Hydroxyzine Hydrochloride

Primary (approved) indications

• Pruritus (itching): Symptomatic relief of itching from allergic conditions (e.g., urticaria, atopic dermatitis) in adults and children (age limits vary by local labeling).
• Anxiety and tension: Short-term management of anxiety or tension associated with psychoneurosis; adjunctive use in anxiety prior to surgery.
• Sedation / Preoperative sedation: As a sedative/hypnotic agent to produce sedation prior to surgery or diagnostic procedures.
• Allergic conditions: Adjunctive therapy to relieve allergic symptoms (rhinitis, urticaria) where sedation is acceptable.

Common clinically accepted (off-label) uses

• Insomnia (short-term), when sedative antihistamine effect is appropriate.
• Adjunct in alcohol withdrawal or agitation (limited/setting-specific).
• Antiemetic adjunct in some settings (rare/limited evidence).

Note: Indications and age approvals vary across regions (HCl vs pamoate formulations). Use pediatric dosing and age limits consistent with local labeling.

General principles

• Use the lowest effective dose for the shortest duration needed. Reduce doses in elderly patients or those with hepatic/renal impairment. Monitor for excessive sedation and anticholinergic effects.

Adults (typical dosing ranges)

• Pruritus / allergic symptoms: 25–100 mg per day in divided doses (commonly 25–50 mg two to four times daily).
• Anxiety / tension / sedation: 50–100 mg as a single dose (often given at bedtime or prior to procedures); some regimens use 50 mg up to 4 times daily for anxiety, individualized by response.
• Preoperative sedation (single dose): Often 25–100 mg PO or IM depending on protocol.

Pediatrics

• Children (age- and product-specific): Weight-based dosing commonly used; typical oral range ~0.5–1 mg/kg per dose given 2–4 times daily (do not exceed product maximum for age). Example: small children 10–25 mg per dose; older children up to 50 mg per dose as guided by labeling. Specialist/pediatric guidance required.

Elderly

• Start at lower end (e.g., 25 mg once or twice daily) and titrate slowly. Increased sensitivity to central nervous system and anticholinergic effects; consider alternate agents if high anticholinergic burden is present.

Renal impairment

• Reduce dose or extend dosing interval in moderate–severe renal impairment; monitor for accumulation (sedation, anticholinergic effects).

Hepatic impairment

• Use lower initial doses and slow titration because hepatic metabolism is a major elimination pathway. In severe hepatic dysfunction avoid or use with extreme caution.

Route & administration notes

• Oral: Capsules, tablets, syrup. May be given with or without food.
• Parenteral: IM or IV formulations available for inpatient/preoperative use — use recommended hospital protocols; IV administration can produce rapid sedation and cardiorespiratory depression at high doses.
• Duration: Short-term use preferred. For chronic pruritus, treat underlying cause and minimize long-term use when possible.

Hydroxyzine is a first-generation (sedating) H₁-antihistamine that competitively blocks histamine H₁ receptors in peripheral tissues and the central nervous system. Central H₁ blockade produces sedation and anxiolysis; peripheral blockade reduces itching, vasodilation and other histamine-mediated allergic symptoms. Hydroxyzine also exhibits significant anticholinergic (antimuscarinic) and some antiemetic/anti-adrenergic effects which contribute to sedation, dryness of mucous membranes, and decreased gastrointestinal motility. Hepatic metabolism produces the active metabolite cetirizine (less sedating) which contributes to some pharmacologic effects.

• Absorption: Well absorbed after oral administration; onset of action within 15–30 minutes for PO, peak plasma concentrations within 2 hours (varies with formulation).
• Distribution: Widely distributed; crosses the blood-brain barrier (explains central sedation).
• Metabolism: Extensively metabolized in the liver; one major metabolite is cetirizine.
• Elimination half-life: Variable; commonly reported roughly 7–20 hours (age and hepatic/renal function influence half-life).
• Excretion: Metabolites and unchanged drug excreted predominantly in urine; some biliary/fecal elimination.
• Onset/duration: Sedative and antihistamine effects typically appear quickly (within an hour) and persist several hours; once-daily or multiple-daily dosing regimens used depending on indication.

• Pregnancy: Historically listed as Category C (no well-controlled studies in pregnant women; animal studies have shown adverse effects at high doses). Use only if clearly needed and after risk–benefit discussion. Avoid routine use in pregnancy where alternative agents with better pregnancy data are suitable. Hydroxyzine should be discontinued when pregnancy is recognized in many cases, unless the treating clinician judges continued therapy necessary (consult obstetrics/perinatal specialists).
• Lactation: Hydroxyzine is excreted into breast milk. Because of potential for infant sedation and feeding difficulties, breastfeeding mothers should use caution; alternatives or temporary discontinuation of drug or breastfeeding may be considered based on clinical need.

• Primary class: Antihistamine (H₁ receptor antagonist).
• Subclass / properties: First-generation (sedating) antihistamine with anxiolytic/sedative properties and anticholinergic effects.

