Quetiapine-SZ - instructions for use, dose, side effects, contraindications

auxiliary substances (core): cellulose microcrystalline - 60, 0 mg, lactose monohydrate (sugar milk) - 44.0 mg, povidone (polyvinylpyrrolidone medium molecular weight) - 9.0 mg, croscarmellose sodium (impellose) - 10.5 mg, magnesium stearate 1.5 mg ;

auxiliary substances (shell): Opadrai II (polyvinyl alcohol, partially hydrolyzed 2.0 mg, macrogol 3350-1.01 mg, talc 0.74 mg, titanium dioxide E 171 1.1333 mg, iron oxide dye yellow (II) yellow E 172, 0.1167 mg).

dosage of 100 mg:

active substance: quetiapine fumarate, in terms of quetiapine - 100 mg;

auxiliary substances (core): microcrystalline cellulose - 40.0 mg, lactose monohydrate (sugar milk) - 32.0 mg, povidone (polyvinylpyrrolidone medium molecular weight) - 12.0 mg, croscarmellose sodium (impellose) - 14.0 mg, magnesium stearate 2.0 mg ;

auxiliary substances (shell): Opadrai II (alcohol polyvinyl, partially hydrolyzed - 2.4 mg, macrogol (polyethylene glycol) 3350 - 1.212 mg, talc - 0.888 mg, titanium dioxide E 171 - 1.3122 mg, aluminum lacquer based on indigocarmine - 0.0012 mg, dye iron oxide (II) yellow E 172 - 0.0018 mg, Aluminum lacquer based on yellow quinoline - 0.1806 mg. aluminum lacquer based on a yellow sunset sunset - 0.0042 mg).

dosage of 200 mg:

active substance: quetiapine fumarate, in terms of quetiapine - 200 mg;

auxiliary substances (core): cellulose microcrystalline - 5.60 mg. lactose monohydrate (sugar milk) - 44.5 mg, povidone (polyvinylpyrrolidone medium-molecular) - 21.0 mg, croscarmellose sodium (impellosis) - 25.0 mg, magnesium stearate - 3.5 mg;

auxiliary substances (shell): Opadrai II (alcohol polyvinyl, partially hydrolyzed - 4.4 mg, macrogol (polyethylene glycol) 3350 1.235 mg talc 2.0 mg, titanium dioxide E 171 1.917 mg, soy lecithin E 322 0.35 mg, aluminum lacquer based on indigo carmine - 0,006 mg, aluminum varnish based on dye azorubin - 0.051 mg, aluminum varnish based on the dye of the crimson [Ponso 4R] - 0.041 mg).

Description:

Dosage of 25 mg. The tablets covered with a film cover from beige-yellow to beige color, round, biconcave.Tablets on a cross-section of white or almost white color.

Dosage of 100 mg. The tablets covered with a film cover of yellow color, round, biconcave. Tablets on a cross-section of white or almost white color.

Dosage 200 mg. The tablets covered with a film cover of pink color, round, biconcave. Tablets on a cross-section of white or almost white color.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.04 Quetiapine

Pharmacodynamics:

Mechanism of action

Quetiapine is an atypical antipsychotic. Quetiapine and its active metabolite N-dealkyl quetiapine interact with neurotransmitter receptors of the brain. Quetiapine and N-dealkyl quetiapine show a high affinity for serotonin receptors such as 5HT₂ and dopamine type receptors D₁ and D₂brain. Higher selectivity for serotonin 5HT receptors₂, than to dopamine receptors of the type D₂, causes the main clinical antipsychotic properties of quetiapine and a low incidence of extrapyramidal side effects. Besides, N-dealkyl quetiapine shows a high affinity for the carrier of norepinephrine. Quetiapine and N-dealkyl quetiapine have a high affinity for histamine and α₁adrenoreceptors and a lower affinity for α₂-adrenoceptors and serotonin receptors of the type 5NT₁.

Quetiapine shows no significant affinity for cholinergic muscarinic and benzodiazepine receptors.

In standard tests quetiapine has antipsychotic activity. The specific contribution of the metabolite N-dealkyl quetiapine in the pharmacological activity of quetiapine is not established.

