Quetiapine release form. Quetiapine - instruction, application, indications, contraindications, action, side effects, analogs, composition, dosage

Patients with hepatic impairment

Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using Quetiapine in patients with hepatic insufficiency, especially at the beginning of therapy. It is recommended to start therapy with Quetiapine with a dose of 25 mg / day and increase the dose daily by 25-50 mg until an effective dose is reached.

Most frequent side effects Quetiapine - drowsiness, dizziness, dry mouth, mild asthenia, constipation, tachycardia, orthostatic hypotension and dyspepsia.

Taking Quetiapine, like other antipsychotic drugs, may be accompanied by an increase in body weight, fainting, the development of neuroleptic malignant syndrome, leukopenia, neutropenia, and peripheral edema.

Frequency adverse reactions given in the form of the following gradation: very often (≥ 1/10); often (≥ 1/100,< 1/10); нечасто (≥ 1/1000, <1/100); редко (≥ 1/10 000, <1/1000); очень редко (<1/10 000) , unspecified frequency.

1. See the section "Special instructions"

2. Drowsiness usually occurs within the first 2 weeks after starting therapy and usually resolves with continued use of Quetiapine.

3. Possibly asymptomatic increase in activityACT, ALT and GGT in serum, as a rule, are reversible with continued use of Quetiapine.

4. Like other antipsychotic drugs and α 1 -adrenergic blockers, often causes orthostatic hypotension, which is accompanied by dizziness, tachycardia, and in some cases - fainting, especially at the beginning of therapy (see section "Special instructions").

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

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

7. Increase in fasting blood glucose concentration ≥126 mg / dL (≥7.0 mmol / L) or post-meal blood glucose ≥200 mg / dL (≥11.1 mmol / L) at least once.

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

9.Mainly occurs at the beginning of therapy.

10. In a study of the withdrawal syndrome in short-term placebo-controlled clinical studies of Quetiapine in monotherapy, the following symptoms were noted: insomnia, nausea, headache, diarrhea, vomiting, dizziness and irritability. The incidence of withdrawal was significantly reduced 1 week after discontinuation of the drug.

11.Increased triglyceride concentration ≥200 mg / dL (≥2,258 mmol / L) in patients ≥18 years of age or ≥150 mg / dL (≥1,694 mmol / L) in patients<18 лет, хотя бы при однократном определении.

12.Increased total cholesterol concentration of ≥240 mg / dL (≥6.2064 mmol / L) in patients ≥18 years of age or ≥200 mg / dL (≥5.172 mmol / L) in patients< 18 лет, хотя бы при однократном определении.

14. Decrease in the number of platelets ≤100 x 10 9 / l, at least with a single determination.

Prolongation of the QT interval, ventricular arrhythmias, sudden death, cardiac arrest, and bidirectional ventricular tachycardia are considered side effects inherent in antipsychotics.

The frequency of EPS in short-term clinical trials in schizophrenia and mania in the structure of bipolar disorder was comparable in the Quetiapine and placebo groups (patients with schizophrenia: 7.8% in the Quetiapine group and 8.0% in the placebo group; mania in the structure of bipolar disorder: 11, 2% in the quetiapine group and 11.4% in the placebo group).

The frequency of EPS in short-term clinical studies with depression in the structure of bipolar disorder in the Quetiapine group was 8.9%, in the placebo group - 3.8%. At the same time, the frequency of individual EPS symptoms (such as akathisia, extrapyramidal disorders, tremor, dyskinesia, dystonia, anxiety, involuntary muscle contractions, psychomotor agitation and muscle rigidity), as a rule, was low and did not exceed 4% in each of the therapeutic groups. In long-term clinical trials of Quetiapine for schizophrenia and bipolar disorder, the frequency of EPS was comparable in the Quetiapine and placebo groups.

Against the background of Quetiapine therapy, there may be a slight dose-dependent decrease in the level of thyroid hormones, in particular, total thyroxine (T 4) and free T 4. The maximum decrease in total and free T 4 was recorded at the 2nd and 4th weeks of treatment with Quetiapine, without further decrease in the concentration of hormones during long-term treatment. In almost all cases, the concentration of total and free T4 returned to the initial level after discontinuation of Quetiapine therapy, regardless of the duration of treatment. A slight decrease in total triiodothyronine (T 3) and reverse T 3 was observed only when using high doses. The level of thyroxine-binding globulin (TSH) remained unchanged, no increase in the level of thyroid-stimulating hormone (TSH) was noted.

