Quetiapine Stada - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrophosphate 12.568 mg, lactose monohydrate 1,000 mg, microcrystalline cellulose 12,000 mg, sodium carboxymethyl starch -2.750 mg, povidone 2,000 mg, magnesium stearate 0.900 mg; shell: hypromellose - 1,250 mg, titanium dioxide - 0,567 mg, macrogol-400 - 0,125 mg, iron oxide yellow - 0,030 mg, iron oxide red - 0,028 mg.

1 tablet of 100 mg contains:

active substance: quetiapine fumarate is 115.130 mg, in terms of quetiapine - 100,000 mg;

auxiliary substances: calcium hydrophosphate -50.270 mg, lactose monohydrate - 4,000 mg, microcrystalline cellulose - 48,000 mg, sodium carboxymethyl starch - 11,000 mg, povidone-8,000 mg, magnesium stearate -3,600 mg; shell: hypromellose - 3,750 mg, titanium dioxide - 1,695 mg, macrogol-400 - 0,375 mg, iron oxide yellow - 0,180 mg.

1 tablet 200 mg contains:

active substance: quetiapine fumarate - 230.260 mg, in terms of quetiapine - 200,000 mg;

Excipients: calcium hydrophosphate -100.540 mg, lactose monohydrate 8,000 mg, microcrystalline cellulose 96,000 mg, sodium carboxymethyl starch 22,000 mg, povidone 16,000 mg, magnesium stearate 7,200 mg; shell: hypromellose - 7,500 mg, titanium dioxide - 3,750 mg, macrogol-400 - 0,750 mg.

Description:Round biconvex tablets covered with a film coating of orange-pink color (dosage 25 mg); yellow color with a risk on one side (dosage of 100 mg); from white to almost white (200 mg dosage).

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.04 Quetiapine

Pharmacodynamics:

Quetiapine is an atypical antipsychotic. Quetiapine and its active metabolite N-dealkalkvetiapine interact with neurotransmitter receptors in the brain. Quetiapine and N-desalkylketiapine show a high affinity for 5-HT₂-serotonin receptors and D₁ and D₂dopamine receptors of the brain. Higher selectivity to 5-HT₂serotonin receptors, than to D₂dopamine receptors determines the main clinical antipsychotic properties of quetiapine and the low incidence of extrapyramidal side effects.In addition, N-desalkylkvetiapine exhibits a high affinity for the carrier of noradrenaline. Quetiapine and N-desalkylketiapine have a high affinity for histamine and α₂adrenoreceptors and a lower affinity for α₂adrenoreceptors and 5-HT1-serotonin receptors. Quetiapine does not show a significant affinity for M-cholino- and benzodiazepine receptors.

The specific contribution of the N-dezalkylkvetiapine metabolite to the pharmacological activity of quetiapine is not established.

Quetiapine causes mild catalepsy in doses effectively blocking D₂ receptors. Quetiapine causes a selective decrease in the activity of mesolimbic A10-dopaminergic neurons in comparison with A9-nigrostriate neurons involved in motor function. Do not cause a prolonged increase in the concentration of prolactin in the blood plasma. The duration of exposure of quetiapine to 5-HT₂ and D₂ receptors is less than 12 hours after taking the drug.

Pharmacokinetics:

Ingestion quetiapine well absorbed from the gastrointestinal tract and actively metabolized. Food intake does not significantly affect the bioavailability of quetiapine.About 83% of quetiapine binds to plasma proteins.

The equilibrium concentration of the active metabolite of N-desalkylkvetiapine is 35% of that of quetiapine.

It is established that the CYP3A4 isoenzyme is the key isoenzyme of quetiapine metabolism, mediated by cytochrome P450. N-dealkylkvetiapine is formed with the participation of the CYP3A4 isoenzyme.

Quetiapine and some of its metabolites, including N-desalkylkvetiapine, have a weak inhibitory effect on cytochrome isoenzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, but only in concentrations 10-50 times higher than those observed at the usual dose of 300- 450 mg per day. Based on in vitro results, simultaneous use of quetiapine with other drugs should not be expected to lead to a clinically pronounced inhibition of the metabolism of other medicaments mediated by cytochrome P450 isoenzymes.

