KVENTIAKS

Active material: Quetiapine
When ATH: N05AH04
CCF: Antipsychotic drug (anxiolytic)
ICD-10 codes (testimony): F20, F21, F22, F23, F25, F29, F30, F31
When CSF: 02.01.02.04
Manufacturer: Krka-RUS LTD (Russia)

Pharmaceutical form, composition and packaging

Pills, Film-coated brownish-red, round, lenticular, chamfered.

Excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, microcrystalline cellulose, povidone, sodium carboxymethyl starch (Type A), magnesium stearate.

The composition of the shell: gipromelloza, Titanium dioxide (E171), macrogol 4000, dye iron oxide yellow (E172), iron oxide red dye (E172).

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.

Pills, Film-coated light yellow, round, lenticular.

Excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, microcrystalline cellulose, povidone, sodium carboxymethyl starch (Type A), magnesium stearate.

The composition of the shell: gipromelloza, Titanium dioxide (E171), macrogol 4000, dye iron oxide yellow (E172).

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.

Pills, Film-coated white, round, lenticular, chamfered.

Excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, microcrystalline cellulose, povidone, sodium carboxymethyl starch (Type A), magnesium stearate.

The composition of the shell: gipromelloza, Titanium dioxide (E171), macrogol 4000.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.

Pills, Film-coated white, round, lenticular.

Excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, microcrystalline cellulose, povidone, sodium carboxymethyl starch (Type A), magnesium stearate.

The composition of the shell: gipromelloza, Titanium dioxide (E171), macrogol 4000.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.

Pills, Film-coated white, Oval, lenticular.

Excipients: lactose monohydrate, calcium hydrogen phosphate dihydrate, microcrystalline cellulose, povidone, sodium carboxymethyl starch (Type A), magnesium stearate.

The composition of the shell: gipromelloza, Titanium dioxide (E171), macrogol 4000.

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.

Pharmacological action

Antipsychotic drug (anxiolytic). Quetiapine is an atypical antipsychotic, which exhibits higher affinity for serotonin 5HT₂-Receptor, than for the dopamine D₁– and D₂-brain receptors. Quetiapine has affinity for histamine and α₁-adrenoceptor, and a lower affinity to α₂-adrenoceptor. There were no appreciable affinity for muscarinic cholinergic quetiapine and benzodiazepine receptors.

The standard tests quetiapine shows antipsychotic activity.

Results of the study of extrapyramidal symptoms in animals revealed, that quetiapine causes weak catalepsy in a dose, effectively blocking the dopamine D₂-receptors. Quetiapine is a selective decrease in the activity-A10 mesolimbic dopaminergic neurons, in comparison with the A9 nigrostriatal neurons,, involved in motor function.

There were no differences between the quetiapine (dose 75-750 mg / day) and placebo in the incidence of cases of extrapyramidal symptoms and concomitant use of anticholinergic drugs. There is no long-term increase of the concentration of prolactin in the blood plasma.

Quetiapine prolonged support clinical improvement in patients, whose positive effect developed at the beginning of treatment.

The duration of exposure of quetiapine on serotonin 5HT₂-and dopamine receptors and D₂-receptors is less than 12 h after dosing.

Pharmacokinetics

Absorption and distribution

Absorption – high, eating does not affect the bioavailability of. Plasma protein binding – 83%.

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

Metabolism

Extensively metabolized in the liver with the formation of pharmacologically inactive metabolites under the influence of CYP3A4. Quetiapine and several of its metabolites are weak inhibitors of isozymes 1A2, 2C9, 2C19, 2D6 and 3A4 human cytochrome P450, but only at concentrations of, least, in 10-50 times the concentration of the drug when used in the range of effective doses 300 to 450 mg / day.

Based on in vitro, not be expected to, that co-administration of quetiapine with other drugs will result in clinically significant inhibition of cytochrome P450 mediated metabolism of other drugs.

Deduction

T_1/2 approximately 7 no. Report the news about 73% and through the intestine – 21%. Less 5% Quetiapine is not metabolized and excreted unchanged.

