Victor - instructions for use, dose, side effects, contraindications

Excipients: povidone K29-32, calcium hydrophosphate dihydrate, microcrystalline cellulose, sodium carboxymethyl starch (type A), lactose monohydrate, magnesium stearate;

sheath: Fallow II pink 33G34594 (tablets 25 mg): hypromellose 6cp, titanium dioxide, lactose monohydrate, macrogol 3350, triacetin, iron dye red oxide (E172), ferric oxide yellow oxide (E172); Fallen II yellow 33G32578 (tablets 100 mg) and Opadrai II yellow 33G32605 (tablets 150 mg): hypromellose 6cp, titanium dioxide, lactose monohydrate, macrogol 3350, triacetin, iron dye yellow oxide (E172); Opadry II white 33G28435 (tablets 200 mg and 300 md): hypromellose 6cP, titanium dioxide, lactose monohydrate, macrogol 3350, triacetin.

Description:

Tablets 25 mg. Round biconvex tablets covered with a film shell, light orange color with engraving "Q" one side.

Tablets of 100 mg. Round biconvex tablets covered with a film shell, yellow with an engraving "Q" one side.

Tablets 150 mg. Oval biconvex tablets covered with a film shell of pale yellow color with engraving "Q" one side.

Tablets 200 mg. Oval biconvex tablets covered with a white film sheath with an engraving "Q" one side.

Tablets 300 mg. Oval biconvex tablets covered with a white film sheath with an engraving "Q" on the one hand and "300" on the other.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.04 Quetiapine

Pharmacodynamics:

Quetiapine is an atypical antipsychotic drug that exhibits a higher affinity for serotonin receptors (5HT₂) than to dopamine receptors D₁ and D₂ in the brain. Quetiapine also has a higher affinity for histamine and α₁-adrenoceptors and less in relation to α₂adrenoreceptors. There was no significant affinity for quetiapine for cholinergic, muscarinic and benzodiazepine receptors. In standard tests quetiapine has antipsychotic activity. The results of the study of extrapyramidal symptoms in animals revealed that quetiapine causes a weak catalepsy in a dose effectively blocking dopamine D₂ receptors. Quetiapine causes a selective decrease in the activity of mesolimbic A₁₀-dophaminergic neurons in comparison with A₉-nigrostriate neurons involved in motor function.

Clinical studies (quetiapine 75-750 mg / day) showed no difference between quetiapine and placebo in the incidence of extrapyramidal symptoms and the concomitant use of anticholinergic drugs.

Quetiapine does not cause a prolonged increase in the concentration of prolactin in the blood plasma. In numerous studies with a fixed dose, there was no difference in the level of prolactin when using quetiapine or placebo.

In clinical trials quetiapine showed efficacy in treating the positive and negative symptoms of schizophrenia.

The effect of quetiapine on 5HT receptors₂ and D₂ lasts up to 12 hours after taking the drug.

Pharmacokinetics:

When administered orally quetiapine well absorbed from the gastrointestinal tract, reaching a maximum concentration in the plasma after 1.5 hours. It is actively metabolized in the liver. The main metabolites in the plasma do not have a pronounced pharmacological activity.

The intake of food does not significantly affect the bioavailability of quetiapine. Half-life is about 7 hours. Approximately 83% of quetiapine binds to plasma proteins. The pharmacokinetics of quetiapine is linear, there is no difference in pharmacokinetic parameters in men and women.

It was found that isoenzyme CYP3A4 is a key enzyme of quetiapine metabolism, mediated by cytochrome P450. The average clearance of quetiapine in elderly patients is 30-50% less than in patients aged 18 to 65 years.

The average plasma clearance of quetiapine is reduced by approximately 25% in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min / 1.73 m²), but individual clearance rates are within the values corresponding to healthy people. In patients with impaired liver function (eg, compensated alcoholic cirrhosis), the mean plasma clearance of quetiapine is reduced by approximately 25%.

Approximately 73% of quetiapine is excreted by the kidneys and 21% by the intestine.Less than 5% of quetiapine is not metabolized and is excreted unchanged by the kidneys or through the intestines.

