma 2, 7
Consider occupation: Avoid in patients requiring optimal cognitive function (drivers, machinery operators, students) 2

Step 2: For Pruritus Management

First-line: Non-sedating antihistamine (cetirizine 10 mg daily, fexofenadine 180 mg daily, or loratadine 10 mg daily) 4, 8
If inadequate after 2-3 days: Add hydroxyzine 25-50 mg at bedtime to non-sedating antihistamine 4
Duration: 2-4 weeks maximum for mild-moderate symptoms 2
Transition to non-sedating antihistamines for long-term management 2

Step 3: For Anxiety Management

Initial dose: 50 mg/day in divided doses or 25 mg QID 3, 5
Assess response at 1 week (efficacy typically evident by this time) 5
Maximum duration: 3 months demonstrated in controlled trials 3
Consider alternatives (SSRIs, SNRIs, buspirone) for long-term management due to performance concerns 2

Step 4: Monitoring

Warn patients about driving impairment even without subjective drowsiness 2, 7
Monitor for anticholinergic effects in elderly patients 1, 7
Assess for sedation tolerance (may not develop) 2
Discontinue if AGEP signs appear (fever, pustular rash) 7

Common Pitfalls and How to Avoid Them

Pitfall 1: AM/PM Split Dosing Strategy

Avoid using hydroxyzine in the morning and non-sedating antihistamines at night as a cost-saving measure. Hydroxyzine's long half-life causes significant daytime impairment even with bedtime-only dosing. 2

Pitfall 2: Underestimating Performance Impairment

Do not rely on patient's subjective report of drowsiness. Performance impairment persists without subjective awareness, affecting reaction times, learning, and driving safety. 1, 2

Pitfall 3: Prolonged Monotherapy

Do not use hydroxyzine as long-term monotherapy. It should be reserved for short-term use (2-4 weeks) or as nighttime adjunct to non-sedating antihistamines. 2

Pitfall 4: Inappropriate Use in Elderly

Avoid hydroxyzine in elderly patients when possible. If absolutely necessary, start at lowest dose and monitor closely for falls, cognitive impairment, and anticholinergic effects. 2, 4, 7

Pitfall 5: Ignoring Drug Interactions

Screen for QT-prolonging medications and CNS depressants before prescribing. The combination dramatically increases risk of cardiac arrhythmias and sedation. 7

Pitfall 6: Using in Delirium Management

Never use hydroxyzine for delirium management. Its sedating and anticholinergic properties worsen delirium. 2

Pitfall 7: Inadequate Dose Adjustment in Renal Impairment

Always check creatinine clearance and reduce dose by 50% in moderate renal impairment (CrCl 10-20 mL/min). Avoid completely in severe impairment. 2, 4

Drug Interactions

Major Interactions:

QT-prolonging drugs: Antiarrhythmics, antipsychotics, antidepressants, macrolides, fluoroquinolones, methadone 7
CNS depressants: Opioids, benzodiazepines, barbiturates, alcohol, sedatives (reduce dosage of both agents) 7
Other anticholinergic medications: Additive anticholinergic effects, particularly problematic in elderly 1, 2

Contraindicated Combinations:

Benzodiazepines with other anxiolytics (when hydroxyzine used for anxiolysis in pediatric procedures) 1

Special Populations

Pregnancy:

Contraindicated in early pregnancy due to fetal abnormalities in animal studies 2, 4, 7
Inadequate human data to establish safety 7

Pediatrics:

Approved for all ages per FDA labeling 1
Optimal dose for pruritus: 0.7 mg/kg TID (higher doses increase sedation without additional benefit) 6
Elimination half-life increases with age in children (r = 0.83) 6
For procedural anxiolysis, must be administered by authorized personnel 1

Geriatrics:

High-risk population for all adverse effects 1, 2, 7
Listed among anticholinergic medications to avoid in older adults 2
Specifically identified for deprescribing due to fall risk 2
If use is unavoidable, start at lowest dose and monitor closely 7

What are the indications, dosing regimens, safety considerations, contraindications, and drug interactions for Atarax (hydroxyzine)?

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