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

Core: active substance: quetiapine fumarate (quetiapine hemifumarate) 28.78 (equivalent to quetiapine 25); Excipients: lactose monohydrate 4.50, calcium hydrophosphate dihydrate 2.50, microcrystalline cellulose 18.97, povidone 1.25, sodium carboxymethyl starch (type A) 5.00, magnesium stearate 1.50.

Film Sheath: hypromellose 1.25, titanium dioxide (E 171) 0.425, macrogol-4000 0.20, iron dye oxide yellow (E 172) 0.075, ferric oxide red oxide (E 172) 0.05.

1 tablet of 100 mg contains:

Core: active substance: quetiapine fumarate (quetiapine hemifumarate) 115.13 (equivalent to quetiapine 100); Excipients: lactose monohydrate 18.00, calcium hydrophosphate dihydrate 10.00, microcrystalline cellulose 75.87, povidone 5.00, sodium carboxymethyl starch (type A) 20.00, magnesium stearate 6.00.

Film Sheath: hypromellose 5.00, titanium dioxide (E 171) 1.85, macrogol-4000 1.00, iron dye oxide yellow (E 172) 0.15.

1 tablet of 150 mg contains:

Core: active substance: quetiapine fumarate (quetiapine hemifumarate) 172.69 (equivalent to quetiapine 150); Excipients: lactose monohydrate 27.00, calcium hydrophosphate dihydrate 15.00, microcrystalline cellulose 113.81, povidone 7.50, sodium carboxymethyl starch (type A) 30.00, magnesium stearate 9.00.

Film sheath: hypromellose 7.50, titanium dioxide (E 171) 3.00, macrogol-4000 1.50.

1 tablet 200 mg contains:

Core:active substance: quetiapine fumarate (quetiapine hemifumarate) 230.26 (equivalent to quetiapine 200); Excipients: lactose monohydrate 36.00, calcium hydrophosphate dihydrate 20.00, microcrystalline cellulose 151.74, povidone 10.00, sodium carboxymethyl starch (type A) 40.00, magnesium stearate 12.00.

Film sheath: hypromellose 10.00, titanium dioxide (E 171) 4.00, macrogol-4000 2.00.

1 tablet 300 mg contains:

Core: active substance: quetiapine fumarate (quetiapine hemifumarate) 345.39 (equivalent to quetiapine 300); Excipients: lactose monohydrate 54.00, calcium hydrophosphate dihydrate 30.00, microcrystalline cellulose 227.61, povidone 15.00, sodium carboxymethyl starch (type A) 60.00, magnesium stearate 18.00.

Film Sheath: hypromellose 15.00, titanium dioxide (E 171) 6.00, macrogol-4000 3.00.

Description:

Pills 25 mg. Round, biconvex tablets, covered with a film coat of a brownish-red color, with a bevel.

Type of tablet on a cross-section: a white rough surface with a shell of a brownish-red color.

Tablets 100 mg. Round, biconvex tablets, covered with a film coating of light yellow color.

Type of tablet on a cross-section: a white rough surface with a cover of light yellow color.

Tablets 150 mg. Round, biconvex tablets, covered with a film shell of white color, with a bevel.

Type of tablet on a cross-section: a white rough surface with a cover of white color.

Tablets 200 mg. Round, biconvex tablets, covered with a film coat of white color.

Type of tablet on a cross-section: a white rough surface with a cover of white color.

Tablets 300 mg. Oval, biconvex tablets, covered with a film shell of white color.

Type of tablet on a cross-section: a white rough surface with a cover of white color.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.04 Quetiapine

Pharmacodynamics:

Mechanism of action

Quetiapine is an atypical antipsychotic drug that exhibits a higher affinity for the receptors of serotonin (5HT2) than for dopamine receptors D1 and D2 of the brain. Quetiapine has an affinity for histamine and alpha-1 receptors, and a lower affinity for alpha-2 receptors. There was no significant affinity for quetiapine for cholinergic muscarinic and benzodiazepine receptors. In standard tests quetiapine has antipsychotic activity.

Pharmacodynamic effects

The results of the study of extrapyramidal symptoms (EPS) in animals revealed that quetiapine causes a weak catalepsy in a dose effectively blocking dopamine D2 receptors. Quetiapine causes a selective decrease in the activity of mesolimbic A10-dopaminergic neurons, in comparison with A9-nigrostriate neurons involved in motor functions.

Clinical efficacy

There was no difference between quetiapine (75-750 mg / day) and placebo in the incidence of extrapyramidal symptoms and concomitant use of anticholinergic drugs.

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

Quetiapine has long maintained clinical improvement in those patients who had a positive effect at the very beginning of treatment.