The results of the study of extrapyramidal symptoms (EPS) in animals revealed that quetiapine causes a weak catalepsy in doses effectively blocking D₂ receptors. Quetiapine causes a selective decrease in the activity of mesolimbic A10 dopaminergic neurons in comparison with A9 nigrostriate neurons involved in motor function.

Efficiency

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

Quetiapine is effective as a monotherapy in manic episodes from moderate to severe severity.Data on the long-term use of quetiapine for the prevention of subsequent manic and depressive episodes are absent. Data on the use of quetiapine in combination with valproate semiotrium or lithium preparations for moderate to severe manic episodes are limited, but this combination therapy was generally well tolerated. Besides, Quetiapine at a dose of 300 mg and 600 mg is effective in patients with type I and II bipolar disorder from moderate to severe severity. In this case, the effectiveness of quetiapine when taken in 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 5HT type receptors₂ and D₂ lasts up to 12 hours after taking the drug.

Quetiapine does not cause a prolonged increase in the concentration of prolactin in the blood plasma. In studies with different fixed doses of the drug, no difference in the level of prolactin was observed with the use of quetiapine or placebo. The level of prolactin when using different fixed doses of quetiapine did not differ from the level of prolactin when taking placebo.

When taking quetiapine with a titration dose in schizophrenia, the frequency of EPS and the concomitant use of anticholinergic drugs was comparable to that of placebo. In appointing quetiapine at fixed doses from 75 to 750 mg / day in patients with schizophrenia, the frequency the occurrence of EPS and the need for concomitant use of anticholinergic drugs did not increase.

With the use of quetiapine in doses up to 800 mg / day for the treatment of moderate to severe manic episodes, either as monotherapy or in combination with lithium preparations or valproate semitrium, the incidence of EPS and the concomitant use of anticholinergic drugs was comparable to that of placebo .

Pharmacokinetics:

When administered orally quetiapine Chorone is absorbed from the gastrointestinal tract and is actively metabolized in the liver.

The intake of food does not significantly affect the bioavailability of quetiapine. Approximately 83% of quetiapine binds to plasma proteins.

The equilibrium molar concentration of the active metabolite N-Dealkyl quetiapine is 35% of that of quetiapine. The half-life of quetiapine and N-Dealkyl quetiapine is about 7 and 12 hours, respectively. The pharmacokinetics of quetiapine and N-Dealkyl quetiapine is linear, there are no differences in pharmacokinetic parameters in men and women.

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

The average plasma clearance of quetiapine is reduced by approximately 25% in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min / 1.73 m²), but individual clearance rates are within the values found in healthy volunteers. In patients with hepatic insufficiency (compensated alcoholic cirrhosis), the mean plasma clearance of quetiapine is reduced by approximately 25%. Because the quetiapine is intensively metabolized in the liver, in patients with hepatic insufficiency it is possible to increase the plasma concentration of quetiapine, which requires a dose adjustment.

On average, less than 5% of the molar dose of the fraction of free quetiapine and N-dezalkil quetiapine plasma is excreted in the urine. Approximately 73% of quetiapine is excreted in urine and 21% with feces. Less than 5% of quetiapine is not metabolized and is excreted unchanged by kidneys or feces.

Determined that CYP3A4 is the key isoenzyme of quetiapine metabolism, mediated by cytochrome P450. N-dealkyl quetiapine is formed with the participation of isoenzyme CYP3A4.

Quetiapine and some of its metabolites (including N-dealkyl quetiapine) have a weak inhibitory activity against cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6 and 3A4, but only at a concentration of 5-50 times the concentration observed at the usual effective dosage of 300-800 mg / day.

Based on the results in vitro, it should not be expected that simultaneous administration of quetiapine with other drugs will lead to a clinically pronounced inhibition of the metabolism of other medicaments mediated by cytochrome P450.

Indications:

- Treatment of schizophrenia.

- Treatment of manic episodes in the structure of bipolar disorder.

- Treatment of depressive episodes from medium to severe severity in the structure of bipolar disorder.

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

Contraindications:

Hypersensitivity to any of the components of the drug, including lactase deficiency, glucose-galactose malabsorption and galactose intolerance.

Co-administration with cytochrome P450 inhibitors, such as antifungal agents of the azole group, erythromycin, clarithromycin and nefazodone, as well as protease inhibitors (see section "Interaction with other drugs").

