Expiration date: 01/2027
Release form
60 long-acting, film-coated tablets.
Dosage form
Oval biconvex tablets covered with a brown-yellow film coating.
View of the fracture: a rough surface of white or almost white color.
Composition
200mg or 300mg per tablet
The core
Active substance: Quetiapine hemifumarate 230.27 mg, equivalent to quetiapine 200.00 mg
Excipients: hypromellose 4000 MPas 42.00 mg, hypromellose 100 MPas 138.00 mg, lactose monohydrate 52.73 mg, microcrystalline cellulose 53.00 mg, sodium hydrophosphate dihydrate 75.00 mg, magnesium stearate 9.00 mg
Film shell: Opadray II HP white 16.55 mg, iron oxide yellow dye (E172) 0.45 mg Opadray II HP white contains: partially hydrolyzed polyvinyl alcohol 6.62 mg, titanium dioxide (E171) 4.14 mg, macrogol/PEG 3000 3.34 mg, talc 2.45 mg
Pharmacotherapeutic group
antipsychotic agent (neuroleptic)
Pharmacodynamics
Mechanism of action
Quetiapine is an atypical antipsychotic drug. Quetiapine and its active metabolite N-disalkylquetiapine (norquetiapine) interact with a wide range of brain neutrotransmitter receptors. Quetiapine and N-disalkylquetiapine exhibit high affinity for 5H2-serotonin receptors and D1-, D2-dopamine receptors in the brain. Antagonism to these receptors, combined with higher selectivity to 5HT2-serotonin receptors than to D2-dopamine receptors, causes the main clinical antipsychotic properties of quetiapine and a low incidence of extrapyramidal adverse reactions. Quetiapine has no affinity for the norepinephrine transporter and has low affinity for 5H1A-serotonin receptors, while N-disalkylquetiapine exhibits high affinity for them. Inhibition of the norepinephrine transporter and partial agonism against 5H1A-serotonin receptors, manifested by N-disalkylquetiapine, may cause the antidepressant effect of the drug Quentiax SR. Quetiapine and N-disalkylquetiapine have high affinity for histamine and ?1-adrenergic receptors and moderate affinity for ?2-adrenergic receptors. In addition, quetiapine has no or low affinity for muscarinic receptors, while N-disalkylquetiapine exhibits moderate or high affinity for several subtypes of muscarinic receptors.
In standard animal tests, quetiapine exhibits antipsychotic activity. The specific contribution of the N-disalkylquetiapine metabolite to the pharmacological activity of quetiapine has not been established.
The results of the study of extrapyramidal symptoms (EPS) in animals revealed that quetiapine causes mild catalepsy in doses that effectively block D2 receptors. Quetiapine causes a selective decrease in the activity of mesolimbic A10-dopaminergic neurons in comparison with A9-nigrostriatal neurons involved in motor function.
In a short-term (9-week) study in patients without dementia aged 66 to 89 years (19% of patients were over 75 years old) with major depressive disorder, long-release quetiapine was administered in doses from 50 mg to 300 mg per day (the dose was selected taking into account tolerability and clinical response, the average daily dose of the drug was 160 mg) reduced the severity of symptoms of depression on the MADRS scale (Montgomery-Asberg Depression Rating Scale, Montgomery-Asberg depression Rating Scale) (mean square change - 7.54 points) compared with placebo. With the exception of the frequency of EPS, the tolerability of long-release quetiapine when taken once a day in elderly patients was comparable to that in patients aged 18-65 years.
The frequency of EPS and body weight gain in stable patients with schizophrenia does not increase with long-term therapy with long-release quetiapine.
In studies of major depressive disorder according to the DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders (4th ed.) - Handbook of Diagnosis and Statistics of Mental Disorders, 4th edition), there was no increase in the risk of suicidal behavior and suicidal thinking when taking long-release quetiapine compared with placebo.
