Instructions for use SEROQUEL
Caution is required when prescribing quetiapine to patients with hepatic impairment, especially at the beginning of therapy, since quetiapine is metabolized primarily in the liver.
Seroquel may cause orthostatic hypotension, especially during the initial dose titration period (more common in older patients than in younger patients).
With abrupt withdrawal of high doses of antipsychotic drugs, acute reactions (withdrawal syndrome) may occur - nausea, vomiting; rarely - insomnia.
Cases of exacerbation of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia) have been reported. Therefore, it is recommended to discontinue the drug gradually.
Given that quetiapine primarily affects the central nervous system, quetiapine should be used with caution in combination with other drugs that have a central depressant effect or with alcohol. During the treatment period, patients are not recommended to drink alcohol.
Elderly patients with dementia
Seroquel is not indicated for the treatment of psychoses associated with dementia. Some atypical antipsychotics in randomized placebo-controlled trials increased the risk of cerebrovascular side effects in patients with dementia by approximately 3-fold. The mechanism of this increase has not been studied. This risk cannot be excluded for other antipsychotic medicinal products or other patient groups. Seroquel should be used with caution in patients at risk of stroke.
An analysis of the use of atypical antipsychotics for the treatment of psychosis associated with dementia in elderly patients showed that the increase in mortality in the group of patients receiving quetiapine was comparable to the placebo group. In addition, two 10-week placebo-controlled studies of quetiapine in a similar group of patients (n=710; mean age 83 years; age range 56-99 years) showed that the mortality rate in the group of patients taking quetiapine was 5.5%, and was 3.2% in the placebo group. No causal relationship has been identified between treatment with quetiapine and the risk of increased mortality in older patients with dementia.
Tardive dyskinesia
There were no differences between the groups of patients receiving quetiapine and placebo in the incidence of extrapyramidal symptoms in the range of recommended doses. It can be assumed that Seroquel, to a lesser extent compared with other antipsychotic drugs, leads to tardive dyskinesia. However, if symptoms of tardive dyskinesia develop, it is recommended to reduce the dose of the drug or gradually discontinue it.
QT prolongation
There was no relationship between quetiapine and an increase in the QTc interval. However, in case of overdose, prolongation of the QTc interval is possible. Therefore, when prescribing quetiapine simultaneously with drugs that prolong the QTc interval, caution must be exercised, especially in elderly patients, in the presence of congenital long QTc interval syndrome, with chronic heart failure, cardiac hypertrophy, hypokalemia or hypomagnesemia.
Seizures
There were no differences in the incidence of seizures in patients taking quetiapine or placebo. However, as with other antipsychotic drugs, caution is recommended when treating patients with a history of seizures.
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome may be associated with antipsychotic treatment. Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscle rigidity, lability of the autonomic nervous system, and increased CPK levels. In such cases, Seroquel should be discontinued and appropriate treatment administered.
Acute reactions associated with drug withdrawal
When abruptly stopping high doses of antipsychotic drugs, the following acute reactions (withdrawal syndrome) may occur:
- nausea, vomiting, rarely - insomnia. Cases of exacerbation of psychotic symptoms and the appearance of involuntary movement disorders (akathisia, dystonia, dyskinesia) have been reported. Therefore, it is recommended to discontinue the drug gradually.
Hyperglycemia
Extremely rare cases of hyperglycemia or exacerbation of diabetes mellitus have been reported in patients with a history of diabetes mellitus during therapy with quetiapine. Clinical monitoring of patients with diabetes mellitus and risk factors for the development of diabetes mellitus is recommended.
Extrapyramidal symptoms
Within the recommended therapeutic doses, there was no difference in the incidence of extrapyramidal symptoms in patients with schizophrenia or mania when taking Seroquel compared to placebo. There was an increase in the incidence of extrapyramidal symptoms in patients with bipolar depression when taking Seroquel compared to placebo.
