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

Kernel composition	For dosage:
	25 mg	100 mg	150 mg	200 mg
Quetiapine fumarate	28.78 mg	115.12 mg	172.68 mg	230.24 mg
in terms of quetiapine (LLC "Technology of medicines", Russia)	25.0 mg	100.0 mg	150.0 mg	200.0 mg
Excipients
Lactose monohydrate (milk sugar) (Ph Eur. USP)	20.0 mg	20.0 mg	30.0 mg	40.0 mg
Calcium Hydrogen Phosphate Dihydrate (Ph Ear.USP)	34.22 mg	30.88 mg	46.32 mg	61.76 mg
Potato starch (USP. Ph Eur)	5.0 mg	10.0 mg	I5,0 mg	20.0 mg
Copovidone (USP, Ph Eur)	4.0 mg	8.0 mg	12.0 mg	16.0 mg
Sodium starch glycolate (Ph Eur. USP)	7.0 mg	14.0 mg	21.0 mg	28.0 mg
Calcium stearate (Ph Eur. USP)	1.0 mg	2.0 mg	3.0 mg	4.0 mg
Total:	100.0 mg	200.0 mg	300.0 mg	400.0 mg
Composition of the film shell
Aquarius Prime BAP21S010 white [hypromellose 65%, titanium dioxide 25%, macrogol 10%] (Ph Eur. USP)	3.0 mg	6.0 mg	9.0 mg	12.0 mg
Film coated tablet weight	103.0 mg	206.0 mg	309.0 mg	412.0 mg

Description:

Round, biconvex tablets, covered with a film coat of white color. Two layers are visible on the section. The core of the tablet is white or almost white.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.04 Quetiapine

Pharmacodynamics:

Quetiapine is an atypical antipsychotic drug that exhibits a higher affinity for serotonin (hydroxytryptamine) receptors (5HT₂) than to dopamine receptors D₁ and D₂ brain. Quetiapine also has a more pronounced affinity for histamine and alpha₁-adrenoceptors and less in relation to alpha₂adrenoreceptors. There was no significant affinity for quetiapine for muscarinic and benzodiazepine receptors. In standard tests quetiapine has antipsychotic activity.

Pharmacokinetics:

When administered orally quetiapine well absorbed from the gastrointestinal tract and actively metabolized in the liver. The main metabolites in the plasma do not have a pronounced pharmacological activity.

The intake of food does not significantly affect the bioavailability of quetiapine. Half-life is about 7 hours. Approximately 83% of quetiapine binds to plasma proteins.

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

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

The mean plasma clearance of quetiapine is less than approximately 25% in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min / 1.73 m²) and in patients with liver damage, but interindividual clearance rates are within the limits corresponding to healthy volunteers. Approximately 73% of quetiapine is excreted in urine and 21% with feces. Less than 5% of quetiapine is not metabolized and is excreted unchanged in kidneys or with feces.

Determined that CYP3A4 is the key isoenzyme of quetiapine metabolism, mediated by cytochrome P450.

In a study of the pharmacokinetics of quetiapine in varying doses, the use of quetiapine prior to the administration of ketoconazole or concomitantly with ketoconazole resulted in an increase, on average, in the maximum concentration (C_mOh) and the area under the curve "concentration-time" (AUC) of quetiapine by 235% and 522% respectively, and to a decrease in the clearance of quetiapine, on average, by 84%. Quetiapine half-life increased, but the mean time to reach maximum concentration (t_max) did not change.

Quetiapine and some of its metabolites have a weak inhibitory activity against cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6 and 3A4, but only at a concentration of 10-50 times the concentration observed at the usual effective dose of 300-450 mg / day.

Based on the results in vitro, it should not be expected that simultaneous use of quetiapine with other drugs will result in clinically significant inhibition of cytochrome P450-mediated metabolism of other drugs.

Indications:

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

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

Contraindications:

Hypersensitivity to any of the components of the drug. Simultaneous reception with inhibitors CYP3A4, such as HIV protease inhibitors, azole antifungal drugs, erythromycin, clarithromycin, nefazodone, children's age till 18 years, lactation period.

