Atarax^® (Tablets) Instructions for Use

Marketing Authorization Holder

UCB Pharma, S.A. (Belgium)

ATC Code

N05BB01 (Hydroxyzine)

Active Substance

Hydroxyzine (Rec.INN registered by WHO)

Dosage Form

Atarax®

Film-coated tablets, 25 mg: 25 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, oblong, with a score on both sides.

Excipients: lactose monohydrate, microcrystalline cellulose PH102, magnesium stearate, colloidal silicon dioxide.

Coating composition Opadry^® Y-1-7000 (titanium dioxide, hypromellose 2910 5cP, macrogol 400).

25 pcs. – blisters (1) – cardboard packs with a first-opening system.

Clinical-Pharmacological Group

Anxiolytic (tranquilizer)

Pharmacotherapeutic Group

Psycholeptics; anxiolytics; diphenylmethane derivatives

Pharmacological Action

A diphenylmethane derivative, it has moderate anxiolytic activity; it also has sedative, antiemetic, antihistamine, and m-cholinolytic effects.

It blocks central m-cholinergic receptors and histamine H₁ receptors and suppresses the activity of certain subcortical zones. It does not cause psychological dependence or addiction. The clinical effect occurs 15-30 minutes after oral administration of the drug.

It has a positive effect on cognitive abilities, improving memory and attention. It relaxes skeletal and smooth muscles, has a bronchodilator and analgesic effect, and a moderate inhibitory effect on gastric secretion.

Hydroxyzine significantly reduces itching in patients with urticaria, eczema, and dermatitis. With long-term use, no withdrawal syndrome or deterioration of cognitive functions has been noted.

Polysomnography in patients with insomnia and anxiety clearly demonstrates an increase in sleep duration and a decrease in the frequency of nighttime awakenings after a single or repeated dose of hydroxyzine at a dose of 50 mg. A reduction in muscle tension in patients with anxiety was noted when taking the drug at a dose of 50 mg 3 times/day.

Pharmacokinetics

Absorption

Hydroxyzine is highly absorbed from the gastrointestinal tract. C_max is noted 2 hours after drug administration.

After a single dose of 25 mg or 50 mg in adults, the plasma concentration is 30 ng/ml and 70 ng/ml, respectively.

Bioavailability after oral and intramuscular administration is 80%.

Distribution

Hydroxyzine is more concentrated in tissues (particularly in the skin) than in plasma. The distribution coefficient is 7-16 L/kg.

Hydroxyzine penetrates the blood-brain barrier and placental barrier, concentrating to a greater extent in fetal tissues than in the maternal body. Metabolites are found in breast milk.

Metabolism and Excretion

Hydroxyzine is metabolized in the liver. The main metabolite (45%) is cetirizine, which is a histamine H₁ receptor blocker. The total clearance of hydroxyzine is 13 ml/min/kg. T_1/2 in adults is 14 hours. Only 0.8% of hydroxyzine is excreted unchanged in the urine.

Pharmacokinetics in Special Clinical Cases

In children, the total clearance is 4 times less than in adults, T_1/2 in children aged 14 years is 11 hours, in children aged 1 year – 4 hours.

In elderly patients, T_1/2 is 29 hours, the distribution coefficient is 22.5 L/kg.

In patients with impaired liver function, T_1/2 increases to 37 hours, the concentration of metabolites in the blood serum is higher than in young patients with normal liver function. The antihistamine effect can persist for up to 96 hours.

Indications

• Adults: for the relief of anxiety, psychomotor agitation, feelings of internal tension, increased irritability in neurological, mental (including generalized anxiety, adjustment disorders) and somatic diseases, chronic alcoholism; withdrawal syndrome in chronic alcoholism accompanied by psychomotor agitation;
• As a sedative during premedication;
• Skin itching (as symptomatic therapy).

ICD codes

Dosage Regimen

The drug is taken orally.

For symptomatic treatment of itchingchildren aged 12 months to 6 years the drug is prescribed at a daily dose of 1-2.5 mg/kg body weight in several doses; children over 6 years of age – at a dose of 1-2 mg/kg/day in several doses.

For premedicationchildren the drug is prescribed at a dose of 1 mg/kg body weight 1 hour before surgery, and also additionally on the night before surgery.

Adults for symptomatic treatment of anxiety are prescribed at a dose of 25-100 mg/day in several doses during the day or at night. The average dose is 50 mg/day (12.5 mg in the morning, 12.5 mg in the afternoon and 25 mg at night). If necessary, the dose can be increased to 300 mg/day.

For symptomatic treatment of itching the initial dose is 25 mg, if necessary the dose can be increased 4 times (25 mg 4 times/day).

The maximum single dose should not exceed 200 mg, the maximum daily dose should not exceed 300 mg.

