Quetiapine Canon Prolong, 150 mg 60 pcs

• treatment of schizophrenia;
• treatment of bipolar disorder;
• moderate and severe manic episodes in the structure of bipolar disorder;
• severe episodes of depression in the structure of bipolar disorder.

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Indications

treatment of schizophrenia;
treatment of bipolar disorder;
moderate and severe manic episodes in the structure of bipolar disorder;
severe episodes of depression in the structure of bipolar disorder.

Special instructions

Children and adolescents (ages 10 to 17 years)

Quetiapine Canon 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 EPS was higher with quetiapine compared with placebo.

Elderly patients with psychosis due to dementia

Results from several placebo-controlled studies have shown that the use of atypical antipsychotic drugs in elderly patients with psychosis due to dementia increased the risk of developing cerebrovascular complications in patients with dementia by approximately 3 times. 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 Canon should be used with caution in patients at risk of stroke.

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.

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, 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 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 0.8% 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% (2/193) for quetiapine and 0% (0/90) for placebo in patients under 18 years of age.

All patients prescribed antidepressants should be monitored for the development of suicidality and behavior changes, especially in the first months of treatment and when the dose of the drug is changed.

Drowsiness and dizziness

During therapy with Quetiapine Canon, drowsiness and associated symptoms, such as sedation, may occur (see section “Side effects”). 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, it may be necessary to discontinue therapy with Quetiapine Canon.

During quetiapine therapy, orthostatic hypotension and dizziness may occur (see section “Side effects”), usually during dose titration at the beginning of therapy. Patients, especially older patients, should be careful to avoid accidental injury (falls).

Patients with cardiovascular diseases

Caution should be exercised when prescribing quetiapine to patients with cardiovascular and cerebrovascular disease, 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 use caution until they adjust to these potential side effects. 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 or placebo. However, as with other antipsychotic drugs, caution is recommended when treating patients with a history of seizures (see section “Side effects”).

Extrapyramidal symptoms

There was an increase in the incidence of EPS in patients with depression in the structure of bipolar disorder when taking quetiapine for depressive episodes compared to placebo (see section “Side effects”).

Tardive dyskinesia

While taking antipsychotics, including quetiapine, tardive dyskinesia may occur, which is manifested by violent involuntary movements and may be irreversible. 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 intensify or even occur after stopping the drug (see section “Side effects”).

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. 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.

Neuroleptic malignant syndrome

While taking antipsychotic drugs, including quetiapine, 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 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 <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).

Interaction with other drugs

Also see the section “Interaction with other drugs”. 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 the blood plasma and may reduce the effectiveness of therapy with Quetiapine Canon.

The use of Quetiapine Canon in patients receiving inducers of microsomal liver enzymes is possible only if the expected benefit from therapy with Quetiapine Canon outweighs the risk associated with discontinuation of inducers of microsomal liver enzymes. Changing the dose of drugs that induce microsomal liver enzymes should be gradual. If necessary, it is possible to replace them with drugs that do not induce microsomal liver enzymes (for example, valproic acid drugs).

Body weight

An increase in body weight was observed while taking quetiapine. Clinical monitoring of patients is recommended in accordance with accepted standards of therapy (see section “Side Effects”).

Hyperglycemia

While taking quetiapine, it is possible to develop hyperglycemia or exacerbation of diabetes mellitus (in some cases, with the development of ketoacidosis or coma, including death), in patients with a history of diabetes mellitus. It is recommended to monitor patients receiving quetiapine and other antipsychotics for possible symptoms of hyperglycemia, such as polyuria (increased amount of urine output), polydipsia (abnormally increased thirst), polyphagia (increased appetite) and weakness. Monitoring of patients with diabetes mellitus and patients with risk factors for developing diabetes mellitus is also recommended to identify possible deterioration of glycemic control (see section “Side effects”). Body weight should be monitored regularly.

Lipid content

While taking quetiapine, there may be an increase in the concentration of triglycerides, cholesterol and LDL, as well as a decrease in the concentration of HDL (see section “Side effects”).

Metabolic disorders

Increased body weight, increased concentrations of glucose and lipids in the blood in some patients can lead to a deterioration in the metabolic profile, which requires appropriate monitoring.

QT prolongation

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. It is also necessary to be careful when prescribing quetiapine simultaneously with drugs that prolong the QT interval, other antipsychotics, especially in the elderly, in patients with congenital long QT syndrome, 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 were observed, but a causal relationship with the drug has not been established. The appropriateness of quetiapine therapy should be assessed in patients with suspected cardiomyopathy or myocarditis.

