Quetiapine pills 100mg №60

Quetiapine

quetiapine

Dosage form

film coated tablets

1 tablet, film coated, contains:

dosage 25 mg:

active substance: quetiapine fumarata, in terms of quetiapine -25 mg;

excipients (core): microcrystalline cellulose -60.0 mg; lactose monohydrate (milk sugar) -44.0 mg; povidone (polyvinylpyrrolidone

weight) -9.0 mg; Croscarmellose sodium (primelloza) -10.5 mg; Magnesium

stearate -1.5 mg;

excipients (shell):

Opadry II (polyvinyl alcohol, partially hydrolyzed -2.0 mg; macrogol

(polyethylene glycol) 3350-1.01 mg; talc - 0.74 mg; titanium dioxide E 171-1.1333 mg;

iron dye oxide (II) yellow E 172 -0.1167 mg).

dosage of 100 mg:

active substance: quetiapine fumarata, in terms of quetiapine -100 mg;

excipients (core): microcrystalline cellulose -40.0 mg;

lactose monohydrate (milk sugar) -32.0 mg; Povidone (medium molecular weight polyvinylpyrrolidone) -12.0 mg; Croscarmellose sodium (primelloza) -14.0 mg; magnesium stearate -2.0 mg; excipients (shell):

Opadry II (polyvinyl alcohol, partially hydrolyzed -2.4 mg; macrogol(polyethylene glycol) 3350-1,212 mg; talc - 0.888 mg; titanium dioxide E 171-1.3122 mg; indigo carmine-based aluminum varnish -0.0012 mg; iron dye oxide (II) yellow E 172-0.0018 mg; yellow lacquer based on quinoline yellow -0.1806 mg; aluminum varnish on the basis of yellow sunsets -0.0042 mg).

dosage 200 mg:

active substance: quetiapine fumarata, in terms of quetiapine -200 mg;

excipients (core): microcrystalline cellulose -56.0 mg; lactose monohydrate (milk sugar) -44.5 mg; povidone (polyvinylpyrrolidone

weight) -21.0 mg; Croscarmellose sodium (primelloza) -25.0 mg; magnesium stearate - 3.5 mg;

excipients (shell):

Opadry II (polyvinyl alcohol, partially hydrolyzed -4.4 mg; macrogol (polyethylene glycol) 3350 -1.235 mg; talc -2.0 mg; titanium dioxide E 171 -1.917 mg; soy lecithin E 322 -0.35 mg; aluminum varnish based on indigo carmine

-0.006 mg; dye-based aluminum lacquer azorubin -0,051 mg; aluminum lacquer on the basis of the crimson dye [Ponso 4R] -0.041 mg).

Tablets, film coated from beige yellow to beige color,

round, biconvex. pills on a cross section of white or almost white color (dosage 25 mg, 100 mg, 200 mg).

Pharmacotherapeutic group of the drug:

antipsychotic (neuroleptic)

Pharmacology

Pharmacodynamics

Mechanism of action:

Quetiapine is an atypical antipsychotic drug.

Quetiapine and its active metabolite N-dezalkyl Quetiapine interact with

neutrotransmitter receptors in the brain.Quetiapine and N-desalkyl

Quetiapine exhibit high affinity for serotonin receptors type 5HT2 and

dopamine receptors types D1 and D2 of the brain.

Higher selectivity to serotonin receptors like 5HT2 than to dopamine receptors like D2 causes the main clinical antipsychotic properties of Quetiapine and the low incidence of extrapyramidal side effects. In addition, N-desalkyl quetiapine exhibits high affinity for the norepinephrine carrier. Quetiapine and N-desalkyl Quetiapine have a high affinity for histamine and α1-adrenoreceptors and a lower affinity for α2-adrenoreceptors and serotonin receptors of the type

5HT1.

Quetiapine does not show a marked affinity for cholinergic muscarinic and

benzodiazepine receptors. In standard tests, quetiapine exhibits

antipsychotic activity. The specific contribution of the metabolite N-desalkyl quetiapine to

pharmacological activity of quetiapine is not installed. The results of the study

extrapyramidal symptoms (EPS) in animals revealed that quetiapine causes

weak catalepsy in doses that effectively block the D2 receptors. Quetiapine

causes a selective decrease in the activity of mesolimbic A10 dopaminergic neurons in comparison with A9 nigrostriatal neurons,

involved in motor function.

