Quentiax, pills 100mg, 60pcs

Composition

1 film-coated tablet,25 mg contains:

Core

Active ingredient:

Quetiapine Fumarate (quetiapine hemifumarate) 28.78 mg (equivalent to quetiapine 25 mg)

Auxiliary substances: lactose monohydrate, calcium hydrophosphate dihydrate, microcrystalline cellulose, type 101, microcrystalline cellulose, type 102, povidone K-25, sodium carboxymethyl starch (type A), magnesium stearate

Film shell

Hypromellose, titanium dioxide (E 171), macrogol-4000, iron oxide yellow dye (E 172), iron oxide red dye (E 172)

1 film-coated tablet,100 mg contains:

Core

Active ingredient:

Quetiapine Fumarate (Quetiapine hemifumarate) 115.13 mg (equivalent to Quetiapine 100 mg)

Auxiliary substances: lactose monohydrate, calcium hydrophosphate dihydrate, microcrystalline cellulose, type 101, microcrystalline cellulose, type 102, povidone K-25, sodium carboxymethyl starch (type A), magnesium stearate

Film shell

Hypromellose, titanium dioxide (E 171), macrogol-4000, iron oxide yellow dye (E 172)

1 film-coated tablet,200 mg/300 mg contains:

Core

Active ingredient:

Quetiapine Fumarate (Quetiapine hemifumarate) 230.26 mg (equivalent to quetiapine 200 mg)/Quetiapine Fumarate (Quetiapine hemifumarate) 345.39 mg (equivalent to Quetiapine 300 mg)

Auxiliary substances: lactose monohydrate, calcium hydrophosphate dihydrate, microcrystalline cellulose, type 101, microcrystalline cellulose, type 102, povidone K-25, sodium carboxymethyl starch (type A), magnesium stearate

Film shell

Hypromellose, titanium dioxide (E 171), macrogol-4000

Pharmacological action

antipsychotic (neuroleptic)

Clinical Pharmacology

Pharmacodynamics

Mechanism of action

Quetiapine is an atypical antipsychotic medication. Quetiapine and its active metabolite N-dealkylquetiapine (norquetiapine) interact with a wide range of brain neutrotransmitter receptors. Quetiapine and N-dealkylquetiapine exhibit high affinity for 5 HT2-serotonin receptors and

_D1-, _D2-dopamine receptors in the brain. Antagonism to these receptors, combined with a higher selectivity to 5 HT2-serotonin receptors than to_D2-dopamine receptors, causes the main clinical antipsychotic properties of quetiapine and a low frequency of extrapyramidal adverse reactions. Quetiapine and norquetiapine do not show significant affinity for benzodiazepine receptors, but they have high affinity for histamine and_α1-adrenergic receptors and moderate affinity for_α2-adrenergic receptors. In addition, quetiapine has no or low affinity for muscarinic receptors, while norquetiapine exhibits moderate or high affinity for several subtypes of muscarinic receptors, which explains the anticholinergic (muscarinic) effects of the drug. Inhibition of the norepinephrine transporter and partial agonism against 5 HT1A-serotonin receptors, manifested by N-dealkylquetiapine, may cause the antidepressant effect of the drug.

Pharmacodynamic effects

Quetiapine has been shown to be active in trials of antipsychotic activity, such as conditioned reflex avoidance. It also blocks the action of dopamine agonists, evaluated either in behavioral or electrophysiological studies, and increases the concentration of the dopamine metabolite, a neurochemical indicator_{of D2}-receptor blockade. The results of studying extrapyramidal symptoms (EPS) in preclinical studies showed that quetiapine differs from standard antipsychotic drugs and has an atypical profile. Quetiapine does not cause hypersensitivity_{of dopamine D2}receptors with prolonged use. Quetiapine causes mild catalepsy at doses that effectively block_D2receptors. Quetiapine selectively affects the limbic system, causing depolarization blockade of mesolimbic, but not nigrostriatal dopaminergic neurons. When administered briefly and for a long time, quetiapine had minimal potential to cause dystonia in capuchin monkeys sensitized to haloperidol or not treated with medication.

Clinical efficacy

Quetiapine is effective against both positive and negative symptoms of schizophrenia.