Quetiapine and some of its metabolites have a weak inhibitory activity against cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6 and 4, but only at concentrations 10-50 times higher than the concentrations observed at the usual effective dosage of 300-450 mg / day.

Based on the results in vitro, it should not be expected that simultaneous administration of quetiapine with other drugs will lead to a clinically pronounced inhibition of cytochrome P450 mediated by the metabolism of other drugs.

Indications:

For the treatment of acute and chronic psychoses, including schizophrenia.

For the treatment of manic episodes in the structure of bipolar disorder.

For the treatment of depressive episodes from medium to severe severity in the structure of bipolar disorder.

The drug is not indicated for the prevention of manic and depressive episodes.

Contraindications:

Hypersensitivity to any of the components of the drug, children under 18 years of age, combined with cytochrome P450 inhibitors (antifungal agents of the azole group, erythromycin, clarithromycin, nefazodone, protease inhibitors); lactation period; patients with rare hereditary diseases, such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption (due to the presence of lactose monohydrate).

Carefully:

In patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension; elderly age, hepatic insufficiency, convulsive fits in the anamnesis, pregnancy.

Pregnancy and lactation:

Category C. The safety and efficacy of quetiapine in pregnancy has not been established.

The use of the drug during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

It is not known whether quetiapine with breast milk. If quetiapine is needed during lactation (breastfeeding), the question of stopping breastfeeding should be addressed.

Dosing and Administration:

Inside, regardless of food intake.

Treatment of acute and chronic psychoses, including schizophrenia

Victor is appointed twice a day.The daily dose for the first 4 days of therapy is: 1st day - 50 mg, Day 2 - 100 mg, Day 3 - 200 mg, 4th day - 300 mg.

Starting from the 4th day, the dose should be titrated to an effective dose, usually in the range of 300 to 450 mg / day. Depending on the clinical effect and individual tolerability patient, the dose can 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

Victor is used as a monotherapy or as an adjuvant therapy for mood stabilization.

Victor is appointed twice a day. The daily dose for the first 4 days of therapy is: the 1st day - 100 mg, the second day - 200 mg, the third day - 300 mg, the 4th day - 400 mg. In the future, 6The 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

ATIctoel 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 the drug is 600 mg.

There was no clinical improvement with a dose increase of more than 600 mg.

Elderly

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

Patients with renal insufficiency

A dose adjustment is not required.

Patients with hepatic insufficiency

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

Side effects:

The most common side effects when taking quetiapine are drowsiness, dizziness, dry mouth, mild asthenia, constipation, tachycardia, orthostatic hypotension and dyspepsia.

The use of quetiapine, as well as other antipsychotics, may be accompanied by weight gain, fainting, malignant neuroleptic syndrome, leukopenia, neutropenia, and peripheral edema.

The frequency of adverse reactions is given in the following gradation: very often (≥ 1/10); often (≥ 1/100, <1/10); infrequently (≥ 1/1000, <1/100); rarely (≥ 1/10 000, <1/1000); very rarely (<1/10 000), including cases whose frequency is unknown.

From the central and peripheral nervous system: very often - drowsiness² , dizziness⁴ headache; often - dysarthria, unusual and nightmarish dreams, fainting⁴, extrapyramidal symptoms; infrequently - convulsions¹, restless legs syndrome; very rarely - tardive dyskinesia⁶.

From the gastrointestinal tract: very often - dry mouth; often - constipation, indigestion; infrequently - dysphagia; rarely - jaundice⁶; very rarely - hepatitis⁶.

From the side of the cardiovascular system: often - orthostatic hypotension⁴(accompanied by dizziness), tachycardia⁴.

On the part of the blood system: often - leukopenia¹, eosinophilia; frequency is unknown - neutropenia¹.

From the immune system: infrequently - hypersensitivity reactions, anaphylactic reactions⁶.

From the skin: very rarely - angioedema⁶, Stevens-Johnson syndrome⁶.

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

Change in laboratory and instrumental indicators: very often - an increase in the concentration of triglycerides, total cholesterol (mainly low-density lipoprotein cholesterol); often - weight gain, increased activity of hepatic transaminases (aspartate aminotransferase (ACT) and alanine aminotransferase (ALT))³, decrease in the number of neutrophils, hyperglycemia⁷; infrequently - increased activity of creatine phosphokinase, not associated with malignant neuroleptic syndrome, thrombocytopenia.

