Expiration date: 12/2025

Structure and Composition: 

Sustained-release tablets, film-coated. One tablet contains Quetiapine fumarate 57.56, 172.69, 230.26, 345.38 or 460.5 mg

(Equivalent to 50, 150, 200, 300 and 400 mg of quetiapine, respectively)

Excipients: lactose monohydrate, sodium citrate dihydrate MCC magnesium stearate, hypromellose

sheath: 400 hypromellose macrogol titania dye E171 iron oxide red E172 (tablet 50 mg), iron oxide yellow colorant E172 (tablet 50, 200 and 300 mg)

in blister 10 pcs. In the paper cartons 6 blisters.

Description pharmaceutical form:

Tablets 50 mg: oblong biconvex, pink, film-coated with an engraving «XR 50" on one side.

Tablet 150 mg: oblong biconvex, white, film-coated with an engraving «XR 150" on one side.

Tablets 200 mg: oblong biconvex, yellow film-coated engraved with «XR 200" on one side.

Tablets 300 mg: oblong biconvex, light yellow, film-coated with an engraving «XR 300" on one side.

Tablets 400 mg: oblong biconvex, white, film-coated with an engraving «XR 400" on one side.

Pharmacokinetics:

Quetiapine is well absorbed from the gastrointestinal tract. Cmax of quetiapine and N-dezalkilkvetiapina plasma levels achieved approximately 6 hours after administration of the drug Seroquel Prolong. The equilibrium molar concentration of the active metabolite N-dezalkilkvetiapina is 35% of that of quetiapine.

The pharmacokinetics of quetiapine and N-dezalkilkvetiapina linear and is dose-dependent while taking the drug Seroquel Prolong at doses up to 800 mg 1 time per day.

Before the drug Seroquel Prolong 1 once daily at a dose equivalent to a daily dose of the drug Seroquel, received for 2 doses, the AUC observed similar, but Cmax was 13% less. Value AUC metabolite N-dezalkilkvetiapina was 18% less.

Studies of the effect of food on the bioavailability of quetiapine have shown that eating a high-fat diet resulted in a statistically significant increase in Cmax and AUC of the drug Seroquel Prolong - about 50 and 20%, respectively. Eating a low-fat diet had no significant effect on Cmax and AUC of quetiapine. It is recommended to take Seroquel Prolong 1 per day apart from the food.

Approximately 83% of quetiapine is bound to plasma proteins.

It is found that CYP3A4 metabolism is a key quetiapine isoenzyme mediated by cytochrome P450. N-dezalkilkvetiapin formed with the participation of isoenzyme CYP3A4.

Quetiapine and some of its metabolites (including N-dezalkilkvetiapin) have weak inhibitory activity against the Cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6 and 3A4, but only at concentrations 5-50 times greater than the concentration observed in effective doses typically used 300-800 mg / day.

Based on the results in vitro, can not be expected that the simultaneous administration of quetiapine with other drugs will result in clinically significant inhibition of the metabolism of other drugs, mediated by cytochrome P450.

T1 / 2 and N-quetiapine dezalkilkvetiapina about 7 and 12 hours, respectively. Approximately 73% of quetiapine is excreted in urine and 21% in faeces. Quetiapine is extensively metabolised in the liver, less than 5% of quetiapine is not metabolized and is excreted unchanged by the kidneys, or the faeces.

Differences pharmacokinetic parameters in men and women is not observed.

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

Average plasma Cl quetiapine is reduced by approximately 25% in patients with severe renal impairment (Cl creatinine <30 ml / min / 1.73 m2), but the individual clearance figures are within the range identified in healthy volunteers.

In patients with hepatic insufficiency (alcoholic cirrhosis compensated) average quetiapine plasma Cl decreased by approximately 25%. As quetiapine is extensively metabolized in the liver, in patients with hepatic insufficiency may increase plasma concentrations of quetiapine, which require dose adjustment.

Description of the pharmacological actions:

Quetiapine is an atypical antipsychotic. Quetiapine and its active metabolite N-dezalkilkvetiapin neytrotransmitternymi interact with brain receptors. Quetiapine and N-dezalkilkvetiapin exhibit high affinity for serotonin receptors of the 5HT2 receptors and dopamine D1 and D2 types brain. Greater selectivity for serotonin 5HT2 receptors, such as dopamine receptors than type D2, causes major clinical antipsychotic drug Quetiapine Prolong properties and low incidence of extrapyramidal side effects. In addition, N-dezalkilkvetiapin exhibits high affinity for the norepinephrine transporter. Quetiapine and N-dezalkilkvetiapin have high affinity for histamine and adrenoceptors & alpha1-and lower affinity for adrenoceptors & alpha2-receptors and serotonin type 5NT1. Quetiapine does not show appreciable affinity for cholinergic muscarinic and benzodiazepine receptors.