Impact on the ability to drive vehicles and operate machinery
Seroquel may cause drowsiness, so patients are not recommended to work with dangerous mechanisms, incl. Driving a car or other moving vehicles is not recommended.
Seroquel 25 mg 60 pcs. film-coated tablets
pharmachologic effect
Antipsychotic.
It has a higher affinity for serotonin 5HT2 receptors compared to dopamine D1 and D2 receptors in the brain, as well as a high affinity for histamine and alpha1 adrenergic receptors.
Composition and release form Seroquel 25 mg 60 pcs. film-coated tablets
Film-coated tablets - 1 tablet:
- quetiapine (in the form of fumarate) - 25/100/200 mg;
- excipients: povidone; dibasic calcium phosphate dihydrate; MCC; starch (sodium glycolate); lactose monohydrate; magnesium stearate;
- shell composition: red iron oxide (25 mg tablets); iron oxide yellow (25 and 100 mg tablets); titanium dioxide; hydroxypropyl methylcellulose; polyethylene glycol 400.
There are 10 pcs in a blister; in a cardboard pack there are 3 or 6 blisters (25 mg tablets); or in a cardboard pack of 3, 6 or 9 blisters (tablets 100 and 200 mg); or in a cardboard pack 1 blister (6 tablets of 25 mg, 3 tablets of 100 mg and 1 tablet of 200 mg).
Description of the dosage form
The tablet is round, 6 mm in diameter, peach-colored, biconvex, film-coated.
Directions for use and doses
Orally, regardless of meals, 2 times a day.
Adults. The daily dose for the first 4 days of therapy is: on the first day - 50 mg, on the second day - 100 mg, on the third day - 200 mg, on the 4th day - 300 mg. Beginning on day 4, the dose should be titrated to the usually effective dosage, ranging from 300 to 450 mg/day. Depending on the clinical effect and individual patient tolerance, the dose can vary from 150 to 750 mg/day.
Elderly. Like other antipsychotic drugs, Seroquel should be used with caution in the elderly, especially during the initial period of therapy. In elderly patients, the initial dose of quetiapine should be 25 mg per day. The dose should be increased daily by 25 to 50 mg until an effective dose is reached, which is likely to be less than in younger patients.
The safety and effectiveness of quetiapine have not been studied in children and adolescents.
In patients with impaired liver and kidney function, Seroquel therapy should begin with a dose of 25 mg/day. The dose should be increased daily by 25–50 mg until an effective dose is reached.
Pharmacokinetics
83% bound to plasma proteins. T1/2 - about 7 hours. Excreted in urine (73%) and feces (21%) in the form of inactive metabolites. Biotransformed with the participation of cytochrome P450.
Indications for use Seroquel 25 mg 60 pcs. film-coated tablets
Acute and chronic psychoses, including schizophrenia.
Contraindications
Hypersensitivity.
Application of Seroquel 25 mg 60 pcs. film-coated tablets during pregnancy and breastfeeding
Possibly if the expected effect of therapy exceeds the potential risk to the fetus. Breastfeeding should be stopped during treatment.
special instructions
Caution should be exercised when combining with other drugs that have central activity, with alcohol, as well as when combined with potential biotransformation inhibitors - ketoconazole, erythromycin, etc.
Overdose
Symptoms: drowsiness, sedation, tachycardia, hypotension.
Treatment: symptomatic; restoration and control of the patency of the upper respiratory tract, ensuring adequate oxygenation and ventilation, monitoring and maintaining the activity of the cardiovascular system.
Side effects Seroquel 25 mg 60 pcs. film-coated tablets
From the cardiovascular system and blood (hematopoiesis, hemostasis): orthostatic hypotension, hypertension, tachycardia, leukopenia.
From the nervous system and sensory organs: drowsiness, dizziness, anxiety, rarely - neuroleptic malignant syndrome.
Metabolic: increased levels of cholesterol, serum triglycerides, ALT and AST, changes in the level of liver enzymes.
