Children and adolescents (aged 10 to 17 years)
The drug Quetiapine Kanon 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 of quetiapine, some side effects (increased appetite, increased serum prolactin concentration, vomiting, runny nose and fainting) in children and adolescents were observed with a greater frequency than in adult patients. Some side effects (EPS) in children and adolescents may have different effects compared to older patients. There was also an increase in blood pressure, not observed in adult patients. In children and adolescents also observed a change in the function of the thyroid gland.
Influence 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 frequency the development of EPS was higher with quetiapine compared with placebo.
Elderly patients with psychoses due to dementia
The results of several placebo-controlled studies showed that the use of atypical antipsychotic drugs in elderly patients with psychoses due to dementia approximately 3-fold increased the risk of developing cerebrovascular complications in patients with dementia. 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. The drug Quetiapine canon should be used with caution in patients at risk of stroke.
Suicide / suicidal thoughts or clinical worsening
Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self harm and suicide (events related to 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. Patients (especially those at high risk for suicide) and their caregivers should be warned about the need to monitor clinical impairment, suicidal behavior or thoughts, unusual behavioral changes, and the need to consult a doctor immediately if they occur.
According to clinical studies in depressed patients with bipolar disorder, the risk of suicidal events was 3.0% (7/233) for quetiapine and 0% (0/120) for placebo in patients aged 18-24 years; 1.8% (19/1616) for quetiapine and 1.8% (11/622) for placebo for patients over 25 years of age.
Other psychiatric disorders for which therapy is prescribed quetiapineare also associated with an increased risk of suicidal events. In addition, such conditions can be comorbid with a depressive episode. Therefore, the precautions used in the therapy of patients with a depressive episode should be taken in the treatment of patients with other psychiatric disorders.With a sharp cessation of quetiapine therapy, the potential risk of suicidal 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 observed during treatment. Conducted FDA (Food and Drug Administration, USA), a meta-analysis of placebo-controlled studies of antidepressants, summarizing data from approximately 4,400 children and adolescents and 7,700 adult patients with mental disorders, revealed an increased risk of suicidal behavior against antidepressants compared with placebo in children, adolescents and adult patients under the age of 25 years. This meta-analysis does not include studies where it was used quetiapine (see the section "Pharmacodynamics").
According to short-term placebo-controlled studies for all indications and in all age groups, the frequency of events associated with suicide, was 0.8% for both quetiapine (76/9327) and placebo (37/4845).
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 placebo in patients older than 25 years; 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% (0/60) 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 older than 25 years; 1.0% (2/193) for quetiapine and 0% (0/90) for placebo in patients under the age of 18 years.
All patients who are prescribed antidepressants should be observed for the development of suicidal tendencies and behavioral changes, especially in the first months of treatment and with a change in the dose of the drug.
Drowsiness and dizziness
During therapy with Quetiapine Canon, drowsiness and related symptoms, for example sedation (see "Side effect"), may be noted. In clinical studies involving patients with depression in the structure of bipolar disorder, sleepiness tended to develop during the first three days of therapy.The severity of this side effect was mostly mild or moderate. With the development of severe drowsiness, patients with depression in the structure of bipolar disorder may need more frequent visits to the doctor within 2 weeks of the onset of drowsiness or to a decrease in the severity of symptoms. In some cases, quetiapine canon therapy may be required.
On the background of quetiapine therapy, orthostatic hypotension and dizziness may occur (see the "Side effect" section), usually during dose selection at the beginning of therapy. Patients, especially the elderly, should be careful to avoid accidental injuries (falls).
Patients with cardiovascular diseases
Caution should be exercised in prescribing quetiapine to patients with cardiovascular and cerebrovascular diseases, and other states predisposing to hypotension. On the background of therapy quetiapine may cause orthostatic hypotension, especially in the time of titration of the dose at the beginning of therapy. Orthostatic hypotension and related dizziness may increase the risk of accidental trauma (fall), especially in elderly patients.Patients should be cautious until they adapt to these potential side effects. If orthostatic hypotension occurs, a dose reduction or slower titration may be required.
Convulsive seizures
There were no differences in the incidence of seizures in patients who took quetiapine or placebo. However, as with other antipsychotic drugs, caution should be exercised in the treatment of patients with a history of seizures (see "Side effect").
Extrapyramidal symptoms
An increase in the incidence of EPS in patients with depression in the structure of bipolar disorder with quetiapine for depressive episodes compared with placebo was noted (see "Side effect"),
Late dyskinesia
Against the background of taking antipsychotics, including quetiapine, tardive dyskinesia may occur, which is manifested by violent involuntary movements and may be irreversible. In the case of the 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 the "Side effect" section).
Against the background of taking quetiapine may occur akathisia, 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 without movement. If such symptoms occur, do not increase the dose of quetiapine. Against the background of taking quetiapine may occur akathisia, which is characterized by an unpleasant feeling of motor anxiety and the need to move, and is manifested by the inability of the patient to sit or stand without movement. If such symptoms occur, do not increase the dose of quetiapine.
