Quetiapine Canon Prolong, 400 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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Active ingredient

Composition

Dosage 400 mg

1 film-coated tablet contains:

Active substances:

Quetiapine 400 mg.

Associates:

Hyprolose (Clucel LF hydroxypropylcellulose),

p> calcium hydrophosphate dihydrate,

calcium stearate,

corn starch pregelatinized,

magnesium stearate,

sodium carboxymethyl starch,

microcrystalline cellulose.

Composition of the film coating:

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

How to take, the dosage

To be taken orally, twice daily, regardless of meals.

The drug should be prescribed by a physician experienced in the therapy of bipolar disorders.

The treatment of schizophrenia.

The daily dose for the first 4 days of therapy is 50 mg (day 1), 100 mg (day 2),
200 mg (day 3), 300 mg (day 4).

From day 4, the dose should be titrated to effective, ranging from
300 to 450 mg/day. Depending on clinical effect and individual patient tolerance, the dose may vary from 150 to 750 mg/day. For treatment of schizophrenia, the maximum recommended daily dose of Quetiapine Canon is
750 mg/day.

The treatment of moderate to severe manic episodes in the structure of bipolar disorder

Quetiapine is used as monotherapy or as adjuvant therapy for mood stabilization.

The daily dose for the first 4 days of therapy is 100 mg (day 1), 200 mg (day 2), 300 mg (day 3), 400 mg (day 4). Further, by the 6th day of therapy, the daily dose of the drug can be increased to 800 mg. Increase in the daily dose should not exceed 200 mg per day.

Depending on clinical effect, individual tolerance, the dose may vary from 200 to 800 mg/day. Typically, the effective dose is 400 to 800 mg/day.

For the treatment of manic episodes within the structure of bipolar disorder, the maximum recommended daily dose of quetiapine is
800 mg/day.

Treatment of severe episodes of depression in the structure of bipolar disorder

Quetiapine is prescribed once/day at bedtime. The recommended dose is 300 mg. The daily dose for the first 4 days of therapy is: Day 1 – 50 mg (1/2 tablet 100 mg), Day 2 – 100 mg, Day 3 – 200 mg, Day 4 – 300 mg. Maximum daily dose is 600 mg. No clinical improvement has been noted with doses greater than 600 mg.

Elderly Patients

In elderly patients, Quetiapine Canon is administered with caution, especially during the initial dose adjustment period, starting with a dose of 25 mg/day, with daily increases of 25-50 mg thereafter until an effective dose is reached, which is likely to be lower than in younger patients. If necessary, the dose of quetiapine may be titrated more slowly, taking into account the therapeutic efficacy and individual patient tolerability.

Renal impairment

Patients with renal impairment do not require dosing adjustments.

Hepatic impairment

Patients with hepatic impairment use Quetiapine Canon with caution, especially during initial dose adjustment, starting therapy at 25 mg/day. Depending on therapeutic activity and individual intolerance, the drug dose may be increased by 25-50 mg/day until an effective dose is achieved.

Interaction

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

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

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

The co-administration of vetiapine with phenytoin, another inducer of microsomal liver enzymes, was accompanied by an even more pronounced (approximately 450%) increase in clearance of vetiapine. The use of quetiapine in patients receiving microsomal liver enzymes inducers is possible only if the expected benefit of quetiapine therapy exceeds the risk associated with withdrawal of the microsomal liver enzymes inducer drug. Changes in the dose of microsomal enzyme inducers should be gradual. If necessary, their substitution with drugs that do not induce microsomal liver enzymes (for example, valproic acid preparations) is possible.

The pharmacokinetics of quetiapine were not significantly changed by concomitant use of the antidepressant imipramine (CYP2D6 isoenzyme inhibitor) or fluoxetine (CYP3A4 and CYP2D6 isoenzyme inhibitor).

The pharmacokinetics of quetiapine are not significantly altered by concomitant use with the antipsychotic drugs risperidone or haloperidol. However, concomitant administration of quetiapine and thioridazine resulted in increased clearance of quetiapine by approximately 70%.

The pharmacokinetics of quetiapine are not significantly altered by concomitant use of cimetidine.

Lorazepam clearance is decreased by approximately 20% when 2 mg of lorazepam is taken once with quetiapine at a dose of 250 mg twice daily.

The pharmacokinetics of lithium preparations are not altered by concomitant use of quetiapine. A higher incidence of EPS-related adverse reactions (particularly tremor), somnolence, and weight gain was noted with concomitant use of quetiapine with lithium drugs in adult patients with an acute manic episode compared with patients taking quetiapine with placebo in a 6-week randomized trial.

There were no clinically significant changes in valproic acid and quetiapine pharmacokinetics when valproate seminatria and quetiapine were used together.