It was reported about the lethal outcome when taking 13.6 g of quetiapine in a patient who participated in a clinical study, as well as death after taking 6 g of quetiapine in a post-marketing study of the drug. At the same time, a case of taking quetiapine in a dose exceeding 30 g without lethal outcome has been described.

There are reports of extremely rare cases of overdose of quetiapine, leading to an increase in the QT C interval, death or coma.

In patients with a history of severe cardiovascular disease, the risk of side effects in case of overdose may increase (see section "Special instructions").

Overdose symptoms were mainly due to increased known pharmacological effects of the drug, such as drowsiness and sedation, tachycardia and a decrease in blood pressure. There are no specific antidotes for quetiapine. In cases of severe intoxication, be aware of the possibility of an overdose of several drugs. It is recommended to carry out activities aimed at maintaining the function of respiration and the cardiovascular system, ensuring adequate oxygenation and ventilation. Gastric lavage (after intubation, if the patient is unconscious) and the administration of activated charcoal and laxatives can help eliminate unabsorbed quetiapine, but the effectiveness of these measures has not been studied.

A drug Quetiapine- antipsychotic agent.
Quetiapine is a dibenzothiazepine derivative that makes antipsychotic effects. Quetiapine and its active metabolite N-desalkyl quetiapine interact with a variety of neurotransmitter receptors. It remains unclear what contribution to the pharmacological effect of the drug is due to the N-dealkylation of the metabolite.
Quetiapine has an affinity for serotonin receptors in the brain 5HT 2 and 5HT 1 A (in vitro Ki is 288 and 557 nM, respectively) and dopamine receptors D 1 and D 2 (in vitro Ki is 558 and 531 nM, respectively). It is believed that this combination of receptor antagonism with a relative selectivity of interaction with 5HT 2 receptors compared to D 2 underlies the clinical antipsychotic properties of the drug, as well as the relatively low incidence of extrapyramidal symptoms. Quetiapine also exhibits high affinity for histamine H 1 receptors (in vitro Ki is 10 nM) and alpha 1 adrenergic receptors (in vitro Ki is 13 nM) with a lower affinity for alpha 2 adrenergic receptors (in vitro Ki is 782 nM). Quetiapine does not bind to cholinergic muscarinic and benzodiazepine receptors.
N-desalkyl quetiapine, similarly to quetiapine, exhibits an affinity for the serotonin receptors in the brain 5HT 2 and dopamine receptors D 1 and D 2.
In addition, like quetiapine, N-dezalkyl quetiapine exhibits high affinity for serotonin 5HT 1 receptors and histaminergic and alpha 1 adrenergic receptors with a lower affinity for alpha 2 adrenergic receptors.
Pharmacokinetics.
In a clinically significant dose range, the pharmacokinetics of quetiapine and N-dealkyl quetiapine are linear. The kinetics of quetiapine in men and women, in smokers and non-smokers, does not differ.
Suction. Quetiapine, when taken orally, is well absorbed in the digestive tract. In a study with a drug, with radioactive isotopes, it was shown that about 73% is excreted in the urine and 21% in the feces within one week. The bioavailability of quetiapine practically does not change when the drug is taken with food, while the C max and AUC values \u200b\u200bincrease by 25% and 15%, respectively. The maximum content of the drug in the blood plasma is reached 2:00 after oral administration. The molar concentration of the active metabolite N-dealkyl quetiapine in the equilibrium state is 35% of this quetiapine.
Distribution. The volume of distribution of quetiapine is 10 ± 4 l / kg, binding to blood plasma proteins is 83%.
Excretion and metabolism. The half-life of quetiapine is approximately 6-7 hours with repeated administration of the drug in clinically recommended doses. This figure for N-dealkyl quetiapine is about 12:00. On average, the molar fraction of free quetiapine and its active metabolite, which is excreted in the urine, is less than 5%.
Quetiapine is extensively metabolized in the liver, while the share of the initial compound in urine and feces one week after taking labeled quetiapine accounts for less than 5% of the dose received. Taking into account the intensive metabolism of quetiapine in the liver, it should be expected that in persons with impaired liver function, the drug content in the blood plasma will be higher, therefore, dose adjustment may be required.
The main reactions of quetiapine metabolism are oxidation of the side alkyl chain, hydroxylation of the dibenzothiazepine ring, sulfoxyluvanium and conjugation (phase 2). The main metabolites of quetiapine in human blood plasma are oxidation and sulfooxidation products, none of which has pharmacological activity.
The main enzyme of the cytochrome P450 system, which is responsible for the metabolism of quetiapine, is 450 ZA4. The formation of N-dealkylpoxide and the elimination of quetiapine are carried out mainly by the action of this enzyme.
In vitro experiments have shown that quetiapine and some of its metabolites (including N-desalkyl-quetiapine) are weak inhibitors of enzymes of the cytochrome P450 system 1A2, 2C9, 2C19, 2D6, and ZA4. However, such in vitro inhibition is observed only in concentrations, 5-50 times over-high concentration in the human body when the drug is taken at a dose of 300-800 mg / day.