• Known hypersensitivity to hydroxyzine or any component of the formulation.
• Early pregnancy (first trimester) — many labels advise avoidance and discontinuation once pregnancy is known unless benefit outweighs risk; follow local labeling.
• Severe central nervous system depression (concurrent use with large amounts of CNS depressants increases risk).
• Caution/relative contraindication: Glaucoma (narrow-angle), urinary retention, prostatic hypertrophy (due to anticholinergic effects). Use with caution in severe respiratory disease (e.g., COPD) because sedation may depress respiratory drive.

• Excessive sedation & CNS depression: May be profound when combined with alcohol, opioids, benzodiazepines, barbiturates, or other sedating medications. Warn patients not to drive or operate machinery until they know individual response.
• Respiratory depression: Risk in patients with compromised respiratory function, neonates, or when used with other depressants.
• QT prolongation and cardiac arrhythmia: At high intravenous doses or overdose, hydroxyzine has been associated with QT prolongation and torsades de pointes in susceptible patients; avoid in patients with known QT prolongation, congenital long QT syndrome, or concurrent QT-prolonging drugs unless monitored.
• Anticholinergic effects: Risk of dry mouth, blurred vision, constipation, urinary retention—use caution in elderly and those with prostatic hypertrophy or narrow-angle glaucoma.
• Seizure threshold: May lower seizure threshold; use cautiously in patients with epilepsy.
• Pediatric caution: Infants and young children are more sensitive to central nervous system effects; dosing per pediatric guidance and close monitoring required.
• Elderly: Increased sensitivity to anticholinergic and sedative effects; falls and cognitive impairment risk—use lower doses and evaluate alternatives.
• Dependence / misuse: Not a controlled substance, but excessive use can cause sedation and impairment—monitor for inappropriate use.

Monitoring

• Observe for excessive sedation, respiratory compromise, anticholinergic symptoms, cardiac symptoms (palpitations, syncope), and signs of allergic reaction.

Common

• Sedation/drowsiness, somnolence
• Dizziness, headache
• Dry mouth
• Blurred vision, diplopia
• Gastrointestinal: nausea, constipation
• Urinary retention (especially in men with prostatic hypertrophy)

Less common / serious

• Severe sedation or coma in overdose or when combined with other CNS depressants
• Respiratory depression (rare)
• Cardiac arrhythmias (QT prolongation, torsades de pointes) in overdose or high IV doses or with interacting drugs
• Allergic reactions (rash, urticaria, anaphylaxis — rare)
• Confusion, agitation, especially in elderly (paradoxical excitation can occur in children/older adults)

Onset & dose-dependence

• Sedation and anticholinergic effects typically appear rapidly after dosing and are dose-dependent. Effects often diminish with continued therapy in some patients (tolerance to sedation), but persistent anticholinergic effects may occur.

Additive CNS depression

• Alcohol, benzodiazepines, opioids, barbiturates, sedative antihistamines, antipsychotics — additive sedation and respiratory depression risk. Avoid or adjust doses and monitor closely.

QT-prolonging drugs

• Concomitant use with other QT-prolonging agents (e.g., certain antiarrhythmics, some antipsychotics, macrolide antibiotics) may increase torsades risk — avoid combinations in high-risk patients and monitor ECG when necessary.

Anticholinergic drugs

• Additive anticholinergic burden when used with tricyclic antidepressants, antimuscarinics, certain antiparkinsonian agents — increases risk of urinary retention, constipation, confusion.

CYP interactions

• Hydroxyzine is metabolized hepatically; strong hepatic enzyme inhibitors or inducers may alter levels (use clinical judgment; monitor for toxicity with CYP inhibitors and for loss of effect with inducers). Specific major CYP interactions are less prominent than with some other drugs, but caution is advised with co-medications that significantly affect hepatic metabolism.

Other

• MAO inhibitors: Co-administration may potentiate anticholinergic and CNS effects — use caution.

Clinical action

• Reduce doses of hydroxyzine when combined with other CNS depressants; avoid dangerous combinations (e.g., hydroxyzine + tizanidine? — check product-specific contraindications). Monitor cardiac status with multiple QT-prolonging agents.

• QT safety awareness: Regulatory warnings and case reports have highlighted QT prolongation risk (especially with parenteral/high-dose use and in combination with other QT-prolongers), so clinicians are advised to assess cardiac risk factors and avoid dangerous drug combinations.
• Preference in special populations: Due to anticholinergic and sedative burden, many guidelines recommend caution or favor second-generation (non-sedating) antihistamines for chronic allergic conditions, particularly in the elderly. Hydroxyzine remains a reasonable short-term option for pruritus when sedation is acceptable or desired.
• Pregnancy/lactation guidance: Current practice emphasizes individualized risk–benefit decisions and specialist consultation for use during pregnancy or breastfeeding.

• Temperature: Store at 20–25°C (68–77°F); short excursions permitted per product labeling.
• Protection: Keep tightly closed, protect from moisture and light.
• Special handling: Oral syrups should be stored and used per manufacturer instructions; parenteral vials used under sterile conditions per facility protocols.
• Expiration: Discard after expiration; avoid using if appearance or odor changes.