Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Antipsychotic agent (antipsychotic). Has a higher affinity for serotonin 5HT 2 receptors, compared with dopamine D 1 - and D 2 receptors in the brain. Has also a high affinity for histamine and? 1 receptors and less pronounced - k? 2 receptors. Has no affinity for m-holinoretseptoram and benzodiazepine receptors.
Quetiapine in a dose effectively blocking dopamine D 2 receptors causes only weak catalepsy. Selectively reduces the activity of mesolimbic A 10 -dopamine neurons compared to A 9 -nigrostriatal neurons involved in motor function.
Does not cause a prolonged increase in the level of prolactin.
In accordance with the results of positron emission tomography, the action of quetiapine on serotonin 5HT 2 - and dopamine D 2 -receptors continues up to 12 hours.
PHARMACOKINETICS
After oral administration, it is well absorbed from the digestive tract. Eating does not significantly affect the bioavailability of quetiapine.
The pharmacokinetics of quetiapine is linear.
Binding to plasma proteins is about 83%.
Exposed to intensive metabolism. In vitro studies found that the key enzyme of quetiapine metabolism is CYP3A4. The main metabolites, determined in 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 intestine. Approximately 73% of metabolites are excreted by the kidneys and 21% by the intestine. The average clearance of quetiapine in elderly patients is 30-50% less than that observed in patients aged 18 to 65 years.
The mean plasma clearance of quetiapine was approximately 25% less in patients with severe renal impairment (QC less than 30 ml / min / 1.73 m 2 ) and in patients with liver damage (alcohol cirrhosis in the compensation stage), but individual clearance rates were within , corresponding to healthy people.
INDICATIONS
Acute and chronic psychoses (including schizophrenia).
DOSING MODE
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 can be 150-750 mg / day.
In patients with impaired liver and / or kidney function, the initial dose is 25 mg / day. Daily dose increase should be 25-50 mg until optimal effect is achieved.
SIDE EFFECT
From the side of the central nervous system: headache, drowsiness, dizziness, anxiety; rarely - ZNS.
From the cardiovascular system: orthostatic hypotension, tachycardia, arterial hypertension.
From the digestive system: constipation, dry mouth, dyspepsia, diarrhea, transient increase in liver enzymes (ALT, AST, GGT), abdominal pain.
From the hematopoiesis: asymptomatic leukopenia and / or neutropenia; rarely - eosinophilia.
From the musculoskeletal system: myalgia.
From the respiratory system: rhinitis.
Dermatological reactions: skin rash, dry skin.
From the side of the organ of hearing: pain in the ear.
From the genitourinary system: infection of the urinary tract.
From the side of metabolism: a slight increase in the content of 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 T 4 ).
Other: asthenia, low back pain, weight gain, fever, chest pain.
CONTRAINDICATIONS
Hypersensitivity to quetiapine.
PREGNANCY AND LACTATION
In pregnancy and lactation, the application is possible in cases where the expected benefit to the mother exceeds the potential risk to the fetus. It is not known whether quetiapine is excreted in breast milk. If it is necessary to use lactation, breastfeeding should be discontinued.
In experimental animal studies, no mutagenic and clastogenic effects of quetiapine were identified. There was no evidence of quetiapine's influence on fertility (reduced male fertility, pseudopregnancy, an increase in the period between two estrus, an increase in the precoital interval and a decrease in the frequency of pregnancy), but one can not directly transfer the obtained data to humans. there are specific differences in the hormonal control of reproduction.
APPLICATION FOR FUNCTIONS OF THE LIVER
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.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Quetiapine is subject to active metabolism in the liver. In patients with impaired hepatic function, quetiapine clearance is reduced by approximately 25%. Therefore, quetiapine should be used with caution in patients with impaired hepatic function.
APPLICATION IN ELDERLY PATIENTS
Use with caution in the elderly, especially with the simultaneous use of drugs that extend the QT interval.
SPECIAL INSTRUCTIONS
Use with caution in patients with cardiovascular diseases and other conditions associated with risk of hypotension, especially at the beginning of treatment and in the elderly; with instructions in an anamnesis for seizures.
Quetiapine is subject to active metabolism in the liver. In patients with impaired liver and kidney function, quetiapine clearance is reduced by approximately 25%.Therefore, quetiapine should be used with caution in patients with impaired hepatic and / or renal function.
With caution apply simultaneously with drugs that extend the QT interval (especially in the elderly); with drugs that exert a depressant effect on the central nervous system, as well as with ethanol; with potential inhibitors of the isoenzyme CYP3A4 (including with ketoconazole, erythromycin).
When developing against the background of NSA treatment, quetiapine should be discontinued and appropriate treatment should be prescribed.
With prolonged use, there is a chance of developing tardive dyskinesia. In such cases, it is necessary to reduce the dose of quetiapine or to cancel it.
Use with caution in combination with other drugs that affect the activity of the central nervous system, as well as with ethanol.
In experimental studies in the study of the carcinogenicity of quetiapine, there was an increase in the incidence of adenocarcinoma of the mammary gland in rats (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 adenomas from thyroid follicular cells, which was associated with a known, rodent-specific mechanism for increasing hepatic clearance of thyroxin.
Impact on the ability to drive vehicles and manage mechanisms
Quetiapine can cause drowsiness, so patients are not recommended to perform work related to the need for concentration of attention and high speed of psychomotor reactions (including driving).
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 with phenytoin, carbamazepine, barbiturates, rifampicin, the clearance of quetiapine increases, and its concentration in the blood plasma decreases.
With simultaneous use with thioridazine, the clearance of quetiapine may be increased.