Quetiapine is effective as monotherapy for moderate to severe manic episodes. There are no data on the long-term use of quetiapine for the prevention of subsequent manic and depressive episodes. Data on the use of quetiapine in combination with seminatria valproate or lithium preparations in moderate to severe manic episodes are limited, but this combination therapy was generally well tolerated. In addition, quetiapine 300 mg and 600 mg is effective in patients with moderate to severe bipolar disorder of type I and II. At the same time, the effectiveness of quetiapine when taken at a dose of 300 mg and 600 mg per day is comparable. Quetiapine is effective in patients with schizophrenia and mania when taking the drug 2 times a day, despite the fact that the half-life of quetiapine is about 7 hours. The effect of quetiapine on the 5 HT2– and D2– receptors lasts up to 12 hours after taking the drug.

When taking quetiapine with dose titration in schizophrenia, the frequency of EPS and concomitant use of m-holinoblockers was comparable to that of placebo. When quetiapine was administered in fixed doses from 75 to 750 mg / day to patients with schizophrenia, the incidence of EPS and the need for concomitant use of m-holinoblockers did not increase.

When quetiapine was administered at doses up to 800 mg/day for the treatment of moderate to severe manic episodes, either as monotherapy or in combination with lithium or seminatria valproate, the incidence of EPS and concomitant use of m-holinoblockers was comparable to that of placebo.

Pharmacokinetics

Suction

Quetiapine is well absorbed from the gastrointestinal tract. Food intake does not significantly affect bioavailability. The equilibrium molar concentration of the active metabolite of N-dealkylquetiapine is 35% of that of quetiapine.

The pharmacokinetics of quetiapine are linear.

Distribution

Approximately 83% of quetiapine binds to plasma proteins.

Metabolism

In vitro studies have shown that the CYP3A4 isoenzyme is a key isoenzyme of quetiapine metabolism mediated by the cytochrome P450 system. N-dealkylquetiapine is formed and eliminated with the participation of the CYP3A4 isoenzyme.

Quetiapine and some of its metabolites (including N-dealkylquetiapine) have weak inhibitory activity against cytochrome P450 isoenzymes 1A2,2C9,2C19,2D6 and 3A4, but only at concentrations 5-50 times higher than those observed at the commonly used effective dose of 300-800 mg / day. Based on the results of in vitro studies, co-use of quetiapine with other drugs should not be expected to result in clinically significant inhibition of cytochrome P450-mediated metabolism of other drugs.

Deduction

The elimination half-lives of quetiapine and N-dealkylquetiapine are approximately 7 and 12 hours, respectively.

Approximately 73% of quetiapine is excreted by the kidneys and 21% by the intestines. Quetiapine is actively metabolized in the liver, less than 5% of quetiapine is not metabolized and is excreted unchanged by the kidneys or through the intestines.

Pharmacokinetics in different groups of patients

Gender

There are no differences in pharmacokinetic parameters in men and women.

Elderly patients

The average clearance of quetiapine in elderly patients is 30-50% lower than in patients aged 18 to 65 years.

Impaired renal function

The average plasma clearance of quetiapine decreases by approximately 25% in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min/1.73 m2), but individual clearance values are within the values found in healthy volunteers.

Impaired liver function

In patients with hepatic insufficiency (compensated alcoholic cirrhosis), the average plasma clearance of quetiapine is reduced by approximately 25%. Since quetiapine is extensively metabolized in the liver, patients with hepatic insufficiency may increase the plasma concentration of quetiapine, which requires dose adjustment.

Indications

For the treatment of schizophrenia.

For the treatment of manic episodes in the structure of bipolar disorder.

For the treatment of depressive episodes of moderate to severe severity in the structure of bipolar disorder.

The drug is not indicated for the prevention of manic and depressive episodes.

Use during pregnancy and lactation

Pregnancy

Published data on use during pregnancy (300-1000 pregnancy outcomes), including isolated reports and observational studies, did not show an increased risk of malformations during treatment. However, it is not possible to draw a definite conclusion based on the available data. Animal studies have revealed the presence of reproductive toxicity. Therefore, during pregnancy, quetiapine can only be used if the expected benefit to the mother justifies the potential risk to the fetus.

When using antipsychotic drugs, including quetiapine, in the third trimester of pregnancy, newborns are at risk of developing adverse reactions of varying severity and duration, including EPS and / or withdrawal syndrome. Agitation, hypertension, hypotension, tremor, drowsiness, respiratory distress syndrome, or feeding disorders have been reported. In this regard, the condition of newborns should be carefully monitored.