Malignant neuroleptic syndrome
Against the background of taking antipsychotic drugs, including quetiapine, can develop malignant neuroleptic syndrome (see the section "Side effect"). Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, lability in the autonomic nervous system, increased activity of creatine phosphokinase.In such cases, it is necessary to cancel quetiapine and conduct appropriate treatment.
Severe neutropenia and agranulocytosis
In the short-term placebo-controlled clinical trials of monotherapy with quetiapine, cases of severe neutropenia (number of neutrophils <0.5 x 109/ l) without infection. Agranulocytosis (severe neutropenia associated with infections) was reported in patients who received quetiapine in clinical trials (rarely), as well as in post-marketing (including fatal) cases. Most of these 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 a history.
The development of agranulocytosis was also noted in patients without risk factors. It is necessary to consider 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 a neutrophil count <1.0 x 109/ l, quetiapine should be discontinued. The patient should be observed to identify possible symptoms of infection and monitor the level of neutrophils (up to a level of 1.5 x 109/ l).
Interaction with other drugs
Also see the section "Interaction with other drugs". 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 can reduce the effectiveness of therapy with Quetiapine Canon.
The use of the preparation Quetiapine canon in patients receiving inducers of microsomal liver enzymes is possible only in that case, if the expected benefit from therapy with Quetiapine Canon exceeds the risk associated with cancellation of inducers of microsomal liver enzymes.The change in the dose of inductor preparations of microsomal liver enzymes should be gradual. If necessary, they can be replaced with drugs that do not induce microsomal liver enzymes (eg, preparations of valproic acid).
Body mass
Against the background of taking quetiapine, there was an increase in body weight. Clinical observation of patients in accordance with established standards of therapy is recommended (see section "Side effect").
Hyperglycaemia
Against the background of taking quetiapine may develop hyperglycemia or exacerbation of diabetes mellitus (in some cases - with the development of ketoacidosis or coma, including fatal), in patients with diabetes mellitus in history. It is recommended that patients who receive quetiapine and other neuroleptics, to identify possible symptoms of hyperglycemia, such as polyuria (increased urine output), polydipsia (pathologically increased thirst), polyphagia (increased appetite), and weakness. It is also recommended to monitor patients with diabetes mellitus and patients with risk factors for the development of diabetes mellitus in order to detect possible impairment of glycemic control.section "Side effect"). Regular body weight should be monitored regularly.
Lipid content
Against the background of taking quetiapine may increase the concentration of triglycerides, cholesterol and LDL, as well as a decrease in the concentration of HDL (see section "Side effect").
Metabolic disorders
An increase in body weight, an increase in the concentration of glucose and lipids in the blood in some patients can lead to a deterioration in the metabolic profile, which requires appropriate monitoring.
Interval lengthening QT
There was no correlation between the use of quetiapine and the steady increase in the absolute value of the interval QT. However, the lengthening of the interval QT was noted during an overdose of the drug (see the section "Overdose"). Caution should be exercised when assigning quetiapine, as well as other antipsychotics, to patients with cardiovascular disease and the previously noted lengthening of the interval QT. Also, care should be taken when administering quetiapine concurrently with drugs that extend the interval QT, other neuroleptics, especially in the elderly, in patients with the syndrome of congenital lengthening of the interval QT, chronic heart failure, myocardial hypertrophy, hypokalemia, or hypomagnesemia (see section "Interaction with other drugs").
Cardiomyopathy and myocarditis
During clinical trials and post-marketing use, cases of cardiomyopathy and myocarditis have been noted, but a causal relationship with the drug has not been established. It is necessary to evaluate the feasibility of quetiapine therapy in patients with suspected cardiomyopathy or myocarditis.
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, the withdrawal of the drug it is advisable to carry out gradually for at least one or two weeks.
Disorders from the side of the liver
If jaundice develops, quetiapine canon should be discontinued.
Dysphagia
Dysphagia (see "Side effect") and aspiration were observed with quetiapine therapy. The causal relationship between the onset of aspiration pneumonia and the administration of quetiapine has not been established.However, care should be taken when prescribing the drug to patients at risk of aspiration pneumonia.
Venous thromboembolism
Against the background of taking neuroleptics, cases of venous thromboembolism were noted. Since patients with antipsychotics often have risk factors for venous thromboembolism, risk factors should be assessed and preventive measures taken before and during therapy with antipsychotics, including quetiapine.
Constipation and obstruction of the intestine
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 "Side effect" section), including fatal cases in patients with a high risk of intestinal obstruction, including those receiving multiple concomitant medications that reduce intestinal motility, even in the absence of complaints for constipation.
Pancreatitis
During clinical trials and post-marketing use, cases of pancreatitis have been noted, but a causal relationship with the drug has not been established. In post-marketing messages it is indicated that many patients were at risk for developing pancreatitis, such as increased triglyceride concentrations, cholelithiasis, and alcohol use.
Additional Information
Data on the combined use of quetiapine with divalproex or lithium in acute manic episodes of mild or moderate severity are limited. A good tolerability of this combination therapy and an additive effect at the third week of therapy were noted.
Long-term safety and efficacy of Quetiapine Canon as an adjunctive therapy for the treatment of major depressive disorder have not been studied, but the safety and efficacy profile has been studied with monotherapy.