Seroquel, 200 mg 60 pcs

Quetiapine is an atypical antipsychotic that exhibits higher affinity for serotonin receptors (5NT₂) than for brain dopamine receptors D₁ and D_{2 . Quetiapine also has higher affinity for histamine and a1 adrenoreceptors and lower affinity for a2 adrenoreceptors. No appreciable affinity of quetiapine for cholinergic muscarinic and benzodiazepine receptors was found. In standard tests, quetiapine exhibits antipsychotic activity.}

Pharmacodynamic Effects

The results of studies of extrapyramidal symptoms (EPS) in animals revealed 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 compared to A9 nigrostriatal neurons involved in motor function.

Clinical efficacy

The clinical studies (using Seroquel at doses of 75-750 mg/day) showed no differences between Seroquel and placebo in the incidence of extrapyramidal symptoms and concomitant use of anticholinergic drugs.

Seroquel does not cause long-term increases in plasma prolactin concentrations. Multiple fixed-dose studies have found 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 effects of quetiapine on the 5NT₂ and D₂ receptors last up to 12 hours after taking the drug.

Pharmacokinetics

Quetiapine is well absorbed from the gastrointestinal tract when taken orally and is actively metabolized in the liver. The major plasma metabolites have no pronounced pharmacological activity.

The bioavailability of quetiapine is not significantly affected by food intake. The elimination half-life is about 7 hours. About 83% of quetiapine is bound to plasma proteins.

The pharmacokinetics of vetiapine are linear; there are no differences in pharmacokinetic parameters in men and women.

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

The mean plasma clearance of quetiapine is about 25% lower in patients with severe renal impairment (creatinine clearance less than 30 mL/min/1.73m²) and in patients with liver damage (stabilized alcoholic cirrhosis), but individual clearance rates are within limits consistent with healthy individuals.

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

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

In a study of the pharmacokinetics of quetiapine in different dosages, administration of quetiapine before ketoconazole or simultaneously with ketoconazole resulted in an increase, on average, in the maximum concentration (C_max) and the area under the concentration-time curve (AUC) of quetiapine by 235% and 522%, respectively, and also resulted in an average 84% decrease in quetiapine clearance. The half-life of vetiapine increased, but the mean time to reach maximum concentration (t_max) did not change.

Quetiapine and some of its metabolites have weak inhibitory activity against cytochrome P450 enzymes 1A2, 2C9, 2C19, 2D6 and WA4, but only at concentrations 10-50 times greater than those observed at the commonly used effective dose of 300-450 mg/day.

Based on in vitro results, concomitant administration of quetiapine with other drugs should not be expected to result in clinically significant inhibition of cytochrome P450 mediated metabolism of other drugs.

Indications

Acute and chronic psychosis, including schizophrenia.

Active ingredient

Composition

1 coated tablet contains:

the active ingredient:

Quetiapine (as fumarate) 200 mg,

excipients:

povidone;

calcium bicarbonate phosphate dihydrate;

MCC;

Starch (sodium glycolate);

Lactose monohydrate;

Magnesium stearate.

How to take, the dosage

Seroquel is prescribed 2 times a day orally, regardless of meals.

Adults

The treatment of acute and chronic psychosis, 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 on day 4, the dose should be adjusted to an effective dosage, usually between 300 and 450 mg/day. Depending on clinical effect and individual patient tolerance, the dose may vary from 150 to 750 mg/day.

The treatment of manic episodes in the structure of bipolar disorder

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

The daily dose for the first 4 days of therapy is: Day 1 is 100 mg, Day 2 is 200 mg, Day 3 is 300 mg, and Day 4 is 400 mg. 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 and individual tolerance, the dose may vary from 200 to 800 mg/day. Typically, the effective dose is 400 to 800 mg/day.

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

Elderly

In elderly patients, the starting 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 lower than in younger patients.

Patients with renal or hepatic impairment

In patients with renal or hepatic impairment, it is recommended that Seroquel therapy be started at 25 mg/day. It is recommended to increase the dose daily by 25-50 mg until an effective dose is achieved.