Breast-feeding period

The excretion of quetiapine in breast milk has been reported, but the degree of excretion has not been established. Due to the lack of reliable data, it is necessary to decide whether to stop breastfeeding or discontinue Quentiax®.

Contraindications

• Hypersensitivity to any of the components of the drug.
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
• Simultaneous use with cytochrome p450 inhibitors, such as azole antifungal drugs, erythromycin, clarithromycin and nefazodone, as well as with protease inhibitors (see the section “Interaction with other drugs”).
• Breast-feeding period.

Although the efficacy and safety of quetiapine in children and adolescents aged 10-17 years have been studied in clinical trials, the use of Quentiax® in patients under the age of 18 years is not indicated.

Interaction

Caution should be exercised when using Quentiax ® concomitantly with other drugs that affect the central nervous system, as well as with alcohol.

Caution should be exercised in patients taking other cholinergic (muscarinic) receptor antagonists.

The cytochrome P4503A4 isoenzyme is the main isoenzyme responsible for the metabolism of quetiapine, which is carried out through the cytochrome P450 system. In healthy volunteers, co-use of quetiapine (25 mg) with ketoconazole, an inhibitor of the CYP3A4 isoenzyme, resulted in a 5-8-fold increase in the area under the concentration-time curve (AUC) of quetiapine.

Therefore, the simultaneous use of quetiapine and inhibitors of the CYP3A4 isoenzyme is contraindicated. During quetiapine therapy, it is not recommended to eat grapefruit juice.

In a pharmacokinetic study, the use of quetiapine in various dosages before or simultaneously with carbamazepine led to a significant increase in quetiapine clearance and, accordingly, a decrease in AUC, on average, by 13%, compared with quetiapine without carbamazepine. In some patients, the decrease in AUC was even more pronounced. This interaction is accompanied by a decrease in the concentration of quetiapine in plasma and may reduce the effectiveness of quetiapine therapy. Co-use of quetiapine with phenytoin, another inducer of microsomal liver enzymes, was accompanied by an even more pronounced (approximately 450%) increase in quetiapine clearance. The use of quetiapine in patients receiving inducers of microsomal liver enzymes is possible only if the expected benefit of quetiapine therapy exceeds the risk associated with discontinuation of the drug-inducer of microsomal liver enzymes. Changes in the dose of drugs that induce microsomal liver enzymes should be gradual. If necessary, they can be replaced with drugs that do not induce microsomal liver enzymes (for example, valproic acid preparations).

The pharmacokinetics of quetiapine did not significantly change with the simultaneous use of the antidepressant imipramine (an inhibitor of the CYP2D6 isoenzyme) or fluoxetine (an inhibitor of the CYP3A4 and CYP2D6 isoenzymes).

The pharmacokinetics of quetiapine do not significantly change when co-administered with the antipsychotic drugs risperidone or haloperidol. However, concomitant use of quetiapine and thioridazine resulted in an increase in quetiapine clearance by approximately 70%.

The pharmacokinetics of quetiapine do not change significantly with concomitant use of cimetidine.

The pharmacokinetics of lithium preparations do not change with the simultaneous use of quetiapine.

When quetiapine was co-administered with lithium preparations in adult patients with an acute manic episode, there was a higher incidence of adverse reactions associated with EPS (especially tremor), drowsiness, and weight gain compared to patients taking quetiapine with placebo in a 6-week randomized trial.

There were no clinically significant changes in the pharmacokinetics of valproic acid and quetiapine with concomitant use of seminodium valproate and quetiapine.

A retrospective study of children and adolescents who received sodium valproate and quetiapine alone or both drugs simultaneously revealed a higher incidence of leukopenia and neutropenia in the combination therapy group compared to the monotherapy group.

Pharmacokinetic studies on the interaction of Quentiax® with drugs used in cardiovascular diseases have not been conducted.

Caution should be exercised when using quetiapine concomitantly with drugs that may cause electrolyte imbalance and prolong the QT interval.

False-positive results of screening tests for methadone and tricyclic antidepressants by enzyme-linked immunosorbent assay were observed in patients taking quetiapine. To confirm the results of screening, it is recommended to conduct a chromatographic study.

With a single dose of 2 mg of lorazepam while taking quetiapine at a dose of 250 mg 2 times a day, the clearance of lorazepam decreases by about 20%.

