Description and instructions for "Seroquel, TBL p / o 200mg № 60"

Pharmacological action

Nejroleptik. Shows a more high affinity to serotonin 5HT2-receptors, in comparison with the dopamine D1 and D2-receptors in the brain. Also has a high affinity to histamine and a1-adrainoretseptoram and less active in relation to the a2-adrainoretseptoram. Has no affinity for m-choline receptor and benzodiazepine receptors.
Showed antipsychotic activity in standard tests.
The results of the study of extrapiramidale symptoms in animals have revealed that quetiapine causes only weak catalepsy at the exposure dose, effectively blocking dopamine D2-receptors. Quetiapine selectively reduces the activity of the mesolimbic dopamine A10-neurons compared with A9-nigrostrialnymi neurons involved in motor function, and shows minimal tendency to violate tone in neuroleptic sensitive monkeys.
The results of three placebo-controlled clinical studies, including one using a dose of Seroquel in the range 75-750 mg / day, revealed no differences between Seroquel and placebo in the frequency of occurrence of extrapiramidale symptoms, and concurrent use of antiholinergicakih drugs.
Seroquel does not cause long-increase the level of prolactin. In numerous studies with a fixed dose revealed no differences in the levels of prolactin when using Seroquel or placebo.
In clinical research has demonstrated the effectiveness of Seroquel in the treatment of positive and negative symptoms of schizophrenia. In one study with chlorpromazine and two studies with haloperidol, Seroquel showed similar short-term effectiveness.
Clinical studies have shown that Seroquel is effective in receiving 2 times / day. According to positron emission tomography impact of quetiapine on 5HT2-and D2-receptors continues until 12 hours.

The Pharmacokinetics Of

Absorption
After oral application of quetiapine well absorbed.
Eating does not significantly affect the bioavailability of quetiapine.
The Distribution Of
Quetiapine approximately 83% bound to plasma proteins.
The pharmacokinetics of quetiapine is linear, and there are differences between men and women.
Metabolism
Actively metabolized.
The studies in vitro, it was established that a key enzyme metabolism of quetiapine is CYP3A4 cytochrome P450.
The main plasma metabolites do not have pronounced pharmacological activity.
Excretion
T1 / 2 is approximately 7 hours. The use of radioactively-labeled quetiapine found that less than 5% of the quetiapine appears unchanged to the kidneys or through the intestines. Approximately 73% of the drug metabolites excreted by the kidneys and 21% - through the intestine.
Pharmacokinetics in special clinical cases
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 less than 25% in patients with severe renal dysfunction (creatinine clearance less than 30 ml/min/1.73 m2) and in patients with liver (alcoholic cirrhosis in the stage of compensation), but individual levels of clearance were within corresponding to healthy people.

Indications

- Acute and chronic psychosis (including schizophrenia).

The dosage

Seroquel should be taken two times per day, regardless of the meal.
Daily dose for adults during the first 4 days of therapy is: 50 mg (day 1), 100 mg (day 2), 200 mg (day 3), 300 mg (4-th day). Starting from the 4 th day dose should titrate up to usually effective dosage, ranging from 300 to 450 mg / day. Depending on the clinical effect and individual tolerance of the patient, the dose can vary from 150 to 750 mg / sut.
Seroquel should be used with caution in the elderly, especially in the initial period of therapy. For older patients initial dose of Seroquel should be 25 mg / day. The dose should be increased daily by 25 to 50 mg to achieve an effective dose, which is likely to be less than in younger patients.
The safety and effectiveness of Seroquel in children and adolescents have not been investigated.
In patients with impaired liver or kidney function therapy Seroquel should begin with a dose of 25 mg / day. The dose should be increased daily by 25 to 50 mg to achieve an effective dose.

