Diphenylmethane derivative has moderate anxiolytic activity; also has sedative, antiemetic, antihistamine, and m-anticholinergic action. Does central m-cholinergic receptors and histamine H1 receptors and inhibits the activity of certain subcortical areas. It does not cause mental dependence and addiction. The clinical effect occurs within 15-30 minutes after ingestion of the drug.
It has a positive influence on cognitive abilities, improves memory and attention. It relaxes skeletal and smooth muscles, has a bronchodilator and analgesic effects, a moderate inhibitory effect on gastric secretion. Hydroxyzine reduces the itching in patients with urticaria, eczema and dermatitis. Chronic administration were observed cindroma cancellations and deterioration of cognitive functions. Polysomnography in patients with insomnia and anxiety demonstrates lengthening the duration of sleep, reduce the frequency of nighttime awakenings after single or repeated administration of hydroxyzine at a dose of 50 mg. Reduced muscular tension in patients with anxiety observed while taking the drug at a dose of 50 mg 3 times / day.
Hydroxyzine is highly absorbed from the gastrointestinal tract. Cmax observed after 2 hours after ingestion.
After a single dose of the drug in a single dose of 25 mg or 50 mg in adults in the plasma concentration is 30 ng / ml and 70 ng / ml, respectively.
Oral bioavailability and the / m is 80%.
Hydroxyzine is more concentrated in the tissues (including the skin) than in plasma. The distribution coefficient of 7-16 L / kg.
Hydroxyzine penetrate the BBB and placental barrier, concentrating mainly in fetal tissues than in the mother. Metabolites detected in breast milk.
Metabolism and excretion
Hydroxyzine is metabolized in the liver. The major metabolite (45%) – cetirizine, which is a blocker of histamine H1 receptors. Hydroxyzine total clearance of 13 ml / min / kg. T1 / 2 in adults is 14 hours. Only 0.8% of Hydroxyzine is excreted unchanged in the urine.
Pharmacokinetics in special clinical situations
In children, the overall clearance of 4 times less than for adults, T1 / 2 in children of 14 years is 11 h in children aged 1 – 4 hours.
In elderly patients T1 / 2 of 29 hours, the distribution ratio is 22.5 L / kg.
Patients with impaired liver function T1 / 2 is increased up to 37 h, the concentration of metabolites in serum is higher than in young patients with normal liver function. The antihistamine effect may persist for 96 hours.
Indications for use of the drug
– For adults: for the relief of anxiety, agitation, feelings of inner tension, irritability with neurological, psychiatric (including generalized anxiety, adjustment disorder) and somatic diseases, chronic alcoholism; abstinence syndrome in chronic alcoholism, accompanied by psychomotor agitation;
– As a sedative during premedication;
– Itching (as symptomatic therapy).
The drug is taken orally.
For the symptomatic treatment of pruritus in children aged 12 months to 6 years, the drug is administered in a daily dose of 1-2.5 mg / kg body weight in divided doses; children older than 6 years – at a dose of 1-2 mg / kg / day in divided doses.
For children sedation drug administered in a dose of 1 mg / kg body weight for 1 hour before the operation, and further the night before the operation.
Adults for the symptomatic treatment of anxiety is prescribed in doses of 25-100 mg / day in divided doses during the day or at night. The average dose is 50 mg / day (12.5 mg in the morning, afternoon 12.5 mg and 25 mg at bedtime). the dose may be increased to 300 mg / day, if necessary.
For symptomatic treatment of pruritus initial dose is 25 mg, if appropriate dose may be increased to four times (4 times 25 mg / day).
The maximum single dose should not exceed 200 mg, the maximum daily dose is not more than 300 mg.
In elderly patients the initial dose should be reduced by 2 times.
Patients with renal failure secondary to severe, and the need to hepatic insufficiency dose reduction.
Side effects associated with anticholinergic effects: rarely (mainly in elderly patients) – dry mouth, urinary retention, constipation, disturbance of accommodation.
CNS: drowsiness, weakness (especially at the beginning of treatment), headache, dizziness. If the weakness and drowsiness do not disappear after a few days of therapy, the drug dose should be reduced. Very rarely (if a large overdose) – tremors, convulsions, disorientation.
Since the cardiovascular system: hypotension, tachycardia.
From the digestive system: nausea, changes in liver function tests.