Quetiapine did not induce microsomal liver enzymes involved in phenazone metabolism.

How to take, course of use and dosage

Inside,2 times a day, regardless of the meal time.

Adults

Treatment of schizophrenia

The daily dose for the first 4 days of therapy is: day 1-50 mg, day 2-100 mg, day 3-200 mg, day 4-300 mg.

Starting from 4 days, the dose should be selected to be effective, usually in the range of 300-450 mg/day. Depending on the clinical effect and individual tolerability of the drug, the dose may vary from 150 mg / day to 750 mg / day. The maximum recommended daily dose is 750 mg.

Treatment of manic episodes in the structure of bipolar disorder

The drug Quentiax® is recommended as monotherapy or in combination with drugs that have a normothymic effect.

The daily dose for the first 4 days of therapy is: day 1-100 mg, day 2-200 mg, day 3-300 mg, day 4-400 mg. In the future, by the 6th day of therapy, the daily dose of the drug can be increased to 800 mg. The increase in the daily dose should not exceed 200 mg / day. Depending on the clinical effect and individual tolerability of the drug, the dose may vary from 200 mg / day to 800 mg / day. Usually, the effective dose is from 400 mg / day to 800 mg / day. The maximum recommended daily dose is 800 mg.

Treatment of depressive episodes in the structure of bipolar disorder

The drug Quentiax® is prescribed once a day at night. The daily dose for the first 4 days of therapy is: day 1-50 mg, day 2-100 mg, day 3-200 mg, day 4-300 mg. The recommended daily dose is 300 mg. The maximum recommended daily dose of Quentiax® is 600 mg.

The antidepressant effect of quetiapine was confirmed at doses of 300 and 600 mg / day.

Doses exceeding 300 mg should be initiated under the supervision of a physician experienced in the treatment of bipolar disorder. In some patients, if poor drug tolerance is suspected, according to the results of clinical studies, it is possible to reduce the dose to a minimum of 200 mg / day.

Elderly patients

Quentiax®, like other antipsychotics, should be used with caution in elderly patients, especially at the beginning of therapy. The dose should be titrated more slowly, and the daily therapeutic dose should be lower than in younger patients, depending on the clinical response and individual tolerability. The average clearance of quetiapine was reduced by 30-50% in elderly patients compared to younger patients.

Efficacy and safety have not been studied in patients over 65 years of age with depressive episodes in the structure of bipolar disorder.

Patients with renal insufficiency

No dose adjustment is required.

Patients with hepatic insufficiency

Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using Quentiax® in patients with hepatic insufficiency, especially at the beginning of therapy. It is recommended to start therapy with a dose of 25 mg / day and increase the dose daily by 25-50 mg until the effective dose is reached.

Overdose

Symptoms

Symptoms reported in overdose were mainly due to an increase in the known pharmacological effects of quetiapine, such as drowsiness and sedation, tachycardia, decreased blood pressure, and anticholinergic effects.

Overdose may result in prolonged QT interval, seizures, status epilepticus, rhabdomyolysis, respiratory depression, urinary retention, confusion, delirium and / or agitation, coma, and death.

In patients with a history of severe cardiovascular diseases, the risk of developing side effects from overdose may increase (see the section “Special instructions”).

Treatment

There are no specific antidotes to quetiapine. In cases of severe intoxication, you should be aware of the possibility of overdose with several medications. It is recommended to carry out measures aimed at maintaining the function of respiration and the cardiovascular system, ensuring adequate oxygenation and ventilation. There have been published reports of resolution of severe adverse effects from the central nervous system( CNS), including coma and delirium, after intravenous use of physostigmine (at a dose of 1-2 mg) under constant monitoring of an electrocardiogram (ECG). This treatment is not recommended as standard due to the potential negative effects of physostigmine on cardiac conduction. The use of physostigmine is possible only if there are no deviations in ECG indicators. Fizostigmine should not be used in cases of cardiac arrhythmia, blockage of any degree, or expansion of the QRS complex.

In case of refractory hypotension due to an overdose of quetiapine, treatment should be carried out by intravenous fluid use and / or sympathomimetic drugs (epinephrine and dopamine should not be prescribed, since beta-adrenergic stimulation can cause an increased decrease in blood pressure against the background of alpha-adrenergic blockade with quetiapine).