In two short-term (6-week) studies of combination therapy of a depressive episode with long-release quetiapine at a dose of 150 mg/day and 300 mg/day with amitriptyline, bupropion, citalopram, duloxetine, escitalopram, fluoxetine, paroxetine, sertraline or venlafaxine, patients with a suboptimal response to antidepressant monotherapy showed an improvement in depression symptoms on a scale of MADRS (mean square change of 2-3.3 points) compared with monotherapy with an antidepressant.
Pharmacokinetics
Suction
Quetiapine is well absorbed from the gastrointestinal tract. The maximum concentration (Cmax) of quetiapine and N-disalkylquetiapine in blood plasma is reached approximately 6 hours after taking long-release quetiapine. The equilibrium molar concentration of the active metabolite N-disalkylquetiapine is 35% of that of quetiapine.
The pharmacokinetics of quetiapine and N-disalkylquetiapine are linear and dose-dependent when taking long-release quetiapine at a dose of up to 800 mg 1 time per day.
When taking long-release quetiapine 1 time per day at a dose equivalent to the daily dose of rapid-release quetiapine taken in 2 doses, similar areas were observed under the concentration-time dependence curve (AUC), but the Cmax was 13% less. The AUC value of the N-disalkylquetiapine metabolite was 18% lower.
Studies of 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 long-release quetiapine - by about 50% and 20%, respectively. Low-fat meals had no significant effect on the Cmax and AUC of quetiapine. It is recommended to take the drug Quentiax SR 1 time a day separately from meals.
Distribution
Approximately 83% of quetiapine binds to plasma proteins.
Metabolism
It has been established that the CYP3A4 isoenzyme is a key isoenzyme of quetiapine metabolism mediated by the cytochrome P450 system. N-disalkylquetiapine is formed with the participation of the CYP3A4 isoenzyme.
Quetiapine and some of its metabolites (including N-disalkylquetiapine) 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 a commonly used effective dose of 300-800 mg/day. Based on the results of in vitro studies, it should not be expected that the simultaneous use of quetiapine with other drugs will lead to a clinically pronounced inhibition of the metabolism of other drugs mediated by the cytochrome P450 system.
Withdrawal
The half-life of quetiapine and N-disalkylquetiapine is about 7 and 12 hours, respectively. On average, less than 5% of the molar dose of the free quetiapine and N-disalkylquetiapine fractions of plasma are excreted by the kidneys. Approximately 73% of quetiapine is excreted by the kidneys and 21% through the intestine. 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 intestine.
Pharmacokinetics in different patient groups
Paul
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 rates 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 intensively metabolized in the liver, in patients with hepatic insufficiency, an increase in the plasma concentration of quetiapine is possible, which requires dose adjustment.
Indications
- Schizophrenia, including:
- prevention of relapses 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 previous effective quetiapine therapy of manic or depressive episodes in the structure of bipolar disorder.
Depressive episode:
- combination therapy with a suboptimal response to antidepressant monotherapy.
Contraindications
Hypersensitivity to any of the components of the drug.
Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
Concomitant use with cytochrome P450 inhibitors, such as antifungal drugs of the azole group, erythromycin, clarithromycin and nefazodone, as well as with protease inhibitors (see the 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 Quentiax® SR is not indicated in patients under the age of 18.
With caution:
Use in patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, use in elderly patients, liver failure, a history of seizures, the risk of stroke and aspiration pneumonia.
Pregnancy and lactation:
Pregnancy
The safety and efficacy of quetiapine in pregnancy have not been established. As a result, during pregnancy, the drug Quentiax® SR 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.
Breastfeeding period
Reports have been published on the excretion of quetiapine in breast milk, but the degree of excretion has not been established. Women should be advised to avoid breastfeeding while taking quetiapine.
Method of administration and dosage
Inside, 1 time a day, on an empty stomach (at least 1 hour before meals).
Tablets must be swallowed whole, not divided, chewed or broken.