From the respiratory system: often - rhinitis.

Metabolic disorders: very rarely - diabetes mellitus^1,5,6.

Other: very often - withdrawal syndrome; often - asthenia, peripheral edema, blurred vision; rarely - priapism, malignant neuroleptic syndrome.

1. See section "Special instructions".

2. Drowsiness usually occurs within the first 2 weeks after initiation of therapy and is usually resolved against the backdrop of continued use of quetiapine.

3. Perhaps an asymptomatic increase in activity ACT, ALT and γ-glutamyltranspeptidase in the blood serum, as a rule, reversible against the background of continued use of quetiapine.

4. Like other antipsychotics quetiapine often causes orthostatic hypotension, which is accompanied by dizziness, tachycardia and in some cases - fainting, especially at the beginning of therapy.

5. Very rare cases of decompensation of diabetes mellitus have been noted.

6. The frequency of this side effect was estimated based on the results of post-marketing surveillance.

7. Increased fasting blood glucose ≥126 mg / dL (≥ 7.0 mmol / L) or post-prandial blood glucose ≥ 200 mg / dL (≥ 11,1 mmol / l), at least for a single application.

When taking antipsychotic drugs, it was reported on the lengthening of the interval QT, ventricular arrhythmias, sudden death, cardiac arrest and tachycardia of the type "pirouette" (torsades de pointes).

Quetiapine therapy is associated with a small dose-dependent decrease in the concentration of thyroid hormones, in particular, total thyroxine (T₄) and free T₄. Maximum reduction in total and free T₄ registered at the 2 nd and 4 th week of quetiapine therapy without further decrease in the concentration of hormones during long-term treatment. Thereafter, there were no signs of clinically significant changes in the concentration of thyroid-stimulating hormone.In practically all cases, the concentration of the total and free T₄returned to baseline after quetiverin therapy ceased regardless of the duration of treatment. A slight decrease in total triiodothyronine (T₃) and the reverse T₃ It was noted only when high doses were used. The level of thyroxine-binding globulin (TSH) remained unchanged, and there was no increase in the thyroid-stimulating hormone (TSH) level.

Overdose:

The cases of taking quetiapine in a dose exceeding 30 g are described, without a lethal outcome. Very rarely reported cases of overdose with quetiapine, leading to an increase in the interval QT, death or coma.

In patients with severe cardiovascular disease in history, the risk of side effects in overdose may increase.

Symptoms: these symptoms were mainly due to the increase in known pharmacological effects of the drug, such as drowsiness and excessive sedation, tachycardia and lowering 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 activities,aimed at maintaining the function of breathing, cardiovascular system, ensuring adequate oxygenation and ventilation of the lungs.

The patient should be under the supervision of a doctor until complete recovery.

Interaction:

With the simultaneous administration of drugs that have a strong inhibitory effect on the isoenzyme CYP3A4 (such as the azole antifungal agents and macrolide antibiotics), the concentration of quetiapine in the plasma may increase.

In a study of the pharmacokinetics of quetiapine in varying dosages with the administration of quetiapine prior to the administration of ketoconazole or concomitantly with ketoconazole, an increase in the average maximum concentration (C_max) and the area under the curve "concentration-time" (AUC) quetiapine by 235% and 522%, respectively, and also led to a decrease in the clearance of quetiapine, on average, by 84%. Quetiapine half-life increased, but the mean time to reach maximum concentration (t_max) did not change. In such cases, lower doses of quetiapine should be used. Particular attention should be paid to elderly and weakened patients. An individual is neededandIt is dual to assess the risk-benefit relationship for each patient. Simultaneous administration of quetiapine with drugs inducing the enzyme system of the liver, such as carbamazepine, it is possible to reduce the concentration of the drug in the plasma, which may require an increase in the dose of quetiapine, depending on the clinical effect. In a study of the pharmacokinetics of quetiapine in varying doses, when administered prior to or concomitantly with carbamazepine (a hepatic enzyme inducer), this simultaneous administration led to a significant increase in the clearance of quetiapine. This increase in quetiapine clearance reduced AUC an average of 13% compared with the use of quetiapine without carbamazepine.