Carefully:

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

Dosing and Administration:

Adults

Treatment of acute and chronic psychoses, including schizophrenia

The daily dose for the first 4 days of therapy is: 1st day - 50 mg, Day 2 - 100 mg, Day 3 - 200 mg, Day 4 - 300 mg. Starting from the 4th day, the dose should be selected up to a clinically effective dose, which usually ranges from 300 to 450 mg / day. Depending on the clinical effect and individual tolerability, the dose can vary from 150 to 750 mg / day.

Treatment of manic episodes in the structure of bipolar disorder

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

The daily dose for the first 4 days of therapy is: the 1st day - 100 mg, the second day - 200 mg, the third day - 300 mg, the 4th day - 400 mg. In the future, 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 / day. Usually the effective dose is from 400 to 800 mg / day.

For the treatment of schizophrenia, the maximum recommended daily dose of quetiapine is 750 mg, for the treatment of manic episodes in the structure of bipolar disorder the maximum recommended daily dose of quetiapine is 800 mg / day.

Elderly

In elderly patients, the initial dose of quetiapine 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 and hepatic insufficiency

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

Side effects:

The most common adverse reactions associated with taking the drug are drowsiness (17.5%), dizziness (10%), constipation (9%), dyspepsia (6%), orthostatic hypotension and tachycardia (7%), dry mouth 7%), an increase in the activity of "liver" enzymes in the blood serum (6%), an increase in the concentration of cholesterol and triglycerides in the blood plasma.

The intake of quetiapine may be accompanied by the development of moderate asthenia, rhinitis and dyspepsia, an increase in body weight (mainly in the first weeks of treatment).

Quetiapine can cause orthostatic hypotension (accompanied by dizziness), tachycardia and in some patients - fainting; these adverse reactions mainly occur during the initial period of dose selection (see section "Special instructions").Quetiapine therapy is associated with a small dose-dependent decrease in the concentration of thyroid hormones, in particular, the general T₄ and free T₄. Maximum reduction in total and free T₄ registered at the second and fourth week of quetiapine therapy, without further reduction in the concentration of hormones during long-term treatment. Thereafter, there were no signs of clinically significant changes in the concentration of thyroid-stimulating hormone.

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

With a sharp cancellation of high doses of antipsychotic drugs, the following acute reactions (withdrawal syndrome) can occur: nausea, vomiting, and rarely insomnia.

There are cases of exacerbation of psychotic symptoms and the emergence of involuntary motor disorders (akathisia, dystonia, dyskinesia), and therefore the elimination of the drug is recommended to be carried out gradually.

The following are the adverse reactions observed with the use of quetiapine and distributed among organs and systems:

From the nervous system: drowsiness, dizziness, headache, anxiety, asthenia, hostility, agitation, insomnia, akathisia, tremor, convulsions, depression, paresthesia, malignant neuroleptic syndrome (hyperthermia, muscle rigidity, changes in mental status, lability in the autonomic nervous system, increased activity of creatine phosphokinase) , restless legs syndrome.

From the side of the cardiovascular system: orthostatic hypotension, tachycardia, lengthening of the interval Q-T.

From the digestive system: dryness of the oral mucosa, nausea, vomiting, abdominal pain, diarrhea or constipation, increased activity of "liver" transaminases, jaundice, hepatitis.

From the respiratory system: pharyngitis, rhinitis.

Allergic reactions: skin rash, eosinophilia, angioedema, Stevens-Johnson syndrome, anaphylactic reactions.

Laboratory indicators: leukopenia, neutropenia, hypercholesterolemia, hypertriglyceridemia, decrease in T4 concentration (the first 4 weeks), hyperglycemia.

Other: back pain, chest pain, subfebrile condition, weight gain (mainly in the first weeks of treatment), myalgia, dry skin, visual impairment, incl.blurred vision, decompensation of existing diabetes, priapism, galactorrhea.

Overdose:

Data on quetiapine overdose are limited. Cases of quetiapine have been reported in a dose exceeding 20 g, without fatal consequences and with complete recovery, but there are reports of extremely rare cases of quetiapine overdose leading to death or coma.

Symptoms may be a consequence of the enhancement of known pharmacological effects of the drug, such as drowsiness and excessive sedation, tachycardia and lowering blood pressure.