The standard tests shows quetiapine antipsychotic activity.

The specific contribution of the metabolite N-dezalkilkvetiapina in the pharmacological activity of quetiapine is not installed.

Results of the study of extrapyramidal symptoms (EPS) in animals revealed that quetiapine causes weak catalepsy at doses effective in blocking the receptors type D2. Quetiapine is a selective decrease in the activity of mesolimbic A10 dopaminergic neurones versus the A9 nigrostriatal neurones involved in motor function.

Seroquel Prolong well tolerated when taken in recommended doses, including elderly patients.

Patients age group of 66 to 89 years with dementia Seroquel Prolong the drug in doses of 50 to 300 mg / day reduces the symptoms of depression.

EPS and weight rate in stable patients with schizophrenia does not increase during prolonged therapy with Seroquel Prolong.

In studies of major depressive disorder according to the criteria of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders (4th ed) -. A Guide to the Diagnostic and Statistical Mental Disorders, 4th edition) did not observe an increased risk of suicidal behavior and suicidal ideation when taking Seroquel drug Prolong compared with placebo.

Indications:

schizophrenia including preventing relapses in stable patients

bipolar disorder, including:

• Moderate to severe manic episodes in bipolar disorder structure
  
• Severe depressive episodes in bipolar disorder structure
  
• Prevention of recurrence of bipolar disorder in patients with a previous effective therapy quetiapine manic or depressive episodes of bipolar disorder in the structure.
  

Contraindications:

• hypersensitivity to any component of the drug
  
• lactase deficiency, glucose-galactose malabsorption and galactose intolerance
  
• concomitant use with inhibitors of cytochrome P450, such as azole antifungals group, erythromycin, clarithromycin and nefazodone, and protease inhibitors (see. "Interaction with other medicinal products and other forms of interaction")
  
• age of 18 years (despite the fact that the effectiveness and safety of Seroquel Prolong in children and adolescents aged 10-17 years, were studied in clinical trials).
  

Carefully:

• cardiovascular and cerebrovascular disease, or other conditions predisposing to hypotension
  
• elderly age
  
• liver failure
  
• seizures in history.
  

Application of pregnancy and breastfeeding:

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

The degree of excretion of quetiapine with human milk is unknown. Women should avoid breastfeeding while taking the drug Seroquel Prolong.

Side effect:

The most common side effects of the drug Seroquel Prolong - drowsiness, dizziness, dry mouth, slightly pronounced asthenia, constipation, tachycardia, orthostatic hypotension and dyspepsia.

The drug Seroquel Prolong, like other antipsychotics, may be associated with weight gain, syncope, neuroleptic malignant syndrome, leucopenia, neutropenia and peripheral edema.

The frequency of adverse reactions is shown in the following grading: very often - & ge1 / 10 often - & ge1 / 100, <1/10 uncommon - & ge1 / 1000, <1/100 rarely - & ge1 / 10,000, <1/1000 rarely - <1 / 10000, unspecified frequency.

Drug Interactions:

Caution must be exercised by the combined use of the drug Seroquel Prolong with other drugs acting on the central nervous system, as well as alcohol.

Isozyme cytochrome P450 (CYP) 3A4 isoenzyme is the main responsible for the metabolism of quetiapine, carried out through the cytochrome P450 system. In the study in healthy volunteers the combined use of quetiapine (25 mg) with ketoconazole, CYP3A4 inhibitor, resulted in an increase in AUC of quetiapine 5-8 times.

Therefore, concomitant use of quetiapine and cytochrome CYP3A4 inhibitors is contraindicated. When quetiapine therapy is not recommended to consume grapefruit juice.

The use of quetiapine pharmacokinetic study in varying doses prior to or simultaneously with carbamazepine resulted in a significant increase quetiapine and Cl, respectively, decrease AUC, on average 13% compared to Quetiapine without receiving carbamazepine. Some patients AUC reduction was even more pronounced. This interaction was associated with decreased plasma concentrations of quetiapine, and could reduce the effectiveness of therapy with Seroquel Prolong. The combined use of quetiapine with phenytoin, another inducer of hepatic microsomal system, accompanied by an even more pronounced (approximately 450%) increase in the clearance of quetiapine. Use of the drug Seroquel Prolong patients receiving inducers of liver enzyme system, is possible only if the expected benefits of therapy with Seroquel Prolong exceeds the risk associated with the abolition of the drug - inducer of liver enzymes. Changing the dose of drugs - inducers of microsomal enzymes should be gradual. If necessary, their replacement drugs may not induce microsomal enzymes (eg drug valproic acid).

