Instruction for use: Seroquel Prolong

Dosage form: film coated tablets

Active substance: Quetiapine*

ATX

N05AH04 Quetiapine

Pharmacological group:

Neuroleptics

The nosological classification (ICD-10)

F20 Schizophrenia: Schizophrenic conditions; Exacerbation of schizophrenia; Schizophrenia; Chronic schizophrenia; Dementia praecox; Bleuler's disease; Psychotic discordant; Dementia early; The febrile form of schizophrenia; Chronic schizophrenic disorder; Psychosis of the schizophrenic type; Acute form of schizophrenia; Acute schizophrenic disorder; Cerebral Organic Insufficiency in Schizophrenia; Acute attack of schizophrenia; Schizophrenic psychosis; Acute schizophrenia; Sluggish schizophrenia; Sluggish schizophrenia with apathoabulic disorders; Acute stage of schizophrenia with excitation

F29 Inorganic psychosis, unspecified: Childhood psychoses; Psychomotor agitation in psychoses; Hallucinatory-delusional disorders; Hallucinatory-delusional syndrome; Intoxication psychosis; Manic-delusional disorders; Manic chronic psychosis; Manic psychosis; Acute psychosis; paranoid psychosis; Paranoid psychosis; Subacute psychosis; Presenile psychosis; Psychosis; Intoxicating psychosis; Psychosis is paranoid; Psychosis in children; Reactive psychosis; Chronic psychosis; Chronic hallucinatory psychosis; Chronic psychosis; Chronic psychotic disorder; Schizophrenic psychosis

F31 Bipolar affective disorder: Mood disorders bipolar; Affective bipolar psychosis; Manic-melancholic psychosis; Intermittent psychosis; Circular psychosis; Cyclophrenia; Bipolar disorders; Bipolar psychosis; Affective insanity; Manic-depressive syndrome; Psycho Manic-Depressive; Depressive episode of bipolar disorder

Composition and release form

Tablets of prolonged action, covered with a film membrane 1 tab.

quetiapine fumarate 57.56 mg; 172.69 mg; 230.26 mg; 345.38 mg; 460.5 mg

(equivalent to 50, 150, 200, 300 and 400 mg of quetiapine, respectively)

auxiliary substances: lactose monohydrate; ICC; sodium citrate dihydrate; hypromellose; magnesium stearate

membrane: hypromellose; macrogol 400; titanium dioxide E171; ferric oxide red oxide E172 (for tablets 50 mg), iron coloring oxide yellow E172 (for tablets 50, 200 and 300 mg)

in a blister of 10 pcs .; in a pack of cardboard 6 blisters.

Descriptionof dosage form

Tablets of 50 mg: oblong biconvex, pink, film-coated; with engraving "XR 50" on one side.

Tablet 150 mg: oblong biconvex, white, film-coated; with engraving "XR 150" on one side.

Tablets of 200 mg: oblong biconvex, yellow, film-coated; with engraving "XR 200" on one side.

Tablets of 300 mg: oblong biconvex, light yellow color, film-coated; with engraving "XR 300" on one side.

Tablets 400 mg: oblong biconvex, white, film-coated; with an engraving "XR 400" on one side.

Pharmachologic effect

Pharmacological action - antipsychotic.

Pharmacodynamics

Quetiapine is an atypical antipsychotic. Quetiapine and its active metabolite N-desalkylkvetiapine interact with neurotransmitter receptors in the brain. Quetiapine and N-desalkylkvetiapine have a high affinity for serotonin receptors such as 5HT2 and dopamine receptors of the brain types D1 and D2.

The frequency of EPS and body weight in stable patients with schizophrenia does not increase with prolonged therapy with Seroquel® Prolong.

In studies of major depressive disorder according to the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders (4th ed.) - Diagnostic and Statistical Manual of Mental Disorders, 4th edition), there was no increase in the risk of suicidal behavior and suicidal thinking when taking Seroquel ® Prolong versus placebo.

