Hydroxyzine is a first-generation piperazine-derivative antihistamine (H1-receptor antagonist) with significant sedative, anxiolytic, antiemetic, anticholinergic, and antipruritic properties. It is a prodrug metabolized to its active form, cetirizine. In the Indian context, it is widely prescribed for anxiety, pruritus, and as a premedication for its sedative effects, though its use is tempered by sedative side effects and the availability of newer agents.
Adult: Anxiety: 50-100 mg daily in divided doses (e.g., 25mg 3-4 times daily). Pruritus: 25 mg at bedtime or 25 mg 3-4 times daily. Premedication: 50-100 mg night before and 50-100 mg 1 hour before surgery.
Note: Oral tablet. Can be taken with or without food. Taking with food may reduce GI upset. Tablet can be split. Administer the last dose of the day at bedtime to utilize sedative effect. Do not crush or chew sustained-release formulations (if available).
Hydroxyzine competitively and reversibly inhibits histamine at H1-receptors in the gastrointestinal tract, uterus, large blood vessels, and bronchial muscle. Its central nervous system effects (sedation, anxiolysis) are mediated through suppression of activity in key subcortical regions, including the hypothalamus and the reticular activating system. It also possesses significant antimuscarinic (anticholinergic) activity.
Pregnancy: Category C (US FDA). Animal studies show risk, human data inadequate. Generally avoided in first trimester. Use only if potential benefit justifies potential fetal risk, particularly late in pregnancy where it may cause neonatal anticholinergic effects or withdrawal.
Driving: PATIENTS MUST NOT DRIVE or operate heavy machinery, especially during initial therapy and dose adjustments. Impairs cognitive and motor functions.
| CNS Depressants (Alcohol, Benzodiazepines, Opioids, Barbiturates) | Potentiated sedation, respiratory depression, impaired psychomotor performance. | Major |
| Enzyme Inhibitors (CYP3A4: Ketoconazole, Clarithromycin, HIV Protease Inhibitors) | Increased hydroxyzine plasma levels, risk of toxicity. | Moderate |
| Enzyme Inducers (CYP3A4: Rifampicin, Carbamazepine, Phenytoin) | Decreased hydroxyzine plasma levels, reduced efficacy. | Moderate |
| Anticholinergic Drugs (Tricyclic Antidepressants, Antipsychotics, Antiparkinsonian agents) | Additive anticholinergic effects (dry mouth, constipation, urinary retention, confusion). | Moderate |
| QT-prolonging Drugs (Class Ia/III antiarrhythmics, Macrolides, Fluoroquinolones, Antipsychotics) | Additive risk of QT prolongation and torsades de pointes. | Major |