Despite the fact that the efficacy and safety of quetiapine in children and adolescents aged 10-17 years have been studied in clinical studies, the use of quetiapine in patients under the age of 18 years is not indicated.

Carefully:

In patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, elderly age, hepatic insufficiency, convulsive fits in the anamnesis.

Pregnancy and lactation:

The safety and effectiveness of quetiapine in pregnant women have not been established. Therefore, during pregnancy Quetiapine It can only be used if the expected benefit for a woman justifies the potential risk to the fetus.

The degree of excretion of quetiapine with human milk is not known. Women should be advised to avoid breastfeeding while taking quetiapine.

Dosing and Administration:

Quetiapine can be used regardless of food intake.

Adults

Treatment of sheaophrenia

Quetiapine is administered twice a day. The daily dose for the first 4 days of therapy is: 1st day - 50 mg, 2nd day - 100 mg, 3rd day - 200 mg, 4th day - 300 mg.

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

Treatment of manic episodes in the structure of bipolar disorder Quetiapine is used as a monotherapy or in combination with drugs that have a normotimic effect.

Quetiapine is administered twice a day. The daily dose for the first 4 days of therapy is: 1st day - 100 mg, 2nd day - 200 mg, 3rd day - 300 mg, 4th day - 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 per day.

Depending on the clinical effect and individual tolerability, the dose may vary from 200 to 800 mg / day. Usually the effective dose is from 400 to 800 mg / day.The maximum recommended daily dose is 800 mg.

Treatment of depressive episodes in the structure of bipolar disorder Quetiapine is prescribed once a day at night. The daily dose for the first 4 days of therapy is: 1st day - 50 mg, 2nd day - 100 mg, 3rd day - 200 mg, 4th day - 300 mg. The recommended dose is 300 mg / day. The maximum recommended daily dose of quetiapine is 600 mg.

The antidepressant effect of quetiapine was confirmed when used at a dose of 300 and 600 mg / day. With short-term therapy, the effectiveness of quetiapine in doses of 300 and 600 mg / day. was comparable (see the section "Pharmaco dynamics").

Elderly

In elderly patients, the initial dose of quetiapine is 25 mg / day. The dose should be increased daily by 25-50 mg until an effective dose is obtained, which is likely to be less than in young patients.

Patients with renal insufficiency

A dose adjustment is not required.

Patients with hepatic insufficiency

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

Side effects:

The most common side effects of quetiapine are drowsiness, dizziness, dry mouth, mild asthenia, constipation, tachycardia, orthostatic hypotension and dyspepsia.

The use of quetiapine, like other antipsychotics, may be accompanied by weight gain, fainting, malignant neuroleptic syndrome, leukopenia, neutropenia, and peripheral edema.

The frequency of adverse reactions is given in the following gradation: very often (≥ 1/10); often (≥ 1/100, <1/10); infrequently (≥ 1/1000, <1/100); rarely (≥ 1/10 000, <1/1000); very rarely (<1 / 10,000), frequency, unspecified.

Often (≥ 1/10)
From the central nervous system:	dizziness⁴, drowsiness², headache
From the gastrointestinal tract:	dry mouth
General disorders:	withdrawal syndrome^1,10
Changes in laboratory and instrumental indicators:	increase in the concentration of triglycerides¹¹, total cholesterol (mainly low-density lipoprotein cholesterol-LDL cholesterol)¹²
Often (≥ 1/100, < 1/10)
On the part of the hematopoiesis system:	leukopenia¹
From the central nervous system:	dysarthria, unusual and nightmarish dreams, fainting⁴, extrapyramidal symptoms^1,13
From the cardiovascular system:	tachycardia⁴ , orthostatic hypotension⁴
From the side of the organ of vision:	blurred vision
From the respiratory system:	rhinitis
From the gastrointestinal tract:	constipation, indigestion
General disorders:	slightly expressed asthenia, peripheral edema
Changes in laboratory and instrumental indicators:	weight gain⁹, increased activity of hepatic transaminases (ACT, ALT)³, decrease in the number of neutrophils, hyperglycemia⁷
Infrequently (≥ 1/1000, < 1/100)
On the part of the blood system:	eosinophilia
From the immune system:	hypersensitivity reactions
From the central nervous system:	convulsions¹, Restless Leg Syndrome
From the gastrointestinal tract:	dysphagia⁸
Changes in laboratory and instrumental indicators:	increased activity of creatine phosphokinase, not associated with malignant neuroleptic syndrome, thrombocytopenia¹⁴
Rarely (≥ 1/10000, < 1/1000)
From the gastrointestinal tract:	jaundice⁶
On the part of the reproductive system:	priapism
General disorders:	malignant neuroleptic syndrome¹
Changes in laboratory and instrumental indicators:	increased activity of creatine phosphokinase
Very rarely (<1/10000)
From the immune system	anaphylactic reactions⁶
Metabolic disorders:	diabetes^1,5,6
From the central nervous system:	late dyskinesia⁶
From the gastrointestinal tract:	hepatitis⁶
From the skin and subcutaneous tissues:	angioedema⁶, Stevens-Johnson syndrome⁶
Unspecified frequency
On the part of the hematopoiesis system:	neutropenia¹