Indications for use:
Quetiapineit is used to treat schizophrenia, manic episodes associated with bipolar disorders.

Mode of application:
Quetiapineused for adults 2 times a day, regardless of food intake.
Schizophrenia.
The total daily dose for the first 4 days of therapy is 50 mg (day 1), 100 mg (day 2), 200 mg (day 3) and 300 mg (day 4).
Starting from the 4th day onwards, the dose should be titrated to the limits of the usual effective dose of 300 - 450 mg per day. Depending on the clinical efficacy and individual tolerance of the treatment, the dose can be adjusted within the range of 150 - 750 mg per day.
The transition from one dose to another occurs within 2 days, since within 1-2 days the equilibrium state for quetiapine in the body has not yet been reached.

If it is necessary to increase or decrease the dose of the drug, it is recommended to change the dose by 25-50 mg each time (when taken 2 times a day).
Bipolar Manic Disorders.
Monotherapy or to supplement therapy with mood stabilizers, the total daily dose for the first 4 days of therapy is 100 mg (day 1), 200 mg (day 2), 300 mg (day 3) and 400 mg (day 4) day). A further increase in the dose to 800 mg per day on the 6th day should occur in stages with an increase in the dose of no more than 200 mg per day.
The dose selection is carried out depending on the clinical response and individual drug tolerance.
Dosage of the drug in certain categories of patients
Elderly persons.
As with other antipsychotic drugs, caution should be used in the treatment of elderly patients, especially at the beginning of treatment. Treatment should be started with a dose of 25 mg / day. The dose should be increased daily by 25-50 mg / day until an effective dose is reached, which is likely to be lower than in younger patients.
Patients with impaired liver and kidney function.
For these categories of patients, the drug should be used with caution. The initial dose of quetiapine is 25 mg / day. This dose can be increased by 25-50 mg / day until an effective dose is reached.
Missed dose.
If a dose is missed, the drug should be taken as soon as possible. However, if the time for taking the next dose is already approaching, it is necessary to switch to a regular intake regimen, and not compensate for the missed dose. In no case should you take a double dose of the drug.