The simultaneous administration of quetiapine to another inducer of microsomal liver enzymes, phenytoin, also led to an increase in the clearance of quetiapine. With the simultaneous administration of quetiapine and phenytoin (or other inducers of hepatic enzymes, such as barbiturates, rifampicin) may require an increase in the dose of quetiapine. It may also be necessary to reduce the dose of quetiapine when the phenytoin or carbamazepine or other inducerenzyme system of the liver or replacement for a drug that does not induce microsomal liver enzymes (for example, valproic acid).

The pharmacokinetics of lithium preparations does not change with the simultaneous administration of quetiapine.

There were no clinically significant changes in the pharmacokinetics of valproic acid and quetiapine in the joint administration of valproate semetriya and quetiapine.

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

The pharmacokinetics of quetiapine does not change significantly when administered concomitantly with antipsychotic drugs: risperidone or haloperidol.

However, simultaneous administration of quetiapine and thioridazine led to increased clearance of quetiapine.

Isozyme CYP3A4 is a key enzyme involved in the metabolism of quetiapine mediated by cytochrome P450. The pharmacokinetics of quetiapine does not change significantly with the simultaneous use of cimetidine, a cytochrome P450 inhibitor.

The pharmacokinetics of quetiapine did not change significantly with the simultaneous administration of an antidepressant imipramine (an inhibitor of the isoenzyme CYP2D6) or fluoxetine (inhibitor of isoenzymes CYP3A4 and CYP2D6).

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

It is not recommended to take quetiapine together with grapefruit juice.

Special instructions:

Patients with cardiovascular diseases

Care should be taken when administering the drug to patients with cardiovascular and cerebrovascular diseases, and other conditions predisposing to hypotension. Against the background of therapy with Vitello, orthostatic hypotension may occur, especially in the initial period of dose selection (in elderly patients it is observed more often than in young patients). If orthostatic hypotension occurs, a dose reduction or slower titration may be required. Patients with hepatic insufficiency '

Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using Vitello in patients with hepatic insufficiency, especially at the beginning of therapy.

Interval lengthening QT

There was no correlation between taking quetiapine and increasing QT interval.However, the lengthening of the interval QT was noted with his overdose (see the section "Overdose"). Caution should be exercised in prescribing the drug to patients with cardiovascular disease and the previously noted lengthening of the interval QT, as well as with simultaneous admission with drugs that extend the interval QT, other neuroleptics, especially in the elderly, patients with the syndrome of congenital lengthening interval QT, chronic heart failure, myocardial hypertrophy, hypokalemia, or hypomagnesemia.

Late dyskinesia

With long-term use of the drug, there is a potential for the development of tardive dyskinesia. If symptoms of tardive dyskinesia occur, reduce the dose or stop further treatment with quetiapine.

Severe neutropenia

In clinical studies of quetiapine, cases of severe neutropenia (number of neutrophils <0.5 * 10⁹/ l). Most cases of severe neutropenia occurred several months after initiation of quetiapine therapy. There was no dose-response effect.Leukopenia and / or neutropenia were resolved after quetiapine treatment was discontinued. A possible risk factor for the onset of neutropenia is a previous decrease in the number of leukocytes and cases of drug-induced neutropenia in the anamnesis. In patients with a neutrophil count <1.0 * 10⁹/ l reception of the drug should be stopped. The patient should be observed to identify possible symptoms of infection and monitor the level of neutrophils (up to a level exceeding 1.5 * 10⁹/ l).

Hyperglycaemia

Against the background of taking Vitell, hyperglycaemia or an exacerbation of diabetes mellitus in patients with diabetes mellitus is possible in the anamnesis. Clinical observation is recommended for patients with diabetes mellitus and patients with risk factors for diabetes mellitus (see section "Side effect").

Level of lipids

Against the background of taking Victor may increase the concentration of triglycerides and cholesterol (see section "Side effect").