Adults
Treatment of schizophrenia, moderate and severe manic episodes in the structure of bipolar disorder
The drug Quentiax® SR should be taken at least 1 hour before meals. The daily dose for the first 2 days of therapy is: day 1 - 300 mg, day 2 - 600 mg. The recommended daily dose is 600 mg, but can be increased to 800 mg/day if necessary. Depending on the clinical effect and individual patient tolerance, the dose may vary from 400 to 800 mg / day. Maintenance therapy for schizophrenia does not require dose adjustment after relief of exacerbation.
Treatment of episodes of depression in the structure of bipolar disorder
The drug Quentiax® SR should be taken before bedtime. 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. Depending on the clinical effect and individual patient tolerance, the dose can be increased to 600 mg. The benefits of using the drug Quentiax® SR at a daily dose of 600 mg compared to 300 mg was not detected. The drug Quentiax® SR in a dose exceeding 300 mg should be prescribed by a doctor who has experience in the treatment of bipolar disorders.
Prevention of recurrence of bipolar disorders in patients with previous effective quetiapine therapy of manic or depressive episodes in the structure of bipolar disorder
For the prevention of relapses of manic, depressive and mixed episodes in bipolar disorders in patients with a positive response to treatment with Quentiax® SR should be continued at the same daily dose as at the beginning of therapy. The drug Quentiax® SR 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, it is recommended to use the minimum effective dose of the drug Quentiax® SR.
Combination therapy of a depressive episode with a suboptimal response to antidepressant monotherapy
The drug Quentiax® SR should be taken before bedtime. The minimum effective dose should be used, starting therapy with 50 mg / day. The daily dose is: 1st and 2nd day - 50 mg, 3rd and 4th day - 150 mg. Increasing the dose from 150 mg/day to 300 mg/ day should be based on an individual assessment of the patient's condition. When using high doses of the drug, the risk of side effects increases.
Transfer from taking quetiapine in the form of rapid release tablets to taking the drug Quentiax® SR
For ease of admission, patients currently receiving fractional quetiapine therapy in the form of rapid-release tablets may be transferred to Quentiax® SR 1 time per day at a dose equivalent to the total daily dose of quetiapine in the form of rapid release tablets. In some cases, dose adjustment may be necessary.
Elderly patients
As well as other neuroleptics, the drug Quentiax® SR should be used with caution in elderly patients, especially at the beginning of therapy. Selection of the effective dose of the drug Quentiax® SR in elderly patients may be slower, and the daily therapeutic dose is lower than in young patients. The average plasma clearance of quetiapine in elderly patients is 30-50% lower than in young patients. In elderly patients, the initial dose of the drug Quentiax® SR is 50 mg/day. The dose can be increased by 50 mg / day until an effective dose is achieved, depending on the clinical response and tolerability of the drug by an individual patient.
In elderly patients with a depressive episode, the daily dose for the first 3 days of therapy is 50 mg / day with an increase to 100 mg / day on the 4th day and up to 150 mg / day on the 8th day. The minimum effective dose of the drug should be used, starting treatment with 50 mg / day. If necessary, the dose of the drug can be increased to 300 mg / day, but not earlier than 22 days of therapy.
Impaired renal function
For patients with renal insufficiency, dose adjustment is not required.
Impaired liver function
Quetiapine is intensively metabolized in the liver. As a result, caution should be exercised when using the drug Quentiax® SR in patients with liver failure, especially at the beginning of therapy. It is recommended to start therapy with Quentiax® Start with a dose of 50 mg / day and increase the dose daily by 50 mg until an effective dose is reached.
Side effects
The use of quetiapine, like other antipsychotic drugs, may be accompanied by an increase in body weight, fainting, the development of malignant neuroleptic syndrome, leukopenia, neutropenia and peripheral edema. The most common adverse reactions of quetiapine (? 10%) - drowsiness, dizziness, headache, dryness of the oral mucosa, withdrawal syndrome, increased concentration of triglycerides (TG), increased concentration of total cholesterol (mainly low-density lipoprotein cholesterol (LDL)), decreased concentration of high-density lipoprotein cholesterol (HDL), weight gain and decrease in hemoglobin.
