Quetiapine (Ketilept, Quentiax, Seroquel, Quetiap)

The most common adverse reactions associated with taking the drug: drowsiness (17.5%), dizziness (10%), constipation (9%), dyspepsia (6%), orthostatic hypotension and tachycardia (7%), dry mouth (7% ), increased activity of “liver” enzymes in the blood serum (6%), increased concentrations of cholesterol and triglycerides in the blood plasma.

Taking quetiapine may be accompanied by the development of moderate asthenia, rhinitis and dyspepsia, and an increase in body weight (mainly in the first weeks of treatment). Quetiapine may cause orthostatic hypotension (accompanied by dizziness), tachycardia and, in some patients, syncope; these adverse reactions mainly occur during the initial period of dose selection (see section "Special Instructions"). Quetiapine therapy is associated with a small dose-dependent decrease in the concentration of thyroid hormones, in particular total T4 and free T4. The maximum decrease in total and free T4 was recorded in the 2nd and 4th weeks of quetiapine therapy, without a further decrease in hormone concentrations during long-term treatment. There were no further signs of clinically significant changes in thyroid-stimulating hormone concentrations.

With long-term use of quetiapine, there is a potential for the development of tardive dyskinesia. If symptoms of tardive dyskinesia occur, reduce the dose or discontinue further treatment with quetiapine. With abrupt withdrawal of high doses of antipsychotic drugs, the following acute reactions (withdrawal syndrome) may be observed: nausea, vomiting, and rarely, insomnia.

There may be cases of exacerbation of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia). Therefore, it is recommended to discontinue the drug gradually.

The following are the adverse reactions observed with the use of quetiapine and distributed among organs and systems:

From the nervous system: drowsiness, dizziness, headache, anxiety, asthenia, hostility, agitation, insomnia, akathisia, tremor, convulsions, depression, paresthesia, neuroleptic malignant syndrome (hyperthermia, muscle rigidity, changes in mental status, lability of the autonomic nervous system, increased activity of creatine phosphokinase), restless legs syndrome.

From the cardiovascular system: orthostatic hypotension, tachycardia, prolongation of the QT interval.

From the digestive system: dryness of the oral mucosa, nausea, vomiting, abdominal pain, diarrhea or constipation, increased activity of liver transaminases, jaundice, hepatitis.

From the respiratory system: pharyngitis, rhinitis.

Allergic reactions: skin rash, eosinophilia, angioedema, Stevens-Johnson syndrome, anaphylactic reactions.

Laboratory indicators: leukopenia, neutropenia, hypercholesterolemia, hypertriglyceridemia, decreased T4 concentration (first 4 weeks), hyperglycemia.

Other: lower back pain, chest pain, low-grade fever, weight gain (mainly in the first weeks of treatment), myalgia, dry skin, blurred vision, incl. blurred visual perception, decompensation of existing diabetes mellitus, priapism, galactorrhea.

Quetiapine, 150 mg, film-coated tablets, 60 pcs.

Children and adolescents (ages 10 to 17 years)

Quetiapine is not indicated for use in children and adolescents under 18 years of age due to insufficient data on use in this age group. According to the results of clinical studies of quetiapine, some side effects (increased appetite, increased concentration of prolactin in the blood serum, vomiting, runny nose and fainting) were observed with a higher frequency in children and adolescents than in adult patients. Some adverse events (AEs) may have different consequences in children and adolescents compared to adult patients. An increase in blood pressure not observed in adult patients was also noted. Changes in thyroid function have also been observed in children and adolescents. The effects on growth, puberty, mental development and behavioral reactions with long-term use (more than 26 weeks) of quetiapine have not been studied.

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

Suicide/suicidal ideation or clinical worsening

Depression in bipolar disorder is associated with an increased risk of suicidal thoughts of self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. Because it may take several weeks or more for the patient's condition to improve from the start 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. Patients (especially those at increased risk for suicide) and their caregivers should be warned to monitor for clinical worsening of suicidal behavior or thoughts of unusual changes in behavior and to seek immediate medical attention if they occur.