Elderly patients with dementia

Some atypical antipsychotics in randomized, placebo-controlled trials increased the risk of developing cerebrovascular complications in patients with dementia.The mechanism of this increase in risk has not been studied. A similar risk of increasing the incidence of cerebrovascular complications can not be ruled out for other antipsychotic drugs or other groups of patients. Vitello should be used with caution in patients at risk of stroke.

Analysis of the use of atypical antipsychotics for the treatment of psychoses associated with dementia in elderly patients revealed an increase in the mortality rate in the group of patients receiving drugs of this group compared with the placebo group. There was no causal relationship between the treatment of quetiapine and the risk of increased mortality in elderly patients with dementia.

Convulsive seizures

There were no differences in the incidence of seizures in patients taking quetiapine or placebo. However, as with other antipsychotics, caution should be exercised in the treatment of patients with a history of seizures.

Malignant neuroleptic syndrome

Malignant neuroleptic syndrome can be associated with ongoing antipsychotic treatment.Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, instability of the autonomic nervous system, an increase in the concentration of creatine phosphokinase. In such cases, Victor should be withdrawn and treated accordingly,

Acute reactions associated with drug withdrawal

With a sharp cancellation of high doses of antipsychotic drugs, the following acute reactions (withdrawal syndrome) can occur: nausea, vomiting, and rarely insomnia. Cases of exacerbation of psychotic symptoms and the appearance of involuntary motor disorders (akathisia, dystonia, dyskinesia) have been reported. In this connection, it is recommended to cancel the drug gradually for at least one or two weeks.

Suicide / suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-injury and suicide in children, adolescents and young people (under 24). This risk remains until the onset of severe remission. In view of the fact that before the improvement of the patient's condition from the beginning of treatment, several weeks or more may pass, patients should be under close medical supervision before the onset of improvement.According to the generally accepted clinical experience, the risk of suicide may increase in the early stages of the onset of remission.

Other psychiatric disorders for which therapy is prescribed quetiapineare also associated with an increased risk of suicidal events. In addition, such conditions can be comorbid with a depressive episode. Therefore, the precautions used in the therapy of patients with a depressive episode should be taken in the treatment of patients with other psychiatric disorders.

Patients with a history of suicidal events, as well as patients who clearly express suicidal thoughts before starting therapy, are at increased risk of suicidal intentions and suicidal attempts and should be carefully observed during treatment.

Taking into account the influence of quetiapine on the central nervous system, Victor should be used with caution in combination with other drugs that have an inhibitory effect on the central nervous system, or alcohol.

Effect on the ability to drive transp. cf. and fur:

Vitello can cause drowsiness, so during treatment patients are not recommended to work with mechanisms that are dangerous,including the management of vehicles is not recommended.

Form release / dosage:

Film coated tablets, 25 mg, 100 mg, 150 mg, 200 mg and 300 mg.

Packaging:

Tablets 25 mg: 6 or 10 tablets per blister PVC / PVDC / Aluminum foil or PVC / Aluminum foil, 1 blister for 6 tablets or 1, 3, 6, 9, 10 blisters for 10 tablets with instructions for use in a cardboard box.

Tablets 100 mg: 10 tablets per blister PVC / PVDC / Aluminum foil or PVC / Aluminum foil, 1, 3, 6, 9, Ublicers with instructions for use in a cardboard box.

Tablets of 150 mg: 5 or 10 tablets per blister PVC / PVDC / Aluminum foil or PVC / Aluminum foil, 2, 6, 10, 12 blisters for 5 tablets or 6 blisters for 10 tablets with instructions for use in a cardboard box.

Tablets 200 mg and 300 mg: 5, 6 or 10 tablets per blister PVC / PVDC / Aluminum foil or PVC / Aluminum foil, 2, 6, 10 blisters for 5 tablets, 6 blisters for 10 tablets or 10 blisters for 6 tablets with instructions for use in cardboard tutu.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children!

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-007277/10

Date of registration:28.07.2010

Expiration Date:Unlimited

The owner of the registration certificate:AKTAVIS GROUP, AO AKTAVIS GROUP, AO Iceland

Manufacturer: & nbsp

AKTAVIS, LTD. Russia

Information update date: & nbsp14.02.2017

Illustrated instructions

Instructions

Victorel (Victoal)