Classification of the incidence of side effects (WHO): very common (>1/10), common (>1/100, <1/10), infrequent (>1/1000, <1/100), rare (>1/10 000, <1/1000), very rare (<1/10 000, including individual reports).
From the hematopoietic system: often - leukopenia; infrequently - eosinophilia; very rarely - neutropenia.
From the central and peripheral nervous system: very often — dizziness, drowsiness, headache; often - syncopal conditions; infrequently - anxiety, agitation, insomnia, akathisia, tremor, convulsions, depression, paresthesia; rarely - malignant neuroleptic syndrome (hyperthermia, impaired consciousness, muscle rigidity, vegetative-vascular disorders, an increase in the concentration of CK); very rarely - tardive dyskinesia.
From the cardiovascular system: often - tachycardia, orthostatic arterial hypotension, prolongation of the QT interval on the ECG.
From the respiratory system: rhinitis, pharyngitis.
From the digestive system: often - dry mouth, constipation, diarrhea, dyspepsia, increased serum transaminases (ACT or ALT); rarely - jaundice, nausea, vomiting, abdominal pain; very rarely - hepatitis.
Allergic reactions: infrequently - skin rash, hypersensitivity reactions; very rarely - angioedema, Stevens-Johnson syndrome.
On the part of the reproductive system: rarely - priapism.
From the endocrine system: often - weight gain (mainly in the first weeks of treatment); very rarely - hyperglycemia or decompensation of diabetes mellitus.
Laboratory parameters: infrequently - increased serum GGT levels and triglycerides (not on an empty stomach), hypercholesterolemia; decreased thyroid hormone levels (total T4 and free T4 / in the first 4 weeks/, as well as total T3 and reversible T3 / only when taking high doses of quetiapine /).
Other: often - peripheral edema, asthenia; rarely - lower back pain, chest pain, subfebrility, myalgia, dry skin, impaired vision.
For more information about side effects, see the instructions for the drug.
Overdose:
A fatal outcome was reported when taking 13.6 g of quetiapine in a patient participating in a clinical trial, as well as a fatal outcome after taking 6 g of quetiapine in a post-registration study of quetiapine. At the same time, a case of taking quetiapine in a dose exceeding 30 g without a fatal outcome has been described. There are reports of extremely rare cases of quetiapine overdose, leading to an elongation of the QTc interval, death or coma.
In patients with a history of severe cardiovascular disease, the risk of side effects from overdose may increase (see the section "Special instructions").
Symptoms
The symptoms noted in overdose were mainly the result of an increase in the known pharmacological effects of quetiapine, such as drowsiness and sedation, tachycardia and a decrease in blood pressure. There are also reports of isolated cases of quetiapine overdose leading to rhabdomyolysis, respiratory depression, urinary retention, confusion, delirium and agitation.
Treatment
There are no specific antidotes to quetiapine. In cases of severe intoxication, one should be aware of the possibility of overdose with several medications. It is recommended to carry out measures aimed at maintaining the function of the respiratory and cardiovascular system, ensuring adequate oxygenation and ventilation.
In case of refractory arterial hypotension with an overdose of quetiapine, treatment should be carried out by intravenous administration of fluid and / or sympathomimetic drugs (epinephrine and dopamine should not be prescribed, since stimulation ?-can adrenoreceptors cause an increased decrease in blood pressure against the background of blockade ?-adrenergic receptors 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 supervision should continue until the patient's condition improves.
Overdose
A fatal outcome was reported when taking 13.6 g of quetiapine in a patient participating in a clinical trial, as well as a fatal outcome after taking 6 g of quetiapine in a post-registration study of quetiapine. At the same time, a case of taking quetiapine in a dose exceeding 30 g without a fatal outcome has been described. There are reports of extremely rare cases of quetiapine overdose, leading to an elongation of the QTc interval, death or coma.
In patients with a history of severe cardiovascular disease, the risk of side effects from overdose may increase (see the section "Special instructions").