1. See section "Special instructions"

2. Drowsiness usually occurs within the first 2 weeks after initiation of therapy and is usually resolved against the backdrop of continued use of quetiapine.

3. Perhaps an asymptomatic increase in activity ACT, ALT and GGT in the blood serum, as a rule, reversible against the background of continued use of Quetiapine.

4. Like other antipsychotics and α_1-adrenoblockers, Quetiapine often causes orthostatic hypotension, which is accompanied by dizziness, tachycardia, in some cases - fainting, especially at the beginning of therapy (see.section "Special instructions").

5. Very rare cases of decompensation of diabetes mellitus have been noted.

6. The frequency of this side effect was estimated based on the results of post-marketing surveillance.

7. Increase in fasting blood glucose ≥126 mg / dL (≥7.0 mmol / l) or post-prandial blood glucose ≥200 mg / dl (≥11.1 mmol / L), at least once.

8. A higher incidence of dysphagia in the background of quetiapine compared with placebo was noted only in patients with depression in the structure of bipolar disorder.

9. Basically, it occurs at the beginning of therapy.

10. When studying the withdrawal syndrome in short-term placebo-controlled clinical trials of quetiapine in monotherapy, the following symptoms were noted: insomnia, nausea, headache, diarrhea, vomiting, dizziness and irritability. The frequency of the "withdrawal" syndrome was significantly reduced 1 week after discontinuation of the drug.

11. Increase in the concentration of triglycerides ≥200 mg / dL (≥2.258 mmol / L) in patients ≥18 years of age or ≥150 mg / dL (≥1.694 mmol / L) in patients <18 years of age, at least once.

12. An increase in the total cholesterol concentration ≥240 mg / dl (≥6.2664 mmol / L) in patients ≥18 years of age or ≥200 mg / dL (≥5,172 mmol / L) in patients <18 years of age, at least once.

13. Cm.further in the text of the Instruction.

14. Decreased platelet count ≤ 100 x 10⁹/ l, at least for a single determination.

Interval lengthening QT, ventricular arrhythmia, sudden death, cardiac arrest and bidirectional ventricular tachycardia are considered side effects of neuroleptics.

The incidence of EPS in short-term clinical trials with schizophrenia and mania in the structure of bipolar disorder was comparable in the quetiapine group and placebo (patients with schizophrenia: 7.8% in the quetiapine group and 8.0% in the placebo group; mania in the structure of bipolar disorder: 11, 2% in the quetiapine group and 11.4% in the placebo group).

The incidence of EPS in short-term clinical trials with depression in the structure of bipolar disorder in the quetiapine group was 8.9%, in the placebo group, 3.8%. The frequency of individual symptoms of EPS (such as akathisia, extrapyramidal disorders, tremor, dyskinesia, dystonia, anxiety, involuntary muscle contractions, psychomotor agitation and muscle rigidity) was generally low and did not exceed 4% in each of the therapeutic groups. In long-term clinical studies of quetiapine in schizophrenia and bipolar disorder, the incidence of EPS was comparable in the quetiapine and placebo groups.

