Hydroxyzine Canon, 25 mg 25 pcs

Pharmacotherapeutic group:

Anxiolytic medicine (tranquilizer)

ATX code: [N05BB01]

Pharmacological properties

Pharmacodynamics

Hydroxyzine is a first-generation blocker of H1-histamine receptors, a phenothiazine derivative with antimuscarinic and sedative properties and diphenylmethane, and promotes inhibition of the activity of certain subcortical areas.

It has H1-histamine-blocking, bronchodilator and antiemetic effects and has a moderate inhibitory effect on gastric secretion. Hydroxyzine significantly reduces itching in patients with urticaria, eczema and dermatitis.

Hydroxyzine has a positive effect on cognitive abilities and improves attention and memory. Hydroxyzine is not addictive or psychologically addictive and no withdrawal syndrome has been noted with prolonged use. Hydroxyzine is able to inhibit the central nervous system, also has anticholinergic, antihistamine, antispasmodic, local anesthetic, sympatho-anesthetic effect, has muscle relaxant activity.

In case of hepatic insufficiency, the H1-histamine-blocking effect may be prolonged up to 96 h after a single dose. It has moderate anxiolytic activity.

Polysomnography in patients with insomnia and anxiety demonstrates prolongation of sleep duration, decreased frequency of nocturnal awakenings after a single or repeated dose of hydroxyzine 50 mg. Reduction of muscle tension in patients with anxiety has been noted when taking the drug in a dose of 50 mg 3 times a day.H1-histamine-blocking effect occurs approximately 1 hour after taking the tablets orally. The sedative effect appears after 30-45 minutes.

Pharmacokinetics.

Absorption: Absorption is high. Time to reach maximum concentration (TSmax) after oral administration is 2 hours. After an average dose of 50 mg, the TSmax in adults is 70 mg/ml.

Distribution: The distribution coefficient is 7-16 l/kg in adults. Hydroxyzine penetrates the blood-brain barrier and the placenta, concentrating more in fetal than in maternal tissues. After oral administration, hydroxyzine penetrates the skin well, with concentrations of hydroxyzine in the skin well in excess of serum concentrations after both single and multiple doses. Plasma concentrations of hydroxyzine do not necessarily reflect its tissue binding or distribution at skin receptors. It has an effect on skin inflammation depending on the serum concentration.

Metabolism: Hydroxyzine is metabolized in the liver. Cetirizine, the main metabolite (45%), is a blocker of H1-histamine receptors. Metabolites are found in breast milk.

Elimination: The elimination half-life (T1/2) in adults is 14 h (range: 7-20 h). The total clearance of hydroxyzine is 13 ml/min/kg. About 0.8% of hydroxyzine is excreted unchanged through the kidneys. The main metabolite cetirizine is excreted mainly in the urine, also unchanged (25% of the taken dose of hydroxyzine).

Pharmacokinetics in special groups of patients.

In elderly patients
In elderly patients, the T1/2 was 29 hours. The volume of distribution is 22.5 L/kg. It is recommended to reduce the daily dose of hydroxyzine when administered to elderly patients.

Children under 1 year
In children the total clearance is 2.5 times higher than in adults. The dose should be adjusted. The elimination half-life is 4 hours.
Children from 1 to 14 years

The elimination half-life is 11 hours.

In patients with hepatic impairment

In patients with secondary hepatic dysfunction due to primary biliary cirrhosis, total clearance was approximately 66% of that recorded in healthy volunteers. In patients with liver disease, the T1/2 increased to 37 hours, with higher serum concentrations of metabolites than in young patients with normal liver function. In patients with hepatic impairment, it is recommended to reduce the daily dose or the frequency of administration.

In patients with renal impairment

The pharmacokinetics of hydroxyzine were studied in 8 patients with severe renal impairment (creatinine clearance 24+7 ml/min). The duration of exposure to hydroxyzine did not change significantly, while the duration of exposure to cetirizine was prolonged. To avoid any significant accumulation of cetirizine metabolite after repeated use of hydroxyzine in patients with impaired renal function, the daily dose of hydroxyzine should be reduced.

Indications

Active ingredient

Composition

1 film-coated tablet contains:

the active ingredient:

hydroxyzine hydrochloride 25 mg;

excipients:

Pregelatinized corn starch 30 mg,

Silicon colloidal dioxide 0.7 mg,

Magnesium stearate 1 mg,

Mannitol 40 mg,

Microcrystalline cellulose 33.3 mg;

Composition of the film coating:

White opadray – 4 mg, including: hypromellose (hydroxypropyl methylcellulose) 1.35 mg, hyprolose (hydroxypropylcellulose) 1.35 mg, talc 0.8 mg, titanium dioxide 0.5 mg.

How to take, the dosage

The drug is administered orally.