The pharmacokinetics of quetiapine were not significantly altered, while the use of the antidepressant imipramine (an inhibitor of CYP2D6) or fluoxetine (an inhibitor of CYP3A4 and CYP2D6).

The pharmacokinetics of quetiapine were not significantly changed by the simultaneous use of antipsychotic drugs - risperidone or haloperidol. However, concomitant use of quetiapine and thioridazine led to an increase in Cl quetiapine of approximately 70%.

The pharmacokinetics of quetiapine were not significantly changed by the simultaneous application of cimetidine.

In single dose of 2 mg of lorazepam in patients receiving quetiapine 250 mg 2 times a day lorazepam clearance is reduced by approximately 20%.

The pharmacokinetics of lithium drugs does not change, while the use of quetiapine. There were no clinically relevant changes in the pharmacokinetics of valproic acid and quetiapine when used together seminatriya valproate and quetiapine.

Pharmacokinetic studies of the interaction of the drug Seroquel Prolong with drugs used in cardiovascular diseases have not been conducted.

Caution must be exercised by the combined use of the drug Seroquel Prolong, and drugs that may cause electrolyte imbalance and lengthening of the QTc interval.

Quetiapine does not cause induction of hepatic enzyme systems involved in the metabolism of phenazone.

Patients treated with quetiapine, were marked false positive screening tests to detect methadone and tricyclic antidepressants by enzyme immunoassay. conducting chromatographic studies it is recommended to confirm the screening results.

Dosage and administration:

Inside, swallowing whole (without sharing, without chewing or breaking), 1 time a day, apart from the food.

Adults

Schizophrenia Treatment of moderate to severe manic episodes in bipolar disorder structure

Seroquel Prolong drug should be taken at least 1 hour before meals.

The daily dose for the first 2 days of therapy is: 1 st day - 300 mg, 2 nd day - 600 mg. The recommended daily dose - 600 mg, but if necessary, it can be increased to 800 mg / day. Depending on the clinical response and tolerance of the individual patient, the dose can vary from 400 to 800 mg / day. For maintenance therapy in schizophrenia no dosage adjustment is required after the acute relief.

Treatment of episodes of depression in the structure of bipolar disorder

Seroquel Prolong should be taken at bedtime. The daily dose for the first 4 days of therapy is: 1 st day - 50 mg, 2 nd day - 100 mg the third day - 200 mg, 4th day - 300 mg. The recommended daily dose - 300 mg. Depending on the clinical effect, and individual patient tolerance dose can be increased to 600 mg. The advantage of using the drug Seroquel Prolong a daily dose of 600 mg compared to 300 mg have been identified. Serokvel® Prolong at a dose greater than 300 mg should be prescribed by a doctor with experience in treatment of bipolar disorder.

Relapse prevention of bipolar disorders in patients with a prior quetiapine effective treatment of manic or depressive episodes of bipolar disorder in the structure

For the prevention of recurrence of manic, depressive or mixed episodes of bipolar disorders in patients with a positive response to treatment with quetiapine therapy should continue Prolong in the same daily dose as the beginning of therapy. Seroquel Prolong should be taken at bedtime. Depending on the clinical effect, and individual patient tolerance dose can vary from 300 to 800 mg / day. For maintenance therapy is recommended to use the minimum effective dose of the drug Seroquel Prolong.

Translation from receiving Seroquel drug on the drug Seroquel Prolong

For the convenience of receiving patients currently receiving fractional therapy with Seroquel, may be transferred to the drug Seroquel Prolong 1 once daily at a dose equivalent to a total daily dose of the drug Seroquel. In some cases, you may need a dosage adjustment.

Elderly patients

As with other antipsychotics, Seroquel Prolong should be used cautiously in elderly patients, especially early in therapy. Selection of an effective dose of Seroquel Prolong the drug in the elderly may be slower, and the daily therapeutic dose lower than for younger patients. The average quetiapine plasma Cl elderly patients by 30-50% compared with young patients. In elderly patients the initial dose of Seroquel Prolong - 50 mg / day. The dose may be increased to 50 mg per day to achieve effective dose depending on clinical response, and tolerability of the individual patient.

Patients with renal failure

For patients with renal insufficiency dose adjustment is required.

Patients with hepatic insufficiency

Quetiapine is extensively metabolized in the liver. Consequently, caution should be exercised when using the drug Seroquel Prolong in patients with hepatic insufficiency, especially at the beginning of therapy. It is recommended to start therapy with Seroquel Prolong a dose of 50 mg / day and increase the dose to 50 mg daily to achieve an effective dose.