The half-life of quetiapine and N-desacilkvetiapine is approximately 7 and 12 hours, respectively. 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 intestine.

The pharmacokinetics of quetiapine and N-desalkylkvetiapine are linear in the therapeutic dose range and are not substantially dependent on sex or race.

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

In severe renal failure (creatinine clearance ≤ 30 ml / min / 1.73 m²), the average plasma clearance of quetiapine is reduced by approximately 25%, but the individual clearance rates are within the values corresponding to healthy volunteers.

In patients with liver failure (compensated cirrhosis), the average plasma clearance of quetiapine decreases by approximately 25%. Because the quetiapine is intensively metabolized in the liver, in patients with liver failure, an increase in the plasma concentration of quetiapine is possible, which requires correction of the dose of the drug.

Indications:

Schizophrenia.

Moderate and severe manic episodes associated with bipolar disorder.

Contraindications:

Hypersensitivity to any of the components of the drug.

Pregnancy.

Breastfeeding period.

Age to 18 years (effectiveness and safety not established).

Simultaneous administration of CYP3A4 inhibitors (such as HIV protease inhibitors, antifungal agents of the azole group, erythromycin, clarithromycin, nefazodone).

Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption (the preparation contains lactose).

Carefully:

Cardiovascular and cerebrovascular diseases and other conditions associated with risk of arterial hypotension, especially at the beginning of treatment; elderly age (efficacy and safety in patients older than 65 with depressive episodes associated with bipolar disorder not established); impaired liver and / or kidney function; convulsive fits in the anamnesis.

Pregnancy and lactation:

Safety and efficacy of the drug during pregnancy are not established, therefore during pregnancy Quetiapine Stad is prescribed only in the case when the expected benefit for the mother exceeds the potential risk to the fetus. In newborns, whose mothers were taking quetiapine during pregnancy, noted the syndrome of "withdrawal" of the drug.

The degree of excretion of quetiapine with human milk is not known.In the case of the drug during lactation it is necessary to stop breastfeeding.

Dosing and Administration:

Inside, 2 times a day, regardless of food intake.

Treatment of schizophrenia

The daily dose for the first 4 days of therapy is 50 mg (day 1), 100 mg (day 2), 200 mg (day 3), 300 mg (day 4). Starting from 4 days, the dose should be selected to an effective dose, ranging from 300 to 450 mg per day. Depending on the clinical effect and individual patient tolerance, the dose may vary from 150 to 750 mg per day.

Treatment of manic episodes associated with bipolar disorder

The daily dose for the first 4 days of therapy is 100 mg (day 1), 200 mg (day 2), 300 mg (day 3), 400 mg (day 4). In the future, by the 6th day of therapy, the daily dose of the drug can be increased to 800 mg. An 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 per day. Usually the effective dose is from 400 to 800 mg per day.

In renal and / or hepatic insufficiency and in elderly patients, the initial dose is 25 mg per day, followed by a daily increase of 25-50 mg until an effective dose is reached.

If you miss a dose, do not double the next.

It is not recommended to drink the drug with grapefruit juice.

Side effects:

Adverse events occurred: very often (≥1 / 10); often (≥1 / 100 and <1/10); infrequently (≥1 / 1000 and <1/100); rarely (≥1 / 10,000 and <1/1000); very rarely (<1/10 000), incl. isolated cases.

From the nervous system: very often - drowsiness^1,2,3, dizziness^1,3,4, headache; often - dysarthria, unusual and nightmarish dreams, fainting^1,3,4, extrapyramidal symptoms¹, increased appetite, suicidal thoughts and behavior¹; infrequently - convulsions¹, restless legs syndrome, tardive dyskinesia¹; rare-malignant neuroleptic syndrome¹, somnambulism and similar phenomena.

From the side of the cardiovascular system: often - tachycardia^1,4, palpitation5, orthostatic hypotension^1,3,4; infrequent - QT interval elongation¹; rarely - venous thromboembolism¹.

On the part of the organs of hematopoiesis: very often - a decrease in the concentration of hemoglobin⁶, often - leukopenia, a decrease in the number of neutrophils; infrequently - eosinophilia, thrombocytopenia⁷; very rarely - neutropenia¹.