Adults:

For symptomatic treatment of anxiety: standard dose of 50 mg daily divided into 3 doses (1/2 tablet (12.5 mg) in the morning, 1/2 tablet (12.5 mg) in the afternoon and 1 tablet (25 mg at night). In severe cases of anxiety, the drug is used in a dose of 50-100 mg 4 times a day.

For symptomatic treatment of pruritus of allergic origin: the initial dose is 1 tablet (25 mg) before bedtime; if necessary, the dose may be increased to 1 tablet (25 mg) 3-4 times a day.

For premedication in surgical practice: 2-8 tablets (50-200 mg) at night before anesthesia.
A single maximum dose for an adult should not exceed 8 tablets (200 mg), the maximum daily dose is no more than 12 tablets (300 mg).

Children:
For symptomatic treatment of pruritus of allergic origin:
Ages 3 to 6 years: 1.0 mg/kg/day to 2.5 mg/kg/day in multiple doses.
Ages 6 years and older: 1.0 mg/kg/day to 2.0 mg/kg/day in multiple doses.

For premedication: 1 mg/kg the night before anesthesia.
The dosage is calculated by the physician individually depending on the body weight of the child in accordance with the recommended doses, and it should be noted that the minimum dosage received, after dividing the tablet, is 12.5 mg.

The use in special groups of patients:
When used in the elderly, the dose is adjusted individually, taking into account comorbidities within the range of recommended doses (see section Pharmacokinetics).

The use in patients with renal insufficiency and hepatic impairment:
Patients with severe to moderate renal insufficiency and hepatic impairment require dose reduction. In patients with hepatic insufficiency it is recommended to reduce daily dose by 33%. In patients with severe and moderate renal insufficiency the drug is used in half dose due to decreased excretion of the main metabolite of hydroxyzine – cetirizine.

Interaction

It is necessary to consider the potentiating effect of hydroxyzine when combined with drugs that depress the central nervous system (CNS), such as narcotic analgesics, barbiturates, tranquilizers, sleeping pills, alcohol. In this case, their doses should be selected individually. Concomitant use with monoamine oxidase inhibitors (MAO) and choline blockers should be avoided. The drug interferes with the pressor effect of epinephrine and anticonvulsant activity of phenytoin as well as interferes with the effect of betahistine and cholinesterase inhibitor drugs.

The use of cimetidine in a dose of 600 mg twice a day was found to increase the serum concentration of hydroxyzine by 36% and decrease the maximum concentration of the metabolite cetirizine by 20%.

The effects of atropine, belladonna alkaloids, cardiac glycosides, hypotensive agents, and H2-histamine receptor blockers are not altered by hydroxyzine. Hydroxyzine is an inhibitor of CYP2D6 isoenzyme and in high doses may cause drug interactions with CYP2D6 substrates.

Because hydroxyzine is metabolized in the liver, an increase in its plasma concentrations can be expected when used concomitantly with microsomal liver enzyme inhibitors.

. Since hydroxyzine is metabolized by alcohol dehydrogenase and CYP3A4/5 isoenzyme, increased concentrations of hydroxyzine in plasma when used concomitantly with drugs potentially inhibiting CYP3A4/5 isoenzyme (telithromycin, clarithromycin, Delavirdine, stiripentol, ketoconazole, voriconazole, intraconazole, posaconazole and some HIV protease inhibitors, including atazanavir, indinavir, nelfinavir, ritonavir, saquinarin, lopinavir/ritonavir, saquinavir/ritonavir and tipranavir/ritonavir.)

The inhibition of one metabolic pathway, however, can be partially offset by the work of the other. Concomitant use of hydroxyzine with drugs that can potentially cause arrhythmias may increase the risk of QT interval prolongation and occurrence of pirouette-type ventricular tachycardia.

The use of the drug concomitantly with drugs with ototoxic effects, such as gentamicin, may mask the symptoms of ototoxicity, such as dizziness. The drug should be discontinued 3 days before the planned allergen skin testing.

Special Instructions

When used concomitantly with drugs with m-cholinoblocking properties and CNS depressant drugs, the dose of hydroxyzine should be reduced.

Hydroxyzine may cause prolongation of the QT interval on the electrocardiogram, so concomitant use with other drugs that can disrupt cardiac function may increase the risk of arrhythmias.

It has been suggested that other drugs that cause electrocardiogram changes (atropine, antiparkinsonian drugs, lithium carbonate, quinidine, phenothiazines, procainamide, tricyclic antidepressants, thioridazine) may exacerbate and amplify the changes that can be caused by hydroxyzine and increase the risk of sudden death.

The simultaneous use of two or more drugs that prolong the QT interval should be avoided because of the danger of additive effects that can cause potentially life-threatening and severe cardiac arrhythmias.
Doses should be reduced if renal and/or hepatic impairment occurs.