Against the background of Quetiapine therapy, there may be a small dose-dependent decrease in thyroid hormone levels, in particular, of total thyroxin (T₄) and free T₄. Maximum reduction in total and free T₄ registered at the 2nd and 4th week of therapy with Quetiapine, without further reduction in the concentration of hormones during long-term treatment. In almost all cases, the concentration of total and free T4 returned to baseline after quitting quetiapine treatment, regardless of the duration of treatment. A slight decrease in total triiodothyronine (T₃) and reverse T₃ It was noted only when high doses were used. The level of thyroxine-binding globulin (TSH) remained unchanged, and there was no increase in the thyroid-stimulating hormone (TSH) level.

Overdose:

A lethal outcome was reported with the admission of 13.6 g quetiapine in a patient who participated in the clinical study, as well as a lethal outcome after taking 6 g quetiapine in a post-marketing study of the drug. At the same time, the case of taking quetiapine in a dose exceeding 30 g is described, without a lethal outcome.

There are reports of extremely rare cases of quetiapine overdose that led to an increase QT_C interval, death or coma.

In patients with severe cardiovascular disease, the risk of developing side effects with an overdose may increase (see section "Special instructions").

Symptoms noted in overdose were mainly due to the increase in known pharmacological effects of the drug, such as drowsiness and sedation, tachycardia and lowering blood pressure. There are no specific antidotes to quetiapine. In cases of serious intoxication, one should remember about the possibility of an overdose of several drugs. It is recommended to carry out activities aimed at maintaining the function of respiration and cardiovascular system, ensuring adequate oxygenation and ventilation. Gastric lavage (after intubation, if the patient is unconscious) and the appointment of activated charcoal and laxatives can promote the removal of unabsorbed quetiapine, but the effectiveness of these measures has not been studied.

Close medical surveillance should continue until the patient's condition improves.

Interaction:

Caution should be exercised in the combined use of quetiapine with other drugs that affect the central nervous system, as well as with alcohol.

Isozyme of cytochrome P450 (CYP) 3A4 is the main isoenzyme responsible for the metabolism of quetiapine, carried out through the cytochrome P450 system. When studying on healthy volunteers, co-administration of quetiapine (at a dose of 25 mg) with ketoconazole, an inhibitor CYP3A4, led to an increase in the area under the "concentration-time" curve (AUC) quetiapine 5-8 times.

Therefore, co-administration of quetiapine and cytochrome inhibitors CYP3A4 is contraindicated. It is also not recommended to take quetiapine together with grapefruit juice.

In a pharmacokinetic study, the administration of quetiapine at various dosages prior to or concomitantly with carbamazepine administration resulted in a significant increase in quetiapine clearance and, accordingly, a decrease AUC, on average, by 13%, compared with the use of quetiapine without carbamazepine. In some patients, a decrease 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-administration of quetiapine with phenytoin, another inducer of the microsomal system of the liver, was accompanied by an even more pronounced (about 450%) increase in quetiapine clearance.The appointment of quetiapine to patients receiving inducers of the liver enzyme system is possible only if the expected benefit of Quetiapine therapy exceeds the risk associated with the abolition of the hepatic enzyme inducer. The change in the dose of inductor preparations of microsomal enzymes should be gradual. If necessary, they can be replaced with drugs that do not induce microsomal enzymes (for example, preparations of valproic acid).

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

The pharmacokinetics of quetiapine does not change significantly when administered simultaneously with antipsychotic drugs risperidone or haloperidol. However, simultaneous administration of quetiapine and thioridazine led to an increase in the clearance of quetiapine by approximately 70%.

The pharmacokinetics of quetiapine does not change significantly with the simultaneous use of cimetidine.

With a single admission of 2 mg of lorazepam against quetiapine 250 mg twice daily, the clearance of lorazepam is reduced by approximately 20%.

The pharmacokinetics of lithium preparations does not change with the simultaneous administration of quetiapine.

There were no clinically significant changes in the pharmacokinetics of valproic acid and quetiapine in the joint administration of valproate semetriya and quetiapine.

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

Caution should be exercised in the combined use of quetiapine and drugs that can cause electrolyte imbalance and lengthening of the interval QTc.

Quetiapine did not induce the induction of hepatic enzyme systems involved in the metabolism of phenazone.

