When is Hydroxyzine (an antihistamine) prescribed, particularly in patients with anxiety disorders, insomnia, or itching due to allergic reactions, and what are the considerations for elderly patients or those with impaired renal (kidney) or hepatic (liver) function?

When to Prescribe Hydroxyzine

Hydroxyzine is primarily prescribed as a sedating antihistamine for nighttime management of pruritus in urticaria and allergic conditions (10-50 mg at bedtime), typically added to a non-sedating daytime antihistamine when sleep disturbance is problematic, though it is not a first-line treatment for anxiety despite some efficacy. 1, 2

Primary Clinical Indications

Pruritus and Urticaria

• Hydroxyzine is most appropriately used for nighttime symptom control in patients with urticaria or allergic dermatological conditions who have sleep disturbances despite daytime non-sedating antihistamine therapy 1, 2
• Typical dosing ranges from 10-50 mg at bedtime, combined with a non-sedating antihistamine (such as loratadine, cetirizine, or fexofenadine) during the day 1, 2
• The British Journal of Dermatology guidelines note that adding hydroxyzine at night "probably has little additional clinical effect on urticaria if the H1 receptor is already saturated" by daytime antihistamines—the primary benefit is improved sleep, not enhanced antihistamine effect 1, 2

Anxiety Disorders

• Hydroxyzine demonstrates efficacy for generalized anxiety disorder at 50 mg daily, with superiority over placebo beginning in the first week of treatment 3, 4, 5
• However, hydroxyzine should not be considered a first-line treatment for anxiety due to limited high-quality evidence, high risk of bias in available studies, and superior alternatives 2, 3
• When used for anxiety, dosing typically ranges from 10-50 mg, though the Cochrane review concluded "it is not possible to recommend hydroxyzine as a reliable first-line treatment in GAD" 2, 3

Other Indications

• Adjunctive treatment for opioid-induced pruritus and nausea per National Comprehensive Cancer Network recommendations 2
• Chemical restraint in agitated pediatric and adolescent patients per American Academy of Pediatrics 2

Critical Safety Considerations and Contraindications

Cardiac Risk

• Hydroxyzine causes QT prolongation and has been associated with Torsade de Pointes in post-marketing surveillance 6
• Contraindicated or use with extreme caution in patients with: congenital long QT syndrome, family history of long QT syndrome, recent myocardial infarction, uncompensated heart failure, bradyarrhythmias, or electrolyte imbalances 6
• Avoid concurrent use with other QT-prolonging medications including Class 1A/III antiarrhythmics, certain antipsychotics (ziprasidone, quetiapine, clozapine), certain antidepressants (citalopram, fluoxetine), macrolide antibiotics, and fluoroquinolones 6

CNS Depression and Driving Impairment

• Hydroxyzine causes significant sedation that impairs driving ability, work performance, and cognitive function—drivers in fatal accidents are 1.5 times more likely to be taking first-generation antihistamines 2
• Performance impairment occurs even without subjective awareness of drowsiness, and worsens with concurrent activities like cell phone use 2
• Recent 2025 data shows hydroxyzine is now the most identified antihistamine in driving under the influence investigations, with common observations including incoordination, slurred speech, erratic driving, and crashes 7
• Patients must be explicitly warned against driving or operating machinery, and the FDA label mandates dosage reduction when combined with other CNS depressants (narcotics, barbiturates, alcohol) 6

Anticholinergic Effects

• Hydroxyzine causes urinary hesitancy and retention through anticholinergic properties that impair bladder contractility and increase urethral sphincter tone 8
• If urinary hesitancy develops, immediately switch to a second-generation antihistamine (fexofenadine 180 mg daily preferred)—do not simply reduce the dose, as anticholinergic effects persist at lower doses 8
• Elderly men with prostatic enlargement are at substantially increased risk for acute urinary retention 8
• Other anticholinergic effects include dry mouth (14% vs 5% placebo) and loss of concentration 5

Dermatologic Reactions

• Hydroxyzine may rarely cause acute generalized exanthematous pustulosis (AGEP), characterized by fever and numerous sterile pustules on edematous erythema 6
• Discontinue immediately at first appearance of skin rash or worsening of pre-existing skin reactions 6
• Avoid cetirizine or levocetirizine in patients with prior hydroxyzine hypersensitivity due to cross-sensitivity risk 6

Special Population Dosing

Renal Impairment

• Moderate renal impairment (creatinine clearance 10-20 mL/min): Reduce hydroxyzine dose by 50% 1, 2
• Severe renal impairment (creatinine clearance <10 mL/min): Avoid hydroxyzine entirely 1, 2

Hepatic Impairment

• Avoid hydroxyzine in severe liver disease because sedating effects are inappropriate 2

Elderly Patients

• Start at the low end of the dosing range (10 mg) due to increased sensitivity to psychomotor impairment, falls, fractures, and anticholinergic effects 2, 6
• Elderly patients are more likely to have decreased renal function requiring dose adjustment 6
• Sedating drugs cause confusion and over-sedation more readily in this population 6

Pregnancy

• Hydroxyzine is specifically contraindicated during early pregnancy 2

Clinical Algorithm for Prescribing Decision

For Pruritus/Urticaria:

1. First-line: Prescribe non-sedating H1 antihistamine for daytime use (cetirizine, loratadine, fexofenadine, desloratadine, or levocetirizine) 1
2. If sleep disturbance persists: Add hydroxyzine 10-50 mg at bedtime 1, 2
3. Adjust dose based on: Renal function (halve dose if CrCl 10-20), age (start low in elderly), and tolerability 1, 2
4. Screen for contraindications: Cardiac disease, QT prolongation risk factors, severe renal/hepatic impairment, pregnancy, prostatic enlargement 1, 2, 6

For Anxiety:

1. Consider hydroxyzine only if: First-line treatments (SSRIs, SNRIs, buspirone) are contraindicated or have failed 3
2. Dose: 50 mg daily has demonstrated efficacy in trials 4, 5
3. Monitor for: Transient sleepiness (appears first week, typically resolves), weight gain (12%), dry mouth (14%) 5
4. Recognize limitations: High risk of bias in supporting studies, not recommended as reliable first-line treatment 3

Critical Pitfalls to Avoid

• Do not use hydroxyzine as monotherapy for daytime urticaria management—second-generation antihistamines are superior due to lack of sedation 2
• Do not assume the AM/PM dosing regimen (non-sedating by day, hydroxyzine at night) eliminates daytime drowsiness—hydroxyzine's prolonged half-life may cause carryover sedation 2
• Do not combine with other alpha-adrenergic antagonists (including risperidone)—case reports document increased priapism risk 9
• Do not prescribe without explicit driving warnings—recent forensic data shows hydroxyzine is increasingly implicated in impaired driving 7
• Do not continue if urinary hesitancy develops—switch immediately to fexofenadine or another second-generation antihistamine rather than dose-reducing 8