Pharmacokinetics

Quetiapine is well absorbed from the digestive tract. Cmax quetiapine and N-desalkylkvetiapine in blood plasma is achieved approximately 6 hours after taking Seroquel® Prolong. The equilibrium molar concentration of the active metabolite of N-desalkylkvetiapine is 35% of that of quetiapine.

The pharmacokinetics of quetiapine and N-desalkylkvetiapine is linear and is dose-dependent when taking Seroquel® Prolong in doses up to 800 mg once a day.

When Seroquel® Prolong was taken once a day, at a dose equivalent to the daily dose of Seroquel® taken in 2 divided doses, similar AUCs were observed, but Cmax was 13% less. The AUC value of the N-dezalkylkvetiapine metabolite was 18% less.

Studies on the effect of food intake on the bioavailability of quetiapine have shown that eating high-fat foods leads to a statistically significant increase in Cmax and AUC for the Seroquel® Prolong preparation by approximately 50% and 20%, respectively. Low-fat diet did not have a significant effect on Cmax and quetiapine AUC. It is recommended to take Seroquel® Prolong once a day, separately from food.

Approximately 83% of quetiapine binds to plasma proteins.

It was found that CYP3A4 is the key isoenzyme of quetiapine metabolism, mediated by cytochrome P450. N-dealkylkvetiapine is formed with the participation of the CYP3A4 isoenzyme.

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

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

T1 / 2 quetiapine and N-desacilkvetiapine is about 7 and 12 hours, respectively. Approximately 73% of quetiapine is excreted in urine and 21% with feces. Quetiapine is actively metabolized in the liver, less than 5% of quetiapine is not metabolized and is excreted unchanged in kidneys or with feces.

Differences in pharmacokinetic parameters in men and women are not observed.

The mean Cl quetiapine in elderly patients is 30-50% less than in patients aged 18 to 65 years.

The mean plasma Cl quetiapine is reduced by approximately 25% in patients with severe renal failure (Cl creatinine <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 Cl quetiapine is reduced by approximately 25%. Because quetiapine is extensively metabolized in the liver, in patients with hepatic insufficiency, an increase in the plasma concentration of quetiapine is possible, which requires dose adjustment.

Indications Seroquel Prolong

schizophrenia, including the prevention of relapse in stable patients;

bipolar disorders, including:

- moderate and severe manic episodes in the structure of bipolar disorder;

- severe episodes of depression in the structure of bipolar disorder;

- prevention of recurrence of bipolar disorders in patients with prior effective quetiapine therapy of manic or depressive episodes in the structure of bipolar disorder.

Contraindications

hypersensitivity to any of the components of the drug;

deficiency of lactase, glucose-galactose malabsorption and galactose intolerance;

combined use with cytochrome P450 inhibitors, such as antifungal agents of the azole group, erythromycin, clarithromycin and nefazodone, as well as protease inhibitors (see "Interaction with other drugs and other interactions");

age to 18 years (despite the fact that the effectiveness and safety of Seroquel® Prolong in children and adolescents aged 10-17 years were studied in clinical studies).

Carefully:

cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension;

elderly age;

liver failure;

convulsive fits in the anamnesis.

Application in pregnancy and lactation

The safety and efficacy of quetiapine in pregnant women have not been established. As a result, during pregnancy Seroquel® Prolong can be used only if the expected benefit for a woman justifies the potential risk to the fetus.

The degree of excretion of quetiapine with human milk is unknown. Women should avoid breastfeeding while taking Seroquel® Prolong.

Side effects

The most frequent side effects of Seroquel ® Prolong are drowsiness, dizziness, dry mouth, mild asthenia, constipation, tachycardia, orthostatic hypotension and dyspepsia.

The use of Seroquel® Prolong, as well as 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 form of the following gradation: very often - ≥1 / 10; often - ≥1 / 100, <1/10; infrequently - ≥1 / 1000, <1/100; rarely - ≥1 / 10000, <1/1000; very rarely - <1/10000, unspecified frequency.

1. See "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 Seroquel® Prolong.

3. There may be an asymptomatic increase in the activity of AST, ALT and GGT in the blood serum, usually reversible against the background of continued use of Seroquel® Prolong.

4. Like other antipsychotics and α1-blockers, Seroquel® Prolong often causes orthostatic hypotension, which is accompanied by dizziness, tachycardia, and in some cases - fainting, especially at the beginning of therapy (see "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 of the Seroquel® Prolong® drug.

7. Increase in fasting blood glucose ≥126 mg / dl (≥7 mmol / l) or postprandial blood glucose ≥200 mg / dl (≥11.1 mmol / l), at least once.

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

9. Over 7% excess of initial body weight. It mainly occurs at the beginning of therapy.

10. In studying the withdrawal syndrome in the short-term placebo-controlled clinical trials of Seroquel® Prolong in monotherapy, the following symptoms were noted: insomnia, nausea, headache, diarrhea, vomiting, dizziness and irritability. The frequency of withdrawal was significantly reduced after 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. Increase in 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. See further in the text of the Instruction.

14. Decrease in the number of platelets ≤100 • 109 / l, at least for a single determination.

15. Without communication with a malignant neuroleptic syndrome. According to clinical studies.

16. Increase in prolactin concentration in patients ≥18 years of age:> 20 μg / L (≥869.56 pmol / L) in men; > 30 μg / l (≥1304.34 pmol / L) in women.

17. May lead to a fall.

18. Decreased HDL cholesterol concentration <40 mg / dl in men and <50 mg / dl in women.

QT interval prolongation, 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 and placebo groups (patients with schizophrenia: 7.8% in the quetiapine group and 8% in the placebo group, mania in the 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%. However, 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 quetiapine and placebo groups.

Against the background of quetiapine therapy, a small dose-dependent decrease in the concentration of thyroid hormones, in particular total thyroxine (T4) and free T4, can be observed. The maximum decrease in total and free T4 was registered at the 2nd and 4th weeks of therapy with the Seroquel® Prolong preparation, 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 discontinuing Seroquel® Prolong, regardless of the duration of treatment. A slight decrease in total triiodothyronine (T3) and inverse T3 was noted only when high doses were used. The concentration of thyroxin-binding globulin (TSG) remained unchanged, no increase in TSH concentration was noted.

Interaction

Care should be taken when combining Seroquel® Prolong with other drugs that affect the central nervous system, as well as with alcohol.

Isozyme cytochrome P450 (CYP) 3A4 is the main isoenzyme responsible for the metabolism of quetiapine, carried out through the cytochrome P450 system. In a study on healthy volunteers, the combined use of quetiapine (25 mg) with ketoconazole, an inhibitor of CYP3A4, increased the quetiapine AUC 5-8 times.

Therefore, the combined use of quetiapine and cytochrome inhibitors CYP3A4 is contraindicated. When quetiapine therapy is not recommended to eat grapefruit juice.

In a pharmacokinetic study, the use of quetiapine at a different dosage before or simultaneously with carbamazepine led to a significant increase in Cl quetiapine and, accordingly, a decrease in AUC, by an average of 13%, compared with quetiapine alone without carbamazepine. In some patients, the decrease in AUC was even more pronounced. This interaction was accompanied by a decrease in the concentration of quetiapine in the plasma and could reduce the effectiveness of therapy with the drug Seroquel® Prolong. The combined use 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 use of Seroquel® Prolong by patients receiving inductors of the liver enzyme system is possible only if the expected benefit from therapy with the Seroquel® Prolong drug exceeds the risk associated with the abolition of the hepatic enzyme inducer. The change in the dose of drugs - inductors of microsomal enzymes should be gradual. If necessary, they can be replaced with drugs that do not induce microsomal enzymes (for example, valproic acid preparations).

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

The pharmacokinetics of quetiapine does not change significantly when used concomitantly with antipsychotic drugs, risperidone or haloperidol. However, simultaneous administration of quetiapine and thioridazine led to an increase in Cl 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 use of quetiapine. There were no clinically significant changes in the pharmacokinetics of valproic acid and quetiapine when co-administered semiotric and quetiapine valproate.

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

Caution should be exercised when combining Seroquel® Prolong and preparations that can cause electrolyte imbalance and prolong the QTc interval.