Children and adolescents

The safety and effectiveness of Seroquel in children and adolescents has not been studied.

Interaction

In concomitant administration of drugs with strong inhibitory effect on CYP3A4 (such as antifungal agents of azole group and macrolide antibiotics), plasma concentration of quetiapine may increase. In such cases, lower doses of Seroquel should be used.

Particular attention should be given to elderly and frail patients. The risk-benefit ratio for each patient should be evaluated individually. Concomitant administration of Seroquel with drugs that induce the liver enzyme system, such as carbamazepine, may decrease plasma concentrations of the drug, which may require increasing the dose of Seroquel, depending on the clinical effect. In a study of the pharmacokinetics of quetiapine in different doses, when administered before or simultaneously with carbamazepine (a hepatic enzyme inducer), such simultaneous administration led to a significant increase in the clearance of quetiapine.

This increase in clearance of quetiapine reduced AUC by an average of 13% compared to the use of quetiapine without carbamazepine. Concomitant administration of Seroquel with another hepatic microsomal enzyme inducer, phenytoin, also resulted in increased clearance of quetiapine. Simultaneous administration of Seroquel and phenytoin (or other hepatic enzyme inducers such as barbiturates, rifampicin) may require increasing the dose of Seroquel. It may also be necessary to reduce the dose of Seroquel when phenytoin or carbamazepine or another hepatic enzyme inducer is withdrawn or replaced with a drug that does not induce hepatic microsomal enzymes (such as sodium valproate).

The pharmacokinetics of lithium preparations are not altered by concomitant administration of Seroquel.

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

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

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

CYP3A4 is a key enzyme involved in cytochrome P450-mediated metabolism of quetiapine. The pharmacokinetics of quetiapine are not significantly altered by concomitant use of cimetidine, which is a P450 inhibitor.

The pharmacokinetics of quetiapine have not been significantly altered by concomitant administration of the antidepressant imipramine (CYP2D6 inhibitor) or fluoxetine (CYP3A4 and CYP2D6 inhibitor). However, caution is recommended when using Seroquel concomitantly with systemic use of strong CYP3A4 inhibitors (such as azole antifungals and macrolide antibiotics).

Drugs that depress the CNS and ethanol increase the risk of side effects.

Special Instructions

Seroquel may cause orthostatic hypotension, especially in the initial period of dose adjustment (seen more often in elderly patients than in younger patients).

The relationship between quetiapine administration and an increase in the QTc interval has not been found. However, caution should be exercised when prescribing quetiapine concomitantly with drugs that prolong the QTc interval, especially in the elderly.

Bearing in mind that quetiapine mainly affects the central nervous system, Seroquel should be used with caution in combination with other drugs that have a depressant effect on the central nervous system or alcohol.

Convulsive seizures

No differences have been found in the incidence of seizures in patients taking Seroquel or placebo. However, as with therapy with other antipsychotics, caution is advised when treating patients with a history of seizures.

Malignant neuroleptic syndrome

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

Acute reactions associated with drug withdrawal

The following acute reactions (withdrawal syndrome) – nausea, vomiting, rarely insomnia – may be observed when abruptly withdrawing high doses of antipsychotic drugs.

Cases of exacerbation of psychotic symptoms and appearance of involuntary motor disorders (akathisia, dystonia, dyskinesia) have been reported. Because of this, withdrawal of the drug is recommended to be done gradually.

WARNING: in patients with cardiovascular and cerebrovascular disease or other conditions predisposing to arterial hypotension, advanced age, hepatic insufficiency, history of seizures.

Effects on the ability to drive a car and other machinery

Seroquel may cause somnolence, so patients should not operate machinery that are dangerous during treatment, including driving and drinking alcohol.

Contraindications

Hypersensitivity to any of the ingredients of Seroquel.