Symptoms
The symptoms noted in overdose were mainly the result of an increase in the known pharmacological effects of quetiapine, such as drowsiness and sedation, tachycardia and a decrease in blood pressure. There are also reports of isolated cases of quetiapine overdose leading to rhabdomyolysis, respiratory depression, urinary retention, confusion, delirium and agitation.
Treatment
Specific antidotes
Drug interaction
Caution should be exercised when using the drug Quentiax® SR at the same time with other drugs that affect the central nervous system, as well as with alcohol.
The cytochrome P450 3A4 isoenzyme is the main isoenzyme responsible for the metabolism of quetiapine, which is carried out through the cytochrome P450 system. In healthy volunteers, the simultaneous use of quetiapine (at a dose of 25 mg) with ketoconazole, an inhibitor of the CYP3A4 isoenzyme, led to an increase in the AUC of quetiapine by 5-8 times.
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 taking carbamazepine led to a significant increase in the clearance of quetiapine and, accordingly, a decrease in AUC, on average, by 13%, compared with taking 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. The simultaneous 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 the withdrawal of the drug inducer of microsomal liver enzymes. The dose change of drugs 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). The pharmacokinetics of quetiapine did not change significantly 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 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 the clearance of quetiapine by about 70%.
The pharmacokinetics of quetiapine does not change significantly with the simultaneous use of cimetidine.
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%.
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 with the simultaneous use of seminatria valproate and quetiapine.
Concomitant use of quetiapine with lithium preparations in adult patients with an acute manic episode showed a higher incidence of adverse reactions associated with EPS (especially tremor), drowsiness and weight gain compared with patients taking quetiapine with placebo in a 6-week randomized trial.
Pharmacokinetic studies on the interaction of the drug Quentiax® SR with drugs used for cardiovascular diseases has not been performed.
Caution should be exercised when using quetiapine and drugs that can cause electrolyte imbalance and prolongation of the QTc interval at the same time.
Quetiapine did not induce induction of microsomal liver enzymes involved in phenazone metabolism.
False positive results of screening tests for the detection of methadone and tricyclic antidepressants by enzyme immunoassay were noted in patients taking quetiapine. Chromatographic examination is recommended to confirm the screening results.
Special instructions
Children and adolescents (aged 10 to 17 years)
The drug Quentiax® SR is not indicated for use in children and adolescents under the age of 18 due to insufficient data on use in this age group. According to the results of clinical studies, some undesirable reactions (increased appetite, increased serum prolactin concentration and EPS) In children and adolescents, it was observed with a higher frequency than in adult patients. 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 effect on growth, puberty, mental development and behavioral reactions with prolonged use (more than 26 weeks) of quetiapine has 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 with placebo.
Suicide/suicidal thoughts or clinical deterioration
Depression 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 before the patient's condition improves from the beginning of treatment, patients should be under close medical supervision until improvement occurs. According to generally accepted clinical experience, the risk of suicide may increase in the early stages of remission.
According to short-term placebo-controlled clinical trials in patients with depression in bipolar disorder, the risk of 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 elderly patients? 25 years old.
Other psychiatric disorders for which quetiapine is used are also associated with an increased risk of suicide-related events. In addition, such conditions may be comorbid with a depressive episode. Thus, 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 increased risk of suicidal intentions and suicidal attempts and should be carefully monitored during treatment.
In patients with mania in bipolar disorder, the risk of suicide-related 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 aged ? 25 years, 1.0% (2/193) for quetiapine and 0% (0/90) for placebo in patients under the age of 18.
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 aged ? 25 years, 1.4% (2/147) for quetiapine and 1.3% (1/75) for placebo in patients under the age of 18.
In patients with a depressive episode, the risk of suicide-related events was 2.1% (3/144) for quetiapine and 1.3% (1/75) for placebo in patients aged 18-24 years; 0.6% (11/1798) for quetiapine and 0.7% (7/1054) for placebo in patients aged ?25 years old. Patients under the age of 18 did not participate in studies for this indication.
In general, 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).