Special instructions:

Drowsiness

During therapy with Quetiapine, drowsiness and related symptoms, for example, sedation (see "Side effect") may be noted. In clinical studies involving patients with depression in the structure of bipolar disorder, sleepiness tended to develop during the first three days of therapy. The severity of this side effect was mostly mild or moderate.With the development of severe drowsiness, patients with depression in the structure of bipolar disorder may need more frequent visits to the doctor within 2 weeks of the onset of drowsiness or to a decrease in the severity of symptoms. In some cases, Quetiapine may be discontinued.

Patients with cardiovascular diseases

Caution should be exercised in appointing quetiapine to patients with cardiovascular and cerebrovascular diseases, and other conditions predisposing to hypotension. On the background of therapy with quetiapine, orthostatic hypotension may occur, especially during titration of the dose at the beginning of therapy. If orthostatic hypotension occurs, a dose reduction or slower titration may be required.

Convulsive seizures

There were no differences in the incidence of seizures in patients who took Quetiapine or placebo. However, as with other antipsychotic drugs, caution should be exercised in the treatment of patients with a history of seizures (see "Side effect").

Extrapyramidal symptoms

An increase in the incidence of EPS in adult patients with depression in the structure of bipolar disorder was observed with quetiapine treatment for depressive episodes compared with placebo (see the "Side effect" section).

Late dyskinesia

In case of development of symptoms of tardive dyskinesia, it is recommended to reduce the dose of the drug or gradually cancel it (see the section "Side effect").

Malignant neuroleptic syndrome

Against the background of taking antipsychotic drugs, including Quetiapine, can develop malignant neuroleptic syndrome (see section "Side effect"). Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, lability in the autonomic nervous system, increased activity of creatine phosphokinase. In such cases, it is necessary to cancel Quetiapine and conduct appropriate treatment.

Severe neutropenia

In clinical studies of Quetiapine, cases of severe neutropenia (number of neutrophils <0.5 x 10⁹/ l), most cases of severe neutropenia occurred several months after the initiation of quetiapine therapy.There was no dose-response effect. Leukopenia and / or neutropenia were resolved after quetiapine therapy was discontinued. A possible risk factor for the onset of neutropenia is a previous lowered number of leukocytes and cases of drug-induced neutropenia in a history. In patients with a neutrophil count <1.0 x 10⁹/ l, quetiapine should be discontinued. The patient should be observed to identify possible symptoms of infection and monitor the level of neutrophils (up to a level of 1.5 x 10⁹/ l).

Interaction with other drugs

Also see the section "Interaction with other medicinal products". The use of quetiapine in combination with strong inducers of the liver enzyme system, such as carbamazepine and phenytoin, helps to reduce the concentration of quetiapine in the plasma and can reduce the effectiveness of quetiapine therapy.

The appointment of quetiapine to patients receiving inducers of the liver enzyme system is possible only if the expected benefit of Quetiapine therapy exceeds the risk associated with the abolition of the hepatic enzyme inducer.The change in the dose of inductor preparations of microsomal enzymes should be gradual. If necessary, they can be replaced with drugs that do not induce microsomal enzymes (for example, preparations of valproic acid).

Hyperglycaemia

Against the background of taking quetiapine, it is possible to develop hyperglycemia or exacerbation of diabetes mellitus, in patients with diabetes mellitus in the anamnesis. Clinical observation is recommended for patients with diabetes mellitus and patients with risk factors for diabetes mellitus (see section "Side effect").

Level of lipids

Against the background of taking quetiapine may increase the concentration of triglycerides and cholesterol (see section "Side effect").

Interval lengthening QT

There was no correlation between the use of quetiapine and the steady increase in the absolute value of the interval QT. However, the lengthening of the interval QT was noted during an overdose of the drug (see the section "Overdose"). Caution should be exercised when assigning quetiapine, as well as other antipsychotics, to patients with cardiovascular disease and the previously noted lengthening of the interval QT. Also, care should be taken when administering quetiapine concurrently with drugs that extend the interval QT_C, other neuroleptics, especially in the elderly, patients with the syndrome of congenital lengthening interval QT, chronic heart failure, myocardial hypertrophy, hypokalemia, or hypomagnesemia (see section "Interaction with Other Drugs").