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

In patients taking quetiapine, false-positive results of screening tests for the detection of methadone and tricyclic antidepressants by the enzyme immunoassay were observed. To confirm the results of screening, a chromatographic study is recommended.

Dosing and Administration

Inside, swallowing whole (without dividing, not chewing and not breaking), 1 time a day apart from food.

Adults

Treatment of schizophrenia, moderate and severe manic episodes in the structure of bipolar disorder

Preparation Seroquel® Prolong should be taken at least 1 hour before meals.

The daily dose for the first 2 days of therapy is: 1st day - 300 mg, 2nd day - 600 mg. The recommended daily dose is 600 mg, but if necessary, it can be increased to 800 mg / day. Depending on the clinical effect and individual patient tolerance, the dose can vary from 400 to 800 mg / day. For maintenance therapy in schizophrenia, there is no need to adjust the dose after relieving the exacerbation.

Treatment of episodes of depression in the structure of bipolar disorder

Seroquel® Prolong should be taken before bedtime. The daily dose for the first 4 days of therapy is: 1st day - 50 mg, 2nd day - 100 mg, 3 days - 200 mg, 4th day - 300 mg. The recommended daily dose is 300 mg. Depending on the clinical effect and individual patient tolerance, the dose can be increased to 600 mg. The advantage of using Seroquel® Prolong in a daily dose of 600 mg compared with 300 mg was not revealed. Seroquel® Prolong in a dose exceeding 300 mg should be prescribed by a physician with experience in the therapy of bipolar disorders.

Prevention of recurrence of bipolar disorder in patients with prior effective quetiapine therapy of manic or depressive episodes in the structure of bipolar disorder

To prevent recurrence of manic, depressive and mixed episodes in bipolar disorders, patients with a positive response to treatment with Seroquel® Prolong should continue therapy at the same daily dose as at the beginning of therapy. Seroquel® Prolong should be taken before bedtime. Depending on the clinical effect and individual patient tolerance, the dose may vary from 300 to 800 mg / day. For maintenance therapy, the minimum effective dose of Seroquel® Prolong is recommended.

Translation from the administration of Seroquel® to Seroquel® Prolong

For convenience of reception, patients currently receiving fractional therapy with Seroquel® can be switched to the Seroquel® Prolong preparation once a day at a dose equivalent to the total daily dose of Seroquel®. In some cases, a dose adjustment may be necessary.

Elderly patients

Like other antipsychotics, Seroquel ® Prolong should be used with caution in elderly patients, especially at the beginning of therapy. Selection of an effective dose of Seroquel® Prolong in elderly patients may be slower, and the daily therapeutic dose is lower than in young patients. The mean plasma Cl quetiapine in elderly patients is 30-50% lower in comparison with younger patients. In elderly patients, the initial dose of Seroquel® Prolong® is 50 mg / day. The dose can be increased by 50 mg per day until an effective dose is obtained, depending on the clinical response and the tolerance of the drug to the individual patient.

Patients with renal insufficiency

For patients with renal insufficiency, dose adjustment is not required.

Patients with hepatic insufficiency

Quetiapine is extensively metabolized in the liver. Therefore, use caution when using Seroquel® Prolong in patients with hepatic insufficiency, especially at the beginning of therapy. It is recommended to start therapy with Seroquel ® Prolong from a dose of 50 mg / day and increase the dose daily by 50 mg until an effective dose is reached.

Overdose

Symptoms. 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, a 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 leading to an increase in the QTc interval, death or coma.

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

Treatment. There are no specific antidotes to quetiapine. In cases of severe 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 use 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.

Special instructions

Drowsiness

During therapy with Seroquel ® Prolong, there may be drowsiness and related symptoms, for example sedation (see "Side effects"). 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, it may be necessary to discontinue therapy with Seroquel® Prolong.

Patients with cardiovascular diseases

Care should be taken when prescribing Seroquel® Prolong to patients with cardiovascular and cerebrovascular diseases and other conditions predisposing to hypotension. On the background of therapy with Seroquel ® Prolong, orthostatic hypotension may occur, especially during the titration of the dose at the beginning of therapy. If orthostatic hypotension occurs, a dose reduction or slower titration may be required.