Gastric lavage (after intubation, if the patient is unconscious) and the use of activated charcoal and laxatives may contribute to the elimination of unabsorbed quetiapine, but the effectiveness of these measures has not been studied.

Close medical monitoring should continue until the patient’s condition improves.

Description

Tablets 25 mg

Round, biconvex tablets, covered with a film-coated brownish-red color, with a chamfer.

View at the break: a rough mass of white color with a film shell of brownish-red color.

Tablets 100 mg

Round, biconvex tablets, covered with a film-coated light yellow color.

View at the break: a rough mass of white color with a film shell of light yellow color.

Tablets 200 mg

Round, biconvex tablets, white film-coated tablets.

View at the break: a rough mass of white color with a film shell of white color.

300 mg tablets

Oval, biconvex tablets, covered with a white film coating.

View at the break: a rough mass of white color with a film shell of white color.

Special instructions

Use in patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, use in elderly patients, liver failure, a history of convulsive seizures, the risk of stroke and aspiration pneumonia.

Although the efficacy and safety of quetiapine in children and adolescents aged 10-17 years have been studied in clinical trials, the use of Quentiax® in patients under the age of 18 years is not indicated.

Elderly patients

Quentiax®, like other antipsychotics, should be used with caution in elderly patients, especially at the beginning of therapy. The dose should be titrated more slowly, and the daily therapeutic dose should be lower than in younger patients, depending on the clinical response and individual tolerability. The average clearance of quetiapine was reduced by 30-50% in elderly patients compared to younger patients.

Efficacy and safety have not been studied in patients over 65 years of age with depressive episodes in the structure of bipolar disorder.

Patients with renal insufficiency

No dose adjustment is required.

Patients with hepatic insufficiency

Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using Quentiax® in patients with hepatic insufficiency, especially at the beginning of therapy. It is recommended to start therapy with a dose of 25 mg / day and increase the dose daily by 25-50 mg until the effective dose is reached.

Since Quentiax® has several indications for use, its safety profile is determined depending on the patient’s diagnosis and dose.

Children and adolescents (aged 10 to 17 years)

Quentiax® is not indicated for use in children and adolescents under 18 years of age due to insufficient data on use in this age group. According to the results of clinical studies, some adverse reactions (increased appetite, increased serum prolactin concentration, vomiting, rhinitis and fainting) in children and adolescents, they were observed with a higher frequency than in adult patients, or had other clinical manifestations (EPS and irritability). There was also an increase in blood pressure, which was not observed in adult patients. Changes in thyroid function were also observed in children and adolescents.

The effects on growth, puberty, mental development, and behavioral responses of long-term use (more than 26 weeks) of quetiapine have not been studied.

In placebo-controlled studies in children and adolescents with schizophrenia and mania in the structure of bipolar disorder, the incidence of EPS was higher with quetiapine compared to placebo.

Suicide / suicidal thoughts or clinical deterioration

Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicide-related events). This risk persists until the onset of severe remission. Due to the fact that it may take several weeks or more for the patient’s condition to improve from the start of treatment, patients should be closely monitored until improvement occurs. According to generally accepted clinical experience, the risk of suicide may increase in the early stages of remission.

Patients (especially those at high risk of suicide) and their caregivers should be warned to monitor clinical deterioration, suicidal behavior or thoughts, unusual behavioral changes, and the need to immediately consult a doctor if they occur.

According to short-term placebo-controlled clinical trials in patients with depression in bipolar disorder, the risk of developing suicide-related events was 3.0% (7/233) for quetiapine and 0% (0/120) for placebo in patients aged 18-24 years,1.8% (19/1616) for quetiapine and 1.8% (11/622) for placebo in patients older than 25 years. A population-based retrospective study of quetiapine use in patients with major depressive disorder found an increased risk of self-harm and suicide attempts in patients aged 25 to 64 years without a history of self-harm taking quetiapine with other antidepressants.

Other psychiatric disorders that quetiapine is used to treat are also associated with an increased risk of suicide-related events. In addition, such conditions may be comorbid with a depressive episode. Thus, the precautions used in the treatment of patients with a depressive episode should also be taken in the treatment of patients with other mental disorders.

When quetiapine therapy is abruptly discontinued, the potential risk of suicide-related events should be taken into account.