Side effects

There were the following most common adverse reactions related to taking of this medicine: somnolence (17.5%), dizziness (10%), constipation (9%), dyspepsia (6%), orthostatic hypotension and tachycardia (7%), dry mouth (7%), increase of liver enzymes activity in serum (6%), (including increase of cholesterol and triglycerides concentration).

The administration of Seroquel may be accompanied by the development of moderate asthenia, rhinitis and dyspepsia, weight gain (mainly in the first weeks of treatment).

Serocquel may cause orthostatic hypotension (accompanied by dizziness), tachycardia, and in some patients, fainting; these adverse reactions occur mostly during the initial period of dose adjustment (see section “Special Precautions”).

In patients taking Seroquel, there have been very rare cases of priapism and seizures.

In rare cases, malignant neuroleptic syndrome (hyperthermia, impaired consciousness, muscle rigidity, vegetative vascular disorders, increased concentration of creatine phosphokinase), leukopenia and/or neutropenia have been observed. No cases of severe neutropenia or agranulocytosis have been reported in patients taking Seroquel. When using Seroquel in routine practice, leukopenia and/or neutropenia resolved after drug withdrawal. Possible risk factors for leukopenia and/or neutropenia include decreased leukocyte counts prior to therapy or a history of drug-induced leukopenia and/or neutropenia. Rarely, cases of eosinophilia, development of peripheral edema, and allergic reactions, including angioedema, have been reported.

Cases of asymptomatic increases in serum transferase activity (alanine and asparagine ALT and ACT, respectively) or gamma-glutamyl transpeptidase (GGT) activity have been reported in patients taking Seroquel. These changes were generally reversible during treatment with Seroquel.

Mild increases in cholesterol and serum triglycerides may occur during treatment with Seroquel.

Therapy with Seroquel is associated with a small dose-dependent decrease in thyroid hormone levels, particularly total T4 and free T4. Maximum reductions in total and free T4 were recorded in the 2nd and 4th weeks of quetiapine therapy, with no further reductions in hormone concentrations during long-term treatment. Thereafter, there were no signs of clinically significant changes in the concentration of thyrotropic hormone.

In almost all cases, total and free T4 concentrations returned to baseline after discontinuation of Seroquelin therapy, regardless of the duration of treatment. Seroquel may cause prolongation of the QTC interval; the relationship of Seroquel use to a permanent increase in QTC has not been identified (see section “Special Precautions”). The following common (1/100) adverse events have also been reported –

increased blood pressure, palpitations, dysarthria, pharyngitis, cough, anorexia, and increased sweating. A causal relationship between these side effects and taking Seroquel has not been established.

Late dyskinesia

With long-term use of Seroquel, there is a potential for the development of tardive dyskinesia. If symptoms of tardive dyskinesia occur, the dose should be reduced or further treatment with Seroquel should be discontinued.

The following acute reactions (withdrawal syndrome) – nausea, vomiting, and rarely insomnia – may occur when abruptly withdrawing high doses of antipsychotic drugs.

Cases of exacerbation of psychotic symptoms and occurrence of involuntary motor disorders (akathisia, dystonia, dyskinesia) have been reported. Because of this, withdrawal of the drug is recommended to be done gradually.

Overdose

The data on Seroquel overdose are limited. Cases of Seroquel doses greater than 20 g have been described without fatal consequences and with complete recovery, but there are reports of extremely rare cases of Seroquel overdose resulting in death or coma.

Symptoms: the symptoms noted were mainly a consequence of an increase in the known pharmacological effects of the drug, such as drowsiness and over-sedation, tachycardia, and decreased blood pressure.

Treatment: there are no specific antidotes to quetiapine. In cases of severe intoxication, symptomatic therapy should be considered and activities aimed at maintaining respiratory function, cardiovascular system, ensuring adequate oxygenation and ventilation are recommended. Careful medical monitoring and observation should be continued until the patient is fully recovered.

Pregnancy use

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

The extent to which quetiapine is excreted with women’s milk is not known. Women should be advised to avoid breastfeeding while taking Seroquel.

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