The duration of action of quetiapine on the receptors of 5HT2-serotonin and D2-dopamine receptors is less than 12 hours after taking the drug.

Pharmacokinetics:

Absorption is high, food intake does not affect bioavailability. The connection with plasma proteins is 83%.

The pharmacokinetics of quetiapine is linear and does not differ between men and women.

It is actively metabolized in the liver with the formation of pharmacologically inactive metabolites under the influence of the enzyme CYP3A4 cytochrome P450. Quetiapine and some of its metabolites are weak inhibitors of isoenzymes 1A2, 2C9, 2C19, 2D6 and 3A4 of human cytochrome P450, but only in concentrations at least 10-50 times higher than the drug concentration when applied in the effective dose range of 300 to 450 mg / day.

Based on the results in vitro, it should not be expected that simultaneous administration of quetiapine with other drugs will lead to a clinically pronounced inhibition of cytochrome P450 mediated metabolism of other drugs.

The half-life (T1 / 2) is approximately 7 hours.

It is excreted by the kidneys approximately 73% and through the intestines - 21%.Less than 5% of quetiapine is not metabolized and is excreted unchanged. The average clearance of quetiapine in elderly patients is 30-50% less than in patients aged 18 to 65 years. Mean clearance of quetiapine plasma in patients with severe renal insufficiency (creatinine clearance <30 mL / min / 1.73 m²) was reduced by approximately 25% and in patients with liver damage (stabilized alcoholic cirrhosis).

Indications:

- Treatment of acute and chronic psychoses, including schizophrenia;

- treatment of manic episodes in bipolar disorder.

Contraindications:

- Hypersensitivity to quetiapine or other components of the drug;

- the period of breastfeeding;

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

Carefully:

Patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, congenital increase in the interval QT on an electrocardiogram (ECG) or in the presence of conditions potentially capable of causing an increase in the interval QT (simultaneous administration of drugs that extend the interval QT, congestive heart failure, hypokalemia, hypomagnesemia), advanced age, hepatic insufficiency, epilepsy, convulsive fits in the anamnesis, pregnancy.

Pregnancy and lactation:

The safety and effectiveness of quetiapine in pregnant women have not been established. Therefore, during pregnancy quetiapine It can only be used if the expected benefit justifies the potential risk. The degree of excretion of quetiapine with mother's milk is not established. Women should be advised to avoid breastfeeding while taking quetiapine.

Dosing and Administration:

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

Treatment of acute and chronic psychoses, including schizophrenia

The daily dose for the first 4 days is: 1st day - 50 mg; The second day - 200 mg; The third day - 200 mg and the 4th day - 300 mg. Starting from the fourth day, the daily dose is recommended: 300 mg. Depending on the clinical effect and the tolerability of the drug, its dose can individually vary from 150 mg / day to 750 mg / day. The maximum daily dose for the treatment of schizophrenia is 750 mg.

Treatment of manic episodes with bipolar disorder

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

The daily dose for the first 4 days is: 1st day - 100 mg; 2nd day - 200 mg; The third day - 300 mg and the 4th day - 400 mg. An increase in the daily dose in the future is possible at 200 mg per day and by the 6th day of therapy is 800 mg. Depending on the clinical effect and the tolerability of the drug, its dose can individually vary from 200 mg / day to 800 mg / day. As a rule, the effective dose is from 400 to 800 mg / day. The maximum daily dose for this indication is 800 mg.

Elderly age

Because the plasma clearance of quetiapine in elderly people is reduced by 30-50%, the drug should be prescribed with caution, especially at the beginning of therapy. The starting dose is 25 mg / day, followed by an increase of 25-50 mg until the effective dose is reached.

Renal and hepatic impairment

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

Side effects:

Classification of the incidence of adverse events (WHO): 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), including individual messages.

On the part of the organs of hematopoiesis and lymphatic system: often - leukopenia; infrequently - eosinophilia; very rarely - neutropenia.

Metabolic and nutritional disorders: often - weight gain (mainly in the first weeks of treatment); very rarely - hyperglycemia or decompensation of diabetes mellitus.

From the central and peripheral nervous system: Often - dizziness, drowsiness, headache; often syncopal states; infrequently - anxiety, agitation, insomnia, akathisia, tremor, convulsions, depression, paresthesia; very rarely: tardive dyskinesia.

From the side of the cardiovascular system: often - tachycardia, orthostatic arterial hypotension, lengthening of the interval QT on the ECG.

On the part of the respiratory system: rhinitis, pharyngitis.

From the gastrointestinal tract: often - dry mouth, constipation, diarrhea, indigestion; rarely - jaundice, nausea, vomiting, abdominal pain; very rarely - hepatitis. Allergic reactions: infrequently - skin rash, hypersensitivity reactions; very rarely - angioedema, Stevens-Johnson syndrome.