Patients with a history of suicidal events, as well as patients who clearly express suicidal thoughts before starting therapy, are at an increased risk of suicidal intentions and suicide attempts and should be carefully monitored during treatment. A meta-analysis of placebo-controlled antidepressant trials conducted by the FDA (Food and Drug use, USA), summarizing data from approximately 4,400 children and adolescents and 7,700 adult patients with mental disorders, found an increased risk of suicidal behavior with antidepressants compared to placebo in children, adolescents and adults under 25 years of age. This meta-analysis does not include studies where quetiapine was used (see section “Pharmacodynamics”).

According to short-term placebo-controlled studies, for all indications and in all age groups, the incidence of suicide-related events was 0.8% for both quetiapine (76/9327) and placebo (37/4845).

In these studies, in patients with schizophrenia, the risk of suicide-related events was 1.4% (3/212) for quetiapine and 1.6% (1/62) for placebo in patients aged 18-24 years,0.8% (13/1663) for quetiapine and 1.1% (5/463) for placebo in patients over 25 years of age,1.4% (2/147) for quetiapine and 1.3% (1/75) for placebo in patients under 18 years of age.

In patients with mania in bipolar disorder, the risk of suicide events was 0% (0/60) for quetiapine and 0% (0/58) for placebo in patients aged 18-24 years,1.2% (6/496) for quetiapine and 1.2% (6/503) for placebo in patients over 25 years,1.0% (2/193) for quetiapine and 0% (0/90) for placebo in patients under 18 years.

Metabolic disorders

Given the risk of deterioration of the metabolic profile, including changes in body weight, glucose and lipid concentrations in blood plasma observed during clinical studies, patients ‘ metabolic parameters should be evaluated at the beginning of therapy and should be regularly monitored during therapy. If these indicators worsen, appropriate treatment should be taken.

Extrapyramidal symptoms

There was an increase in the incidence of EPS when taking quetiapine in adult patients with a major depressive episode in the structure of bipolar disorder or major depressive disorder compared to placebo (see the section “Side effects”).

Quetiapine use was associated with the development of akathisia, which was characterized by subjectively unpleasant restlessness or anxiety, and was often accompanied by an inability to sit or stand still. Such phenomena are most often observed in the first few weeks of treatment. Increasing the dose to patients who develop such symptoms may have a negative impact.

Tardive dyskinesia

If symptoms of tardive dyskinesia develop, it is recommended to reduce the dose of the drug or gradually cancel it. Symptoms of tardive dyskinesia may increase or even occur after discontinuation of the drug (see section “Side effects”).

Drowsiness and dizziness

During quetiapine therapy, drowsiness and related symptoms may occur, such as sedation (see section “Side effects”). In clinical studies involving patients with depression in the structure of bipolar disorder and with a depressive episode, drowsiness usually developed during the first three days of therapy. The severity of this adverse reaction was generally mild or moderate. If severe drowsiness develops, patients with depression in the structure of bipolar disorder and patients with a depressive episode may need more frequent visits to the doctor within 2 weeks from the onset of drowsiness or until the severity of symptoms decreases. In some cases, quetiapine therapy may need to be discontinued.

During quetiapine therapy, orthostatic hypotension and dizziness may occur (see section “Side effects”), usually during dose selection at the beginning of therapy. Patients, especially the elderly, should be careful to avoid accidental injuries (falls).

Patients with cardiovascular diseases

Caution should be exercised when using quetiapine in patients with cardiovascular, cerebrovascular diseases and other conditions predisposing to arterial hypotension. In such patients, dose selection should be carried out more slowly. Orthostatic hypotension may occur during quetiapine therapy, especially during dose selection at the beginning of therapy. If orthostatic hypotension occurs, it may be necessary to reduce the dose or adjust it more gradually.

Sleep apnea syndrome

Patients taking quetiapine experienced sleep apnea syndrome. In patients taking concomitant medications that depress the central nervous system, or who have a history of sleep apnea (for example, in overweight/obese patients, male patients), quetiapine should be used with caution.

Convulsive seizures

There was no difference in the incidence of seizures in patients taking quetiapine or placebo. However, as with other antipsychotic medications, caution is recommended when treating patients with a history of seizures (see section “Side effects”).

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome may develop while taking antipsychotic medications, including quetiapine (see section “Side effects”). Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, lability of the autonomic nervous system, and increased creatine phosphokinase activity. In such cases, it is necessary to stop taking quetiapine and conduct appropriate treatment.