Side effects:
Frequency of adverse reactions: very often (≥ 10%), often (≥ 1%,<10%), редкие (≥ 0,1%, <1%), редкие (0,01%, <0,1%) , очень редкие (<0,01%).
The following adverse reactions have been reported with quetiapine treatment.
On the part of the nervous system: often - drowsiness, which develops more often during the first two weeks of treatment and, as a rule, later disappears, and dizziness; development of extrapyramidal symptoms infrequently - restless legs syndrome; seizures; rare - neuroleptic malignant syndrome.
The body as a whole: often - headache, abdominal pain, back pain, fever, weight gain (occurs mainly in the first weeks of treatment). Like other antipsychotics, quetiapine can cause peripheral edema and mild asthenia (common side effects).
With the abrupt withdrawal of quetiapine, like other antipsychotics, symptoms of abrupt withdrawal of the drug are noted, such as insomnia, nausea, headache, diarrhea, vomiting, dizziness, irritability. It is advisable to cancel the drug not abruptly, but gradually reducing the dose within 1-2 weeks. These symptoms usually disappear within a week after discontinuation of the drug.
On the part of the digestive tract: often - constipation, dry mouth, dyspepsia, increased levels of gamma-glutamyl transpeptidase, noted isolated cases of dysphagia.
From the side of the skin: often - a rash. In some cases, allergic reactions are possible, including angioedema, Stevens-Johnson syndrome.
From the side of the cardiovascular system: often - orthostatic hypotension, tachycardia infrequently - an increase in heart rate. Like other antipsychotics, quetiapine can cause postural hypotension, which is accompanied by dizziness, tachycardia, and in some cases - fainting, especially during the initial period of drug dose selection. In patients with schizophrenia, the incidence of postural hypotension was 8%.
From the reproductive system: when taking quetiapine, isolated cases of priapism have been described.
From the side of the organ of vision: infrequently - pain in the eyes, blurred vision.
From the respiratory system: often - rhinitis.
From the endocrine system: infrequently - hypothyroidism.
From the hematopoietic system: often - lymphopenia.
As with other antipsychotics, rare cases of leukopenia and / or neutropenia have been reported with quetiapine. Eosinophilia is rarely noted.
Changes in laboratory parameters: in some patients, when using quetiapine, an asymptomatic increase in the level of transaminases in the blood serum was noted, such an increase was usually reversible, and the level of transaminases decreased with continued therapy.
The study of quetiapine showed a dose-dependent decrease in the content of total and free thyroxine (T4). The maximum decrease in thyroxine content was noted in the first 2-4 weeks of treatment. The lowered level of thyroxine persists without further progress and with prolonged use of the drug. The decrease in thyroxine content is not accompanied by systematic changes in TSH content or clinical symptoms of hypothyroidism. Termination of treatment leads to the return of the content of total and free thyroxine to the initial level. A slight decrease in total TS was observed only at high doses of the drug. The TBG content has not changed. Thus, there was no clinically significant hypothyroidism with quetiapine.
An increase in blood glucose to a state of hyperglycemia (fasting glucose more than 7 mmol / L and after meals more than 11.1 mmol / L) has often been observed with quetiapine in studies.
When using quetiapine, an increase in the content of triglycerides in the blood serum of more than 2.258 mmol / L and an increase in the content of cholesterol (mainly low-density lipoproteins) of more than 6.2064 mmol / L were quite often noted.
Post-marketing research data
According to these data, cases of leukopenia and / or neutropenia have been reported with quetiapine. The neutrophil count returned to normal after discontinuation of treatment. Possible risk factors for the development of leukopenia and / or neutropenia were a preexisting low leukocyte count and leukopenia and / or neutropenia with a history of drug use.
As with the use of other antipsychotics, when taking quetiapine, hyperglycemia with diabetes mellitus (including complications of pre-existing diabetes) was observed relatively rarely (frequency less than 0.1%). Sometimes such side effects occurred in patients without a history of hyperglycemia.
There are reports of jaundice.
Anaphylactic reactions have been reported very rarely. If signs of anaphylactic reactions appear, quetiapine should be discontinued and switched to another drug.
Like other antipsychotic drugs, quetiapine can cause prolongation of the QT interval, but studies have not found an association with a permanent increase in QT.
Acute withdrawal reactions have been reported (see section "Peculiarities of use").

Contraindications:
Contraindications to the use of the drug Quetiapineare:
- Hypersensitivity to the components that make up the drug.
- Concomitant use of cytochrome 450 inhibitors, such as HIV protease inhibitors, azole antifungal drugs, erythromycin, clarithromycin and nefazodone.

Pregnancy:
During treatment Quetiapinepatients should warn the doctor about pregnancy or planning a pregnancy. The safety and effectiveness of quetiapine in pregnancy have not been studied. Therefore, when prescribing quetiapine to pregnant women, the possible benefits of such therapy should be weighed against the potential risk to the fetus.
It is not known how much quetiapine passes into breast milk. Given the potential for adverse reactions, quetiapine is contraindicated while breastfeeding.