Overdose:

Symptoms. It has been reported of deaths while taking 13.6 grams of quetiapine in patients participating in a clinical trial, as well as the lethal outcome after taking 6 grams of quetiapine during postmarketing study of drug. At the same time, a case receiving quetiapine exceeding 30 g, of non-fatal.

There are reports of very rare cases of quetiapine overdose, resulting in an increase QTc interval, coma or death.

In patients with severe cardiovascular disease in the history of the risk of side effects may increase in overdose (see. "Special Instructions").

Signs marked with an overdose, were mainly the result of strengthening of the known pharmacological effects of the drug such as drowsiness and sedation, tachycardia and blood pressure reduction.

Treatment. Specific antidote to quetiapine no. In cases of severe intoxication should be aware of the possibility of an overdose of several medications. It is recommended to carry out activities aimed at the maintenance of respiratory function and the cardiovascular system, ensuring adequate oxygenation and ventilation. Gastric lavage (after intubation if the patient is unconscious) and administration of activated charcoal and laxatives can contribute to the removal of unabsorbed quetiapine, however the effectiveness of these measures has not been studied.

Careful medical supervision must continue to improve the patient's condition.

Special instructions:

Drowsiness

During therapy with Seroquel Prolong may experience drowsiness and related symptoms, such as sedation (see. "Side effects"). In clinical studies in patients with depression in the structure of bipolar disorder, somnolence, usually developed during the first three days of treatment. Intensity of this side effect was mainly mild or moderate. If severe sleepiness in patients with depression in the structure of bipolar disorder may need more frequent visits to the doctor for 2 weeks from the date of occurrence of drowsiness, or to reduce the severity of symptoms. In some cases, it may require discontinuation of therapy with Seroquel Prolong.

Patients with cardiovascular disease

Caution should be exercised when administering the drug Seroquel Prolong patients with cardiovascular and cerebrovascular diseases and other conditions predisposing to hypotension. Against the background of therapy with Seroquel Prolong can occur orthostatic hypotension, especially during dose titration at the start of therapy. In the event of orthostatic hypotension may require dose reduction or a slower titration of it.

Dysphagia (see. "Side effects") and aspiration have been observed in the treatment of drug Seroquel Prolong. A causal relationship with the occurrence of aspiration pneumonia taking Seroquel Prolong the drug has not been established. However, caution should be exercised when administering the drug to patients at risk for aspiration pneumonia.

seizures

There were no differences in the incidence of seizures in patients treated with quetiapine or placebo. However, as in the treatment of other antipsychotic drugs, it is advisable to use caution when treating patients with the presence of seizures in history (see. "Side effects").

Extrapyramidal symptoms

An increasing incidence of EPS in adult patients with depression, bipolar disorder in the structure when taking quetiapine about depressive episodes, compared to placebo (see., "Side effects"). However quetiapine therapy of patients with schizophrenia and manic bipolar disorder in the structure is not revealed increasing incidence of EPS compared to placebo.

tardive dyskinesia

In the case of symptoms of tardive dyskinesia it is recommended to reduce the dose gradually or cancel it. The symptoms of tardive dyskinesia may increase or even arise after discontinuation of the drug (see. "Side effects").

Neuroleptic malignant syndrome

In patients receiving antipsychotic drugs, including quetiapine, neuroleptic malignant syndrome may occur (see. "Side effects"). The clinical manifestations of the syndrome include hyperthermia, altered mental status, muscular rigidity, autonomic lability, increased creatine phosphokinase activity. In such cases, you must stop taking the drug Seroquel Prolong, and hold the appropriate treatment.

Severe neutropenia

In clinical trials, there have been cases quetiapine infrequently severe neutropenia (neutrophil count <0.5 x 109 / L). Most cases of severe neutropenia occurred several months after initiation of therapy with quetiapine. There was no dose-response effect. Leukopenia and / or neutropenia resolved after cessation of therapy with quetiapine. A possible risk factor for the occurrence of neutropenia, a low white blood cell count prior and cases of drug-induced neutropenia in history. In patients with a neutrophil count <1 x 109 / l receiving quetiapine should be discontinued. The patient should be monitored for possible symptoms of infection and to control the number of neutrophils (up to the level exceeding 1.5 x 109 / L).

Interaction with other drugs

Also see. "Interaction".

Use of the drug Seroquel Prolong in combination with potent inducers of the enzyme system of the liver, such as phenytoin and carbamazepine, thereby reducing the concentration of quetiapine in the plasma and may reduce the effectiveness of therapy with Seroquel Prolong.