According to clinical studies in patients with depression in bipolar disorder, the risk of suicide-related events was 30% (7/233) for quetiapine and 0% (0/120) for placebo in patients aged 18-24 years; 18% (19/1616) for quetiapine and 18% (11/622) for placebo in patients over 25 years of age.

Other psychiatric disorders treated with quetiapine are also associated with an increased risk of suicide-related events. In addition, such conditions may be comorbid with a depressive episode. Thus, the precautions taken when treating patients with a depressive episode should also be taken when treating patients with other mental disorders.

If 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 suicide attempts and should be carefully monitored during treatment.

An FDA meta-analysis of placebo-controlled studies of antidepressants summarizing data from approximately 4,400 children and adolescents and 7,700 adult patients with mental disorders found an increased risk of suicidal behavior with antidepressants compared with placebo in child adolescents and adult patients. under the age of 25. This meta-analysis does not include studies where quetiapine was used.

In short-term, placebo-controlled studies across all indications and in all age groups, the incidence of suicide events was 08% for both quetiapine (76/9327) and placebo (37/4845).

In these studies in patients with schizophrenia, the risk of suicide-related events was 14% (3/212) for quetiapine and 16% (1/62) for placebo in patients aged 18–24 years; 08% (13/1663) for quetiapine and 11% (5/463) for placebo in patients over 25 years of age; 14% (2/147) for quetiapine and 13% (1/75) for placebo in patients under 18 years of age.

In patients with manic 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; 12% (6/496) for quetiapine and 12% (6/503) for placebo in patients over 25 years of age; 10% (2/192) for quetiapine and 0% (0/90) for placebo in patients under 18 years of age.

Drowsiness

During quetiapine therapy, drowsiness and associated symptoms such as sedation may occur. In clinical studies involving patients with depression as part of bipolar disorder, somnolence typically developed during the first three days of therapy. The severity of this side effect was generally minor or moderate. If severe sleepiness develops, patients with depression as part of bipolar disorder may require more frequent visits to the doctor for 2 weeks after the onset of sleepiness or until symptoms improve. In some cases, discontinuation of quetiapine therapy may be necessary.

Patients with cardiovascular diseases

Caution should be exercised when prescribing quetiapine to patients with cardiovascular and cerebrovascular diseases and other conditions predisposing to hypotension.

Orthostatic hypotension may occur during quetiapine therapy, especially during dose titration at the beginning of therapy. Orthostatic hypotension and associated dizziness may increase the risk of accidental injury (fall), especially in older patients.

Patients should exercise caution until they adjust to these potential side effects. If orthostatic hypotension occurs, dose reduction or slower titration may be necessary.

Sleep apnea syndrome

Sleep apnea syndrome has been reported in patients taking quetiapine. Caution should be exercised when prescribing quetiapine to patients receiving drugs that have a depressant effect on the central nervous system, as well as patients with risk factors for sleep apnea (for example, overweight/obese male gender) or with a history of sleep apnea.

Seizures

There were no differences in the incidence of seizures in patients taking quetiapine or placebo. However, as with other antipsychotic drugs, caution is recommended when treating patients with a history of seizures with quetiapine.

Extrapyramidal symptoms

There was an increase in the incidence of EPS in adult patients with depression in the structure of bipolar disorder when taking quetiapine for depressive episodes compared to placebo.

While taking quetiapine, akathisia may occur, which is characterized by an unpleasant feeling of motor restlessness and the need to move and is manifested by the patient’s inability to sit or stand without moving. If such symptoms occur, the dose of quetiapine should not be increased.

Tardive dyskinesia

If symptoms of tardive dyskinesia develop, it is recommended to reduce the dose of the drug or gradually discontinue it. Symptoms of tardive dyskinesia may worsen or even occur after you stop taking the drug.

