Quentiax Table 25mg №60

pharmachologic effect

Antipsychotic (neuroleptic). Shows higher affinity for serotonin 5HT₂-receptors, compared with dopamine D₁- and D₂receptors in the brain. It also has a high affinity for histamine and α₁-receptors and less pronounced - to α₂-receptors. Does not possess affinity to m-cholinergic receptors and benzodiazepine receptors.

Quetiapine in a dose that effectively blocks dopamine D₂receptors, causes only weak catalepsy. Selectively reduces the activity of mesolimbic A₁₀dopamine neurons compared to A₉-nigrostriatal neurons involved in motor function.

Does not cause prolonged increase in prolactin levels.

According to the results of positron emission tomography, Quetiapine acts on serotonin 5HT₂- and dopamine D₂receptors lasts up to 12 hours

Pharmacokinetics

After ingestion is well absorbed from the gastrointestinal tract. Eating does not have a significant effect on the bioavailability of quetiapine.

The pharmacokinetics of quetiapine is linear.

Plasma protein binding is about 83%.

Subjected to intensive metabolism. In vitro studies have established that CYP3A4 is a key enzyme in the metabolism of quetiapine.The major metabolites, which are detected in the blood plasma, do not have a pronounced pharmacological activity.

T_1/2 is about 7 hours. Less than 5% of quetiapine is excreted unchanged by the kidneys or through the intestines. Approximately 73% of metabolites excreted by the kidneys and 21% through the intestines. The average clearance of quetiapine in elderly patients is 30-50% less than that observed in patients aged 18 to 65 years.

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

Indications

Acute and chronic psychoses (including schizophrenia).

Dosing regimen

When used in adults, the initial dose is 50 mg / day, for elderly patients - 25 mg / day. Then the dose is gradually increased according to the scheme. Depending on the clinical effect and individual sensitivity, the effective therapeutic dose may be 150-750 mg / day.

In patients with impaired liver and / or kidney function, the initial dose is 25 mg / day. Daily dose increases should be 25-50 mg to achieve optimal effect.

Side effect

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

Cardiovascular: orthostatic hypotension, tachycardia, arterial hypertension.

Gastrointestinal: constipation, dry mouth, dyspepsia, diarrhea, transient increase in liver enzymes (ALT, AST, GGT), abdominal pain.

From the side of blood-forming organs: asymptomatic leukopenia and / or neutropenia; rarely eosinophilia.

Musculoskeletal system: myalgia.

Respiratory: rhinitis.

Dermatologic: skin rash, dry skin.

From the organ of hearing: earache.

From the genitourinary system: urinary tract infection.

On the part of metabolism: a slight increase in cholesterol and triglycerides in the blood.

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

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

Contraindications

Hypersensitivity to quetiapine.

Use during pregnancy and lactation

In 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 no mutagenic and clastogenic effects of quetiapine were detected in animals. No effect of quetiapine on fertility (reduced male fertility, pseudo-pregnancy,an increase in the period between two estrus, an increase in the precoital interval and a decrease in the frequency of the onset of pregnancy), however, it is impossible to directly transfer the data to a person, because There are specific differences in the hormonal control of reproduction.

Application for violations of the liver

Quetiapine undergoes active metabolism 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 violations of kidney 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.

Use in elderly patients

With caution used in the elderly, especially with simultaneous use of drugs that extend the QT interval.

special instructions

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

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

With caution used simultaneously with drugs that extend the QT interval (especially in the elderly); with drugs that have a depressant effect on the central nervous system, as well as with ethanol; with potential inhibitors of an isoenzyme CYP3A4 (including with Ketoconazole, erythromycin).

With the development during the treatment of ZNS, quetiapine should be canceled and appropriate treatment should be prescribed.

With prolonged use, there is a likelihood of tardive dyskinesia. In such cases, you must reduce the dose of quetiapine or cancel it.

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

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

In male rats (250 mg / kg / day) and mice (250 and 750 mg / kg / day), there was an increase in the incidence of benign thyroid follicular cell adenomas, which was associated with the well-known rodent-specific mechanism for increasing thyroid clearance of thyroxine.

Influence on ability to drive motor transport and control mechanisms

Quetiapine may cause drowsiness, so patients are not recommended to perform work related to the need for concentration and high-speed psychomotor reactions (includingdrive vehicles).

Drug interaction

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 of phenytoin, Carbamazepine, barbiturates, rifampicin, the clearance of quetiapine increases, its concentration in blood plasma decreases.

With simultaneous use with thioridazine may increase the clearance of quetiapine.