Hydroxyzine Canon pills 25mg, 25pcs

Composition

1 film-coated tablet contains: :

Active ingredient:

hydroxyzine hydrochloride 25 mg;

excipients:

pre-gelatinized corn starch 30 mg,

colloidal silicon dioxide 0.7 mg,

magnesium stearate 1 mg,

mannitol 40 mg,

microcrystalline cellulose 33.3 mg;

composition of the film shell:

 opadray white – 4 mg, including: hypromellose (hydroxypropylmethylcellulose) 1.35 mg, hyprolose (hydroxypropylcellulose) 1.35 mg, talc 0.8 mg, titanium dioxide 0.5 mg

Pharmacological action

Pharmacotherapy group:

anxiolytic agent (tranquilizer)

ATX Code: [N05BB01]

Pharmacological properties

Pharmacodynamics

Hydroxyzine is a blocker of H1-histamine receptors of the first generation, a derivative of phenothiazine with antimuscarinic and sedative properties and diphenylmethane, helps to inhibit the activity of certain subcortical zones.

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

Hydroxyzine has a positive effect on cognitive abilities, improves attention and memory. Hydroxyzine is not addictive and does not cause mental dependence, with prolonged use of withdrawal syndrome was not noted. Hydroxyzine is able to depress the central nervous system, also has an anticholinergic, antihistamine, antispasmodic, local anesthetic, sympatholytic effect, and has muscle relaxant activity.

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

Polysomnography in patients with insomnia and anxiety shows an extension of sleep duration, a decrease in the frequency of nighttime awakenings after taking a single or repeated dose of hydroxyzine 50 mg. A decrease in muscle tension in patients with anxiety was noted when taking the drug at a dose of 50 mg 3 times a day. H1-histamine blocking effect occurs approximately 1 hour after ingestion of tablets. The sedative effect appears after 30-45 minutes.

Pharmacokinetics.

Suction:  Absorption is high. The time to reach the maximum concentration (TMAX) after oral use is 2 hours. After taking an average dose of 50 mg, 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 use, hydroxyzine penetrates well into the skin, while the concentrations of hydroxyzine in the skin are much higher than those in the blood serum after both single and multiple doses. The plasma concentration of hydroxyzine does not necessarily reflect its binding to tissues or distribution in 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.

Deduction:  The half-life (T1/2) in adults is 14 hours (range: 7-20 hours). 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 in unchanged form (25% of the accepted dose of hydroxyzine).

Pharmacokinetics in special groups of patients.

In elderly patients, T 1/2 was 29 hours in elderly patients. The volume of distribution is 22.5 l/kg. It is recommended to reduce the daily dose of hydroxyzine when prescribed to elderly patients.

Children under 1 year of age 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 of age

The elimination half-life is 11 hours.

In patients with hepatic insufficiency

In patients with secondary liver dysfunction due to primary biliary cirrhosis, the total clearance was approximately 66% of the value recorded in healthy volunteers. In patients with liver diseases, T 1/2 increased to 37 hours, and the concentration of metabolites in the blood serum was higher than in young patients with normal liver function. Patients with hepatic insufficiency are recommended to reduce the daily dose or frequency of use.

In patients with renal insufficiency

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

Indications

• Symptomatic treatment of anxiety in adults.
• As a sedative during premedication.
• Symptomatic treatment of pruritus of allergic origin

Contraindications

• Hypersensitivity to any of the components of the drug, cetirizine and other piperazine derivatives, aminophylline or ethylenediamine;
• porphyria;
• children under 3 years of age;
• pregnancy, childbirth and breastfeeding.

With caution:  myasthenia gravis, prostatic hyperplasia with clinical manifestations, difficulty urinating, constipation, glaucoma, dementia, convulsive disorders, including epilepsy, with a tendency to arrhythmia, including electrolyte imbalance (hypokalemia, hypomagnesemia), in patients with a history of heart disease (with heart failure and arterial hypertension) or when using drugs that can cause arrhythmia, with hyperthyroidism. Hydroxyzine contributes to a decrease in gastrointestinal motility, the development of stenosing peptic ulcer, and respiratory disorders.