Quetiapine is effective against both positive and negative symptoms.

schizophrenia.

Quetiapine is effective as monotherapy for manic episodes from

moderate to severe severity. Long term use data

Quetiapine for the prevention of subsequent manic and depressive episodes

are missing. Information on the use of Quetiapine in combination with valproate

with lithium manganese episodes or moderately to manic episodes.

severe severity is limited, however, this combination therapy was generally well tolerated. In addition, quetiapine 300 mg and 600 mg.

effective in patients with bipolar disorder type I and II moderate to

severe severity. At the same time, the effectiveness of Quetiapine when taken at a dose of 300 mg and 600 mg per day is comparable.

Quetiapine is effective in patients with schizophrenia and mania when taking the drug 2 times a day, despite the fact that the half-life of quetiapine is about 7 hours. The effect of quetiapine on receptors of type 5HT2 and D2 lasts up to 12 hours after taking the drug.

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

blood. In studies with different fixed doses of the drug is not

revealed differences in the level of prolactin when using quetiapine or placebo.

The level of prolactin when using different fixed doses of Quetiapine did not differ from the level of prolactin when taking placebo.

When taking Quetiapine with dose titration in schizophrenia, the frequency of EPS and

concomitant use of anticholinergic drugs was comparable to

such when taking placebo.When prescribing quetiapine in fixed doses from

75 to 750 mg / day in patients with schizophrenia, the incidence of EPS and

the need for concomitant use of anticholinergic drugs is not

increased.

When using Quetiapine in doses up to 800 mg / day for the treatment of manic

episodes of moderate to severe severity in the form of monotherapy, and in combination with lithium preparations or valproate seminary, the frequency of EPS and

concomitant use of anticholinergic drugs was comparable to

such when taking placebo.

When administered orally, quetiapine is well absorbed from the gastrointestinal tract and is actively metabolized in the liver. Eating is not significantly

affects the bioavailability of quetiapine. Approximately 83% of quetiapine is bound to plasma proteins. The equilibrium molar concentration of the active metabolite N-dezalkyl quetiapine is 35% of that of quetiapine. The half-life of quetiapine and quetiapine N-dezalkyl is about 7 and 12 hours, respectively.

The pharmacokinetics of quetiapine and quetiapine N-dezalkyl are linear; there are no differences in pharmacokinetic parameters in men and women.

The average clearance of quetiapine in elderly patients is 30-50% less than that of

patients aged 18 to 65 years.

The average plasma clearance of quetiapine is reduced by approximately 25% in

patients with severe renal insufficiency (creatinine clearance less than 30

ml / min / 1.73 m2), but individual clearance indicators are within

values ​​found in healthy volunteers. In patients with hepatic

insufficiency (compensated alcoholic cirrhosis) medium plasma

Quetiapine clearance is reduced by approximately 25%. Since quetiapine

extensively metabolized in the liver, in patients with liver failure

may increase the plasma concentration of quetiapine, which requires

dose adjustments.

On average, less than 5% of the molar dose of the fraction of free quetiapine and N-dezalkyl

Quetiapine plasma is excreted in the urine. Approximately 73% of quetiapine is excreted in the urine and 21% in feces. Less than 5% of quetiapine is not exposed.

I am metabolized and excreted unchanged by the kidneys or with feces. It has been established that CYPZA4 is a key isoenzyme of quetiapine metabolism mediated by cytochrome P450. N-dezalkyl quetiapine is formed with the participation of the isoenzyme CYRZA4.

Quetiapine and some of its metabolites (including N-dezalkyl Quetiapine) possess

weak inhibitory activity against cytochrome P450 isoenzymes

1A2, 2S9, 2C19, 2D6 and ZA4, but only at a concentration 5-50 times higher than

concentrations observed at the commonly used effective dosage of 300-800 mg / day.

Based on the results of invitro, one should not expect that simultaneous

prescription of quetiapine with other drugs will result in a clinically pronounced

inhibition of the metabolism of other drugs mediated by cytochrome P450.

- Treatment of schizophrenia.