Neuroleptic malignant syndrome

While taking antipsychotic drugs, including quetiapine, neuroleptic malignant syndrome may develop. Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, lability of the autonomic nervous system, and increased creatine phosphokinase activity. In such cases, it is necessary to discontinue quetiapine and carry out appropriate treatment.

Severe neutropenia and agranulocytosis

In short-term, placebo-controlled clinical trials of quetiapine monotherapy, cases of severe neutropenia (neutrophil count <05 x 109/L) without infection were reported infrequently. The development of agranulocytosis (severe neutropenia associated with infections) has been reported in patients receiving quetiapine in clinical trials (rare) and during post-marketing use (including death). Most of these cases of severe neutropenia occurred several months after initiation of quetiapine therapy. No dose-dependent effect was found.

Leukopenia and/or neutropenia resolved after discontinuation of quetiapine therapy. A possible risk factor for the occurrence of neutropenia is a previous low white blood cell count and a history of drug-induced neutropenia. The development of agranulocytosis was also noted in patients without risk factors. The possibility of developing neutropenia in patients with infection must be considered, especially in the absence of obvious predisposing factors or in patients with unexplained fever; these cases should be managed in accordance with clinical guidelines.

In patients with a neutrophil count <10 x 109/L, quetiapine should be discontinued. The patient should be observed for possible symptoms of infection and the neutrophil level should be monitored (until the level exceeds 15 x 109/L).

Quetiapine

Children and adolescents (ages 10 to 17 years)

Quetiapine is not indicated for use in children and adolescents under 18 years of age due to insufficient data on use in this age group. According to the results of clinical studies of quetiapine, some side effects (increased appetite, increased serum prolactin concentrations, vomiting, runny nose and fainting) were observed with a higher frequency in children and adolescents than in adult patients. Some adverse events (AEs) may have different consequences in children and adolescents compared to adult patients. An increase in blood pressure was also noted, which was not observed in adult patients. Changes in thyroid function have also been observed in children and adolescents. The effects on growth, puberty, mental development and behavioral reactions with long-term use (more than 26 weeks) of quetiapine have not been studied.

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

Suicide/suicidal ideation or clinical worsening

Depression in bipolar disorder is associated with an increased risk of suicidal ideation, self-harm, and suicide (suicide-related events). This risk persists until significant remission occurs. Because it may take several weeks or more for the patient's condition to improve from the start 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. Patients (especially those at increased risk for suicide) and their caregivers should be warned to monitor for clinical worsening, suicidal behavior or thoughts, unusual changes in behavior, and to seek immediate medical attention if these occur.

In clinical trials in depressed patients with 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 patients over 25 years of age.

Other mental disorders for which quetiapine is prescribed are also associated with an increased risk of suicide-related events. In addition, such conditions may be comorbid with a depressive episode. Thus, the precautions used when treating patients with a depressive episode should also be taken when treating patients with other mental disorders.

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

An FDA meta-analysis of placebo-controlled studies of antidepressants, summing up data from approximately 4,400 children and adolescents and 7,700 adult patients with mental disorders, found an increased risk of suicidal behavior with antidepressants compared with placebo in children. adolescents and adult patients under 25 years of age. This meta-analysis does not include studies that used quetiapine.

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

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

In patients with manic 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 over 25 years of age; 1.0% (2/192) for quetiapine and 0% (0/90) for placebo in patients under 18 years of age.

Drowsiness

Drowsiness and associated symptoms such as sedation may occur during quetiapine therapy. In clinical studies involving patients with depression as part of bipolar disorder, somnolence usually developed during the first three days of therapy. The severity of this side effect was generally minor or moderate. If severe sleepiness develops, patients with depression as part of bipolar disorder may require more frequent visits to the doctor for 2 weeks after the onset of sleepiness or until symptoms improve. In some cases, discontinuation of quetiapine therapy may be necessary.