Severe neutropenia and agranulocytosis

In short-term placebo-controlled clinical trials of quetiapine monotherapy, cases of severe neutropenia (neutrophil count) were infrequently reported. Agranulocytosis (severe neutropenia associated with infections) has been reported in patients treated with quetiapine in clinical trials (rarely), as well as with post-marketing use (including fatal outcomes). Most of these cases of severe neutropenia occurred within 2 months of starting quetiapine therapy. No dose-dependent effect was detected. Leukopenia and / or neutropenia resolved after quetiapine therapy was discontinued. A possible risk factor for neutropenia is a previous reduced white blood cell count and a history of drug-induced neutropenia. The development of agranulocytosis was also observed in patients without risk factors. Consideration should be given to the possibility of developing neutropenia in patients with infection, especially in the absence of obvious predisposing factors, or in patients with unexplained fever, and these cases should be managed in accordance with clinical guidelines.

In patients with neutrophil counts The patient should be monitored for possible symptoms of infection and the number of neutrophils should be monitored (until their number increases to 1.5 x 109/l).

Patients should be informed and immediately report any signs/symptoms of agranulocytosis or infection (e. g. fever, weakness, lethargy, sore throat) throughout treatment with Quentiax®.

Anticholinergic (muscarinic) effects

Norquetiapine, an active metabolite of quetiapine, exhibits moderate to high affinity for several subtypes of muscarinic receptors, which explains the development of NLR due to the anticholinergic effect when quetiapine is used at the recommended doses, with the simultaneous use of other anticholinergic drugs, as well as in overdose. Caution should be exercised when using quetiapine in patients taking cholinergic (muscarinic) receptor antagonists, as well as in patients with urinary retention, including in the anamnesis, clinically significant prostatic hypertrophy, intestinal obstruction or related conditions, with increased intraocular pressure or angle-closure glaucoma.

Interaction with other medicinal products

Also see the section “Interaction with other medicinal products”.

Concomitant use of quetiapine with potent inducers of microsomal liver enzymes, such as carbamazepine and phenytoin, reduces the concentration of quetiapine in blood plasma and may reduce the effectiveness of therapy with Quentiax®.

The use of Quentiax® in patients receiving inducers of microsomal liver enzymes is possible only if the expected benefit of therapy with the drug exceeds the risk associated with the withdrawal of inducers of microsomal liver enzymes. Changes in the dose of inducers of microsomal liver enzymes should be gradual. If necessary, they can be replaced with drugs that do not induce microsomal liver enzymes (for example, valproic acid preparations).

Body weight

While taking quetiapine, an increase in body weight was noted. Clinical observation of patients is recommended in accordance with the accepted standards of therapy (see the section “Side effects”).

Hyperglycemia

While taking quetiapine, hyperglycemia and/or the development and exacerbation of diabetes mellitus may occur, sometimes accompanied by the development of ketoacidosis or coma, including with a fatal outcome. In some cases, there was a previous increase in body weight, which may be a predisposing factor. Regular monitoring of body weight and hyperglycemic symptoms, such as polydipsia, polyuria, polyphagia, and weakness, is recommended in patients taking antipsychotics, including quetiapine. Clinical monitoring of patients with diabetes mellitus and patients with risk factors for developing diabetes mellitus is recommended (see the section “Side effects”).

Lipid concentration

While taking quetiapine, it is possible to increase the concentration of triglycerides, total cholesterol and LDL cholesterol, as well as a decrease in the concentration of HDL in blood plasma (see the section “Side effects”). These changes should be adjusted in accordance with the current recommendations.

Prolongation of the QT interval

There was no correlation between quetiapine intake and a persistent increase in the absolute value of the QT interval. However, prolongation of the QT interval was observed with the use of quetiapine in therapeutic doses and with an overdose of quetiapine (see the section “Overdose”). Caution should be exercised when using quetiapine, as well as other antipsychotic drugs, in patients with cardiovascular diseases and with a history of prolongation of the QT interval. Caution should also be exercised when using quetiapine concomitantly with drugs that prolong the QT interval_. other antipsychotics, especially in the elderly, in patients with congenital QT prolongation syndrome, chronic heart failure, myocardial hypertrophy, hypokalemia or hypomagnesemia (see the section “Interaction with other drugs”).

Cardiomyopathy and myocarditis

During clinical trials and post-marketing use, cases of cardiomyopathy and myocarditis were noted, but a causal relationship with taking the drug was not established. The feasibility of quetiapine therapy in patients with suspected cardiomyopathy or myocarditis should be evaluated.