Interaction with other medicinal products:
Considering that Quetiapineaffects the central nervous system, it should be used with caution in combination with other drugs acting on the central nervous system.
Alcohol. Quetiapine potentiates the effects of alcohol, so alcohol should be avoided when treating quetiapine.
Antihypertensive drugs. Since quetiapine can induce arterial hypotension, it can enhance the hypotensive effect of other drugs.
Levodopa and dopamine agonists. Quetiapine can act as a levodopa antagonist and a dopamine agonist.
Lithium preparations. Combined use with quetiapine does not affect the pharmacokinetics of a single dose of lithium.
Lorazepam. Combined use with quetiapine does not affect the pharmacokinetics of a single dose of lorazepam.
Antipyrine. Quetiapine does NOT induce enzymatic systems in the liver involved in the metabolism of antipyrine.
Divalproex. The combined use of quetiapine (150 mg 2 times a day) and divalproex (500 mg 2 times a day) increases the maximum concentration (C max) of total valproic acid in blood plasma by 11%. These changes are not clinically significant.
Inducers of enzymes of metabolism in the liver
Carbamazepine significantly reduces plasma levels of quetiapine. The area under the concentration-time curve (AUC) of quetiapine is reduced by an average of 13%. Similar effects are observed when taking other drugs, induce symbionts of enzymes in the liver. Thus, when used together with such drugs, it is necessary to select the dose of quetiapine. However, it should be borne in mind that the recommended maximum daily dose of quetiapine is 800 mg. Long-term use of the drug in high doses in individual cases is possible only when comparing the possible benefits and potential risks of using the drug.
With the simultaneous administration of quetiapine and another inducer of microsomal enzymes, phenytoin, a 5-fold increase in the clearance of quetiapine is noted. Therefore, an increase in the dose of quetiapine may be required to adequately control the mental symptoms. Other inducers of microsomal enzymes, such as barbiturates, rifampicin, have a similar effect.
When you stop taking drugs that are inducers of microsomal enzymes, it is necessary to reconsider the dose of quetiapine, if necessary, reduce it.
Inhibitors of cytochrome P450 ZA4 (CYP ZA4)
CYP ZA4 is the main enzyme of the cytochrome P450 system, which is responsible for the metabolism of quetiapine. Therefore, the use of drugs such as ketoconazole, erythromycin, clarithromycin, diltiazem, verapamil or nefazodone, which are inhibitors of CYP 3A4, may lead to an increase in the concentration of quetiapine.
The combined intake of ketoconazole leads to an increase in C max and AUC for quetiapine by 235% and 522%, respectively, while the average clearance for oral administration of the drug decreases by 84%. The half-life of quetiapine increases from 2.6 to 6.8 hours, but the mean maximum half-life (T max) does not change.
Given these data, while the use of quetiapine with such CYP ZA4 inhibitors as azole antifungal drugs, macrolide antibiotics, protease inhibitors, the dose of quetiapine should be reduced, especially in the elderly and debilitated patients.
Cimetidine. There were no clinically significant interactions.
Thioridazine. The combined use of thioridazine (200 mg 2 times a day) and quetiapine (300 mg 2 times a day) increases the clearance of quetiapine by 65%.
Fluoxetine, imipramine, haloperidol, risperidone. Taking fluoxetine (daily dose - 60 mg), imipramine (75 mg 2 times a day), haloperidol (7.5 mg 2 times a day), risperidone (3 mg 2 times a day) does not significantly change the equilibrium pharmacokinetics of quetiapine.

Overdose:
Patients with concomitant cardiovascular diseases in total may be susceptible to the negative consequences of an overdose.
Overdose data Quetiapinelimited. Cases of the use of quetiapine in a dose exceeding 20 g have been described, there were no fatal cases, the patients recovered without consequences. After widespread introduction into medical practice, there have been very rare reports of an overdose of quetiapine, which resulted in death or coma, or QT prolongation.
Symptoms As a rule, these are symptoms, more pronounced manifestations of the usual pharmacological effects of the drug (for example, drowsiness, sedation, tachycardia, arterial hypotension).
Treatment. There is no specific antidote for quetiapine. In case of severe poisoning, it should also be borne in mind that the poisoning could be when taking several drugs. In cases of severe poisoning, intensive care is necessary, including maintaining airway patency, ensuring adequate oxygenation and ventilation, and taking measures to support the functioning of the cardiovascular system.
Careful medical supervision is necessary until the patient's condition is completely normalized.