Pharmacokinetic studies to study the interaction of quetiapine with drugs used for cardiovascular disease have not been conducted.

Caution should be exercised when combining quetiapine with drugs that may cause electrolyte imbalance and QT interval prolongation.

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

False positive screening tests for methadone and tricyclic antidepressants by enzyme immunoassay have been reported in patients taking quetiapine. Chromatographic testing is recommended to confirm screening results.

Special Instructions

Children and adolescents (10 to 17 years of age)

The drug Quetiapine Canon is not indicated for use in children and adolescents under the age of 18 years due to insufficient data on use in this age group. According to the results of clinical trials of quetiapine, some side effects (increased appetite, increased serum prolactin concentration, vomiting, runny nose and fainting) were observed with a higher frequency in children and adolescents than in adult patients. Some side effects (EPS) in children and adolescents may have different effects compared to adult patients. Increased blood pressure not seen in adult patients has also been noted. Changes in thyroid function have also been observed in children and adolescents.

The effects on growth, puberty, mental development, and behavioral responses have not been studied with long-term use (more than 26 weeks) of quetiapine.

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

Elderly patients with psychosis due to dementia

The results of several placebo-controlled studies have shown that the use of atypical antipsychotic medications by elderly patients with psychosis due to dementia increased the risk of cerebrovascular complications in patients with dementia by approximately 3-fold. The mechanism of this increased risk is not understood. A similar risk of increased incidence of cerebrovascular complications cannot be excluded for other antipsychotic medications or other patient groups. Quetiapine Canon should be used with caution in patients at risk of stroke.

Suicidal ideation/suicidal thoughts or clinical deterioration

Depression in bipolar disorder is associated with an increased risk of suicidal ideation, self-harm and suicide (suicide-related events). This risk persists until the onset of significant remission. Because it may be several weeks or more before a patient’s condition improves from the start of treatment, patients must be under close medical observation until improvement occurs.

Common clinical experience suggests that the risk of suicide may increase in the early stages of remission. Patients (especially those at high risk for suicide) and their caregivers should be warned to monitor for clinical deterioration, suicidal behavior or thoughts, unusual behavioral changes, and the need to see a physician immediately if they occur.

In clinical trials 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 in patients over 25 years.

Other psychiatric 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 in therapy for patients with a depressive episode should also be taken when treating patients with other psychiatric disorders. When stopping quetiapine therapy abruptly, the potential risk of suicidal events should be taken into account.

Patients with a history of suicidal events, as well as patients clearly expressing suicidal thoughts before initiating therapy, are at increased risk for suicidal intentions and suicide attempts and should be closely monitored during treatment. An FDA (Food and Drug Administration, USA) meta-analysis of placebo-controlled trials of antidepressants, summarizing data from approximately 4,400 children and adolescents and 7,700 adult patients with psychiatric disorders, found an increased risk of suicidal behavior on antidepressants compared to placebo in children, adolescents and adult patients under 25 years of age. This meta-analysis does not include studies using quetiapine (see Pharmacodynamics).

The rate of suicide-related events was 0.8% for both quetiapine (76/9327) and placebo (37/4845), based on short-term placebo-controlled studies in all indications and in all age groups.

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 older than 25 years; 1.4% (2/147) for quetiapine and 1.3% (1/75) for placebo in patients under 18 years of age.

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 18 years of age.

All patients prescribed antidepressants should be monitored for suicidal tendencies and behavioral changes, especially during the first months of treatment and when the drug dose is changed.

Sleepiness and dizziness

Sleepiness and associated symptoms, such as sedation, may occur during therapy with Quetiapine Canon (see section “Side effects”). In clinical studies involving patients with depression in the structure of bipolar disorder, somnolence usually developed during the first three days of therapy. The severity of this side effect was mostly mild to moderate. If severe somnolence develops, patients with depression in the structure of bipolar disorder may require more frequent visits to the physician within 2 weeks from the onset of somnolence or until the severity of symptoms decreases. In some cases, therapy with Quetiapine Canon may need to be discontinued.

In therapy with quetiapine, orthostatic hypotension and dizziness may occur (see section “Side effects”) usually during dose adjustment at the beginning of therapy. Patients, especially elderly patients, should be careful to avoid accidental injuries (falls).

Patients with cardiovascular disease

Patients with cardiovascular and cerebrovascular disease, and other conditions predisposing to hypotension should be cautious when prescribing quetiapine. Orthostatic hypotension may occur during therapy with quetiapine, especially during dose titration at the beginning of therapy. Orthostatic hypotension and associated dizziness may increase the risk of accidental injury (falling), especially in elderly patients. Patients should exercise caution until they adjust to these potential side effects. If orthostatic hypotension occurs, dose reduction or slower titration may be required.

Convulsive seizures

No differences were found in the incidence of seizures in patients taking quetiapine or placebo. However, as with therapy with other antipsychotic medications, caution is advised when treating patients with a history of seizures (see side effects).

Extrapyramidal symptoms

There has been an increased incidence of EPS in depressed patients with bipolar disorder when taking quetiapine for depressive episodes compared to placebo (see section “Side effects”).

Late dyskinesia

Late dyskinesia, which is manifested by violent involuntary movements and may be irreversible, may occur while taking neuroleptics, including quetiapine. If symptoms of tardive dyskinesia develop, it is recommended that the dose of the drug be reduced or gradually withdrawn. The symptoms of tardive dyskinesia may worsen or even occur after discontinuation of the drug (see section “Side effects”).

Akathisia, which is characterized by an uncomfortable feeling of motor restlessness and a need to move and is manifested by the patient’s inability to sit or stand without moving, may occur while taking quetiapine. If such symptoms occur, the dose of vetiapine should not be increased. Akathisia, characterized by an uncomfortable feeling of motor restlessness and a need to move, and manifested by the patient’s inability to sit or stand without movement, may occur while taking quetiapine. The dose of quetiapine should not be increased if these symptoms occur.

Malignant neuroleptic syndrome

Malignant neuroleptic syndrome can occur with antipsychotic drugs, including quetiapine (see section “Side effects”). Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, autonomic nervous system lability, and increased creatine phosphokinase activity. In such cases, quetiapine should be withdrawn and appropriate treatment should be given.

Severe neutropenia and agranulocytosis

In short-term placebo-controlled clinical trials of quetiapine monotherapy, severe neutropenia (neutrophil count <0.5 x 109/L) without infection has been reported infrequently. Agranulocytosis (severe neutropenia associated with infections) has been reported in patients receiving quetiapine as part of clinical trials (rare) and also during post-marketing use (including fatal). Most of these cases of severe neutropenia occurred several months after the start of quetiapine therapy. No dose-dependent effects have been identified. 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 has also been noted in patients without risk factors. The possibility of neutropenia in patients with infection, especially in the absence of obvious predisposing factors, or in patients with unexplained fever should be considered; these cases should be managed according to clinical guidelines.

In patients with a neutrophil count of <1.0 x 109/L, quetiapine should be discontinued. The patient should be monitored for possible symptoms of infection and neutrophil counts should be controlled (until they exceed 1.5 x 109/L).

Interaction with other medicinal products

Also see section “Interaction with other medicinal products”. Concomitant use of quetiapine with potent inducers of microsomal liver enzymes, such as carbamazepine and phenytoin, decreases the plasma concentration of quetiapine and may decrease the effectiveness of therapy with Quetiapine Canon.

The use of Quetiapine Canon in patients receiving liver microsomal enzyme inducers is possible only if the expected benefit of therapy with Quetiapine Canon exceeds the risk associated with withdrawal of liver microsomal enzyme inducers. Changes in the dose of microsomal liver enzyme inducers should be gradual. If necessary, they may be replaced with drugs that do not induce microsomal liver enzymes (e.g., valproic acid preparations).

Body weight

An increase in body weight has been noted during quetiapine administration. Clinical monitoring of patients is recommended according to the accepted standards of therapy (see section “Side effects”).

Hyperglycemia

Hyperglycemia or diabetes exacerbation (in some cases with the development of ketoacidosis or coma, including death) may develop during quetiapine use, in patients with a history of diabetes. It is recommended to monitor patients receiving quetiapine and other neuroleptics to detect possible symptoms of hyperglycemia, such as polyuria (increased urine output), polydipsia (abnormally increased thirst), polyphagia (increased appetite) and weakness. It is also recommended to monitor patients with diabetes mellitus and patients with risk factors of diabetes mellitus in order to detect possible worsening of glycemic control (see section “Side effects”). Body weight should be monitored regularly.

Lipid content

Quetiapine administration may increase triglyceride, cholesterol and LDL concentrations and decrease HDL concentrations (see section “Adverse effects”).

Metabolic disorders

Body weight gain and elevated blood glucose and lipid concentrations in some patients may lead to a worsening of the metabolic profile, which requires appropriate monitoring.

Long QT interval

There has been no identified relationship between quetiapine administration and persistent increase in absolute QT interval value. However, prolongation of the QT interval has been observed in overdose of the drug (see section “Overdose”). Caution should be exercised when prescribing quetiapine, as well as other antipsychotic drugs, to patients with cardiovascular diseases and previously observed prolongation of the QT interval. Caution is also required when prescribing quetiapine concomitantly with QT interval prolongers, other neuroleptics, especially in elderly patients, patients with congenital QT interval prolongation syndrome, chronic heart failure, myocardial hypertrophy, hypokalemia or hypomagnesemia (see section “Interaction with other medicinal products”).

Cardiomyopathy and Myocarditis

In clinical trials and post-marketing use, there have been cases of cardiomyopathy and myocarditis, but a causal relationship to drug administration has not been established. The appropriateness of quetiapine therapy in patients with suspected cardiomyopathy or myocarditis should be evaluated.

Acute reactions associated with drug withdrawal

The following acute reactions (withdrawal syndrome) – nausea, vomiting, insomnia, headache, dizziness and irritability – may occur if quetiapine is abruptly withdrawn. Therefore, it is recommended that the drug be withdrawn gradually over at least one or two weeks.

Liver disorders

If jaundice develops, Quetiapine Canon should be discontinued.

Dysphagia

Dysphagia (see side effects) and aspiration have been observed with quetiapine therapy. A causal relationship between aspiration pneumonia and taking quetiapine has not been established. However, caution should be exercised when prescribing the drug in patients at risk of aspiration pneumonia.

Venous thromboembolism

Cases of venous thromboembolism have been reported with neuroleptics. Because patients taking neuroleptics often have risk factors for venous thromboembolism, risk factors should be evaluated before and during therapy with antipsychotics, including quetiapine, and preventive measures should be taken.

Constipation and bowel obstruction

Contipation is a risk factor for bowel obstruction. Constipation and bowel obstruction have been reported with quetiapine (see section “Adverse effects”), including fatal cases in patients at high risk for bowel obstruction, including those receiving multiple concomitant medications that decrease bowel motility, even in the absence of constipation.

Pancreatitis

In clinical trials and post-marketing use, cases of pancreatitis have been reported, but a causal association with drug administration has not been established. Postmarketing reports indicate that many patients had risk factors for pancreatitis, such as elevated triglyceride concentrations, cholelithiasis, and alcohol consumption.

Particular information

There are limited data on the combined use of quetiapine with divalproate or lithium in mild to moderate acute manic episodes. Good tolerability of this combination therapy and additive effect at week 3 of therapy have been reported.

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

Influence on the ability to drive vehicles and other mechanisms

Due to the effect on the central nervous system, quetiapine may affect the speed of psychomotor reactions and cause dizziness and somnolence. Therefore, during treatment patients are not recommended to work with mechanisms requiring high concentration, including driving vehicles, until individual tolerance of therapy is established.

Contraindications

Cautious

In patients with cardiovascular and cerebrovascular disease or other conditions predisposing to arterial hypotension; concomitant administration with QT interval prolonging drugs (including with neuroleptics), especially in elderly patients, in patients with congenital QT interval prolongation syndrome, congestive heart failure, myocardial hypertrophy, hypokalemia or hypomagnesemia; combination with drugs that have depressing effect on the central nervous system (CNS) or alcohol; epilepsy and epileptic seizures (in anamnesis); with risk of stroke and aspiration pneumonia; in elderly patients; in patients with liver failure; dementia; Parkinson’s disease; diabetes.

Side effects

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of occurrence as follows: Very common (>1/10); common (>1/100, <1/10); infrequent (>1/1000, <1/100); rare (>1/10000, <1/1000); very rare (<1/10000); frequency unknown – it was impossible to determine the frequency of occurrence from the available data.

The administration of quetiapine, as well as other antipsychotics, may be accompanied by syncope, the development of malignant neuroleptic syndrome, leukopenia, neutropenia, and peripheral edema.

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

Overdose

A lethal outcome has been reported with 13.6 g of quetiapine in a patient participating in a clinical trial, as well as a lethal outcome after taking 6 g of quetiapine in a post-marketing study of the drug. At the same time, there has been a non-fatal case of quetiapine administered in doses greater than 30 g.

There have been reports of extremely rare cases of quetiapine overdose resulting in prolonged QT interval, death or coma.

In patients with a history of severe cardiovascular disease, the risk of side effects may increase with overdose (see Cautionary Note).

Symptoms

The symptoms reported in overdose have mostly resulted from an increase in the known pharmacological effects of the drug, such as drowsiness and sedation, tachycardia, and decreased blood pressure. There have also been reports of single cases of quetiapine overdose resulting in rhabdomyolysis, respiratory depression, urinary retention, confusion, delirium and agitation.

Treatment

There are no specific antidotes to quetiapine. In cases of severe intoxication it is necessary to remember about the possibility of overdose with several drugs. It is recommended to carry out measures aimed at maintaining respiratory and cardiovascular function, ensuring adequate oxygenation and ventilation.

In case of refractory hypotension in quetiapine overdose, treatment should be performed by intravenous administration of fluids and/or sympathomimetic drugs (epinephrine and dopamine should not be administered, as stimulation of β-adrenoreceptors may cause increased hypotension against blockade of alpha-adrenoreceptors by quetiapine).

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

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