Seroquel, pills 200mg, 60pcs

Composition

1 coated tablet contains:

Active ingredient:

quetiapine (in the form of fumarate) 200 mg,

excipients:

povidone;

dihydrate of dibasic calcium phosphate;

MCC;

starch (sodium glycolate);

lactose monohydrate;

magnesium stearate.

Pharmacological action

Quetiapine is an atypical antipsychotic drug that exhibits a higher affinity for serotonin receptors (5 HT2) than for dopamine_D1 and D2 receptorsin the brain. Quetiapine also has a higher affinity for histamine and_a1-adrenergic receptors and a lower affinity for_a2-adrenergic receptors. No significant affinity of quetiapine to cholinergic muscarinic and benzodiazepine receptors was found. In standard tests, quetiapine shows antipsychotic activity.

Pharmacodynamic effects

Results of the study of extrapyramidal symptoms (EPS)  the animals were found to have, that quetiapine causes mild catalepsy at a dose that effectively blocks dopamine_D2 receptors. Quetiapine causes a selective decrease in the activity of mesolimbic A10 dopaminergic neurons in comparison with A9 nigrostriar neurons involved in motor function.

Clinical efficacy

In clinical trials (using Seroquel at a dose of 75-750 mg / day) There were no differences between the use of Seroquel and placebo in the incidence of extrapyramidal symptoms and concomitant use of anticholinergic drugs.

Seroquel does not cause a prolonged increase in the concentration of prolactin in blood plasma. Numerous fixed-dose studies have shown no difference in prolactin levels when using Seroquel or placebo.

In clinical trials, Seroquel has been shown to be effective in treating both positive and negative symptoms of schizophrenia. The effect of quetiapine on the 5 HT2 and D2 receptors lasts up to 12 hours after taking the drug.

Pharmacokinetics

When administered orally, quetiapine is well absorbed from the gastrointestinal tract and is actively metabolized in the liver. The main metabolites present in plasma do not have pronounced pharmacological activity.

Food intake does not significantly affect the bioavailability of quetiapine. The elimination half-life is about 7 hours. Approximately 83% of quetiapine binds to plasma proteins.

The pharmacokinetics of quetiapine are linear, and there are no differences in pharmacokinetic parameters in men and women.

The average clearance of quetiapine in elderly patients is 30-50% lower than in patients aged 18 to 65 years.

The average plasma clearance of quetiapine is approximately 25% lower in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min/1.73 m2) and in patients with liver damage (stable alcoholic cirrhosis), but individual clearance values are within the limits corresponding to healthy people.

Approximately 73% of quetiapine is excreted in the urine and 21% in the faeces. Less than 5% of quetiapine is not metabolized and is excreted unchanged by the kidneys or faeces

CYP3A4 has been found to be a key enzyme of cytochrome P450-mediated quetiapine metabolism.

The study of pharmacokinetics quetiapine in different dosage when assigning quetiapina before taking ketoconazole or simultaneously with ketoconazole resulted in increases in average maximum concentration (C_max) and area under the curve “concentration – time” (AUC) quetiapine by 235% and 522%, respectively, and resulted in a decrease in the clearance quetiapine, on average,84%. The elimination half-life of quetiapine increased, but the average time to reach the maximum concentration (tmax) did not change.

Quetiapine and some of its metabolites have weak inhibitory activity against cytochrome P450 enzymes 1A2,2C9,2C19,2D6 and ZA4, but only at concentrations 10-50 times higher than those observed at the commonly used effective dosage of 300-450 mg / day.

Based on in vitro results, co-use of quetiapine with other drugs should not be expected to result in clinically significant inhibition of cytochrome P 450-mediated metabolism of other drugs.

Indications

Acute and chronic psychoses, including schizophrenia.

Use during pregnancy and lactation

The safety and efficacy of Seroquel in pregnant women have not been established. Therefore, Seroquel should only be used during pregnancy if the expected benefit justifies the potential risk.

The degree of excretion of quetiapine in human milk is not known. Women should be advised to avoid breastfeeding while taking Seroquel.

Contraindications

Hypersensitivity to any of the components of the drug Seroquel.

Side effects

The following most common adverse reactions associated with taking the drug were noted: drowsiness (17.5%), dizziness (10%), constipation (9%), dyspepsia (6%), orthostatic hypotension and tachycardia (7%), dry mouth (7%), increased activity of liver enzymes in the blood serum (6%), (including increased cholesterol and triglyceride concentrations).