A meta-analysis of placebo-controlled antidepressant trials conducted by the FDA (Food and Drug Administration, USA), summarizing data from approximately 4,400 children and adolescents and 7,700 adult patients with mental disorders, revealed an increased risk of suicidal behavior on antidepressants compared with placebo in children, adolescents and adult patients under the age of 25 years old. This meta-analysis does not include studies where quetiapine was used (see the section "Pharmacodynamics").
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 with placebo (see the section "Side effect"). However, during quetiapine therapy in patients with schizophrenia and mania, there was no increase in the incidence of EPS in the structure of bipolar disorder compared with placebo.
Late dyskinesia
Against the background of taking neuroleptics, including quetiapine, late dyskinesia may occur, which manifests itself by violent involuntary movements and may be irreversible. In case of symptoms of tardive dyskinesia, it is recommended to reduce the dose of the drug or gradually cancel it. Symptoms of tardive dyskinesia may worsen or even occur after discontinuation of the drug (see the section "Side effects").
Against the background of taking quetiapine, akathisia may occur, which is characterized by an unpleasant feeling of motor anxiety and the need to move and is manifested by the patient's inability to sit or stand motionless. If such symptoms occur, do not increase the dose of quetiapine.
Drowsiness and dizziness
During quetiapine therapy, drowsiness and related symptoms may occur, such as sedation (see the section "Side effect"). 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 mostly minor or moderate. With the development of severe drowsiness, 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.
Orthostatic hypotension and dizziness may occur during quetiapine therapy (see the section "Side effect") usually during dose adjustment 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 adjustment at the beginning of therapy. If orthostatic hypotension occurs, it may be necessary to reduce the dose or select it more gradually.
Convulsive seizures
There were no differences in the frequency of seizures in patients taking quetiapine or placebo. However, as with therapy with other antipsychotic drugs, caution is recommended when treating patients with a history of seizures (see the section "Side effects").
Malignant neuroleptic syndrome
While taking antipsychotic drugs, including quetiapine, a malignant neuroleptic syndrome may develop (see the section "Side effect"). 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, quetiapine should be discontinued and appropriate treatment should be carried out.
Severe neutropenia and agranulocytosis
In short-term placebo-controlled clinical trials of quetiapine monotherapy, cases of severe neutropenia (neutrophil count < 0.5 x 109 /l) without infection were infrequently observed. The development of agranulocytosis (severe neutropenia associated with infections) has been reported in patients treated with quetiapine in clinical trials (rarely), as well as with post-registration use (including fatal). Most of these cases of severe neutropenia occurred several months after the start of quetiapine therapy. There was no dose-dependent effect. Leukopenia and/or neutropenia resolved after quetiapine therapy was discontinued. A possible risk factor for the occurrence of neutropenia is a previous reduced white blood cell count and a history of drug-induced neutropenia. The development of agranulocytosis was also noted in patients without risk factors. It is necessary to take into account the possibility of developing neutropenia in patients with infection, especially in the absence of obvious predisposing factors, or in patients with unexplained fever, these cases should be conducted in accordance with clinical recommendations.
In patients with neutrophil counts < 1.0 x 109 /l, quetiapine should be discontinued. The patient should be monitored to identify possible symptoms of infection and control the number of neutrophils (before increasing their number to 1.5 x 109 / l).
Interaction with other medicinal products
Also see the section "Interaction with other medicines". The simultaneous use of quetiapine with powerful inducers of microsomal liver enzymes, such as carbamazepine and phenytoin, helps to reduce the concentration of quetiapine in blood plasma and may reduce the effectiveness of therapy with Quentiax® SR.
The use of the drug Quentiax® SR in patients receiving inducers of microsomal liver enzymes is possible only if the expected benefit from therapy with Quentiax® SR exceeds the risk associated with the cancellation of inducers of microsomal liver enzymes. The dose change of drugs 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
Against the background of taking quetiapine, an increase in body weight was noted. Clinical observation of patients in accordance with accepted therapy standards is recommended (see the section "Side effect").
Hyperglycemia
While taking quetiapine, hyperglycemia and / or the development and exacerbation of diabetes mellitus, sometimes accompanied by ketoacidosis or coma, may develop. Regular monitoring of body weight and symptoms of hyperglycemia, 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 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 effect"). These changes should be adjusted in accordance with the current recommendations.
Metabolic disorders
An increase in body weight, an increase in the concentration of glucose and lipids in blood plasma in some patients may lead to a deterioration in the metabolic profile, which requires appropriate monitoring.
Prolongation of the QT interval
There was no relationship between quetiapine intake and a persistent increase in the absolute value of the QT interval. However, prolongation of the QT interval was noted 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 simultaneously with drugs that prolong the QTc interval, other neuroleptics, especially in the elderly, in patients with congenital prolongation of the QT interval, chronic heart failure, myocardial hypertrophy, hypokalemia or hypomagnesemia (see the section "Interaction with other drugs").
Acute reactions associated with drug withdrawal
With the abrupt withdrawal of quetiapine, the following acute reactions (withdrawal syndrome) may occur - nausea, vomiting, insomnia, headache, dizziness and irritability. Therefore, the cancellation of the drug Quentiax® SR is recommended to be carried out gradually for at least one or two weeks.
Elderly patients with dementia
The drug Quentiax® SR is not indicated for the treatment of dementia-related psychoses. Some atypical neuroleptics in randomized placebo-controlled trials increased the risk of cerebrovascular complications in patients with dementia by about 3 times. The mechanism of this increase in 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. The drug Quentiax® SR should be used with caution in patients at risk of stroke.
An analysis of the use of atypical neuroleptics for the treatment of psychoses associated with dementia in elderly patients revealed an increase in the mortality rate in the group of patients receiving drugs from this group, compared with the placebo group. Two 10-week placebo-controlled studies of quetiapine in a similar group of patients (n=710, mean age: 83 years, age range: 56-99 years) showed that mortality 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 corresponded to those expected for this population. There was no causal relationship between quetiapine treatment and the risk of increased mortality in elderly patients with dementia.
Liver disorders
In case of jaundice, quetiapine should be discontinued.
Dysphagia
Dysphagia (see the section "Side effect") and aspiration was observed during quetiapine therapy. The causal relationship of aspiration pneumonia with quetiapine intake has not been established. However, caution should be exercised when using the drug Quentiax® SR in patients at risk of aspiration pneumonia.
Venous thromboembolism
Against the background of taking neuroleptics, cases of venous thromboembolism have been noted. Before and during therapy with antipsychotic drugs, including quetiapine, risk factors should be assessed and preventive measures taken.
Pancreatitis
During clinical trials and post-registration use, cases of pancreatitis have been noted, but a causal relationship with taking the drug has not been established. Post-registration reports indicated that many patients had risk factors for pancreatitis, such as increased triglyceride concentrations (see subsection "Lipid concentration"), cholelithiasis and alcohol consumption.
Constipation and intestinal obstruction
Constipation is a risk factor for intestinal obstruction. Against the background of the use of quetiapine, the development of constipation and intestinal obstruction was noted (see the section "Side effect"), including fatal cases in patients at high risk of intestinal obstruction, including those receiving multiple concomitant medications that reduce intestinal motility, even in the absence of complaints of constipation.
Cardiomyopathy and myocarditis
During clinical trials and post-registration use, cases of cardiomyopathy and myocarditis have been noted, but a causal relationship with taking the drug has not been established. The expediency of quetiapine therapy in patients with suspected cardiomyopathy or myocarditis should be evaluated.
Additional information
Long-term safety and efficacy of Quentiax® SR as an additional therapy in the treatment of major depressive disorder has not been studied, but the safety and efficacy profile has been studied with monotherapy.
Special information on excipients
The drug Quentiax® SR contains lactose, therefore it should not be used in the following conditions: lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
Influence on the ability to drive vehicles and mechanisms:
The drug Quentiax SR can cause drowsiness, therefore, during treatment, patients are not recommended to work with mechanisms that require increased concentration of attention, including driving vehicles.
Storage temperature
from 2℃ to 25℃