Patients with cardiovascular diseases

Caution should be exercised when prescribing quetiapine to patients with cardiovascular and cerebrovascular disease, and other conditions predisposing to hypotension.

Patients should use caution until they adjust to these potential side effects. If orthostatic hypotension occurs, dose reduction or slower titration may be necessary.

Sleep apnea syndrome

Seizures

Extrapyramidal symptoms

There was an increase in the incidence of EPS in adult patients with depression in the structure of bipolar disorder when taking quetiapine for depressive episodes compared to placebo.

While taking quetiapine, akathisia may occur, which is characterized by an unpleasant feeling of motor restlessness and the need to move, and is manifested by the patient's inability to sit or stand without moving. If such symptoms occur, the dose of quetiapine should not be increased.

Tardive dyskinesia

Neuroleptic malignant syndrome

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 reported infrequently. The development of agranulocytosis (severe neutropenia associated with infections) has been reported in patients receiving quetiapine in clinical trials (rare), as well as during post-marketing use (including death). Most of these cases of severe neutropenia occurred several months after initiation of quetiapine therapy. No dose-dependent effect was found.

Leukopenia and/or neutropenia resolved after discontinuation of quetiapine therapy.
A possible risk factor for the occurrence of neutropenia is a previous low white blood cell count and a history of drug-induced neutropenia. The development of agranulocytosis was also noted in patients without risk factors. The possibility of neutropenia should be considered in patients with infection, especially in the absence of obvious predisposing factors, or in patients with unexplained fever; these cases should be managed in accordance with clinical guidelines. In patients with a neutrophil count <1.0 x 109/L, quetiapine should be discontinued. The patient should be observed for possible symptoms of infection and the neutrophil level should be monitored (until the level exceeds 1.5 x 109/L).

Quetiapine-sz tablet p/o film 25mg 60 pcs

Somnolence During therapy with Quetiapine-SZ, somnolence and associated symptoms, such as sedation, may be observed (see section "Side effects"). In clinical studies involving patients with depression in the structure of bipolar disorder, somnolence usually developed over the course of the first three days of therapy. The severity of this side effect was generally minor or moderate. If severe sleepiness develops, patients with depression as part of bipolar disorder may require more frequent visits to the doctor for 2 weeks after the onset of sleepiness or until symptoms improve. In some cases, it may be necessary to discontinue therapy with Quetiapine-SZ. Patients with cardiovascular diseases Caution should be exercised when prescribing Quetiapine-SZ to patients with cardiovascular and cerebrovascular diseases, and other conditions predisposing to hypotension. During therapy with Quetiapine-SZ, orthostatic hypotension may occur, especially during dose titration at the beginning of therapy. If orthostatic hypotension occurs, dose reduction or slower titration may be necessary.

Seizures There were no differences in the incidence of seizures in patients taking Quetiapine-SZ or placebo. However, as with the treatment of other antipsychotic drugs, it is recommended to exercise caution when treating patients with a history of seizures (see section “Side Effects”). Extrapyramidal symptoms An increase in the incidence of EPS has been noted in adult patients with depression in the structure of bipolar disorder with taking Quetiapine-SZ for depressive episodes compared to placebo (see section “Side effects”).

Tardive dyskinesia If symptoms of tardive dyskinesia develop, it is recommended to reduce the dose of the drug or gradually discontinue it (see section “Side effects”). Neuroleptic malignant syndrome While taking antipsychotic drugs, including Quetiapine-SZ, neuroleptic malignant syndrome may develop (see section “Side effects”). Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, lability of the autonomic nervous system, and increased creatine phosphokinase activity. In such cases, it is necessary to discontinue Quetiapine-SZ and carry out appropriate treatment.