-Treatment of manic episodes in the structure of bipolar disorder.

- Treatment of depressive episodes from moderate to severe severity in

structure of bipolar disorder.

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

Hypersensitivity to any of the components of the drug, including

lactase deficiency, glucose-galactose malabsorption and intolerance

galactose. Combined use with cytochrome P450 inhibitors, such as

antifungal drugs azoles, Erythromycin , Clarithromycin and

nefazodone, as well as protease inhibitors (see the section "Interaction with other

drugs ”). Although efficiency and safety

Quetiapine in children and adolescents aged 10-17 years have been studied in clinical

studies, the use of quetiapine in patients under the age of 18 years is not shown.

Carefully

In patients with cardiovascular and cerebrovascular diseases or

other conditions predisposing to arterial hypotension, the elderly

age, liver failure, convulsive seizures in history.

Use during pregnancy and lactation

The safety and effectiveness of quetiapine in pregnant women have not been established.

Therefore, during pregnancy Quetiapine can only be used if the expected benefit to the woman justifies the potential risk to the fetus.

The degree of excretion of quetiapine with human milk is not known. For women

It is recommended to avoid breastfeeding while taking

Quetiapine.

Quetiapine can be used regardless of the meal.

Adults

Treatment of schizophrenia:

Quetiapine is administered 2 times a day. The daily dose for the first 4 days of therapy is: 1st day -50 mg, 2nd day -100 mg, 3rd day -200 mg, 4th day -300 mg. Starting from the 4th day, the dose should be adjusted to the effective, usual

but in the range of 300 to 450 mg / day. Depending on the clinical effect and

individual tolerance by the patient, the dose may vary from 150 to 750 mg / day. The maximum recommended daily dose is 750 mg.

Treatment of manic episodes in the structure of bipolar disorder

Quetiapine is used as monotherapy or in combination with drugs.

having a normochemical effect.

Quetiapine is administered 2 times a day. Daily dose for the first 4 days of therapy

makes: 1st day - 100 mg, 2nd day - 200 mg, 3rd day - 300 mg, 4th day - 400 mg.

Further, by the 6th day of therapy, the daily dose of the drug can be increased to

800 mg. Increasing the daily dose should not exceed 200 mg per day.

Depending on the clinical effect and individual tolerance, the dose

may vary from 200 to 800 mg / day. Usually effective dose

ranges from 400 to 800 mg / day. Maximum recommended daily intake

makes 800 mg.

Treatment of depressive episodes in the structure of bipolar disorder

Quetiapine is administered once a day at night. Daily dose for the first 4 days

therapy is: 1st day -50 mg, 2nd day -100 mg, 3rd day -200 mg, 4th day -300 mg. The recommended dose is 300 mg / day. Maximum recommended

The daily dose of Quetiapine is 600 mg.

The antidepressant effect of Quetiapine has been confirmed when used in

a dose of 300 and 600 mg / day. With short-term therapy, the efficacy of quetiapine in doses

300 and 600 mg / day. was comparable (see Pharmacodynamics section).

Elderly:

In elderly patients, the initial dose of Quetiapine is 25 mg / day.

The dose should be increased daily by 25-50 mg to achieve an effective dose,

which is likely to be less than in younger patients.

Patients with renal failure:

Dose adjustment is not required.

Patients with liver failure:

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

The most common side effects of quetiapine are drowsiness, dizziness,

dry mouth, mild asthenia, constipation, tachycardia, orthostatic hypotension and dyspepsia.

Quetiapine, like other antipsychotic drugs, may

accompanied by an increase in body weight, fainting, the development of malignant

neuroleptic syndrome, leukopenia, neutropenia and peripheral edema.

The frequency of adverse reactions is given in the form of the following gradation: very often (≥

1/10); often (≥ 1/100, <1/10); infrequently (≥ 1/1000, <1/100); rarely (≥ 1/10000, <1/1000);

very rarely (<1/10000), unspecified frequency.

Drowsiness usually occurs during the first 2 weeks after the start of therapy and, as a rule, is resolved against the background of continuing quetiapine.

Perhaps asymptomatic increase in the activity of AST, ALT and GGT in serum,

usually reversible amid ongoing Quetiapine intake.

Like other antipsychotics and α1-blockers, quetiapine is often

causes orthostatic hypotension, which is accompanied by dizziness,

tachycardia, in some cases, fainting, especially at the beginning of therapy (see section "Special Instructions").

Very rare cases of diabetes mellitus decompensation are noted.

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

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 at

single definition.

The higher incidence of dysphagia in patients with Quetiapine compared with placebo was

only observed in patients with depression in the structure of bipolar disorder.

Mostly occurs at the start of therapy.

When studying withdrawal syndrome in short-term placebo-controlled

clinical trials of quetiapine in monotherapy regimen were noted

the following symptoms: insomnia, nausea, headache, diarrhea, vomiting,

dizziness and irritability. Frequency of a syndrome of "cancellation" significantly

decreased after 1 week after discontinuation of the drug.

Increased triglycerides ≥ 200 mg / dL (≥ 2.258 mmol / L) in patients ≥

18 years or ≥ 150 mg / dL (≥ 1.694 mmol / l) in patients <18 years old, at least with

single definition.

Increasing total cholesterol concentration ≥ 240 mg / dL (≥ 6.2064 mmol / L) in

patients ≥ 18 years old or ≥ 200 mg / dL (≥ 5.172 mmol / l) in patients <18 years old, at least

with a single definition.

See below for instructions.

Platelet count ≤ 100 x 109 / L, at least once

the definition of.

The prolongation of the QT interval, ventricular arrhythmia, sudden death, cardiac arrest and bidirectional ventricular tachycardia are considered to be side effects inherent in neuroleptics.

The frequency of EPS in short-term clinical studies with schizophrenia and mania in

The structure of bipolar disorder was comparable in the Quetiapine group and

placebo (patients with schizophrenia: 7.8% in the Quetiapine group and 8.0% in the

placebo; 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

bipolar disorder in the Quetiapine group was 8.9%, in the PL group

acebo -3.8%. The frequency of individual symptoms of EPS (such as akathisia,

extrapyramidal disorders, tremor, dyskinesia, dystonia, anxiety,

involuntary muscle contractions, psychomotor agitation and muscular

rigidity), as a rule, was low and did not exceed 4% in each of

therapeutic groups. In long-term clinical studies of quetiapine with

schizophrenia and bipolar disorder, the incidence of EPS was comparable in groups

Quetiapine and placebo.

During Quetiapine therapy, a small dose-dependent decrease in thyroid hormone levels, in particular, total thyroxin (T4) and

free T4. The maximum decrease in total and free T4 was registered on the 2nd and 4th week of Quetiapine therapy, without further reducing the concentration of hormones during prolonged treatment. In almost all cases, the concentration of total and free T4 returned to the initial level after stopping Quetiapine therapy, regardless of the duration of treatment. A slight decrease in total triiodothyronine (T3) and reverse T3 was noted only when using high doses. The level of thyroxin-binding globulin (TSH) remained unchanged, there was no increase in the level of thyroid-stimulating hormone (TSH).

A fatal outcome was reported when a patient received 13.6 g of quetiapine,

participated in a clinical study, as well as a lethal outcome after

taking 6 g of quetiapine in post-marketing study of the drug. In the same time,

described case of taking quetiapine in a dose exceeding 30 g, without lethal ismove.

There are reports of extremely rare cases of quetiapine overdose,

leading to an increase in QTc interval, death or coma.

History of patients with severe cardiovascular disease risk

side effects in overdose may increase (see

"Special instructions").

The symptoms noted during overdose were mainly due to increased

known pharmacological effects of the drug, such as drowsiness and sedation,

tachycardia and lowering blood pressure.

There are no specific antidotes for Quetiapine. In cases of severe intoxication

should be aware of the possibility of an overdose of several drugs

drugs. It is recommended to carry out activities aimed at maintaining

respiratory and cardiovascular functions, ensuring adequate

oxygenation and ventilation. Gastric lavage (after intubation, if the patient is without

consciousness) and the appointment of Activated carbon and laxatives can

promote the elimination of unabsorbed quetiapine, but the effectiveness

these measures have not been studied. Close medical surveillance should continue until the patient's condition improves.

In a dry, dark place, at a temperature not higher than 25 ° C.

Keep out of the reach of children.