Pharmacotherapeutic group: anxiolytics, diphenylmethane derivatives
ATC code: N05BB01
The active substance hydroxyzine dihydrochloride is a diphenylmethane derivative which is chemically distinct from phenothiazines, reserpine, meprobamate, or benzodiazepines.
Mechanism of action
Hydroxyzine dihydrochloride does not depress cortical activity, but its effect is mediated by suppression of activity in certain key areas of the subcortical region of the central nervous system.
Pharmacodynamic effects
Antihistaminic and bronchodilatory effects have been demonstrated experimentally and confirmed clinically. The antiemetic effect has been confirmed by apomorphine and veriloid tests. Pharmacological and clinical studies indicate that hydroxyzine at therapeutic doses does not increase gastric secretion or acidity, and in most cases exerts a mild antisecretory effect. Following intradermal administration of histamine or antigens, a reduction in wheal and flare response was demonstrated in healthy adult volunteers and in children. Hydroxyzine also effectively relieves pruritus in various forms of urticaria, eczema, and dermatitis.
In hepatic impairment, the antihistaminic effect of a single dose may persist for up to 96 hours after administration.
EEG recordings in healthy volunteers show anxiolytic and sedative effects. The anxiolytic effect has been confirmed using various standardised psychometric tests. Polysomnographic recordings in patients with anxiety and insomnia demonstrated an increase in total sleep time, a decrease in total nocturnal wakefulness, and a reduction in sleep onset latency, either after a single dose or after repeated daily doses of 50 mg. In anxious patients, a dose of 50 mg three times daily reduced muscle tension. No memory impairment was observed. After discontinuation of 4-week treatment in anxiety patients, no withdrawal symptoms occurred.
Onset of action
The antihistaminic effect occurs approximately 1 hour after oral administration. Sedative effects manifest 30–45 minutes after tablet administration.
Hydroxyzine also has spasmolytic and sympatholytic effects. It has a weak affinity for muscarinic receptors. Hydroxyzine also exhibits mild analgesic activity.
⚠️ Warnings
Hydroxyzine must be used with caution in patients with an increased risk of convulsions.
Young children are more susceptible to developing adverse effects on the central nervous system (see section 4.8). Convulsions have also been reported more frequently in children than in adults.
Hydroxyzine has anticholinergic activity. Caution is therefore required when administering it to patients with glaucoma, urinary tract obstruction, decreased gastrointestinal motility, myasthenia gravis, or dementia.
If hydroxyzine is administered concomitantly with other central nervous system depressants or medicinal products with anticholinergic properties, dosage adjustment is required (see section 4.5).
Alcohol should not be consumed during treatment with hydroxyzine (see section 4.5).
QT interval prolongation
Hydroxyzine has been associated with QT interval prolongation on the ECG. Cases of QT prolongation and torsade de pointes have been reported during post-marketing surveillance in patients using hydroxyzine. Most of these patients had other risk factors, electrolyte abnormalities, and concomitant medications that may have contributed (see section 4.8).
Hydroxyzine should be used at the lowest effective dose and for the shortest possible duration.
Treatment with hydroxyzine must be discontinued if signs and symptoms that may be associated with cardiac arrhythmia occur, and patients must seek immediate medical attention.
Patients must be advised to report any cardiac symptoms promptly.
Elderly patients
The use of hydroxyzine in elderly patients is not recommended due to reduced elimination of hydroxyzine in this population compared with adult patients and an increased risk of adverse effects (e.g. anticholinergic effects) (see sections 4.2 and 4.8). In elderly patients, it is recommended to initiate treatment at half the recommended dose due to the prolonged duration of action (see section 4.2).
Hepatic and renal impairment
In patients with hepatic impairment or moderate to severe renal impairment, the usual daily dose should be reduced (see section 4.2).
The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
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