Dysphagia (see "Side effects") and aspiration were observed with therapy with Seroquel® Prolong. The causal relationship between the onset of aspiration pneumonia and the administration of Seroquel® Prolong was not established. However, care should be taken when prescribing the drug to patients at risk of aspiration pneumonia.

Convulsive seizures

There were no differences in the incidence of seizures in patients taking 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 effects").

Extrapyramidal symptoms

An increase in the incidence of EPS in adults with depression in the structure of bipolar disorder with quetiapine for depressive episodes compared with placebo has been noted (see "Side effects"). However, when quetiapine treatment of patients with schizophrenia and mania in the structure of bipolar disorder did not reveal an increase in the incidence of EPS in comparison with placebo.

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. Symptoms of tardive dyskinesia may increase or even occur after discontinuation of the drug (see "Side effects").

Malignant neuroleptic syndrome

Against the background of taking antipsychotic drugs, incl. quetiapine, can develop malignant neuroleptic syndrome (see "Side effects"). 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 the use of Seroquel® Prolong and to take appropriate treatment.

Severe neutropenia

In clinical studies of quetiapine, cases of severe neutropenia (the number of neutrophils <0.5 · 109 / L) were infrequent. Most cases of severe neutropenia occurred several months after 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 the anamnesis. In patients with a neutrophil count <1 · 109 / L, quetiapine should be discontinued. The patient should be observed to identify possible symptoms of infection and control the number of neutrophils (up to a level exceeding 1.5 · 109 / L).

Interaction with other drugs

Also see "Interaction".

The use of Seroquel® Prolong in combination with powerful inducers of the liver enzyme system, such as carbamazepine and phenytoin, helps to reduce quetiapine plasma concentrations and may reduce the effectiveness of Seroquel® Prolong therapy.

The appointment of Seroquel® Prolong to patients receiving inductors of the enzyme system of the liver is possible only if the expected benefit from therapy with the Seroquel® Prolong drug exceeds the risk associated with the abolition of the hepatic enzyme inducer. The change in the dose of drugs - inductors 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 quetiapine may develop hyperglycemia or exacerbation of diabetes, in patients with diabetes mellitus in history. Clinical observation of patients with diabetes mellitus and patients with risk factors for the development of diabetes is recommended (see "Side effects").

Concentration of lipids

Against the background of taking quetiapine, an increase in the concentration of triglycerides and cholesterol and a decrease in the concentration of HDL is possible (see "Side effects").

QT interval extension

There was no correlation between the intake of quetiapine and the steady increase in the absolute value of the QT interval. However, the prolongation of the QT interval was noted with an overdose of the drug (see "Overdose"). Caution should be exercised when assigning quetiapine, as well as other antipsychotics, to patients with cardiovascular disease and the previously noted QT interval elongation. Care should also be taken when administering quetiapine concomitantly with QTc-prolonging drugs, other antipsychotics, especially in the elderly, patients with congenital QT prolongation syndrome, chronic heart failure, myocardial hypertrophy, hypokalemia, or hypomagnesemia (see "Interaction").

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

Seroquel® Prolong 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. Seroquel® Prolong 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 showed an increase in mortality in the group of patients receiving drugs of 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 mortality in the quetiapine group was 5.5%, in placebo group - 3.2%. The causes of deaths noted 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 before the improvement of the patient's condition from the beginning of treatment, several weeks or more may pass, 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 quetiapine is administered are 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.

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 schizophrenic patients, the risk of suicidal 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 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% (2/193) for quetiapine and 0% (0/90) for placebo in patients under the age of 18 (see "Special instructions").

In patients with depression in bipolar disorder, the risk of suicidal events was 3% (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.

Seroquel® Prolonging can cause drowsiness, therefore, during the treatment period, it is not recommended for patients to work with mechanisms that present a danger, incl. it is not recommended to drive vehicles.

Storage conditions of the drug Seroquel Prolong

At temperatures not higher than 30 ° C.

Keep out of the reach of children.

Shelf life of the drug Seroquel Prolong

3 years.

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