Quetiapine, 25 mg 60 pcs

– Treatment of schizophrenia.

Active ingredient

Quetiapine

Composition

1 tablet:

quetiapine fumarate, in terms of quetiapine – 25 mg;

auxiliary substances (core):

Microcrystalline cellulose, 60.0 mg;

Lactose monohydrate (milk sugar), 44.0 mg;

Povidone (polyvinylpyrrolidone medium molecular weight), 9.0 mg;

croscarmellose sodium (primellose) – 10.5 mg;

Magnesium stearate – 1.5 mg;

accompanied substances (coating):

Opadray II (polyvinyl alcohol, partially hydrolyzed, 2.0 mg; macrogol (polyethylene glycol) 3350, 1.01 mg; talc, 0.74 mg; titanium dioxide E 171, 1.1333 mg; iron oxide (II) yellow dye E 172, 0.1167 mg).

How to take, the dosage

Quetiapine can be used regardless of food intake.

Adults

The treatment of schizophrenia:

Quetiapine is prescribed twice daily. The daily dose for the first 4 days of therapy is: 1st day – 50 mg, 2nd day – 100 mg, 3rd day – 200 mg, 4th day – 300 mg. Starting from the 4th day, the dose should be adjusted to an effective one, usually in the range of 300 to 450 mg/day. Depending on clinical effect and individual patient tolerance, the dose may vary from 150 to 750 mg/day. The maximum recommended daily dose is 750 mg.

The treatment of manic episodes in the structure of bipolar disorder

Quetiapine is used as monotherapy or in combination with drugs with normotensive effects. Quetiapine is prescribed 2 times a day. The daily dose for the first 4 days of therapy is: 1st day – 100 mg, 2nd day – 200 mg, 3rd day – 300 mg, 4th day – 400 mg. By the 6th day of therapy, the daily dose can be increased to 800 mg. Increase in daily dose should not exceed 200 mg per day. Depending on clinical effect and individual tolerance, the dose may vary from 200 to 800 mg/day. Usually the effective dose is 400 to 800 mg/day. The maximum recommended daily dose is 800 mg.

The treatment of depressive episodes in the structure of bipolar disorder

Quetiapine is prescribed once daily at bedtime. The daily dose for the first 4 days of therapy is: 1st day – 50 mg, 2nd day – 100 mg, 3rd day – 200 mg, 4th day – 300 mg. Recommended dose is 300 mg/day. The maximum recommended daily dose of Quetiapine is 600 mg. The antidepressant effect of Quetiapine has been confirmed when used at doses of 300 and 600 mg/day. In short-term therapy, the efficacy of Quetiapine at doses of 300 and 600 mg/day was comparable (see section “Pharmacodynamics”).

Elderly:

In elderly patients, the starting dose of Quetiapine is 25 mg/day. The dose should be increased daily by 25-50 mg until an effective dose is reached, which is likely to be lower than in younger patients.

Patients with renal impairment:

Dose adjustment is not necessary.

Patients with hepatic impairment:

Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using Quetiapine in patients with hepatic impairment, especially at the beginning of therapy. It is recommended to start Quetiapine therapy with a dose of 25 mg/day and increase the dose daily by 25-50 mg 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. Cytochrome P450 isoenzyme (CYP) ZA4 is the main isoenzyme responsible for the metabolism of quetiapine through the cytochrome P450 system.

In studies in healthy volunteers, co-administration of quetiapine (in dose 25 mg) with ketoconazole, a CYP3A4 inhibitor, resulted in a 5-8 fold increase in the area under the “concentration-time” curve (AUC) of quetiapine. Therefore, co-administration of quetiapine and cytochrome CYP3A4 inhibitors is contraindicated.

It is also not recommended to take vetiapine together with grapefruit juice. In a pharmacokinetic study, administration of quetiapine in varying doses before 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 concentrations of quetiapine and may reduce the effectiveness of quetiapine therapy. Co-administration of Quetiapine with phenytoin, another inducer of the microsomal liver system, was accompanied by an even more pronounced (approximately 450%) increase in clearance of Quetiapine.

The administration of Quetiapine to patients receiving hepatic enzyme system inducers is possible only if the expected benefit of Quetiapine therapy outweighs the risk associated with withdrawal of the hepatic enzyme inducer drug. Changing the dose of microsomal enzyme inducer drugs should be gradual.

If necessary, they may be replaced by drugs that do not induce microsomal enzymes (e.g., valproic acid preparations). Pharmacokinetics of quetiapine was not significantly changed with concomitant administration of antidepressant imipramine (CYP2D6 inhibitor) or fluoxetine (CYPZA4 and CYP2D6 inhibitor).

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

Lorazepam clearance is decreased by approximately 20% when 2 mg lorazepam is administered once with quetiapine at a dose of 250 mg twice daily. Pharmacokinetics of lithium preparations are not changed when concomitant administration of Quetiapine. No clinically significant changes in valproic acid and quetiapine pharmacokinetics have been observed when valproate and quetiapine are co-administered.

Pharmacokinetic studies to study the interaction of Quetiapine with drugs used for cardiovascular diseases have not been conducted. Caution should be exercised when combining Quetiapine with drugs that may cause electrolyte imbalance and QTc interval prolongation. Quetiapine did not induce induction of hepatic enzyme systems involved in phenazone metabolism.

Special Instructions

Sleepiness

Drowsiness and associated symptoms such as sedation may occur during therapy with Quetiapine (see section “Side effects”). In clinical studies involving depressed patients with bipolar disorder, somnolence usually developed during the first three days of therapy.

The severity of this side effect was generally 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 of the onset of somnolence or until the severity of symptoms decreases. In some cases, Quetiapine therapy may need to be discontinued.

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. 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 adult patients with bipolar depression when taking Quetiapine for depressive episodes compared to placebo (see side effects section).

Late dyskinesia

If symptoms of late dyskinesia develop, it is recommended that the drug dose be reduced or gradually withdrawn (see side effects section). Malignant neuroleptic syndrome

Malignant neuroleptic syndrome may develop 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 discontinued and appropriate treatment should be given.

Expressed neutropenia

In clinical trials of Quetiapine there have been infrequent cases of marked neutropenia (neutrophil count

Interaction with other medicinal products

Also see “Interaction with other drugs. See also “Interaction with other medicinal products”. The use of Quetiapine in combination with strong hepatic enzyme system inducers, such as carbamazepine and phenytoin, reduces the plasma concentration of Quetiapine and may decrease the effectiveness of Quetiapine therapy. Administration of quetiapine to patients receiving liver enzyme inducers is possible only if the expected benefit of quetiapine therapy exceeds the risk associated with withdrawal of the liver enzyme inducer drug. Changes in the dose of microsomal enzyme inducers should be gradual. If necessary, they may be replaced by drugs that do not induce microsomal enzymes (e.g., valproic acid drugs).

Hyperglycemia

Hyperglycemia or worsening of diabetes mellitus in patients with a history of diabetes mellitus may develop against the background of taking quetiapine. Clinical monitoring of patients with diabetes mellitus and patients with risk factors for diabetes mellitus is recommended (see section “Side effects”). Lipid levels

At the time of quetiapine administration, triglyceride and cholesterol concentrations may increase (see section “Adverse effects”).

Long QT interval

There is no established relationship between taking quetiapine and a 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 QTc prolongers, other neuroleptics, especially in elderly persons, patients with congenital QT interval prolongation syndrome, chronic heart failure, myocardial hypertrophy, hypokalemia or hypomagnesemia (see section “Interaction with other medicinal products”).

Acute reactions associated with withdrawal of the drug

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

Elderly patients with dementia

Quetiapine is not indicated for the treatment of psychosis associated with dementia. Some atypical neuroleptics in randomized placebo-controlled trials increased the risk of cerebrovascular complications by about 3-fold in patients with dementia. The mechanism of this increased risk is not understood. A similar risk of increased incidence of cerebrovascular complications cannot be ruled out for other antipsychotic medications or other patient groups. Quetiapine should be used with caution in patients at risk of stroke.

An analysis of the use of atypical neuroleptics for the treatment of psychosis associated with dementia in elderly patients found an increased mortality rate in the group of patients receiving the drugs in this group compared with the placebo group. In addition, two 10-week placebo-controlled trials of Quetiapine in a similar group of patients (n = 710; mean age: 83 years; age range: 56-99 years) showed a mortality rate of 5.5% in the patient group receiving Quetiapine and 3.2% in the placebo group. The causes of death observed in these patients were consistent with those expected in this population. No causal relationship was found between treatment with Quetiapine and the risk of increased mortality in older patients with dementia.

Suicidal ideation/suicidal thoughts or clinical deterioration

Depression 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. Due to the fact that it may take several weeks or more before a patient’s condition improves from the start of treatment, patients should be under close medical supervision until improvement occurs. Conventional clinical experience suggests that the risk of suicide may increase in the early stages of remission.

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

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 that used quetiapine (see Pharmacodynamics). The short-term placebo-controlled studies for all indications and in all age groups reported an event rate for suicide of 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 for 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% (0/67) 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 Special Indications). 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. There have been no studies involving depressed patients with bipolar disorder under 18 years of age.

Influence on driving and operating machinery

Quetiapine may cause drowsiness, so patients are not recommended to operate machinery that are hazardous during treatment, including driving vehicles.

Synopsis

Beige to beige colored, round, biconvex, film-coated tablets. The cross-section of the tablets is white or almost white (dosage 25 mg, 100 mg, 200 mg).

Contraindications

Hypersensitivity to any of the drug components, including lactase deficiency, glucose-galactose malabsorption and galactose intolerance. Co-administration with cytochrome P450 inhibitors, such as antifungal drugs of azole group, erythromycin, clarithromycin and nefazodone, as well as protease inhibitors (see section “Interaction with other medicinal products”). Although the efficacy and safety of Quetiapine in children and adolescents aged 10-17 years has been studied in clinical trials, the use of Quetiapine in patients younger than 18 years is not indicated.

With caution

In patients with cardiovascular and cerebrovascular disease or other conditions predisposing to arterial hypotension, advanced age, hepatic impairment, history of seizures.

Side effects

CNS disorders: headache, drowsiness, dizziness, anxiety; rarely – ANS.

Cardiovascular system: orthostatic hypotension, tachycardia, arterial hypertension.

Digestive system disorders: constipation, dry mouth, dyspepsia, diarrhea, transient increase of liver enzymes activity (ALT, AST, GGT), abdominal pain.

Hematopoietic organs: asymptomatic leukopenia and/or neutropenia; rarely – eosinophilia.

Muscular system disorders: myalgia.

Respiratory system: rhinitis.

Dermatological reactions: skin rash, dry skin.

Hearing organ: ear pain.

Treatment of the urinary system: urinary tract infections.

Metabolic side: slight increase in cholesterol and triglycerides in the blood.

Endocrine system disorders: slight dose-dependent reversible decrease of thyroid hormone levels (in particular, total and free T4).

Others: asthenia, low back pain, weight gain, fever, chest pain.

Overdose

A lethal outcome has been reported when 13.6 g of quetiapine was taken in a patient participating in a clinical trial and a lethal outcome after taking 6 g of quetiapine in a post-marketing study of the drug. At the same time, a case of quetiapine administered in a dose greater than 30 g without lethal outcome has been described.

Similarities

Seroquel, Seroquel Prolong, Quetiapine