Storage conditions:
Keep out of the reach of children at a temperature not exceeding 30 ° C.

Release form:
Quetiapine -film-coated tablets.
Packing: the preparation of 25 mg, 100 mg and 200 mg is produced in blisters No. 10, 3 blisters per package, 300 mg - No. 100 in vials.

Composition:
1 tablet Quetiapinecontains 25 mg, 100 mg, 200 mg or 300 mg quetiapine (in the form of quetiapine fumarate).
Excipients: lactose, microcrystalline cellulose, sodium starch (type A), povidone, dibasic calcium phosphate dihydrate, magnesium stearate
tablet shell 25 mg polyethylene glycol, titanium dioxide (E 171), hydroxypropyl methyl cellulose, iron oxide red (E172), iron oxide yellow (E172)
tablet shell 100 mg polyethylene glycol, titanium dioxide (E 171), hydroxypropyl methyl cellulose, iron oxide yellow (E172)
tablet shell 200 mg and 300 mg polyethylene glycol, hydroxypropyl methylcellulose, titanium dioxide (E 171), talc.

Additionally:
Children. Safety and effectiveness of use Quetiapinehave not been studied in children, therefore the drug is not used in pediatric practice.
Complications from the cardiovascular system
Quetiapine can cause orthostatic hypotension, dizziness, and in some cases, loss of consciousness, especially in the initial period of taking the drug.

The likelihood of developing such complications can be minimized by reducing the magnitude of the dose increment.
Patients with a history of clinically significant cardiovascular disorders (heart failure, myocardial infarction, coronary heart disease, cerebrovascular accidents, conduction disorders), patients with cerebrovascular accidents or other conditions that lead to arterial hypotension (dehydration, use of antihypertensive drugs) the use of quetiapine should be done with caution.
Convulsive seizures. When quetiapine was used in patients with schizophrenia, there were no differences in the frequency of seizures between patients receiving the drug and placebo. However, like other antipsychotics, the drug should be administered with caution to patients with a history of seizures or in conditions leading to a decrease in the threshold at which there is a risk of seizure development.
Tardive dyskinesia and extrapyramidal symptoms.
This complication can occur when taking antipsychotics, most often in the elderly, especially in women. At the same time, there are no prognostic signs by which one could predict the appearance of tardive dyskinesia in a particular patient.
If signs and symptoms of tardive dyskinesia appear, the dose of quetiapine should be reduced or stopped. However, this issue should be resolved individually, since in some cases the use of quetiapine may be extremely necessary, despite the presence of tardive dyskinesia syndrome.
The risk of developing these complications increases with the duration of therapy and the cumulation of the neuroleptic.
Malignant neuroleptic syndrome can develop when taking neuroleptics, including quetiapine.
Manifestations of neuroleptic malignant syndrome: hyperthermia, muscle stiffness, changes in mental state, instability from the autonomic nervous system, increased CPK levels, myoglobinuria, acute renal failure.
With the development of neuroleptic malignant syndrome, it is necessary to stop taking quetiapine and conduct intensive symptomatic therapy.
If, after the treatment for neuroleptic malignant syndrome, the patient needs to continue taking the neuroleptic, this should be done very carefully.
Neutropenia. In some cases, with the use of quetiapine, the development of severe neutropenia (the number of neutrophils<0,5 · 10 9 / л) без явной дозозависимости.