Severe neutropenia In clinical studies of Quetiapine-SZ, cases of severe neutropenia (neutrophil count

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

Prescribing Quetiapine-SZ to patients receiving liver enzyme inducers is possible only if the expected benefit from therapy with Quetiapine-SZ outweighs the risk associated with discontinuation of the liver enzyme inducer drug. Changing the dose of drugs that induce microsomal enzymes should be gradual. If necessary, they can be replaced with drugs that do not induce microsomal enzymes (for example, valproic acid drugs). Hyperglycemia While taking quetiapine, hyperglycemia or exacerbation of diabetes mellitus may develop in patients with a history of diabetes mellitus. Clinical monitoring of patients with diabetes mellitus and patients with risk factors for developing diabetes mellitus is recommended (see section "Side effects").

Lipid levels While taking quetiapine, the concentration of triglycerides and cholesterol may increase (see section “Side effects”). Prolongation of the QT interval There was no relationship between taking quetiapine and a persistent increase in the absolute value of the QT interval. However, prolongation of the QT interval was observed with an overdose of the drug (see section "Overdose"). Caution should be exercised when prescribing quetiapine, as with other antipsychotic drugs, to patients with cardiovascular disease and a history of QT prolongation. Caution should also be exercised when prescribing quetiapine concomitantly with drugs that prolong the QTc interval, other antipsychotics, especially in the elderly, patients with congenital long QT syndrome, chronic heart failure, myocardial hypertrophy, hypokalemia or hypomagnesemia (see section "Interaction with Others"). drugs").

Acute reactions associated with drug withdrawal When abruptly discontinuing quetiapine, the following acute reactions (withdrawal syndrome) may occur: nausea, vomiting, insomnia, headache, dizziness and irritability. Therefore, it is recommended to discontinue the drug gradually over at least one or two weeks. Elderly patients with dementia

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

An analysis of the use of atypical antipsychotics for the treatment of psychosis associated with dementia in elderly patients revealed an increased mortality 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; mean 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 death observed in these patients were consistent with those expected for this population. No causal relationship has been identified between treatment with Quetiapine-SZ and the risk of increased mortality in elderly patients with dementia. Suicide/suicidal ideation or clinical worsening Depression is associated with an increased risk of suicidal ideation, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. Because it may take several weeks or more for the patient's condition to improve from the start 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.

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 intent and suicide attempts and should be carefully monitored during treatment. An FDA meta-analysis of placebo-controlled studies of antidepressants, summing up data from approximately 4,400 children and adolescents and 7,700 adult patients with mental disorders, found an increased risk of suicidal behavior with antidepressants compared with placebo in children, adolescents and adult patients under 25 years of age. This meta-analysis does not include studies where quetiapine was used (see Pharmacodynamics section).

In short-term, placebo-controlled studies across all indications and all age groups, the incidence of suicide events was 0.9% for both quetiapine (61/6270) and placebo (27/3047). In these studies in patients with schizophrenia, the risk of suicide-related events was 1.4% (3/212) for quetiapine and 1.6% (1/62) for placebo in patients aged 18–24 years; 0.8% (13/1663) for quetiapine and 1.1% (5/463) for placebo in patients over 25 years of age; 1.4% (2/147) for quetiapine and 1.3% (1/75) for placebo in patients under 18 years of age.

In patients with manic bipolar disorder, the risk of suicide-related 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 over 25 years of age;

1.0% (2/193) for quetiapine and 0% (0/90) for placebo in patients under 18 years of age (see section "Special Instructions"). In patients with depression due to bipolar disorder, the risk of developing events related to with suicide was 3.0% (7/233) for quetiapine and 0% (0/120) for placebo in patients aged 18-24 years; 1.8% (19/1616) for quetiapine and 1.8% (11/622) for placebo in patients over 25 years of age. No studies have been conducted in patients with depression due to bipolar disorder under the age of 18 years.

Impact on the ability to drive vehicles or operate machinery Quetiapine-SZ may cause drowsiness, therefore, during the treatment period, patients are not recommended to work with dangerous mechanisms, including driving.