Acute reactions associated with drug withdrawal

With the sharp cancellation of quetiapine, the following acute reactions (withdrawal syndrome) can occur: nausea, vomiting, insomnia, headache, dizziness and irritability. Therefore, it is recommended to cancel the drug gradually for at least one or two weeks.

Elderly patients with dementia

Quetiapine is not indicated for the treatment of psychoses associated with dementia. Some atypical antipsychotics in randomized placebo-controlled trials increased the risk of developing cerebrovascular complications in patients with dementia approximately 3-fold. The mechanism of this increase in risk has not been studied. A similar risk of increasing the incidence of cerebrovascular complications can not be ruled out for other antipsychotic drugs or other groups of patients. Quetiapine should be used with caution in patients at risk of stroke.

Analysis of the use of atypical antipsychotics for the treatment of psychoses associated with dementia in elderly patients revealed an increase in the death rate in the group of patients receiving drugs of this group, compared with the placebo group. In addition, two 10-week placebo-controlled studies of quetiapine in a similar group of patients (n = 710; average age: 83 years; age range: 56-99 years) showed that the mortality rate in the group of patients taking Quetiapine, was 5.5%, and 3.2%% in the placebo group. The causes of deaths observed in these patients were consistent with those expected for this population. There was no causal relationship between the treatment of quetiapine and the risk of increased mortality in elderly patients with dementia.

Suicide / suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (events associated with suicide). This risk remains until the onset of severe remission. In view of the fact that it may take several weeks or more to improve a patient's condition from the beginning of treatment,patients should be under close medical supervision before the onset of improvement. According to the generally accepted clinical experience, the risk of suicide may increase in the early stages of the onset of remission.

Other psychiatric disorders for which therapy is prescribed quetiapineare also associated with an increased risk of suicidal events. In addition, such conditions can be comorbid with a depressive episode. Therefore, the precautions used in the therapy of patients with a depressive episode should be taken in the treatment of patients with other psychiatric disorders.

Patients with a history of suicidal events, as well as patients who clearly express suicidal thoughts before starting therapy, are at increased risk of suicidal intentions and suicidal attempts and should be carefully observed during treatment. Conducted FDA (The Food and Drug Administration, USA), a meta-analysis of placebo-controlled studies of antidepressants, summarizing data from approximately 4,400 children and adolescents and 7,700 adults with mental disorders,revealed an increased risk of suicidal behavior against antidepressant drugs compared with placebo in children, adolescents and adult patients under the age of 25 years. This meta-analysis does not include studies where it was used quetiapine (see the section "Pharmacodynamics").

According to short-term placebo-controlled studies for all indications and in all age groups, the incidence of events associated with suicide was 0.9% for both quetiapine (61/6270) and placebo (27/3047).

In these studies in patients with schizophrenia, the risk of events associated with suicide 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 for patients over 25 years of age; 1.4% (2/147) for quetiapine and 1.3% (1/75) for placebo in patients under the age of 18 years.

In patients with mania in bipolar disorder, the risk of suicidal events was 0% (0/67) for quetiapine and 0% (1/57) for placebo in patients aged 18-24 years; 1.2% (6/496) for quetiapine and 1.2% (6/503) for placebo in patients older than 25 years; 1.0% (2/193) for quetiapine and 0% (0/90) for placebo in patients under the age of 18 (see "Specific guidance").

In patients with depression in bipolar disorder, the risk of suicidal 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 for patients over 25 years of age. Studies involving patients with depression in bipolar disorder under the age of 18 years have not been conducted.

Effect on the ability to drive transp. cf. and fur:

Quetiapine can cause drowsiness, so during treatment, patients are not recommended to work with mechanisms that are dangerous, including the management of vehicles is not recommended.

Form release / dosage:

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

Packaging:

For 10 or 30 tablets in a contour cell package.

For 30, 60 or 90 tablets in a jar of polymeric or a bottle of polymer. Each can or bottle, 3, 6, 9 contour packs of 10 tablets or 1, 2, 3 contour packs of 30 tablets together with the instructions for use are placed in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002334

Date of registration:18.12.2013 / 21.09.2016

Expiration Date:18.12.2018

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Representation: & nbspNORTH STAR CJSC NORTH STAR CJSC Russia

Information update date: & nbsp27.12.2017

Illustrated instructions

Instructions

Quetiapine-SZ (Quetiapine-SZ)