Possible risk factors for the development of leukopenia and / or neutropenia include a low leukocyte count before starting treatment and the presence of leukopenia and / or neutropenia with a history of medication. With a decrease in the content of neutrophils below 1.0 · 10 9 / l, the drug should be discontinued. Patients should be monitored. Control of the content of neutrophils should be carried out until their number rises to a value of 1.5 · 10 9 / l.
Sudden discontinuation of the drug. Very rarely, acute withdrawal symptoms such as nausea, vomiting, and insomnia have been reported after sudden discontinuation of high-dose antipsychotic medication. Recurrences of psychotic symptoms and the appearance of disorders such as involuntary movements (eg akathisia, dystonia, and dyskinesia) have been reported. Therefore, it is recommended to gradually stop taking the drug for at least one to two weeks.
Hyperglycemia. With the use of quetiapine, hyperglycemia and diabetes mellitus (including exacerbation of preexisting diabetes mellitus) develop quite rarely, they can also occur in patients without a history of hyperglycemia.
In some cases, symptoms of hyperglycemia resolve after stopping the drug. Patients with diabetes or patients with risk factors for developing diabetes mellitus are advised to carry out appropriate clinical monitoring.
Use by the elderly with dementia
The drug is indicated for use in the elderly with dementia.
In patients with dementia, with the use of some atypical antipsychotics, an almost 3-fold increase in the risk of undesirable cerebrovascular events was observed. The mechanism for this increased risk is unknown. The increased risk cannot be excluded for other antipsychotics or for other patient categories.
Quetiapine should be used with caution in patients with risk factors for stroke.
Use by patients with impaired renal function
The drug should be used with caution in such patients, especially in the initial period.
Use in the elderly
In the elderly, the plasma clearance of quetiapine decreases on average by 30-50% compared to that in patients aged 18-65 years. In addition, in this category of patients, dysfunctions of the liver, kidneys, central nervous system and cardiovascular system are usually more often noted. All this requires caution when using the drug in the elderly.
Liver dysfunction
The use of quetiapine in patients with existing liver disease requires caution. It is necessary to take precautions when using concomitant drugs with potential hepatotoxicity. Before starting therapy with quetiapine, patients with known or suspected liver dysfunction are recommended to determine the content of transaminases. The same studies must be performed periodically during treatment.

Instructions for use

Quetiapin-sz 0.1 n60 tab p / plen / shell instructions for use

Dosage form

Film-coated tablets, yellow, round, biconvex; in cross section white or almost white.

Composition

Quetiapine (in the form of fumarate) 100 mg

Excipients: microcrystalline cellulose 40 mg, lactose monohydrate 32 mg, povidone 12 mg, croscarmellose sodium 14 mg, magnesium stearate 2 mg.

Pharmacodynamics

Antipsychotic (neuroleptic). Shows a higher affinity for serotonin 5HT2 receptors compared to dopamine D1 and D2 receptors in the brain. It also has a high affinity for histamine and β 1 -receptors and less pronounced - for α2-receptors. It has no affinity for m-cholinergic receptors and benzodiazepine receptors.

Quetiapine at a dose that effectively blocks dopamine D2 receptors produces only mild catalepsy. Selectively reduces the activity of mesolimbic A10-dopamine neurons compared to A9-nigrostriatal neurons involved in motor function.

Does not cause prolonged increases in prolactin levels.

In accordance with the results of positron emission tomography, the effect of quetiapine on serotonin 5HT2 and dopamine D2 receptors lasts up to 12 hours.

Pharmacokinetics

After oral administration, it is well absorbed from the gastrointestinal tract. Food intake does not significantly affect the bioavailability of quetiapine.

The pharmacokinetics of quetiapine are linear.

Plasma protein binding is about 83%.

Undergoes intensive metabolism. In vitro studies have shown that the key enzyme in quetiapine metabolism is CYP3A4. The main metabolites, which are determined in blood plasma, do not have pronounced pharmacological activity.

T1 / 2 is about 7 hours. Less than 5% of quetiapine is excreted unchanged by the kidneys or through the intestines. Approximately 73% of metabolites are excreted by the kidneys and 21% through the intestines. Average clearance of quetiapine in elderly patients is 30-50% less than that observed in patients aged 18 to 65 years.

The mean plasma clearance of quetiapine was approximately 25% lower in patients with severely impaired renal function (CC less than 30 ml / min / 1.73 m2) and in patients with liver damage (alcoholic cirrhosis in the compensating stage), but individual clearance levels were within, appropriate for healthy people.

Side effects

From the side of the central nervous system: headache, drowsiness, dizziness, anxiety; rarely - ZNS.

From the side of the cardiovascular system: orthostatic hypotension, tachycardia, arterial hypertension.

From the digestive system: constipation, dry mouth, dyspepsia, diarrhea, transient increase in the activity of liver enzymes (ALT, AST, GGT), abdominal pain.

From the side of the hematopoietic system: asymptomatic leukopenia and / or neutropenia; rarely, eosinophilia.

From the musculoskeletal system: myalgia.

From the respiratory system: rhinitis.

Dermatological reactions: skin rash, dry skin.

From the organ of hearing: ear pain

From the genitourinary system: urinary tract infections.

On the metabolic side: a slight increase in the content of cholesterol and triglycerides in the blood.

From the endocrine system: a small dose-dependent reversible decrease in the level of thyroid hormones (in particular, total and free T4).

Others: asthenia, back pain, weight gain, fever, chest pain.

Selling features

prescription

Special conditions

use with caution in patients with cardiovascular diseases and other conditions associated with the risk of arterial hypotension, especially at the beginning of treatment and in the elderly; with indications of a history of seizures.

Quetiapine is actively metabolized in the liver. In patients with impaired liver and kidney function, the clearance of quetiapine decreases by approximately 25%. Therefore, quetiapine should be used with caution in patients with impaired liver and / or kidney function.

Use with caution simultaneously with drugs that lengthen the QT interval (especially in the elderly); with drugs that have a depressing effect on the central nervous system, as well as with ethanol; with potential inhibitors of the isoenzyme CYP3A4 (including with ketoconazole, erythromycin).

If NMS develops on the background of treatment, quetiapine should be discontinued and appropriate treatment should be prescribed.

With prolonged use, there is a possibility of developing tardive dyskinesia. In such cases, it is necessary to reduce the dose of quetiapine or cancel it.

Use with caution in combination with other drugs that affect the activity of the central nervous system, as well as with ethanol.

In experimental studies, when studying the carcinogenicity of quetiapine, an increase in the incidence of mammary adenocarcinomas in rats (at doses of 20, 75 and 250 mg / kg / day) was noted, which is associated with prolonged hyperprolactinemia.

In male rats (250 mg / kg / day) and mice (250 and 750 mg / kg / day), an increase in the incidence of benign adenomas from thyroid follicular cells was noted, which was associated with a known rodent-specific mechanism of increased hepatic clearance of thyroxine.

Influence on the ability to drive vehicles and use mechanisms

Quetiapine can cause drowsiness, therefore, patients are not recommended to perform work associated with the need for concentration of attention and high speed of psychomotor reactions (including driving vehicles).

See instructions for details.

Indications

Schizophrenia treatment

Treatment of manic episodes in the structure of bipolar disorder,

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

Contraindications

Hypersensitivity to quetiapine, age up to 18 years.

Application during pregnancy and lactation.

During pregnancy and lactation, use is possible in cases where the expected benefit to the mother outweighs the potential risk to the fetus. It is not known whether quetiapine is excreted in breast milk. If necessary, use during lactation, breastfeeding should be discontinued.

In experimental studies on animals, no mutagenic and clastogenic effects of quetiapine were detected. No effect of quetiapine on fertility has been revealed (decreased male fertility, pseudopregnancy, increased period between two estrus, increased precoital interval and decreased pregnancy rate), however, the obtained data cannot be directly transferred to humans, because there are specific differences in hormonal control of reproduction.

Application for violations of liver function

Quetiapine is actively metabolized in the liver. In patients with impaired liver function, the clearance of quetiapine is reduced by approximately 25%. Therefore, quetiapine should be used with caution in patients with impaired liver function.

Application for impaired renal function

In patients with impaired renal function, the clearance of quetiapine is reduced by approximately 25%. Therefore, quetiapine should be used with caution in patients with impaired renal function.

Drug interactions

With simultaneous use with ketoconazole, erythromycin, it is theoretically possible to increase the concentration of quetiapine in the blood plasma and the development of side effects.

With simultaneous use with phenytoin, carbamazepine, barbiturates, rifampicin, the clearance of quetiapine increases, its concentration in blood plasma decreases.

With simultaneous use with thioridazine, an increase in the clearance of quetiapine is possible.

See instructions for details

Mode of application

Dosage

In patients with impaired liver and / or kidney function, the initial dose is 25 mg / day. The daily dose increase should be 25-50 mg until optimal effect is achieved.

See instructions for details.