In elderly patients the initial dose should be reduced by half.

Patients with moderate and severe renal impairment, as well as with hepatic impairment require a dose reduction.

Adverse Reactions

Side effects associated with anticholinergic action rarely (mainly in elderly patients) – dry mouth, urinary retention, constipation, accommodation disturbance.

From the central nervous system drowsiness, general weakness (especially at the beginning of treatment), headache, dizziness. If weakness and drowsiness do not disappear within a few days after the start of therapy, the dose of the drug should be reduced. Very rarely (with significant overdose) – tremor, convulsions, disorientation.

From the cardiovascular system arterial hypotension, tachycardia.

From the digestive system nausea, changes in liver function tests.

Other increased sweating, allergic reactions, fever, bronchospasm.

When using the drug in recommended doses, no clinically significant respiratory depression was noted. Involuntary motor activity (including very rare cases of tremor and convulsions), disorientation were observed with significant overdose.

Side effects observed when taking Atarax^® are usually mild, transient and disappear within a few days after the start of treatment or after dose reduction.

Contraindications

• Porphyria;
• Pregnancy;
• Labor;
• Lactation period (breastfeeding);
• Hypersensitivity to the components of the drug;
• Hypersensitivity to cetirizine and other piperazine derivatives, aminophylline or ethylenediamine.

Atarax^® tablets are not recommended for patients with hereditary galactose intolerance, as well as with glucose and galactose malabsorption, because the tablets contain lactose.

With caution the drug should be prescribed for myasthenia gravis, prostate hyperplasia with clinical manifestations, difficulty urinating, constipation, with increased intraocular pressure, dementia, predisposition to seizures; with a predisposition to the development of arrhythmia; with simultaneous use of drugs that have an arrhythmogenic effect; simultaneously with other agents that depress the central nervous system, or anticholinergics (a dose reduction is required). A dose reduction of the drug is required in patients with severe and moderate renal failure, with hepatic failure, in elderly patients with reduced glomerular filtration.

Use in Pregnancy and Lactation

Atarax^® is contraindicated for use during pregnancy, during labor.

If it is necessary to use Atarax^® during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Patients with hepatic impairment require a dose reduction.

Use in Renal Impairment

Patients with moderate and severe renal impairment require a dose reduction.

Pediatric Use

For symptomatic treatment of itchingchildren aged 12 months to 6 years the drug is prescribed at a daily dose of 1-2.5 mg/kg body weight in several doses; children over 6 years of age – at a dose of 1-2 mg/kg/day in several doses.

For premedicationchildren the drug is prescribed at a dose of 1 mg/kg body weight 1 hour before surgery, and also additionally on the night before surgery.

Geriatric Use

A dose reduction of the drug is required in elderly patients with reduced glomerular filtration.

Special Precautions

If it is necessary to conduct allergy tests, Atarax^® should be discontinued 5 days before the study.

Patients taking Atarax^® should refrain from drinking alcohol.

Effect on the ability to drive vehicles and mechanisms

Patients taking Atarax^®, if it is necessary to drive a car and mechanisms, should be warned that the drug may affect concentration and the speed of psychomotor reactions.

Overdose

Symptoms increased anticholinergic effects, depression or paradoxical stimulation of the central nervous system, nausea, vomiting, involuntary motor activity, hallucinations, impaired consciousness, arrhythmia, arterial hypotension; rarely – tremor, convulsions, disorientation, which occur with significant overdose.

Treatment if spontaneous vomiting is absent, it is necessary to induce it artificially or perform gastric lavage. General measures aimed at maintaining vital body functions are carried out, and the patient is monitored until the symptoms of intoxication disappear in the next 24 hours.

If a vasopressor effect is necessary, norepinephrine or metaraminol is prescribed. Epinephrine should not be used. There is no specific antidote. Hemodialysis is ineffective.

Drug Interactions

Atarax^® potentiates the effect of drugs that depress the central nervous system, such as opioid analgesics, barbiturates, tranquilizers, hypnotics, ethanol (with combinations, individual dose selection of drugs is required).

Atarax^® when used simultaneously prevents the pressor effect of epinephrine and the anticonvulsant activity of phenytoin, and also prevents the action of betahistine and cholinesterase blockers.

When used simultaneously, Atarax^® does not affect the activity of atropine, belladonna alkaloids, cardiac glycosides, antihypertensive agents, histamine H₂ receptor blockers.

Concomitant administration of Atarax^® with MAO inhibitors and anticholinergics should be avoided.

Hydroxyzine is an inhibitor of the CYP2D6 isoenzyme and when used in high doses can cause interactions with CYP2D6 substrates. Since Hydroxyzine is metabolized in the liver, an increase in its blood concentration can be expected when co-administered with liver enzyme inhibitors.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 5 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.