Seroquel, 25 mg 60 pcs

Quetiapine is an atypical antipsychotic. Quetiapine and its active metabolite N-dezalkylquetiapine (norquetiapine) interact with a wide range of brain neutrotransmitter receptors. Quetiapine and N-dezalkylquetiapine exhibit high affinity for 5HT2-serotonin receptors and brain D1- and D2-dopamine receptors. This receptor antagonism combined with a higher selectivity for 5HT2-serotonin receptors than for D2-dopamine receptors provides the clinical antipsychotic properties of Seroquel® and the low frequency of extrapyramidal side effects.

Quetiapine has no affinity for the noradrenaline transporter and low affinity for the 5HT1A-serotonin receptor, whereas N-dezalkylquetiapine has high affinity for both. Inhibition of the noradrenaline transporter and partial agonism at the 5HT1A-serotonin receptor by N-desalkylquetiapine may account for the antidepressant effects of Seroquel®. Quetiapine and N-desalkylquetiapine have a high affinity for histamine and α1-adrenoreceptors and a moderate affinity for α2-adrenoreceptors. In addition, quetiapine has no or low affinity for muscarinic receptors, whereas N-dezalkylquetiapine has moderate to high affinity for several muscarinic receptor subtypes.
In standard tests, quetiapine exhibits antipsychotic activity.

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

The results of a 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 compared to A9-nigrostriate neurons involved in motor function.

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

The data on the use of Seroquel® in combination with valproate seminatria or lithium preparations for moderate to severe manic episodes are limited, but this combination therapy was generally well tolerated. In addition, Seroquel® at doses of 300 mg and 600 mg is effective in patients with moderate to severe bipolar disorder types I and II. The efficacy of Seroquel® is comparable when administered in doses of 300 mg and 600 mg per day.

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 effects of quetiapine on 5NT2- and D2-receptors last up to 12 hours after taking the drug.

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

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

Indications

Active ingredient

Composition

1 coated tablet contains:

the active ingredient:

quetiapine (in the form of fumarate) 25 mg,

excipients:

povidone;

Calcium bicarbonate phosphate dihydrate;

MC;

starch (sodium glycolate);

Lactose monohydrate;

Magnesium stearate

coating composition:

Red iron oxide; titanium dioxide; hydroxypropyl methylcellulose; polyethylene glycol 400.

How to take, the dosage

The drug Seroquel® can be used regardless of food intake.

Adults
The treatment of schizophrenia

The drug Seroquel® is prescribed 2 times a day. 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.

From the 4th day the dose should be adjusted to an effective dose, usually within 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

The drug Seroquel® is used as monotherapy or in combination with drugs with normotensive effects.

Seroquel® 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 of 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

The drug Seroquel® 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. The recommended dose is 300 mg/day. Maximum recommended daily dose of the preparation Seroquel® is 600 mg.

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

Elderly

In elderly patients, the starting dose of Seroquel® is 25 mg/day. The dose should be increased daily by 25-50 mg until an effective dose is achieved, which is likely to be lower than in younger patients.
Patients with renal impairment

Dose adjustment is not required.

Patients with hepatic insufficiency

Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using Seroquel® in patients with hepatic impairment, especially at the beginning of therapy. It is recommended that therapy with Seroquel® be initiated with a dose of 25 mg/day and the dose be increased daily by 25-50 mg until an effective dose is achieved.

Interaction

In concomitant administration of drugs with strong inhibitory effect on CYP3A4 isoenzyme (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. Special attention should be given to elderly and debilitated patients. The risk-benefit ratio for each patient should be evaluated individually.

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

Concomitant administration of Seroquel with another microsomal liver enzyme inducer (phenytoin), also resulted in increased clearance of quetiapine. If Seroquel and phenytoin (or other hepatic enzyme inducers such as barbiturates, rifampicin) are prescribed concomitantly, the dose of Seroquel may need to be increased. 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 is 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.

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

The pharmacokinetics of quetiapine was not 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 isoenzyme inhibitors (such as azole antifungals and macrolide antibiotics).

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

Special Instructions

Caution should be exercised when prescribing Seroquel in patients with cardiovascular and cerebrovascular disease or other conditions predisposing to arterial hypotension, as well as in elderly patients, with hepatic insufficiency, history of seizures.

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

The following acute reactions (withdrawal syndrome) – nausea, vomiting; 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.

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

No differences in the incidence of seizures have been found in patients taking Seroquel or placebo. However, caution is recommended during therapy in patients with a history of seizures.

The relationship between quetiapine administration and QTc interval prolongation has not been found. However, caution is required when prescribing quetiapine concomitantly with drugs that prolong the QTc interval, especially in the elderly.

Bearing in mind that quetiapine mainly affects the CNS, Seroquel should be used with caution in combination with other CNS-depressant drugs or alcohol.

Influence on driving and operating machinery

Seroquel may cause drowsiness, so patients are not advised to operate machinery that are hazardous, including driving a motor vehicle and other moving vehicles.

Contraindications

Hypersensitivity to any of the ingredients 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 section “Interaction with other medicinal products and other types of interaction”).
Although the efficacy and safety of Seroquel® in children and adolescents aged 10-17 years has been studied in clinical trials, the use of Seroquel® in patients under 18 years is not indicated.

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

Side effects

CNS and peripheral nervous system: often – somnolence (17.5%), dizziness (10%); rarely – malignant neuroleptic syndrome (hyperthermia, impaired consciousness, muscle rigidity, vegetovascular disorders, increased CPK concentration); very rarely – seizures. 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.

Digestive system disorders: often – constipation (9%), dyspepsia (6%), dry mouth (7%); increase of liver enzymes activity (ALT, AST, GGT) in serum (6%), and increase of cholesterol and triglycerides concentration (during Seroquel treatment these changes were generally reversible).

Cardiovascular system disorders: common – orthostatic hypotension (accompanied by dizziness), tachycardia (7%), fainting; these adverse reactions occur mostly in the initial period of dose adjustment.

Hematopoietic system: rarely – leukopenia and/or neutropenia. No cases of severe neutropenia or agranulocytosis have been reported in patients taking Seroquel. When using Seroquel in clinical 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.

Endocrine system disorders: therapy with Seroquel is associated with a slight dose-dependent decrease in thyroid hormone levels, in particular, total T4 and free T4. The maximum decrease in total and free T4 was registered at the 2nd and 4th weeks of quetiapine therapy with no further decrease in hormone concentrations during long-term treatment. Subsequently, 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.

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

Others: rare – peripheral edema, mild asthenia, rhinitis, weight gain (mostly in the first weeks of treatment); very rare – priapism.

Seroquel may cause prolongation of the QTc interval; no relationship of Seroquel use with persistent QTc prolongation has been identified.

The following common (1/100) adverse events have also been reported – increased BP, palpitations, dysarthria, pharyngitis, cough, anorexia, increased sweating. The cause-and-effect relation of these side effects with taking Seroquel has not been established.

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 mostly the result of an increase in the known pharmacological effects of the drug, such as drowsiness and over-sedation, tachycardia, and decreased BP.

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

Pregnancy use

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

The use of antipsychotic drugs, including quetiapine, in the third trimester of pregnancy puts newborns at risk for adverse reactions of varying severity and duration, including EPS and/or withdrawal syndrome.

Hypotension, hypertension, hypotension, tremor, somnolence, respiratory distress syndrome, or feeding disturbances have been reported. Consequently, the condition of newborns should be closely monitored.

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

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