Side effects

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

WHO classification of frequency of side effects: very often – >1/10 appointments (>>10%)common – >1/100 to >< 1/10 appointments (>1% and < 1/10 appointments (><10%) uncommon – >1/1000 to <10%) uncommon – ><1/100 appointments (>0.1% and <1/100 appointments (><1%) rare – >1/10000 to <1%) rare – ><1/1000 appointments (>0.01% and <1/1000 appointments (>very rare – <1/10000 appointments (

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

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

Nervous system disorders: infrequently: dizziness, insomnia, tremor; rarely: convulsions, dyskinesia.

Mental disorders: infrequently: agitation, confusion; rarely: hallucinations, disorientation.

Visual disturbances: rare: accommodation disorders, visual disturbances.

Cardiac disorders: rare: tachycardia; frequency unknown: prolongation of the QT interval on the electrocardiogram, ventricular tachycardia of the “pirouette” type.

Vascular disorders: rare: low blood pressure.

Respiratory, thoracic and mediastinal disorders: very rare: bronchospasm.

Disorders of the gastrointestinal tract: infrequently: nausea; rarely: vomiting, constipation.

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

Kidney and urinary tract disorders: rare: delayed urination.

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

Common disorders: rarely: hyperthermia, malaise.

The following side effects were observed when taking cetirizine, the main metabolite of hydroxyzine: thrombocytopenia, aggression, depression, tic, dystonia, paresthesia, oculohiric crisis, diarrhea, dysuria, enuresis, asthenia, edema, weight gain and can be observed when taking hydroxyzine.

Interaction

It is necessary to take into account 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 (MAO) inhibitors and holinoblockers should be avoided. The drug interferes with the pressor action of epinephrine and the anticonvulsant activity of phenytoin, and also interferes with the action of betahistine and cholinesterase inhibitors.

It was found that the use of cimetidine at a dose of 600 mg twice a day increases the concentration of hydroxyzine in serum by 36% and reduces the maximum concentration of the cetirizine metabolite by 20%.

The effect of atropine, belladonna alkaloids, cardiac glycosides, antihypertensive agents, and H2-histamine receptor blockers does not change under the action of hydroxyzine. Hydroxyzine is an inhibitor of the CYP2D6 isoenzyme and may cause drug interactions with CYP2D6 substrates in high doses.

Since hydroxyzine is metabolized in the liver, an increase in its concentration in blood plasma can be expected when used simultaneously with inhibitors of microsomal liver enzymes.

Since hydroxyzine is metabolized by alcohol dehydrogenase and the CYP3A4/5 isoenzyme, it is possible to increase the concentration of hydroxyzine in blood plasma when used simultaneously with drugs that potentially inhibit the CYP3A4/5 isoenzyme (telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, intraconazole, posaconazole and some HIV protease inhibitors including atazanavir, indinavir, nelfinavir, ritonavir, saquinarin, lopinavir/ritonavir, saquinarin/ritonavir, and tipranavir/ritonavir).

However, the inhibition of one metabolic pathway may be partially compensated by the work of another. Concomitant use of hydroxyzine with medications that may potentially cause arrhythmia may increase the risk of prolongation of the QT interval and the occurrence of ventricular tachycardia of the “pirouette”type.

The use of the drug simultaneously with agents that have an ototoxic effect, for example gentamicin, can mask such symptoms of ototoxicity as dizziness. The drug should be discontinued 3 days before the planned skin tests with allergens.

How to take, course of use and dosage

The drug is used internally.

For adults:

For symptomatic treatment of anxiety: the standard dose is 50 mg per day, 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 case of anxiety in severe cases, the drug is used in a dose of 50-100 mg 4 times a day.

For the symptomatic treatment of pruritus of allergic origin: the initial dose is 1 tablet (25 mg) before bedtime, if necessary, the dose can 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).

For children:For the symptomatic treatment of pruritus of allergic origin:At the age of 3 to 6 years: from 1.0 mg / kg / day to 2.5 mg / kg/day in several doses. At the age of 6 years and older: from 1.0 mg / kg / day to 2.0 mg / kg/day in several doses.

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

Use in special patient groups:When used in the elderly, the dose is selected individually, taking into account concomitant diseases in the recommended dose range (see section Pharmacokinetics).

Use in patients with renal insufficiency and impaired liver function:Patients with severe and moderate renal insufficiency, as well as with hepatic insufficiency, should reduce the dose. In patients with hepatic insufficiency, it is recommended to reduce the daily dose by 33%. In patients with severe and moderate renal insufficiency, the drug is used in a half dose due to a decrease in the excretion of the main metabolite of hydroxyzine — cetirizine.

Overdose

Symptoms of CNS toxicity are associated with excessive m-cholinoblocking, suppression or paradoxical stimulation of the central nervous system. These symptoms include nausea, vomiting, tachycardia, hyperthermia, drowsiness, impaired pupillary reflex, tremor, confusion, or hallucinations.

Subsequently, depression of consciousness, breathing, convulsions, decreased blood pressure, and arrhythmia may develop. Possible worsening of the comatose state and cardiopulmonary collapse.

Treatment: It is necessary to monitor the state of the respiratory tract, the state of respiration and blood circulation using Electrocardiographic (ECG) monitoring, to ensure adequate oxygenation. Heart activity and blood pressure should be monitored within 24 hours after symptoms disappear.

In high doses, hydroxyzine can lead to prolongation of the QT interval and obvious changes in the electrocardiogram.

In case of a mental disorder, it is necessary to exclude the use of other drugs or alcohol, if necessary, the patient should be inhaled with oxygen, enter naloxone, dextrose (glucose) and thiamine. The use of analeptics is not allowed.

If it is necessary to obtain a vasopressor effect, norepinephrine or metaraminol is prescribed. Do not use epinephrine. In the case of ingestion of a significant amount of the drug, gastric lavage can be performed with previous endotracheal intubation.

It is possible to use activated carbon, but there is insufficient evidence of its effectiveness. There is no specific antidote. Hemodialysis is not effective.

Literature data indicate that in the case of severe, life-threatening, difficult-to-treat m-holinoblocking effects that are not stopped by other drugs, it is possible to use a therapeutic dose of physostigmine. Physostigmine should not be used only to bring the patient to consciousness.

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

Special instructions

When used concomitantly with drugs that have m-holinoblocking properties and drugs that depress the central nervous system, the dose of hydroxyzine should be reduced.

Hydroxyzine can lead to prolongation of the QT interval on the electrocardiogram, so simultaneous use with other drugs that can disrupt cardiac activity may increase the risk of arrhythmias.

It is assumed that other drugs that cause changes in the electrocardiogram (atropine, antiparkinsonian agents, lithium carbonate, quinidine, phenothiazines, procainamide, tricyclic antidepressants, thioridazine) can aggravate and increase the changes that can be caused by hydroxyzine, and increase the risk of sudden death.

Concomitant use of two or more drugs that prolong the QT interval should be avoided because of the risk of additive effects that can lead to potentially life-threatening and severe cardiac arrhythmias. In case of renal and/or hepatic insufficiency, the dose should be reduced.

In the elderly, the dosage should be selected individually, starting with half the minimum dose, and adjusting in the recommended dose range. If it is necessary to set up allergological tests or conduct a methacholine test, taking the drug Hydroxyzine Canon should be stopped 5 days before the study to prevent obtaining distorted data.

Alcohol should be avoided during treatment with Hydroxyzine Canon.

Influence on the ability to drive vehicles and mechanisms

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

Therefore, you should refrain from driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Product form

round, biconvex tablets with a risk, coated with a white film coating. The cross-section is almost white in color.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf life

2 years

Active ingredient

Hydroxyzine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Mental Disorders