In the elderly, the dosage should be adjusted individually, starting at half the minimum dose and adjusting within the range of recommended doses. If allergy testing or methacholine testing is necessary, the use of Hydroxyzine Canon should be discontinued 5 days prior to the study to prevent misleading data.

Alcohol should be avoided during treatment with Hydroxyzine Canon.

Impact on driving and operating ability

Hydroxyzine Canon may impair the ability to concentrate and the speed of psychomotor reactions. Taking other sedative medications may exacerbate this effect.

Therefore, you should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and rapid psychomotor reactions.

Contraindications

With caution: In myasthenia gravis, prostatic hyperplasia with clinical manifestations, difficulty urinating, constipation, glaucoma, dementia, seizure disorders, including epilepsy, with a tendency to arrhythmia, including electrolyte imbalance (hypokalemia, hypomagnesemia), in patients with a history of heart disease (in heart failure and arterial hypertension) or when using drugs that may cause arrhythmias, in hyperthyroidism. Hydroxyzine contributes to decreased GI motility, development of stenotic peptic ulcer, respiratory impairment.

Side effects

Possible side effects are listed below by body system and frequency of occurrence.

WHO classification of the frequency of side effects:
very often – >1/10 appointments (>10%)
often – >1/100 to <1/10 appointments (>1% and <10%)
infrequent – >1/1000 to <1/100 appointments (>0.1 % and <1 %)
rarely – from >1/10000 to <1/1000 appointments (>0.01 % and <0.1 %)
very rarely – <1/10000 appointments (<0.01 %)

The most common adverse reactions were somnolence, headache, lethargy, dry mouth, and fatigue.

Immune system disorders:
rarely: hypersensitivity;
very rarely: anaphylactic shock.

Nervous system disorders:
infrequent: dizziness, insomnia, tremor;
rare: seizures, dyskinesia.

Psychiatric disorders:
infrequent: agitation, confusion;
rare: hallucinations, disorientation.

Visual disorders:
rarely: accommodation disorder, visual impairment.

Heart disorders:
rare: tachycardia;
frequency unknown: prolongation of QT interval on electrocardiogram, pirouette-type ventricular tachycardia.

Vascular disorders:
rare: decreased blood pressure.

Respiratory system, thorax and mediastinum disorders:
very rare: bronchospasm.

Gastrointestinal tract disorders:
infrequent: nausea;
rare: vomiting, constipation.

Liver and biliary tract disorders:
rare: impaired liver function tests;
frequency unknown: hepatitis.

Renal and urinary tract disorders:
rare: urinary retention.

Skin and subcutaneous tissue disorders:
rare: itching, rash (erythematous, maculopapular), urticaria, dermatitis;
very rare: angioedema, increased sweating, acute generalized exanthematous-pustular rash, erythema multiforme, Stevens-Johnson syndrome.

General disorders:
rarely: hyperthermia, malaise.

The following side effects have been observed with cetirizine, the main metabolite of hydroxyzine: thrombocytopenia, aggression, depression, tics, dystonia, paresthesia, oculogyric crisis, diarrhea, dysuria, enuresis, asthenia, edema, weight gain and may occur with hydroxyzine.

Overdose

Symptoms of CNS toxicity are associated with excessive m-cholin blocking, suppression, or paradoxical CNS stimulation. These symptoms include nausea, vomiting, tachycardia, hyperthermia, somnolence, impaired pupillary reflex, tremor, confusion or hallucinations.

Subsequently, depression of consciousness, respiration, seizures, decreased blood pressure, arrhythmia may develop. Worsening of the coma state and cardiopulmonary collapse are possible.

Treatment: Airway, respiratory, and circulatory status should be monitored with Electrocardiographic (ECG) monitoring, and adequate oxygenation should be provided. Cardiac activity and blood pressure should be monitored for 24 hours after the disappearance of symptoms.

High doses of hydroxyzine may cause prolongation of the QT interval and obvious changes on the electrocardiogram.

In case of impaired mental status, the administration of other drugs or alcohol should be excluded; if necessary, the patient should be given oxygen inhalation, naloxone, dextrose (glucose) and thiamine. The use of analeptics is not acceptable.

If a vasopressor effect is necessary, norepinephrine or metharaminol should be administered. Epinephrine should not be used. If a significant amount of the drug is ingested, gastric lavage may be performed, preceded by endotracheal intubation.

The use of activated charcoal is possible, but there is insufficient data to indicate its effectiveness. There is no specific antidote. Hemodialysis is not effective.

The literature suggests that if severe, life-threatening, intractable m-cholin-blocking effects develop that are not managed with other drugs, a therapeutic dose of physostigmine may be used. Physostigmine should not be used only to render the patient conscious.

If the patient has taken tricyclic antidepressants, use of physostigmine may provoke seizures and irreversible cardiac arrest. Physostigmine should also be avoided in patients with cardiac conduction disorders.

Similarities