From the gastrointestinal tract: dry mouth, diarrhea or constipation, dyspepsia.
From the skin: rash, dry skin.
Other: pain syndrome (abdominal pain, headache, lower back pain, muscle pain, chest pain, ear pain), asthenia, rhinitis, urinary tract infections, fever, weight gain.
Drug interactions
The effect is weakened by inducers of microsomal liver enzymes (phenytoin, carbamazepine, barbiturates, rifampicin) and thioridazine (increases Cl).
Seroquel tablet p/pl/o 200 mg N60 (AstraZeneca)
Quetiapine is an atypical antipsychotic drug that exhibits higher affinity for serotonin receptors (5HT2) than for dopamine D1 and D2 receptors in the brain. Quetiapine also has a higher affinity for histamine and α1-adrenergic receptors and a lower affinity for α2-adrenergic receptors. No significant affinity of quetiapine for cholinergic muscarinic and benzodiazepine receptors was found. In standard tests, quetiapine exhibits antipsychotic activity. Pharmacodynamic effects Results from studies of extrapyramidal symptoms (EPS) in animals revealed that quetiapine causes mild catalepsy at a dose that effectively blocks dopamine D2 receptors. Quetiapine causes a selective decrease in the activity of mesolimbic A10 dopaminergic neurons compared to A9 nigrostriatal neurons involved in motor function. Clinical efficacy During clinical studies (using Seroquel at a dose of 75-750 mg / day), no differences were found between the use of Seroquel and placebo in the incidence of cases of extrapyramidal symptoms and the concomitant use of anticholinergic drugs. Seroquel does not cause a long-term increase in the concentration of prolactin in the blood plasma. Multiple fixed-dose studies have shown no difference in prolactin levels between quetiapine and placebo. In clinical studies, quetiapine has been shown to be effective in treating both positive and negative symptoms of schizophrenia. The effect of quetiapine on 5HT2 and D2 receptors lasts up to 12 hours after taking the drug. Pharmacokinetics: When administered orally, quetiapine is well absorbed from the gastrointestinal tract and is actively metabolized in the liver. The main metabolites found in plasma do not have pronounced pharmacological activity. Food intake does not significantly affect the bioavailability of quetiapine. The half-life is approximately 7 hours. Approximately 83% of quetiapine is bound to plasma proteins. The pharmacokinetics of quetiapine are linear, there are no differences in pharmacokinetic parameters between men and women. The average clearance of quetiapine in elderly patients is 30-50% less than in patients aged 18 to 65 years. Average plasma clearance Quetiapine is reduced by approximately 25% in patients with severe renal impairment (creatinine clearance less than 30 ml/min/1.73 m2) and in patients with liver damage (stable alcoholic cirrhosis), but individual clearance rates are within the range corresponding to healthy people. Approximately 73 % of quetiapine is excreted in urine and 21% in feces. Less than 5% of quetiapine is not metabolized and is excreted unchanged by the kidneys or feces. It has been established that CYP3A4 is a key enzyme in the metabolism of quetiapine, mediated by cytochrome P450. In a study of the pharmacokinetics of quetiapine at various dosages, when quetiapine was prescribed before taking ketoconazole or simultaneously with ketoconazole, it led to an increase , on average, the maximum concentration (Cmax) and area under the concentration-time curve (AUC) of quetiapine by 235% and 522%, respectively, and also led to a decrease in quetiapine clearance by an average of 84%. The half-life of quetiapine increased, but the mean time to reach maximum concentration (tmax) did not change. Quetiapine and some of its metabolites have weak inhibitory activity against the enzymes cytochrome P450 1A2, 2C9, 2C19, 2D6 and 3A4, but only at a concentration of 10- 50 times higher than the concentrations observed at the commonly used effective dosage of 300-450 mg/day. Based on in vitro results, it should not be expected that the simultaneous administration of quetiapine with other drugs will lead to clinically significant inhibition of cytochrome P450 mediated metabolism of other drugs.