Treatment: there are no specific antidotes to quetiapine. In cases of overdose, gastric lavage may be possible (after intubation, if the patient is unconscious), taking activated charcoal and laxatives to excrete unabsorbed quetiapine, however, the effectiveness of these measures has not been studied. Symptomatic therapy and measures aimed at maintaining the function of respiration, cardiovascular system, providing adequate oxygenation and ventilation are shown. Medical supervision and surveillance should be continued until the patient is fully recovered.

Interaction:

With the simultaneous use of drugs that have a powerful inhibitory effect on the isoenzyme CYP3A4 (such as antifungal agents of the azole group and erythromycin, clarithromycin, nefazodone) the concentration of quetiapine in the plasma is increased, so the simultaneous reception of them with quetiapine is contraindicated.

The simultaneous use of quetiapine with preparations inducing the enzyme system of the liver, such as carbamazepine, it is possible to reduce the concentration of the drug in the plasma, which may require an increase in the dose of quetiapine, depending on the clinical effect. In a study of the pharmacokinetics of quetiapine in varying doses, when applied before or simultaneously with carbamazepine (a hepatic enzyme inducer), the quetiapine clearance significantly increased. This increase in quetiapine clearance reduced AUC an average of 13% compared with the use of quetiapine without carbamazepine.

The simultaneous use of quetiapine with another inducer of microsomal liver enzymes - phenytoin, also led to an increase in clearance of quetiapine. With the simultaneous use of quetiapine and phenytoin (or other inducers of hepatic enzymes, such as barbiturates, rifampicin) may require an increase in the dose of quetiapine.

It may also be necessary to reduce the dose of quetiapine when the phenytoin or carbamazepine or other inducer of the liver enzyme system is abolished or replaced with a drug that does not induce microsomal liver enzymes (eg, valproic acid).

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

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

The pharmacokinetics of quetiapine does not change significantly with simultaneous use with antipsychotic drugs - risperidone or haloperidol. However, simultaneous administration of quetiapine and thioridazine led to increased clearance of quetiapine.

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

The pharmacokinetics of quetiapine did not change significantly with the simultaneous use of imipramine (CYP2D6 inhibitor) or fluoxetine (CYP3A4 and CYP2D6 inhibitor).

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

Special instructions:

Quetiapine can cause orthostatic hypotension, especially in the initial period of dose selection (in elderly patients it is observed more often than in young patients).

There was no correlation between taking quetiapine and increasing QT_c-Interval. However, when quetiapine is used concomitantly with drugs that extend the interval QT_from, care must be taken, especially in the elderly.

During treatment with a decrease in the number of neutrophils less than 1000 / μL, quetiapine should be discontinued.

With the development of orthostatic hypotension against the background of drug treatment, it is necessary to reduce the dose or more slowly to titrate doses.

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

If the symptoms of tardive dyskinesia develop, the dose of the drug should be reduced or gradually canceled. Symptoms of tardive dyskinesia may increase or even appear even after discontinuation of the drug.

In the case of malignant neuroleptic syndrome, the drug should be withdrawn.

Taking into account that quetiapine, mainly affects the central nervous system, the drug should be used with caution in combination with other drugs that depress the central nervous system, or alcohol. In children, adolescents and young people (under 24 years) with depression, other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when assigning Quetiapine or any other antidepressants in children, adolescents and young people (younger than 24 years), the risk of suicide and the benefits of their use should be correlated. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. Any depressive disorder in itself increases the risk of suicide. Therefore, during treatment with antidepressants, all patients should be monitored for early detection of abnormalities or behavioral changes, as well as suicidal tendencies.

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

Quetiapine can cause drowsiness, so during treatment, patients are advised to refrain from driving motor vehicles and classes of activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Film-coated tablets, 25 mg, 100 mg, 150 mg or 200 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 30, 60 tablets or 90 tablets per can of polymer for medicines.

To the bank, 3 or 6 outline packages together with the instruction for use are placed in a cardboard pack.

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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008008/10

Date of registration:12.08.2010 / 28.11.2017

Expiration Date:Unlimited

The owner of the registration certificate:TECHNOLOGY OF DRUGS, LTD. TECHNOLOGY OF DRUGS, LTD. Russia

Manufacturer: & nbsp

TECHNOLOGY OF DRUGS, LTD. Russia

Representation: & nbspR-PHARM, JSC R-PHARM, JSC Russia

Information update date: & nbsp27.12.2017

Illustrated instructions

Instructions

Quetiapine (Quetiapine)