Pharmacokinetics in special clinical situations

The average clearance of quetiapine in elderly patients 30-50% less, than in patients between the ages of 18 to 65 years.

The average plasma clearance of quetiapine in patients with severe renal insufficiency (creatinine clearance < 30 ml / min / 1.73 m³) and in patients with liver disease (stable alcoholic cirrhosis) reduced by about 25%.

Testimony

- Treatment of acute and chronic psychoses, including schizophrenia;

- Treatment of manic episodes in bipolar disorder.

Dosage regimen

The drug is prescribed inside, 2 times / day, regardless of the meal.

At treatment of acute and chronic psychoses, including schizophrenia, daily dose in the first 4 day is: 1-Day – 50 mg; 2-Day – 200 mg; 3-Day – 200 mg and 4th day – 300 mg. Starting from 4th day, daily dose is 300 mg. Depending on the clinical effect and tolerability of the dose may vary individually from 150 mg / day to 750 mg / day. The maximum daily dose for the treatment of schizophrenia – 750 mg.

At the treatment of manic episodes in bipolar disorder quetiapine is recommended as monotherapy or as adjunctive therapy to mood stabilization.

The daily dose in the first 4 day is: 1-Day – 100 mg; 2-Day – 200 mg; 3-Day – 300 mg and 4th day – 400 mg. Increasing daily dose may subsequently by 200 mg / day to 6 Day care is 800 mg. Depending on the clinical effect and tolerability of the dose may vary individually from 200 mg / day to 800 mg / day. Usually, effective dose ranges from 400 mg 800 mg / day. The maximum daily dose – 800 mg.

Unnecessarily. plasma clearance of quetiapine in elderly patients reduced by 30-50%, prescribed the drug with caution, especially early in treatment. The starting dose – 25 mg / day, followed by an increase of 25-50 mg to achieve effective dose.

In Patients with kidney and liver failure It recommended to start therapy with 25 mg / day. In the future, it is recommended to increase the dose daily 25-50 mg to achieve effective dose.

Side effect

Classification of the incidence of side effects (WHO): Often (> 1/10), often (> 1/100, < 1/10), infrequently (> 1/1000, < 1/100), rarely (>1/10 000, < 1/1000), rarely (< 1/10 000, including isolated reports).

From the hematopoietic system: often – leukopenia; infrequently – eozinofilija; rarely – neutropenia.

Part of the central and peripheral nervous system: very often - dizziness, drowsiness, headache; often – syncope; infrequently – anxiety, excitation, insomnia, akathisia, tremor, convulsions, depression, paresthesia; rarely – neuroleptic malignant syndrome (hyperthermia, disturbance of consciousness, muscle rigidity, vegetative-vascular disorders, an increase concentrations of CPK); rarely – pozdnyaya dyskinesia.

Cardio-vascular system: often – tachycardia, orthostatic hypotension, QT prolongation on the ECG.

The respiratory system: rhinitis, pharyngitis.

From the digestive system: often – dry mouth, constipation, diarrhea, dyspepsia, increase in serum transaminases (ACT или АЛТ); rarely – jaundice, nausea, vomiting, abdominal pain; rarely – hepatitis.

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

On the part of the reproductive system: rarely – priapism.

On the part of the endocrine system: often – weight gain (particularly in the first weeks of treatment); rarely – hyperglycemia or diabetes decompensation.

Laboratory findings: infrequently – Increases in serum levels of GGT and triglycerides (non-fasting), hypercholesterolemia; reduction in thyroid hormone (the total T4 and free T4 / in the first 4 Week /, as well as total T3 and rT3 / Only high doses of quetiapine /).

Other: often – peripheral edema, asthenia; rarely – lower back pain, chest pain, subfebrilitet, myalgia, xerosis, caligation.

Contraindications

- Breastfeeding;

- Children and adolescents up to 18 years (efficacy and safety have not been established);

- Hypersensitivity to quetiapine or other ingredients.