Acute reactions associated with drug withdrawal

If quetiapine is abruptly discontinued, 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.

Liver disorders

If jaundice develops, Quetiapine Canon should be discontinued.

Dysphagia

Dysphagia (see section “Side effects”) and aspiration were observed during therapy with quetiapine. The cause-and-effect relationship between the occurrence of aspiration pneumonia and the use of quetiapine has not been established. However, caution should be exercised when prescribing the drug to patients at risk of aspiration pneumonia.

Venous thromboembolism

Cases of venous thromboembolism have been reported while taking antipsychotics. Because risk factors for venous thromboembolism are common in patients taking antipsychotics, risk factors should be assessed and preventive measures taken before and during therapy with antipsychotics, including quetiapine.

Constipation and intestinal obstruction

Constipation is a risk factor for intestinal obstruction. During the use of quetiapine, the development of constipation and intestinal obstruction was noted (see section “Side effects”), including cases with a fatal outcome 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.

Pancreatitis

During clinical trials and post-marketing use, cases of pancreatitis were observed, but a causal relationship with the drug has not been established. Post-marketing reports indicate that many patients had risk factors for pancreatitis, such as elevated triglyceride concentrations, cholelithiasis and alcohol consumption.

Additional information

There are limited data on the concomitant use of quetiapine with divalproate or lithium for acute mild to moderate manic episodes. This combination therapy was well tolerated and had an additive effect in the 3rd week of therapy.

The long-term safety and efficacy of Quetiapine Canon as an adjunctive therapy in the treatment of major depressive disorder have not been studied, but the safety and efficacy profile has been studied in monotherapy.

Impact on the ability to drive vehicles and other mechanisms

Due to its effect on the central nervous system, quetiapine can affect the speed of psychomotor reactions and cause dizziness and drowsiness. Therefore, during the treatment period, patients are not recommended to work with mechanisms that require increased concentration, including driving, until individual tolerance to therapy has been established.

Active ingredient

Quetiapine

Composition

Dosage 150 mg

1 film-coated tablet contains:

Active ingredients:

quetiapine 150 mg.

Excipients:

hyprolose (hydroxypropylcellulose Klucel LF),

calcium hydrogen phosphate dihydrate,

calcium stearate,

pregelatinized corn starch,

magnesium stearate,

sodium carboxymethyl starch,

microcrystalline cellulose.

Film shell composition:

AquaPolish® D blue, incl. [hypromellose (hydroxypropyl methylcellulose), glycerol (glycerin), microcrystalline cellulose, talc, kandurin silver shine dye, indigo carmine dye.

Contraindications

Hypersensitivity to any of the components of the drug (including congenital deficiency of amylase or specific disaccharidases).
Childhood. (Although the effectiveness and safety of quetiapine in children and adolescents aged 10-17 years have been studied in clinical studies, the use of Quetiapine Canon in patients under the age of 18 years is not indicated).
Pregnancy and breastfeeding period.
Combined use with cytochrome P450 inhibitors, such as azole antifungals, erythromycin, clarithromycin and nefazodone, as well as HIV protease inhibitors (see section “Interaction with other drugs”).
Psychosis in elderly patients (over 65 years old) suffering from dementia.

With caution

In patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension; simultaneous administration with drugs that increase the QT interval (including antipsychotics), especially in elderly patients, in patients with congenital long QT interval syndrome, congestive heart failure, myocardial hypertrophy, hypokalemia or hypomagnesemia; combination with drugs that have a depressant effect on the central nervous system (CNS) or alcohol; epilepsy and epileptic seizures (history); with a risk of stroke and aspiration pneumonia; in elderly patients; in patients with liver failure; dementia; Parkinson’s disease; diabetes mellitus

Side Effects

According to the World Health Organization (WHO), adverse reactions are classified according to the frequency of their development as follows: very often (>1/10); often (>1/100, 1/1000, 1/10000, <1/1000); very rare (< 1/10000); frequency unknown - based on available data, it was not possible to determine the frequency of occurrence.

Taking quetiapine, like other antipsychotic drugs, may be accompanied by fainting, the development of neuroleptic malignant syndrome, leukopenia, neutropenia and peripheral edema.

The most common side effects of quetiapine (>10%) are drowsiness, dizziness, dry mouth, withdrawal syndrome, increased triglyceride concentrations, increased total cholesterol concentrations (mainly low-density lipoprotein cholesterol – LDL), decreased high-density lipoprotein cholesterol (HDL) concentrations, weight gain, decreased hemoglobin concentrations and extrapyramidal symptoms.

Interaction

Caution should be exercised when combining quetiapine with other drugs that affect the central nervous system, as well as with alcohol. The use of quetiapine with alcohol or drugs that affect the central nervous system may increase the sedative effect.

Cytochrome P450 isoenzyme (CYP) 3A4 is the main isoenzyme responsible for the metabolism of quetiapine through the cytochrome P450 system. In healthy volunteers, co-administration of quetiapine (at a dose of 25 mg) with ketoconazole, an inhibitor of the CYP3A4 isoenzyme, led to an increase in the area under the concentration-time curve (AUC) of quetiapine by 5-8 times. Therefore, the combined use of quetiapine and inhibitors of the CYP3A4 isoenzyme (ketoconazole, HIV protease inhibitors, erythromycin, clarithromycin, etc.) is contraindicated. It is also not recommended to take quetiapine with grapefruit juice.

Dopamine agonists and/or antiparkinsonian drugs have an antagonistic effect on quetiapine. In a pharmacokinetic study, repeated dosing of quetiapine before or concomitantly with carbamazepine resulted in a significant increase in quetiapine clearance and a corresponding decrease in AUC by an average of 13% compared to quetiapine administered without carbamazepine. In some patients, the decrease in AUC was even more pronounced. This interaction is accompanied by a decrease in quetiapine plasma concentrations and may reduce the effectiveness of quetiapine therapy.

The combined use of quetiapine with phenytoin, another inducer of microsomal liver enzymes, was accompanied by an even more pronounced (approximately 450%) increase in the clearance of quetiapine. The use of quetiapine in patients receiving microsomal liver enzyme inducers is possible only if the expected benefit from quetiapine therapy outweighs the risk associated with discontinuation of the microsomal liver enzyme inducer drug. Changing the dose of drugs that induce microsomal liver enzymes should be gradual. If necessary, it is possible to replace them with drugs that do not induce microsomal liver enzymes (for example, valproic acid drugs).

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

The pharmacokinetics of quetiapine does not change significantly when used concomitantly with the antipsychotic drugs risperidone or haloperidol. However, concomitant use of quetiapine and thioridazine resulted in an approximately 70% increase in quetiapine clearance.

The pharmacokinetics of quetiapine does not change significantly with 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 is reduced by approximately 20%.

The pharmacokinetics of lithium preparations does not change with simultaneous use of quetiapine. When quetiapine was coadministered with lithium in adult patients with an acute manic episode, there was a higher incidence of EPS-related adverse reactions (especially tremor), somnolence, and weight gain compared with patients taking quetiapine with placebo in a 6-week randomized trial.

There were no clinically significant changes in the pharmacokinetics of valproic acid and quetiapine with the combined use of semisodium valproate and quetiapine.

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

Caution should be exercised when using quetiapine in combination with drugs that can cause electrolyte imbalance and prolongation of the QT interval.

Quetiapine did not induce liver microsomal enzymes involved in the metabolism of phenazone.

False-positive results of screening tests for methadone and tricyclic antidepressants using enzyme-linked immunosorbent assays have been reported in patients taking quetiapine. To confirm the screening results, a chromatographic study is recommended.

Overdose

A death was reported with 13.6 g of quetiapine in a patient participating in a clinical trial, and a death was reported with 6 g of quetiapine in a post-marketing study. At the same time, a case of taking quetiapine in a dose exceeding 30 g without death has been described.

There are reports of extremely rare cases of quetiapine overdose, leading to an increase in the QT interval, death or coma.

In patients with a history of severe cardiovascular disease, the risk of side effects from overdose may increase (see section “Special Instructions”).

Symptoms

Symptoms noted in overdose were mainly due to an increase in the known pharmacological effects of the drug, such as drowsiness and sedation, tachycardia and decreased 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 drugs. It is recommended to take measures aimed at maintaining respiratory and cardiovascular function, ensuring adequate oxygenation and ventilation.

If refractory hypotension occurs with quetiapine overdose, treatment should be with intravenous fluids and/or sympathomimetic drugs (epinephrine and dopamine should not be given, since stimulation of β-adrenergic receptors may cause increased hypotension due to alpha-adrenergic receptor blockade with quetiapine).

Gastric lavage (after intubation if the patient is unconscious) and the administration of activated charcoal and laxatives may help eliminate unabsorbed quetiapine, but the effectiveness of these measures has not been studied. Close medical observation should continue until the patient’s condition improves.

Storage conditions

In a place protected from light, at a temperature not exceeding 25 °C.

Shelf life

4 years

Manufacturer

Kanonpharma production CJSC, Russia