Side effect

Listed below are the adverse reactions that were encountered in patients taking Seroquel in the placebo-controlled studies, more often than when receiving placebo.
On the part of the organism as a whole: headache (19.4%), asthenia (3.5%), abdominal pain (3.1%), pain (2%), weight gain (2%), fever (1.6%), pain in chest (1.8%).
From CNS: drowsiness (17.5%), dizziness (9.6%), anxiety (3.1%).
From the cardiovascular system: orthostatic hypotension (7.1%), tachycardia (7.1%), hypertension (1.8%).
From the digestive system: constipation (8.6%), dry mouth (6.5%), dyspepsia (6.3%), diarrhea (2%), increased activity of hepatic transaminases (ALT 6.1%, ACT 3.5%, GGT 1.6%), which yourself back to the original values ​​while continuing treatment Seroquel.
On the part of hematopoiesis: prostate leukopenia and / or neutropenia (1.6%); rarely - eosinophilia.
From the musculoskeletal system: myalgia (1.2%).
From the respiratory system: rhinitis (3.3%).
From the skin: rash (4.3%), dryness (1.2%).
On the part of the organ of hearing: a pain in the ear (1.2%).
On the part of the genitourinary system: urinary tract infections (1.4%).
Adverse reactions encountered when receiving Seroquel with equal to or from a lower frequency compared with placebo, included pain, infection, accidental injury, nausea, vomiting, agitation, depression, insomnia, nervousness, hostility, akathisia, tremor, convulsions, paresthesia, hypertension, hypotension, pharyngitis, the weakening of view.
In addition, there were reports of rare cases of malignant neuroleptic syndrome (NMS) during the reception of Seroquel.
During treatment Seroquel there was a small rise in the level of cholesterol and serum triglycerides.
In the period of treatment Seroquel observed a slight dose-dependent decrease in thyroid hormone level, in particular, total and free T4. The maximum reduction of the total and free T4 were registered on 2-nd and 4-th week of therapy with quetiapine, without further reduction of the level of hormones in long-term care. There was no evidence of clinically significant changes in the concentration of thyroid-stimulating hormone. In almost all cases, the level of total and free T4 returned to the original after the cessation of therapy Seroquel, regardless of the duration of treatment.
Seroquel, like other antipsychotic medications, can cause lengthening of the interval QT, but in clinical trials did not reveal the relationship between taking Seroquel and permanent elongation of the interval QT.

Contraindications

- Hypersensitivity to any component of the drug.

Pregnancy and lactation

Studies on the safety and effectiveness of Seroquel in pregnant women were not conducted. Thus, Seroquel can be used during pregnancy only if the expected benefits of the drug justifies the potential risk.
The extent to which the quetiapine is secreted by a woman's milk is not known. In case of need destination of Seroquel in the period of lactation should stop breastfeeding.
In experimental studies did not reveal mutagenic, clastogenic or tertogennogo action of quetiapine.
In experimental animal studies revealed the influence of quetiapine on fertility (reduced male fertility, pseudopregnant, increase in the period between the two heats, increase prekoitalnogo interval and reduced frequency of occurrence of pregnancy), but you cannot directly transfer the data obtained in person, because there are specific differences in hormonal control of reproduction.

Special instructions

Caution must be exercised in the appointment of Seroquel patients with cardiovascular disease or other conditions predisposing to hypotension, because. Seroquel may cause orthostatic hypotension, especially in the initial period of selection of the dose that older patients is observed more often than the young. Caution should be exercised in the appointment of quetiapine at the same time with drugs that prolong the QT interval, especially in the elderly.
The clearance of quetiapine in the oral is reduced by approximately 25% in patients with impaired renal or hepatic function. Quetiapine actively metabolized in the liver and, thus, should be used with caution in patients with impaired liver function.
In controlled clinical studies there were no differences in the frequency of development of seizures in patients taking Seroquel or a placebo. However, we recommend caution when therapy for patients with convulsive seizures in history.
Seroquel should be cautious to appoint, in combination with other drugs affecting the activity of the central nervous system, as well as with ethanol.
The occurrence of NMS may be associated with the antipsychotic treatment. Clinical manifestation of the syndrome include: hyperthermia, altered mental status, muscle rigidity, autonomic instability of the nervous system, increasing the level of CPK. In such cases, Seroquel should be lifted and carried out the appropriate treatment.
The long reception of Seroquel could potentially be the cause of psoriasis later. If the symptoms of psoriasis later appeared, it is necessary to reduce the dose or stop further treatment Seroquel.
The results of experimental studies
In a study of carcinogenicity in rats (dose of 0, 20, 75 and 250 mg / kg / day) was observed increase in the frequency of breast cancer patients at all doses, which is associated with prolonged hyperprolactinemia.
In male rats (250 mg / kg / day) and mice (250 and 750