Taking Seroquel may be accompanied by the development of moderate asthenia, rhinitis and dyspepsia, an increase in body weight (mainly in the first weeks of treatment).

Seroquel may cause orthostatic hypotension (accompanied by dizziness), tachycardia and, in some patients, syncope; these adverse reactions mainly occur during the initial dose selection period (see section “Special instructions”).

Very rare cases of priapism and seizures have been reported in patients treated with Seroquel.

In rare cases, neuroleptic malignant syndrome was observed (hyperthermia, impaired consciousness, muscle rigidity, vegetative-vascular disorders, increased creatine phosphokinase concentration), leukopenia and/or neutropenia were observed. There were no cases of severe neutropenia or agranulocytosis in patients treated with Seroquel. When using  In general practice, leukopenia and/or neutropenia resolved after discontinuation of Seroquel. 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. Rare cases of eosinophilia, peripheral edema, and allergic reactions, including angioedema, have been reported.

Asymptomatic increases in serum transferase activity (alanine and aspartic ALT and ACT, respectively) or gamma-glutamyltranspeptidase (GGT) activity have been reported in patients treated with Seroquel. During treatment with Seroquel, these changes were usually reversible.

During treatment with Seroquel, there may be a slight increase in the concentration of cholesterol and serum triglycerides.

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 concentration of total and free  T4 returned to baseline after discontinuation of Seroquel therapy, regardless of the duration of treatment. Seroquel may cause prolongation of the QT interval_C, the relationship between the use of Seroquel and a constant increase in QT_C was not revealed (see the section “Special instructions”). The following common cases were also reported (1/100):   side effects –

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.

Tardive dyskinesia

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.

When high doses of antipsychotic drugs are abruptly discontinued, the following acute reactions may occur (withdrawal syndrome):  – 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.

Interaction

Concomitant use of drugs that have a strong inhibitory effect on CYP3A4 (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. Simultaneous assignment  Seroquel with drugs that induce the liver enzyme system, such as carbamazepine, it is possible to 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 in various dosages, when administered before or simultaneously with carbamazepine (an inducer of liver enzymes), such simultaneous use led to a significant increase in quetiapine clearance.

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.

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

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 using Seroquel concomitantly with the systemic use of strong CYP3A4 inhibitors (such as azole antifungal agents and macrolide antibiotics).

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

How to take, course of use and dosage

Seroquel is prescribed 2 times a day inside, regardless of food intake.

Adults

Treatment of acute and chronic psychoses, including schizophrenia

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 adjusted to the effective dosage, 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.

Treatment of manic episodes in the structure of bipolar disorder

Seroquel is used as monotherapy or as adjuvant therapy to stabilize mood.

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.

For the treatment of schizophrenia, the maximum recommended daily dose of Seroquel is 750 mg, for the treatment of manic episodes in the structure of bipolar disorder, the maximum recommended daily dose of Seroquel is 800 mg / day.

Elderly people

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

Patients with renal and hepatic insufficiency

In patients with renal or hepatic insufficiency, it is recommended to start therapy with Seroquel at 25 mg / day. It is recommended to increase the dose daily by 25-50 mg until the effective dose is reached.

Children and teenagers

The safety and efficacy of Seroquel in children and adolescents have not been studied.

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: The reported 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. Careful medical monitoring and monitoring should continue until the patient is fully recovered.

Special instructions

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

There was no correlation between quetiapine intake and an increase in the QT_-cinterval. However, caution should be exercised when prescribing quetiapine concomitantly with drugs that prolong the QT_{-c 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.

Convulsive seizures

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

Neuroleptic malignant syndrome Neuroleptic malignant syndrome may be associated with ongoing antipsychotic treatment. Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, instability of the autonomic nervous system, and increased creatine phosphokinase levels.In such cases, Seroquel should be discontinued and appropriate treatment should be given.

Acute reactions associated with drug withdrawal

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

WITH CAUTION:  in patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to hypotension, elderly age, liver failure, convulsive seizures in the anamnesis.

INFLUENCE ON THE ABILITY TO DRIVE A CAR AND OTHER MECHANISMS

Seroquel can cause drowsiness, so during the treatment period, patients are not recommended to work with mechanisms that pose a danger, including driving vehicles, as well as taking alcohol.

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