From the side of metabolism: very often - an increase in body weight (mainly in the first weeks of treatment); often hyperglycemia^1,8; very rarely - diabetes mellitus⁹.

From the respiratory system: often - rhinitis, dyspnea⁵.

From the digestive system: very often - dry mouth; often - constipation, indigestion, vomiting¹⁰, increased activity of "hepatic" transaminases (alanine aminotransferase, aspartate aminotransferase); infrequently - dysphagia^1,11; rarely-zheltuha; very rarely - hepatitis.

Allergic reactions: infrequently - hypersensitivity reactions (skin rash); very rarely - anaphylactic reactions, angioedema, Stevens-Johnson syndrome.

From the side of reproductive organs and mammary glands: rarely - priapism, galactorrhea.

From the side of the organ of vision: often - blurred vision.

Laboratory indicators: very often - an increase in the concentration of triglycerides in the blood serum¹², total cholesterol (mainly low-density lipoprotein cholesterol-LDL cholesterol)¹³ in the blood, lowering the concentration of HDL cholesterol¹⁴ in blood; often - an increase in the concentration of prolactin in the blood serum, a decrease in the concentration of total thyroxin (T₄) and free T₄ in the blood (in the first 4 weeks), a decrease in the concentration of total triiodothyronine in the blood, an increase in the concentration of thyroid-stimulating hormone in the blood; infrequently - increased activity γ-glutamyltranspeptidase, a decrease in the concentration of free triiodothyronine in the blood; rarely - increased activity of creatine phosphokinase.

Other: very often - withdrawal syndrome; often - slightly expressed asthenia, irritability, peripheral edema, fever; rarely - hypothermia.

1.Sm. section "Special instructions".

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

3. It can lead to a fall.

4. Like other antipsychotic drugs with ss-adrenergic blocking activity, quetiapine often causes orthostatic hypotension, accompanied by dizziness, tachycardia and in some cases - fainting, especially at the beginning of therapy.

5.This phenomena are often noted against a background of tachycardia, dizziness, orthostatic hypotension and / or concomitant pathology of the cardiovascular or respiratory system.

6. Reduction of hemoglobin concentration ≤13 g / dl in males and ≤12 g / dl in females, at least once in 11% of patients on quetiapine in all clinical trials.

7. Reducing the number of platelets ≤100x10⁹/ l, at least for a single application.

8. Increase in fasting blood glucose ≥126 mg / dl (≥7.0 mmol / l) or blood glucose after meals ≥200 mg / dl (≥11.1 mmol / l), at least once.

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

10. Based on increased incidence of vomiting in elderly patients (age ≥ 65 years).

11. A higher incidence of dysphagia with quetiapine compared with placebo was noted only in patients with depression in the structure of bipolar disorder.

12. Increase in the concentration of triglycerides ≥200 mg / dl (≥2.258 mmol / L) in patients ≥18 years of age or ≥150 mg / dL (≥1.694 mmol / L) in patients <18 years of age, at least once.

13. Increase in the total cholesterol concentration ≥240 mg / dL (≥6.2664 mmol / L) in patients ≥18 years of age or ≥200 mg / dl (≥5,172 mmol / L) in patients <18 years of age, at least once. Very often an increase in LDL cholesterol ≥30 mg / dl (≥ 0.769 mmol / L) was noted, an average of 41.7 mg / dl (≥1.07 mmol / l).

14. Reducing the concentration of HDL cholesterol <40 mg / dl in men and <50 mg / dl in women.

QT interval prolongation, ventricular arrhythmia, sudden death, cardiac arrest and bidirectional ventricular tachycardia are considered side effects of neuroleptics.

Overdose:

Symptoms: dizziness, sedation, tachycardia, lowering blood pressure.

In patients with severe cardiovascular disease, the risk of prolonging the QT interval is high against an overdose.

Treatment: there is no specific antidote. In cases of severe intoxication, symptomatic therapy should be considered and measures recommended to maintain respiratory function, cardiovascular system, adequate oxygenation and ventilation should be carried out. Medical supervision and surveillance should be continued until the patient is fully recovered.

Interaction:

With the simultaneous use of potent CYP3A4 isoenzyme inhibitors (such as HIV protease inhibitors, azoles antifungal agents and macrolide antibiotics), the concentration of quetiapine in plasma may increase.

Simultaneous use of quetiapine (25 mg dose) with ketoconazole (inhibitor of the isoenzyme CYP3A4) led to an increase in the area under the concentration-time curve (AUC) of quetiapine 5-8 times. Therefore, the simultaneous use of quetiapine and inhibitors of the isoenzyme CYP3A4 is contraindicated. It is also not recommended to take quetiapine together with grapefruit juice.

In a pharmacokinetic study, the use of quetiapine in various doses before or simultaneously with the administration of carbamazepine (a potent inducer of microsomal liver enzymes) led to a significant increase in the clearance of quetiapine. This increase in quetiapine clearance reduced the AUC by an average of 13% compared with the use of quetiapine without carbamazepine. In some patients, the decrease in AUC was even more pronounced. This interaction is accompanied by a decrease in the concentration of quetiapine in plasma and may reduce the effectiveness of drug therapy. The simultaneous use of quetiapine with phenytoin, another powerful inducer of microsomal liver enzymes, was accompanied by an even more pronounced (approximately 450%) increase in quetiapine clearance. The use of the drug in patients using inductors of microsomal liver enzymes is possible only if the expected benefit from quetiapine therapy exceeds the risk associated with the cancellation of the inductor preparation of microsomal liver enzymes. The change in the dose of inductor preparations of microsomal liver enzymes should be gradual.If necessary, they can be replaced with drugs that do not induce microsomal liver enzymes (for example, preparations of valproic acid).

The simultaneous use of quetiapine and antidepressants - imipramine (inhibitor of the isoenzyme CYP2D6) or fluoxetine (inhibitor of isoenzymes CYP3A4 and CYP2D6) does not significantly affect its pharmacokinetics.

The pharmacokinetics of quetiapine did not change significantly with the simultaneous use of such antipsychotics as risperidone or haloperidol. Simultaneous use of quetiapine and thioridazine increased quetiapine clearance by approximately 70%.

Quetiapine does not induce the induction of microsomal liver enzymes involved in the metabolism of phenazone.

Cimetidine does not affect the pharmacokinetics of quetiapine.

Quetiapine does not affect the pharmacokinetics of lithium preparations.

There were no clinically significant changes in the pharmacokinetics of valproic acid and quetiapine when used concomitantly.

Studies to study the interaction of quetiapine with drugs used in cardiovascular disease have not been conducted.

Caution should be exercised while using quetiapine and drugs that can cause electrolyte imbalance or prolong the QT interval.

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

Patients who used quetiapine, there were cases of erroneous positive results of enzyme immunoassay for the determination of methadone and tricyclic antidepressants. It is recommended to check the questionable results of the screening immunoassay using the appropriate chromatographic method.

Special instructions:

Suicide / suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal ideation and suicidal behavior in children, adolescents and young adults (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 suicidal events in history, as well as patients who clearly expresses suicidal thoughts before starting therapy are at increased risk of suicidal ideation and suicide attempts, and should be monitored closely during treatment.

Drowsiness

During treatment with quetiapine, drowsiness and related symptoms may occur, for example, sedation (see section "Side effect"). In clinical trials involving patients with depression in the structure of bipolar disorder, sleepiness tended to develop during the first three days of therapy.The severity of this side effect was mostly mild or moderate. With the development of severe drowsiness, patients with depression in the structure of bipolar disorder may need more frequent visits to the doctor within 2 weeks of the onset of drowsiness or to a decrease in the severity of symptoms. In some cases, discontinuation of therapy with the drug may be required.

Patients with cardiovascular diseases

Caution should be exercised when assigning quetiapine to patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to hypotension. On the background of quetiapine therapy, orthostatic hypotension may occur, especially during titration of the dose at the beginning of therapy. If orthostatic hypotension occurs, a dose reduction or slower titration may be required.

Convulsions

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

Extrapyramidal symptoms (EPS)

An increase in the incidence of EPS in adult patients with depression in the structure of bipolar disorder with quetiapine was noted.

Late dyskinesia

In the case of the development of symptoms of tardive dyskinesia, it is recommended to reduce the dose of the drug or gradually cancel it.

Malignant neuroleptic syndrome

Against the background of taking antipsychotic drugs, including quetiapine, a malignant neuroleptic syndrome can develop that can threaten life. Clinical manifestations of the syndrome include hyperthermia, altered mental status, rigidity of muscles, lability in the autonomic nervous system, increased activity of creatine phosphokinase. In such cases, it is necessary to immediately cancel the drug and carry out emergency treatment.

Severe neutropenia

In clinical studies, infrequent cases of severe neutropenia (neutrophil count <0.5·10⁹/ l). Most cases of severe neutropenia occurred several months after initiation of therapy with the drug. There was no dose-response effect. Leukopenia and / or neutropenia were resolved after quetiapine therapy was discontinued.A possible risk factor for neutropenia is the previous decrease in the number of leukocytes in the blood and the cases of drug-induced neutropenia in the anamnesis. In patients with a neutrophil count <1·10⁹/ l, quetiapine should be discontinued. The patient should be observed to identify possible symptoms of infection and monitor the neutrophil count (up to a level of 1.5·10⁹/ l).

Hyperglycaemia

Against the background of taking quetiapine may develop hyperglycemia or exacerbation of concomitant diabetes. Clinical observation of patients with diabetes mellitus and patients with risk factors for developing diabetes is recommended.

Concentration of lipids

Against the background of taking quetiapine may increase the concentration of triglycerides, total cholesterol and LDL cholesterol, as well as a decrease in the concentration of HDL in the blood.

Elderly patients with dementia

Quetiapine is not indicated for the treatment of psychoses associated with dementia.

In randomized, placebo-controlled trials, it was shown that some "atypical" antipsychotics approximately tripled 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.

Quetiapine should be used with caution in patients at risk of stroke.

Dysphagia

When quetiapine was used, dysphagia was noted. Care should be taken when prescribing the drug to patients at risk of aspiration pneumonia.

Metabolic disorders

An increase in body weight, an increase in the concentration of glucose and lipids in the blood in some patients can lead to a deterioration in the metabolic profile, which requires appropriate monitoring.

QT interval extension

There was no correlation between the use of quetiapine and the prolonged QT interval elongation. However, the prolongation of the QT interval was noted with an overdose of the drug. Patients with cardiovascular disease and the previously noted QT interval elongation should be treated with caution when applying quetiapine. Also, care should be taken when applying quetiapine concomitantly with drugs that extend the QT interval, other antipsychotics,especially in the elderly, in patients with the syndrome of congenital prolongation of the QT interval, chronic heart failure, myocardial hypertrophy, hypokalemia, or hypomagnesemia.

Acute reactions associated with drug withdrawal

With the sharp cancellation of quetiapine, the following acute reactions (withdrawal syndrome) can occur: nausea, vomiting, insomnia, headache, dizziness and irritability. Therefore, it is recommended to cancel the drug gradually for at least one or two weeks.

Venous thromboembolism

Against the background of taking neuroleptics, there are cases of venous thromboembolism. Before and during therapy with antipsychotic drugs, including the drug Quetiapine STADA®, risk factors should be assessed and preventative measures taken.

Care should be taken when applying quetiapine 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:During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Film-coated tablets, 25 mg, 100 mg and 200 mg.

Packaging:

10 tablets per blister of aluminum foil and polyvinylchloride / polyethylene / polyvinylidene chloride film.

6 blisters with instructions for medical use of the drug in a cardboard box.

Storage conditions:

In a place protected from light and moisture at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001860

Date of registration:27.09.2012

Expiration Date:27.09.2017

The owner of the registration certificate:SHTADA Artznajmittel AGSHTADA Artznajmittel AG Germany

Manufacturer: & nbsp

MATRIX Laboratories, Limited India

Representation: & nbspSTADA CISASTADA CISARussia

Information update date: & nbsp27.12.2017

Illustrated instructions

Instructions

Quetiapine Stade (Quetiapine Stada)