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

Other: often - peripheral edema, asthenia; rarely - back pain, chest pain, subfebrile condition, myalgia, dry skin, decreased vision, antipsychotic malignant syndrome (hyperthermia, impaired consciousness, muscle rigidity, vegetative-vascular disorders, increase in the concentration of creatine phosphokinase).

Laboratory indicators: often - increased serum transaminase levels (ACT or ALT); infrequently - increase of serum GGT level and triglyceride content (not on an empty stomach), hypercholesterolemia; decrease in thyroid hormone levels: total T₄ and free T₄ (in the first 4 weeks), as well as the general T₃ and reversible T₃ (only when taking high doses of quetiapine).

Overdose:

Data on quetiapine overdose are limited. Cases of quetiapine administration in a dose exceeding 30 g are described. In most patients, side effects were not observed, but in cases of their development, side effects were treated independently. A case of a lethal outcome was registered with the intake of 13.6 grams of quetiapine. Very rarely reported cases of overdose with quetiapine, which led to lengthening of the interval QT, coma or death.In patients with severe cardiovascular disease in history, the risk of side effects in overdose may increase.

Symptoms: excessive sedation, drowsiness, tachycardia, lowering blood pressure.

Treatment: symptomatic; activities aimed at maintaining the function of respiration, cardiovascular system, adequate oxygenation and ventilation of the lungs. There are no specific antidotes.

Interaction:

Quetiapine does not induce induction of liver enzyme systems involved in metabolism phenazone and lithium.

Simultaneous administration of quetiapine with drugs potentially inhibiting hepatic enzymes, such as carbamazepine or phenytoin, as well as with barbiturates, rifampicin, it is possible to reduce plasma concentrations of quetiapine, which may require an increase in the dose of Quentiaks, depending on the clinical effect. This should also be taken into account when removing phenytoin or carbamazepine, or another inducer of the liver enzyme system or replacing with a drug that does not induce microsomal liver enzymes (for example, valproic acid).

The main enzyme responsible for the metabolism of quetiapine cytochrome P450 is CYP3A4. The pharmacokinetics of quetiapine does not change with the simultaneous use of both cimitidine (inhibitor P450) or fluoxetine (inhibitor CYP3A4 and CYP2D6), an antidepressant imipramine (inhibitor CYP2D6).

It is advisable to use caution while using quetiapine and systemic use of inhibitors CYP3A4 (antifungal agents of the azole group and macrolide antibiotics), since plasma concentrations of quetiapine may increase. Therefore, lower doses of quetiapine should be used. Particular attention should be paid to the elderly and weakened patients.

The pharmacokinetics of quetiapine did not change significantly with simultaneous administration with antipsychotic agents - risperidone or haloperidone. However, simultaneous administration of quetiapine with thioridazine led to an increase in the clearance of quetiapine.

Medicines, oppressing the central nervous system (CNS), and ethanol increase the risk of side effects.

Special instructions:

With a sharp cancellation of high doses of antipsychotic drugs, the following acute reactions ("withdrawal syndrome") - nausea, vomiting, rarely insomnia. Cases of exacerbation of psychotic symptoms and the appearance of involuntary motor disorders (akathisia, dystonia, dyskinesia) have been reported, and therefore it is recommended to gradually phase out the drug.

In the appointment of quetiapine at the same time from drugs that extend the interval QT, care must be taken, especially in the elderly. With congestive heart failure, with hypokalemia and hypomagnesemia.

Given that quetiapine affects the central nervous system, the drug should be used with caution in combination with other drugs that have an inhibitory effect on the central nervous system.

It is recommended to refrain from drinking alcohol.

When symptoms appear tardive dyskinesia should reduce the dose or stop using quetiapine.

Convulsive seizures

In controlled clinical trials, there was no difference in the incidence of seizures between quetiapine and placebo. However, as with other antipsychotics, caution should be exercised in the treatment of patients withconvulsive attacks in the anamnesis.

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, instability of the autonomic nervous system, increase in the level of creatine phosphokinase. With the development of this syndrome quetiapine should be canceled and the appropriate treatment performed.

Effect on the ability to drive transp. cf. and fur:During treatment with quetiapine, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Film-coated tablets of 25 mg, 100 mg, 150 mg, 200 mg and 300 mg.

Packaging:

For 10 tablets in a blister (contour squamous packaging).

3, 6 or 9 blisters (contour mesh packages) together with instructions for use in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005227/09

Date of registration:30.06.2009

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp18.11.2013

Illustrated instructions

Instructions

Quentiax® (Kventiax®)