FROM caution should be prescribed to patients with cardiovascular and cerebrovascular disease, or other conditions, predisposing to hypotension, congenital QT prolongation on the ECG or in the presence of conditions, potential to cause QT prolongation (co-administration of drugs, prolonging the QT interval, congestive heart failure, kaliopenia, gipomagniemiya), hepatic failure, epilepsy, seizures in history, pregnancy, elderly patients.

Pregnancy and lactation

The safety and efficacy of quetiapine in pregnant women have not been established. Therefore, pregnancy can be applied only quetiapine, if the expected benefit justifies the potential risk.

The degree of excretion of quetiapine with mother's milk is not installed. Women should be advised to avoid breast-feeding while taking quetiapine.

Cautions

When abrupt cancellation of high doses of antipsychotic drugs may experience the following severe reactions (withdrawal) – nausea, vomiting, rarely insomnia. Cases of exacerbation of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia). In this connection,, abolition of the drug is recommended to gradually.

In the appointment of quetiapine together with drugs, prolonging the QT interval, Care must be taken, especially in elderly patients, congestive heart failure, hypokalemia and hypomagnesemia.

Considering, quetiapine that affect the central nervous system, the drug must be used with caution in combination with other drugs, having a depressing effect on the central nervous system. It is recommended to abstain from alcohol.

When symptoms of tardive dyskinesia should reduce the dose or discontinue the use of quetiapine.

In controlled clinical trials there was no difference found in the incidence of seizures between quetiapine and placebo. But, as well as in the treatment of other antipsychotics, It recommended caution in patients with the presence of a history of seizures.

Neuroleptic malignant syndrome may be associated with the ongoing antipsychotic treatment. The clinical manifestations of the syndrome include: hyperthermia, altered mental status, muscle rigidity, volatility of the autonomic nervous system, an increase CPK urovnja. With the development of this syndrome, quetiapine should be discontinued and appropriate treatment.

Effects on ability to drive vehicles and management mechanisms

During treatment with quetiapine is recommended to be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Overdose

Data on overdose of quetiapine limited. There are cases of receiving quetiapine, exceeding 30 g. In most patients, side effects are not observed, in the case of their own side effects were. Joined case of death while taking 13.6 Mr. quetiapine. Very rarely reported cases of overdose with quetiapine, leads to a lengthening of the QT interval, coma or death. In patients with severe cardiovascular disease history of the risk of side effects may increase in overdose.

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

Treatment: symptomatic therapy, Events, aimed at maintaining respiratory function, Cardiovascular, adequate oxygenation and ventilation. No specific antidote.

Drug Interactions

Quetiapine does not cause induction of the liver enzyme systems, involved in the metabolism of phenazone and lithium.

Co-administration of quetiapine with drugs, potentially inhibiting liver enzymes, Taki how carbamazepine or phenytoin, as well as with barbiturates, rifampicin, may reduce plasma concentrations of quetiapine, which may require increased doses Kventiaksa, depending on the clinical effect. It is also necessary to consider the abolition of phenytoin or carbamazepine, or any other inducer of liver enzyme system or replace the drug, non-inducing hepatic microsomal enzymes (eg, valproic acid).

The main enzyme, responsible for the metabolism of quetiapine, является изофермент CYP3A4. The pharmacokinetics of quetiapine does not change while the application of cimetidine (P450 inhibitor), fluoxetine (inhibitor of CYP3A4 and CYP2D6) or antidepressant imipramine (inhibitor of CYP2D6).

It is recommended to exercise caution while quetiapine and systemic administration of inhibitors of CYP3A4 (azole antifungals and macrolide antibiotics), tk. plasma concentrations of quetiapine may increase. Therefore it is necessary to use lower doses of Quetiapine. Particular attention should be given to the elderly and debilitated patients.

The pharmacokinetics of quetiapine were not significantly altered when administered simultaneously with antipsychotics – risperidone or haloperidol. However, concomitant use of quetiapine with thioridazine led to increased clearance of quetiapine.

Drugs, CNS depressants, and ethanol increases the risk of side effects.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, at a temperature no higher than 30 ° C. Shelf life – 2 year.

Do not use the medication after the expiration date.