Acute reactions associated with drug withdrawal

When quetiapine is abruptly discontinued, the following acute reactions (withdrawal syndrome) may occur – nausea, vomiting, insomnia, headache, dizziness, and irritability. Therefore, discontinuation of Quentiax® is recommended gradually over a period of at least one or two weeks.

Elderly patients with dementia

Quentiax® is not indicated for the treatment of dementia-related psychoses. Some atypical antipsychotics in randomized placebo-controlled trials increased the risk of developing cerebrovascular complications in patients with dementia by about 3 times. The mechanism of this increased risk has not been studied. A similar risk of increased incidence of cerebrovascular complications cannot be excluded for other antipsychotic medications or other patient groups. Quentiax® should be used with caution in patients at risk of stroke.

An analysis of the use of atypical antipsychotics for the treatment of dementia-related psychoses in elderly patients revealed an increase in the mortality rate in the group of patients treated with this group, compared with the placebo group. Two 10-week placebo-controlled trials of quetiapine in a similar group of patients (n=710, mean age: 83 years, age range: 56-99 years) showed that the mortality rate in the quetiapine-treated group was 5.5%, and 3.2% in the placebo group. The causes of deaths reported in these patients were consistent with those expected for this population. There was no causal relationship between quetiapine treatment and the risk of increased mortality in elderly patients with dementia.

Elderly patients with Parkinson’s disease/parkinsonism

A population-based retrospective study of the use of quetiapine in patients with major depressive disorder revealed an increased risk of death in patients aged > 65 years. The increased risk was not determined when patients with Parkinson’s disease were excluded from the analysis. Caution should be exercised when prescribing quetiapine to elderly patients with Parkinson’s disease.

Dysphagia

Dysphagia (see section “Side effects”) and aspiration were observed during quetiapine therapy. A causal relationship between the occurrence of aspiration pneumonia and quetiapine has not been established. However, caution should be exercised when using Quentiax® in patients at risk of aspiration pneumonia.

Constipation and bowel obstruction

Constipation is a risk factor for bowel obstruction. Constipation and bowel obstruction have been reported with quetiapine (see section “Side effects”), including fatal cases in patients at high risk of bowel obstruction, including those receiving multiple concomitant medications that reduce bowel motility, even in the absence of constipation complaints. Patients with intestinal obstruction / ileus require urgent measures and close monitoring.

Venous thromboembolism

Cases of venous thromboembolism have been reported while taking neuroleptics. Risk factors should be assessed and preventive measures taken before and during therapy with antipsychotic drugs, including quetiapine.

Pancreatitis

Cases of pancreatitis have been reported during clinical trials and post-marketing use, but no causal relationship with the drug has been established. Post-marketing reports indicate that many patients present with risk factors for pancreatitis, such as elevated triglyceride concentrations (see section “Lipid concentrations”), cholelithiasis, and alcohol use.

Liver disorders

If jaundice develops, quetiapine should be discontinued.

Additional information

There are limited data on the concomitant use of quetiapine with divalproate or lithium in acute moderate or severe manic episodes. Good tolerability of this combination therapy and an additive effect at 3 weeks of treatment were noted.

Misuse and abuse

Cases of misuse and abuse have been reported. Caution should be exercised when prescribing quetiapine to patients with a history of alcohol or drug abuse.

Special information on excipients

Quentiax ® contains lactose, so it should not be used in the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

The drug Quentiax® can cause drowsiness, so during treatment, patients are not recommended to work with mechanisms that require increased concentration of attention, including driving vehicles.

Form of production

Film-coated tablets,25 mg,100 mg,200 mg,300 mg.

10 tablets each in a contour cell pack (blister) made of PVC and aluminum foil.

3,6 or 9 contour cell packages (blisters) together with the instructions for use are placed in a cardboard pack.

Storage conditions

During production at KRKA-RUS LLC, Russia:

At a temperature not exceeding 25 ° C, in the original packaging (contour cell packaging).

During production at JSC “KRKA, D. D., Novo Mesto”, Slovenia:

At a temperature not exceeding 25 ° C, in the original packaging (blister).

Keep out of reach of children.

Shelf

life is 5 years.

Do not use the drug after the expiration date.

Active ingredient

Quetiapine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets