Seroquel, pills 25mg, 60pcs

Composition

1 coated tablet contains:

Active ingredient:

quetiapine (as fumarate) 25 mg,

excipients:

povidone;

dihydrate of dibasic calcium phosphate;

MCC;

starch (sodium glycolate);

lactose monohydrate;

magnesium stearate

shell composition:

red iron oxide; titanium dioxide; hydroxypropylmethylcellulose; polyethylene glycol 400.

Pharmacological action

Quetiapine is an atypical antipsychotic medication. Quetiapine and its active metabolite N-dealkylquetiapine (norquetiapine) interact with a wide range of brain neutrotransmitter receptors. Quetiapine and N-dealkylquetiapine exhibit high affinity for 5 HT2-serotonin receptors and D1-and D2-dopamine receptors in the brain. Antagonism to these receptors, combined with a higher selectivity to 5 HT2-serotonin receptors than to D2-dopamine receptors, causes the clinical antipsychotic properties of Seroquel® and a low incidence of extrapyramidal side effects.

Quetiapine has no affinity for the norepinephrine transporter and has a low affinity for the 5HT1A-serotonin receptor, while N-dealkylquetiapine shows a high affinity for both. Inhibition of the norepinephrine transporter and partial agonism against 5 HT 1A-serotonin receptors, manifested by N-dealkylquetiapine, may cause the antidepressant effect of Seroquel®. Quetiapine and N-dealkylquetiapine have high affinity for histamine and α1-adrenergic receptors and moderate affinity for α2-adrenergic receptors. In addition, quetiapine has no or low affinity for muscarinic receptors, while N-dealkylquetiapine exhibits moderate or high affinity for several subtypes of muscarinic receptors. In standard tests, quetiapine shows antipsychotic activity.

The specific contribution of the N-dealkylquetiapine metabolite to the pharmacological activity of quetiapine has not been established.

The results of the study of extrapyramidal symptoms (EPS) in animals revealed that quetiapine causes mild catalepsy at doses that effectively block D2 receptors. Quetiapine causes a selective decrease in the activity of mesolimbic A10-dopaminergic neurons in comparison with A9-nigrostriate neurons involved in motor function.

Seroquel® is effective against both positive and negative symptoms of schizophrenia. Seroquel® is effective as monotherapy for moderate to severe manic episodes. There are no data on the long-term use of Seroquel for the prevention of subsequent manic and depressive episodes.

Data on the use of Seroquel® in combination with seminatria valproate or lithium preparations in moderate to severe manic episodes are limited, but this combination therapy was generally well tolerated. In addition, Seroquel® 300 mg and 600 mg is effective in patients with moderate to severe bipolar disorder of type I and II. At the same time, the effectiveness of Seroquel® when taken at a dose of 300 mg and 600 mg per day is comparable.

Seroquel® is effective in patients with schizophrenia and mania when taken twice daily, despite the fact that the half-life of quetiapine is about 7 hours.

The effect of quetiapine on the 5 HT2 – and D2-receptors lasts up to 12 hours after taking the drug.

When taking Seroquel® with dose titration in schizophrenia, the frequency of EPS and concomitant use of m-holinoblockers was comparable to that of placebo. When Seroquel® was administered in fixed doses from 75 to 750 mg / day to patients with schizophrenia, the incidence of EPS and the need for concomitant use of m-holinoblockers did not increase.

When using Seroquel® in doses up to 800 mg / day. for the treatment of moderate to severe manic episodes, either as monotherapy or in combination with lithium or seminatria valproate, the incidence of EPS and concomitant use of m-holinoblockers was comparable to that of placebo.

Indications

• For the treatment of schizophrenia.
• For the treatment of manic episodes in the structure of bipolar disorder.
• For the treatment of depressive episodes of moderate to severe severity in the structure of bipolar disorder.

Use during pregnancy and lactation

The safety and efficacy of quetiapine in pregnant women have not been established. Therefore, during pregnancy, quetiapine can only be used if the expected benefit to the woman justifies the potential risk to the fetus.

When using antipsychotic drugs, including quetiapine, in the third trimester of pregnancy, newborns are at risk of developing adverse reactions of varying severity and duration, including EPS and / or withdrawal syndrome.

Agitation, hypertension, hypotension, tremor, drowsiness, respiratory distress syndrome, or feeding disorders have been reported. In this regard, the condition of newborns should be carefully monitored.

The excretion of quetiapine in breast milk has been reported, but the degree of excretion has not been established. Women should be advised to avoid breastfeeding while taking quetiapine.

Contraindications

Hypersensitivity to any of the components of the drug, including lactase deficiency, glucose-galactose malabsorption and galactose intolerance. Co-use with cytochrome p450 inhibitors, such as azole antifungal drugs, erythromycin, clarithromycin and nefazodone, as well as HIV protease inhibitors (see the section “Interaction with other drugs and other types of interaction”). Although the efficacy and safety of Seroquel® in children and adolescents aged 10-17 years have been studied in clinical trials, the use of Seroquel® in patients under the age of 18 years is not indicated.

With caution: in patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to hypotension, elderly age, liver failure, history of seizures, risk of stroke and aspiration pneumonia.

Side effects

From the central nervous system and peripheral nervous system:  often-drowsiness (17.5%), dizziness (10%); rarely-neuroleptic malignant syndrome (hyperthermia, impaired consciousness, muscle rigidity, vegetative-vascular disorders, increased CPK concentration); very rarely – convulsions. With prolonged use of Seroquel, there is a potential for the development of tardive dyskinesia. If symptoms of tardive dyskinesia occur, reduce the dose or discontinue further treatment with Seroquel.

From the digestive system:  often-constipation (9%), dyspepsia (6%), dry mouth (7%); increased activity of liver enzymes (ALT, AST, GGT) in blood serum (6%), as well as increased cholesterol and triglyceride concentrations (these changes were usually reversible during treatment with Seroquel).

From the cardiovascular system:  often-orthostatic hypotension (accompanied by dizziness), tachycardia (7%), syncope; these adverse reactions mainly occur during the initial period of dose selection.

From the hematopoietic system:  rarely-leukopenia and / or neutropenia. There were no cases of severe neutropenia or agranulocytosis in patients treated with Seroquel. When using Seroquel in clinical practice, leukopenia and / or neutropenia resolved after discontinuation of the drug. Possible risk factors for developing leukopenia and/or neutropenia include a decrease in the number of white blood cells before starting therapy or a history of drug-induced leukopenia and / or neutropenia.

From the endocrine system:  Seroquel therapy is associated with a small dose-dependent decrease in the level of thyroid hormones, in particular, total T4 and free T4. The maximum decrease in total and free T4 was recorded at the 2nd and 4th weeks of quetiapine therapy without further reduction in the concentration of hormones during long-term treatment. There were no further signs of clinically significant changes in the thyroid-stimulating hormone concentration. In almost all cases, the total and free T4 concentrations returned to baseline after discontinuation of Seroquel therapy, regardless of the duration of treatment.

Allergic reactions:  rarely – eosinophilia, allergic reactions, including angioedema.

Other services:  rarely-peripheral edema, moderate asthenia, rhinitis, weight gain (mainly in the first weeks of treatment); very rarely-priapism.

Seroquel may cause prolongation of the QT interval, but the relationship between the use of Seroquel and a constant increase in QT was not revealed.

The following common (1/100) adverse events were also reported: increased blood pressure, palpitations, dysarthria, pharyngitis, cough, anorexia, increased sweating. The causal relationship of these side effects with the use of Seroquel has not been established.

Interaction

Concomitant use of drugs that have a strong inhibitory effect on the CYP3A4 isoenzyme (such as azole antifungal agents and macrolide antibiotics), the concentration of quetiapine in plasma may increase. In such cases, lower doses of Seroquel should be used. Special attention should be paid to elderly and debilitated patients.It is necessary to individually assess the risk-benefit ratio for each patient.

Concomitant use of Seroquel with drugs that induce the liver enzyme system, such as carbamazepine, may reduce the concentration of the drug in plasma, which may require an increase in the dose of Seroquel, depending on the clinical effect. In a study of the pharmacokinetics of quetiapine at various doses, when administered before or simultaneously with carbamazepine (an inducer of liver enzymes), a significant increase in quetiapine clearance is possible. This increase in quetiapine clearance reduced AUC by an average of 13% compared to quetiapine without carbamazepine.

Concomitant use of Seroquel with another inducer of microsomal liver enzymes (phenytoin) also resulted in increased clearance of quetiapine. When Seroquel is co-administered with phenytoin (or other inducers of liver enzymes, such as barbiturates, rifampicin), an increase in the dose of Seroquel may be required. It may also be necessary to reduce the dose of Seroquel when phenytoin or carbamazepine or another inducer of the liver enzyme system are discontinued or replaced with a drug that does not induce microsomal liver enzymes (for example, sodium valproate).

The pharmacokinetics of lithium preparations do not change with simultaneous use of Seroquel.

There were no clinically significant changes in the pharmacokinetics of valproic acid and quetiapine when divalproex sodium was co-administered (sodium valproate and valproic acid in a molar ratio of 1:1) and Seroquel (quetiapine).

Quetiapine did not induce induction of hepatic enzyme systems involved in the metabolism of antipyrine.

The pharmacokinetics of quetiapine do not significantly change when co-administered with the antipsychotic drugs risperidone or haloperidol. However, concomitant use of Seroquel and thioridazine resulted in increased clearance of quetiapine.

The CYP3A4 isoenzyme is a key enzyme involved in cytochrome P450-mediated quetiapine metabolism. The pharmacokinetics of quetiapine did not change significantly with concomitant use of cimetidine, which is an inhibitor of cytochrome P450.

The pharmacokinetics of quetiapine did not change significantly with concomitant use of the antidepressant imipramine (CYP2D6-inhibitor) or fluoxetine (CYP3A4 – and CYP2D6-inhibitor). However, caution is recommended when concomitant use of Seroquel and systemic use of strong inhibitors of the CYP3A4 isoenzyme (such as azole antifungal agents and macrolide antibiotics).

Medications that depress the central nervous system and ethanol increase the risk of Seroquel side effects.

How to take, course of use and dosage

Seroquel® can be used regardless of food intake.

Adults Treatment of schizophrenia

The drug Seroquel® is prescribed 2 times a day. The daily dose for the first 4 days of therapy is: day 1-50 mg, day 2-100 mg, day 3-200 mg, day 4-300 mg.

Starting from day 4, the dose should be selected to be effective, usually in the range of 300 to 450 mg / day. Depending on the clinical effect and individual patient tolerance, the dose may vary from 150 to 750 mg / day. The maximum recommended daily dose is 750 mg.

Treatment of manic episodes in the structure of bipolar disorder

Seroquel® is used as monotherapy or in combination with drugs that have a normothymic effect.

The drug Seroquel® is prescribed 2 times a day. The daily dose for the first 4 days of therapy is: day 1-100 mg, day 2-200 mg, day 3-300 mg, day 4-400 mg. In the future, by the 6th day of therapy, the daily dose of the drug can be increased to 800 mg. The increase in the daily dose should not exceed 200 mg per day.

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

The maximum recommended daily dose is 800 mg.

Treatment of depressive episodes in the structure of bipolar disorder

The drug Seroquel® is prescribed once a day at night. The daily dose for the first 4 days of therapy is: day 1-50 mg, day 2-100 mg, day 3-200 mg, day 4-300 mg. The recommended dose is 300 mg/day. The maximum recommended daily dose of Seroquel® is 600 mg.

The antidepressant effect of Seroquel® was confirmed when it was used at doses of 300 and 600 mg / day. In short-term therapy, Seroquel ® is effective at doses of 300 and 600 mg / day. it was comparable (see the section “Pharmacodynamics”).

Elderly people

In elderly patients, the initial dose of Seroquel 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 less than in younger patients. Patients with renal insufficiency

No dose adjustment is required.

Patients with hepatic insufficiency

Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using Seroquel in patients with hepatic insufficiency, especially at the beginning of therapy. It is recommended to start therapy with Seroquel® at a dose of 25 mg / day. and increase the dose daily by 25-50 mg until the effective dose is reached.

Overdose

Data on Seroquel overdose are limited. Cases of taking Seroquel in a dose exceeding 20 g, without fatal consequences and with full recovery, have been described, but there are reports of extremely rare cases of Seroquel overdose that led to death or coma.

Symptoms: These symptoms were mainly due to an increase in the known pharmacological effects of the drug, such as drowsiness and excessive sedation, tachycardia and a decrease in blood pressure.

Treatment: there are no specific antidotes to quetiapine. In cases of serious intoxication, it is necessary to consider the possibility of symptomatic therapy and it is recommended to carry out measures aimed at maintaining the function of respiration, cardiovascular system, ensuring adequate oxygenation and ventilation. Medical monitoring and follow-up should continue until the patient is fully recovered.

Special instructions

Caution should be exercised when prescribing Seroquel to patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, as well as to elderly patients with liver failure, convulsive seizures in the anamnesis.

Seroquel may cause orthostatic hypotension, especially during the initial dose adjustment period (it is observed more often in elderly patients than in young ones).

When high doses of antipsychotic drugs are abruptly discontinued, the following acute reactions (withdrawal syndrome) may occur: nausea, vomiting; rarely, insomnia.

Cases of acute psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia) have been reported. In this regard, it is recommended to cancel the drug gradually.

The occurrence of NMS may be associated with ongoing antipsychotic treatment. The clinical manifestation of the syndrome includes: hyperthermia, altered mental status, muscle rigidity, instability of the autonomic nervous system, increased CPK levels. In such cases, Seroquel should be discontinued and appropriate treatment should be given.

There was no difference in the incidence of seizures in patients taking Seroquel or placebo. However, caution is recommended when treating patients with a history of seizures.

There was no correlation between quetiapine intake and an increase in the QTc interval. However, caution should be exercised when prescribing quetiapine concomitantly with drugs that prolong the QTc interval, especially in the elderly.

Taking into account that quetiapine mainly affects the central nervous system, Seroquel should be used with caution in combination with other drugs that have a depressing effect on the central nervous system, or alcohol.

Influence on the ability to drive motor vehicles and manage mechanisms

Seroquel can cause drowsiness, so patients are not recommended to work with dangerous mechanisms, including driving a car and other moving vehicles.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Quetiapine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets