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

Excipients: [microcellulose cellulose 98%, silicon dioxide colloid 2%] - 15.05 mg, crospovidone - 4.13 mg, silicon dioxide colloid - 0.31 mg, citric acid - 0.31 mg, polysorbate-80 - 0.17 mg, silicon dioxide - 0.25 mg, magnesium stearate - 1.00 mg;

Shell: opadrai pink (II 33F84535) [color of iron oxide red (E172) - 1.05%, titanium dioxide (E171) - 21.98%, iron dye oxide yellow (E172) - 0.97%, macrogol 4000 - 8.0%, hypromellose 2910 (E464) - 28.0%, lactose monohydrate - 40.0%] - 1.50 mg.

Dosage of 100 mg

active substance: quetiapine - 100 mg (in the form of quetiapine fumarate 115.12 mg);

Excipients: [microcrystalline cellulose 98%, colloidal silicon dioxide 2%] - 60.20 mg, crospovidone - 16.52 mg, silicon dioxide colloid - 1.24 mg, citric acid - 1.24 mg, polysorbate 80 - 0.68 mg, silicon dioxide - 1.00 mg, magnesium stearate - 4.00 mg;

Shell: fall off yellow (II 33F82557) [Macrogol 4000 8.0%, iron dye oxide yellow (E172) 2.0%, titanium dioxide (E171) 22.0%, hypromellose 2910 (E464) 28.0%, lactose monohydrate 40 , 0%] - 6.00 mg;

Dosage 200 mg

active substance: quetiapine - 200 mg (in the form of quetiapine fumarate 230.24 mg);

Excipients: [microcrystalline cellulose 98%, silicon dioxide colloid 2%] -120.40 mg, crospovidone 33.04 mg, silicon dioxide colloid - 2.48 mg, citric acid - 2.48 mg, polysorbate 80 - 1.36 mg, silicon dioxide -2.00 mg, magnesium stearate - 8.00 mg;

Shell: opada white (II 33F5861) [Macrogol 4000 - 8.0%, titanium dioxide (E171) - 24.0%, hypromellose 2910 (E464) - 28.0%, lactose monohydrate - 40.0%] - 12.00 mg.

Dosage of 300 mg

active substance: quetiapine 300 mg (in the form of quetiapine fumarate 345.36 mg);

Excipients: [microcellulose cellulose 98%, silicon dioxide colloid 2%] - 180.60 mg, crospovidone - 49.56 mg, silicon colloidal dioxide - 3.72 mg, citric acid - 3.72 mg, polysorbate-80 - 2.04 mg, silicon dioxide - 3.00 mg, magnesium stearate - 12.00 mg;

Shell: opada white (II 33F5861) [Macrogol 4000 - 8.0%, titanium dioxide (E171) - 24.0%, hypromellose 2910 (E464) - 28.0%, lactose monohydrate - 40.0%] - 18.00 mg.

Description:

Dosage of 25 mg. Round biconvex tablets, covered with a film membrane, pink. Tablet type on cross-section: the core is white or almost white and the shell is pink.

Dosage of 100 mg. Round biconvex tablets covered with a film membrane, yellow, with a risk on one side. Type of tablet in cross section: the core is white or almost white and the shell is yellow.

Dosage of 200 mg. Round biconvex tablets covered with a film coat, white, with a risk on one side. Tablet type on cross-section: the core is white or almost white and the shell is white.

Dosage of 300 mg. Oval biconvex tablets covered with a film coat, white or almost white, with a risk on one side. Tablet type on cross-section: The core is white or almost white and the shell is white or almost white.

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-dealkylketiapine interacts with neurotransmitter receptors of the brain. Quetiapine and N-desalkylketiapine show a high affinity for serotonin receptors of the type 5NT₂ and dopamine type receptors D₁ and D₂ head the brain. Higher selectivity for serotonin 5HT receptors₂, than to dopamine receptors of the type D₂, causes the main clinical antipsychotic properties of quetiapine and a low incidence of extrapyramidal side effects. Quetiapine and N-dealkalketiapine have a high affinity for histamine and α₁adrenoreceptors and a lower affinity for α₂-adrenoceptors and serotonin receptors of the type 5NT₁. Quetiapine does not show a significant affinity for the cholinergic muscarinic and benzodiazepine receptors. The specific contribution of the metabolite N-dealkylkvetiapine in the pharmacological activity of quetiapine is not established.

Quetiapine causes a weak catalepsy in doses effectively blocking D₂receptors. Quetiapine causes a selective decrease in the activity of mesolimbic A10 dopaminergic neurons in comparison with A9 nigrostriate neurons involved in motor function.

Quetiapine does not cause a prolonged increase in the concentration of prolactin in the blood plasma.

Pharmacokinetics:

Suction

When administered orally quetiapine well absorbed from the gastrointestinal tract. The intake of food does not significantly affect the bioavailability of quetiapine.

Distribution

Binding to plasma proteins is approximately 83%.

Metabolism

Quetiapine is actively metabolized in the liver. It was found that isoenzyme CYP3A4 is the key isoenzyme of CYP-mediated metabolism of quetiapine. The main metabolites in the plasma do not have a pronounced pharmacological activity. Quetiapine and some of its metabolites have a weak inhibitory activity against isoenzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, but only at a concentration 10-50 times higher than the concentration observed at the usual effective dose of 300-450 mg / day.

Excretion

T1/2 is about 7 hours. Approximately 73% of quetiapine is excreted in the urine and 21% with feces. Less than 5% of quetiapine is not metabolized and is excreted unchanged by kidneys or feces.

Pharmacokinetics in special clinical cases

The mean plasma clearance of quetiapine is less than approximately 25% in patients with severe renal insufficiency (CC <30 mL / min / 1.73 m²) and in patients with liver damage (compensated alcoholic cirrhosis of the liver), but individual clearance rates are within the limits corresponding to healthy people.

In a study of the pharmacokinetics of quetiapine in a different dosage for the administration of quetiapine prior to the administration of ketoconazole or concomitantly with ketoconazole, an increase in mean C_mOh and AUC quetiapine by 235% and 522%, respectively, and also led to a decrease in the clearance of quetiapine, on average, by 84%. T_1/2 Quetiapine increased, but the mean time to reach C_mOh did not change.

Based on the results in vitro, it should not be expected that simultaneous administration of quetiapine with other drugs will lead to clinically expressed inhibition CYP-mediated metabolism of other drugs.

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

The pharmacokinetics of quetiapine is linear, there is no difference in pharmacokinetic parameters in men and women.

Indications:

Treatment of schizophrenia.

Treatment of manic episodes in the structure of bipolar disorder.

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 in bipolar disorder.

Contraindications:

- Hypersensitivity to any component of the drug;

- Lactase deficiency, lactose intolerance, glucosogalactose malabsorption;

- simultaneous use with inhibitors of cytochrome P450 isoenzymes, including antifungal agents, azole derivatives, erythromycin, clarithromycin, nefadozone, HIV protease inhibitors;

- Pregnancy;

- lactation period (breastfeeding);

- Children under 18 years of age (efficacy and safety not established).

Carefully:

In patients with hepatic insufficiency, history of seizures, cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, the elderly.

Pregnancy and lactation:

Safety and effectiveness of quetiapine in pregnancy is not established. Therefore, the use of quetiapine in pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

When using antipsychotics, including quetiapine, in the third trimester of pregnancy, neonates have the risk of developing adverse reactions of varying severity and duration, including extrapyramidal symptoms (EPS) and / or withdrawal syndrome. There was reported on excitation, hypertension, hypotension, tremor, drowsiness, respiratory distress syndrome or feeding disorders. In this regard, you should carefully monitor the condition of newborns. Quetiapine excretion with breast milk has been reported, but excretion has not been established. Women should be advised to avoid breastfeeding while taking quetiapine. In experimental animal studies, no mutagenic and clastogenic effects of quetiapine were identified. For quetiapine in doses less than /₄ of the maximum recommended dose for humans (800 mg), embryo and fetotoxic effects are not established. There are data on the embryotoxicity of quetiapine, which was manifested when applied in rats and rabbits at doses equivalent to one or two of the maximum recommended doses of quetiapine for humans,in the form of a delay in the skeletal ossification of young rats and rabbits, and in the form of an increase in the incidence of minor abnormalities of the soft tissues of the cubs' limbs. Also at doses equivalent to two maximum recommended doses for humans, the toxic effect of quetiapine on the body of pregnant animals (female rats and rabbits) was noted, which manifested itself as a reduction in the body weight of females and / or an increase in mortality among them. When quetiapine was administered to pregnant female rats at doses equivalent to three maximum recommended doses for humans, there was an increase in mortality in offspring in the pre- and postnatal periods. The negative effect of quetiapine on fertility in rats (decreased male fertility, pseudopregnancy, an increase in the period between two estrus, an increase in the precoital interval, and a decrease in the frequency of pregnancy) were revealed. However, you can not directly transfer the received data to a person, because there are specific differences in the hormonal control of reproduction.

Dosing and Administration:

Inside, 2-3 times a day, regardless of the reception of poverty.

Adults

Treatment of schizophrenia

The daily dose for the first 4 days of therapy is 50 mg (1 day), 100 mg (2 day), 200 mg (3 day), 300 mg (4 day). Starting from the 4th day, the dose should be adjusted to an effective dosage, usually in the range of 300 to 450 mg / day. In the future, in case of need for dose adjustment, an increase in the daily dose by 50-100 mg with intervals of 2 days is recommended. Depending on the clinical effect and individual patient tolerance, the dose may vary from 150 to 750 mg / day. The maximum daily dose of quetiapine is 750 mg. The daily dose is divided into 2 divided doses.

Treatment of manic episodes in the structure of bipolar disorder

The daily dose for the first 4 days of therapy is: 100 mg (1 day), 200 mg (2 day), 300 mg (3 day), 400 mg (4 day). 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 occur rapidly than 200 mg per day. The daily dose is divided into 2 divided doses. Depending on the clinical effect and individual patient tolerance, the dose may vary from 200 to 800 mg / day. The maximum daily dose of quetiapine is 800 mg. The daily dose is divided into 2 divided doses.

Treatment of depressive episodes from moderate to severe in the structure of bipolar disorder

Quetiapine is prescribed 1 time per 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 daily dose is 600 mg. Quetiapine in a dose exceeding 300 mg, should be appointed by a doctor who has experience in the therapy of bipolar disorders. Clinical studies have shown that for some patients with poor drug tolerance the dose should be reduced to a minimum of 200 mg.

Elderly patients

In elderly patients, the initial dose of the drug 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

Correction of the dose is not required.

Patients with hepatic insufficiency Quetiapine intensively metabolized in the liver. Therefore, care should be taken when using the drug in a patient with hepatic insufficiency, especially at the beginning of therapy. It is recommended to begin therapy with quetiapine at a dose of 25 mg / day and increase the dose daily by 25-50 mg until a therapeutic effect is achieved.

Side effects:

The most frequent side effects of quetiapine are drowsiness, dizziness, dry mouth, mild asthenia, constipation, tachycardia, orthostatic hypotension and dyspepsia.According to the summary of clinical studies, the number of patients who discontinued the drug due to side effects is approximately the same in the groups receiving placebo and quetiapine. As with other antipsychotics, fainting, malignant neuroleptic syndrome, leukopenia, neutropenia, and peripheral edema were noted during the administration of quetiapine.

The undesirable phenomena observed when taking quetiapine and classified according to the body systems are listed in the following order: 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).

On the part of the hematopoiesis system: often - leukopenia; infrequently - eosinophilia, thrombocytopenia; very rarely - neutropenia.

From the side of metabolism: often - weight gain (mainly in the first weeks of treatment), hyperglycemia or decompensation of diabetes mellitus; very rarely - diabetes.

From the side of the central nervous system and peripheral nervous system: very often - dizziness, drowsiness, headache; often syncope, unusual and nightmarish dreams, fainting,extrapyramidal symptoms, anorexia; infrequently - anxiety, hostility, psychomotor agitation, insomnia, akathisia, tremor, convulsions, depression, dysarthria, paresthesia; rarely - malignant neuroleptic syndrome (hyperthermia, muscle rigidity, altered mental status, lability in the autonomic nervous system, increased activity of creatine phosphokinase); very rarely - tardive dyskinesia.

From the cardiovascular system: often - tachycardia, orthostatic hypotension, palpitations, increased blood pressure, lengthening interval QT on the ECG.

From the respiratory system: often - rhinitis, pharyngitis.

From the digestive system: very often - dry mouth; often - nausea, vomiting, constipation, diarrhea, indigestion; infrequently - dysphagia; rarely - abdominal pain, jaundice; very rarely - hepatitis.

From the side of the reproductive system: rarely - priapism (painful erection).

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

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

From the immune system: infrequently - hypersensitivity reactions; very rarely - angioedema, Stevens-Johnson syndrome.

Laboratory indicators: very often - hypercholesterolemia, hypertriglyceridemia; often - increased activity of "liver" transaminases; infrequent increase in γ-glutamyltransferase activity, decrease in the concentration of total and free thyroxine (in the first 4 weeks), as well as concentrations of total and reversible triiodothyronine (only with high doses of quetiapine), increased activity of creatine phosphokinase not associated with malignant neuroleptic syndrome; rarely - increased activity of creatine phosphokinase.

Other: often - withdrawal syndrome; often - asthenia, peripheral edema, increased sweating; rarely - back pain, chest pain, subfebrile condition, myalgia, dry skin, weak eyesight.

Overdose:

A lethal outcome was reported with the admission of 13.6 g quetiapine in a patient who participated in the clinical trial, as well as a fatal outcome after taking 6 g quetiapine during post-marketing surveillance of the drug.

At the same time, a case of taking quetiapine in a dose exceeding 30 g is described, without a lethal outcome.

There are reports of extremely rare cases of quetiapine overdose leading to an increase in the QTc interval, seizures, epilepsy, rhabdomyolysis, respiratory depression, urinary retention, delirium, death or coma.

In patients with severe cardiovascular disease, the risk of developing side effects with an overdose may increase (see section "Special instructions").

Symptoms noted in overdose were mainly due to increased dose-related side effects of the drug, such as drowsiness and sedation, tachycardia and lowering blood pressure.

There is no specific antidote. In cases of severe intoxication, one should remember about the possibility of an overdose with several medications. It is recommended to carry out activities aimed at maintaining the function of breathing and cardiovascular system, ensuring adequate ventilation and oxygenation. Reports have been published on the development of severe adverse reactions from the central nervous system, including coma and delirium, after intravenous injection of physostigmine (1-2 mg) under constant ECG monitoring.

If refractory hypotension occurs with an overdose of quetiapine treatment should be carried out by intravenous fluid and / or symptomatic drugs (should not be prescribed epinephrine and dopamine, since stimulation of β-adrenergic receptors may cause an increase in hypotension while blocking α-adrenergic receptors with quetiapine).

Gastric lavage (after intubation, if the patient is unconscious) and the use of activated charcoal and laxatives can promote the removal of unabsorbed quetiapine, but the effectiveness of these measures has not been studied.

Careful medical supervision should continue until the patient's condition improves.

Interaction:

Special caution is required in the appointment of quetiapine in combination with other drugs acting on the central nervous system.

Results of the study in vitro showed that quetiapine of its metabolites in vivo are weak inhibitors of metabolic processes mediated by isoenzymes of the cytochrome P450 system (1A2, 2C9, 2C19, 2D6 and 3A4). CYP3A4 is the main enzyme mediating P450 mediated quetiapine metabolism.

The effect of other drugs on quetiapine

Phenytoin: simultaneous use of quetiapine with phenytoin leads to increased clearance of quetiapine in plasma, because phenytoin induces isoenzyme 3A4 cytochrome P450. The combination of quetiapine (but 250 mg 3 times / day) and phenytoin (100 mg 2 times / day) increased the average clearance of quetiapine after oral administration five times.

To correct the symptoms of schizophrenia in patients receiving concomitantly quetiapine and phenytoin, higher doses of quetiapine or other inducers of microsomal liver enzymes (including carbamazepine, barbiturates, rifampicin, GCS) may be required. In these cases, care should be taken when phenytoin is withdrawn and / or switched to valproic acid, which does not possess enzyme-inducing properties.

Carbamazepine: simultaneous use of quetiapine with carbamazepine significantly increases the clearance of quetiapine, which leads to a decrease in the systemic exposure of quetiapine. Because of this interaction, higher doses of quetiapine may be required.

CYP3A Inhibitors: simultaneous use of quetiapine with ketoconazole (200 mg / day for 4 days),potent inhibitor of the isoenzyme CYP3A, reduces the clearance of quetiapine after oral administration for clearance of quetiapine after oral administration by 84%, as a result of which the concentration of quetiapine in the blood plasma increases, on average, by 235%. With the simultaneous use of quetiapine with ketoconazole, other inhibitors of cytochrome P450 isoenzymes (including antifungal agents, azole derivatives (including itraconazole, fluconazole), macrolide antibiotics (including erythrocin) should correct the dose of quetiapine.

Cimetidine: daily regular use of cimetidine (400 mg 3 times / day) for 4 days), which is a nonspecific inhibitor of enzymes, resulted in a 20% decrease in the average clearance of quetiapine (150 mg 3 times / day) from plasma after ingestion . With the simultaneous use of quetiapine with cimetidine, there is no need to change the dose of the first.

Thioridazine: thioridazine (200 mg twice a day) increased the clearance of quetiapine (300 mg 2 times / day) from plasma after ingestion by 65%.

Risperidone and haloperidol: simultaneous use of quetiapine (300 mg twice a day) with haloperidol (7.5 mg 2 times / day) or risperidone (3 mg 2 times / day) did not change the pharmacokinetics of quetiapine in the equilibrium state.

Fluoxetine and imipramine: simultaneous use of quetiapine (300 mg twice a day) with an antidepressant and an inhibitor of CYP3A4 and CYP2D6 fluoxetine (60 mg once a day) or a known inhibitor of CYP2D6 imipramine (75 mg 2 times / day) did not alter the equilibrium pharmacokinetics of quetiapine.

Valproic Acid: In groups of patients taking both quetiapine and valproic acid preparations, including those in prolonged form, as well as a combination of valproate with quetiapine, cases of a higher level of leukopenia and neutropenia were recorded compared with the monotherapy groups.

Effect of quetiapine on other drugs

Fenazone: repeated daily administration of quetiapine (up to 750 mg / day) with a 3-fold intake did not cause clinically significant changes in the clearance of phenazone or its metabolites. This indicates that quetiapine does not have a significant inhibitory effect on hepatic enzymes involved in the metabolism of phenazone, mediated by cytochrome P450.

Lithium: simultaneous use of quetiapine (250 mg 3 times / day) with lithium did not affect any pharmacokinetic parameters of lithium in the equilibrium state.

Lorazepam: the average clearance of lorazepam after oral administration (a single dose of 2 mg) was reduced by 20% during the administration of quetiapine (250 mg 3 times / day).

Caution should be exercised in the combined use of quetiapine and drugs extending the interval QTc, including antiarrhythmic drugs of class 1A (for example, quinidine. procainamide), or class 3 (for example, amiodarone, sotalol), antibiotics (for example, gatifloxacin, moxifloxacin), or other drugs that extend the QTc interval (eg, pentamidine, methadone, etc.). With the use of quetiapine, cases of prolongation of the QTc interval in patients with concomitant diseases, patients taking medications that cause electrolyte imbalance or an increase in the QTc interval, as well as in case of an overdose of quetiapine have been documented.

In patients who took quetiapine, false-positive results of screening tests for the detection of methadone and three cyclic antidepressants by the method of enzyme immunoassay were soaked. To confirm the results of screening, a chromatographic study is recommended.

Smoking did not affect the clearance of quetiapine from the blood plasma.

Since clinical studies have shown that quetiapine potentiates the cognitive and motor effects of alcohol in patients with psychoses, should not take alcohol during the course of treatment with the drug quetiapine.

Special instructions:

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, it may be necessary to discontinue therapy with the drug.

Dizziness

Treatment with quetiapine can cause orthostatic hypotension and, as a result, dizziness, which occurs, as a rule, in the initial period of dose selection. Dizziness may increase the risk of accidental injuries (falls), especially in elderly patients. Therefore, patients should be cautious at the beginning of the drug.

Patients with cardiovascular diseases

Quetiapine should be used with caution in patients with diagnosed cardiovascular disease, vascular disease and the brain or other conditions predisposing to hypotension.

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. Caution should also be exercised when using quetiapine concomitantly with QT prolonging drugs, other antipsychotics, especially in the elderly, in patients with congenital QT prolongation syndrome, chronic heart failure, myocardial hypertrophy, hypokalemia, or hypomagnesemia.

Convulsions

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 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 has been noted.

Late dyskinesia

Quetiapine, like other antipsychotics, with prolonged use may cause tardive dyskinesia. In case of signs and symptoms of tardive dyskinesia, the question of dose reduction or drug cancellation should be considered.

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, lability in the autonomic nervous system, an increase in the level of activity of creatine phosphokinase. In such cases, it is necessary to cancel the drug and conduct appropriate treatment.

Severe neutropenia and agranulocytosis

In the short-term placebo-controlled clinical trials of monotherapy with quetiapine, cases of severe neutropenia (neutrophil count <0.5 x10⁹/ l) without infection.Agranulocytosis (severe neutropenia associated with infections) was reported in patients who received quetiapine in clinical trials (rarely), as well as in postmarketing use (including fatal).

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 therapy was discontinued. A possible risk factor for neutropenia is a previous reduced number of leukocytes in the blood and cases of drug-induced neutropenia in the anamnesis.

The development of agranulocytosis was also noted in patients without risk factors. It is necessary to consider the possibility of developing neutropenia in patients with infection, especially in the absence of obvious predisposing factors. Or in patients with unexplained fever; these cases should be conducted in accordance with clinical recommendations.

In patients with a neutrophil count <1x10⁹/ l, quetiapine should be discontinued. The patient should be observed to identify possible symptoms of infection and monitor the neutrophil count (before exceeding the level of 1.5 x 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 in plasma

Against the background of taking quetiapine, an increase in the concentration of triglycerides and cholesterol in the plasma, as well as a decrease in the concentration of HDL.

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. Perhaps an asymptomatic increase (> 3 times the upper limit of the norm when measured at any time) of ALT, ACT and GGT activity in the blood plasma is usually reversible against the background of continued use of quetiapine.

Body mass

A 6-week, placebo-controlled clinical trial of quetiapine resulted in a more than 7% increase in the body weight of patients treated with quetiapine in the treatment of schizophrenia (23% quetiapine versus 6% placebo), monotherapy with mania (21% of quetiapine compared with 7% of the placebo group), and in combination therapy, 13% of the patients in the group who received quetiapine, compared with 4% placebo. In the treatment of depression in bipolar disorder, there was an increase in body weight of 8% of patients who received quetiapine against 2% of the group receiving the placebo. In this regard, a basic and regular monitoring of body weight of patients should be carried out.

Reactions of sudden cancellation

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.

Elderly patients with dementia

Quetiapine is indicated for the treatment of psychoses associated with dementia.

In randomized trials, it was shown that some "atypical" antipsychotics approximately 3-fold 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.

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

Suicide / suicidal thoughts or clinical worsening

Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self harm and suicide (events related to suicide). 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.

With a sharp cessation of quetiapine therapy, the potential risk of suicidal events should be taken into account.

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. According to clinical studies in patients, suicide occurred in 3.0% of cases of quetiapine versus 0% placebo in persons under 25 years of age. This meta-analysis does not include studies where quetiapine.

The FDA conducted a meta-analysis of placebo-controlled studies of antidepressants, summarizing data from approximately 4,400 children and adolescents and 7,700 adult patients with mental disorders, revealed an increased risk of suicidal behavior compared with antidepressants compared with antidepressant drugs placebo in children, adolescents and adult patients under the age of 25 years.

Venous thromboembolism

Against the background of taking neuroleptics, cases of venous thromboembolism were noted. Before and during therapy with antipsychotic drugs, including quetiapine, risk factors should be assessed and preventative measures taken.

Cardiomyopathy and myocarditis

During clinical trials and post-registration use, cases of cardiomyopathy and myocarditis have been noted, but a causal relationship with the drug has not been established. It should be assessed the feasibility of quetiapine therapy in patients with suspected cardiomyopathy and myocarditis.

Dysphagia

Dysphagia and aspiration were observed with quetiapine therapy. The causal relationship between the onset of aspiration pneumonia and the administration of quetiapine has not been established. However, care should be taken when prescribing the drug to patients at risk of aspiration pneumonia.

Constipation and obstruction of the intestine

Constipation is a risk factor for intestinal obstruction. Against the background of quetiapine, the development of constipation and intestinal obstruction, including fatal cases in patients at high risk of intestinal obstruction, including those receiving multiple concomitant medications that reduce intestinal motility, even in the absence of complaints of constipation, have been noted.

Pancreatitis

During clinical trials and post-marketing use, cases of pancreatitis have been noted, but a causal relationship with the drug has not been established.Postmarketing reports indicate that many patients had pancreatitis development factors, such as increased triglyceride concentrations, cholelithiasis, and alcohol use.

Form release / dosage:

Tablets, film-coated 25 mg, 100 mg, 200 mg, 300 mg.

Packaging:

10 tablets in a blister made of PVC film and aluminum foil. For 3, 5 or 6 blisters together with the instructions for use are placed in a cardboard box.

Storage conditions:

In a dry, the dark place 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 expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001733

Date of registration:02.07.2012

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp05.05.2015

Illustrated instructions

Instructions

Quetiapin San (Quetiapine Sun)