Composition, form of production and packaging
Tablets, film-coated 1 tab.
quetiapine 200 mg
10 pieces. - packings cellular planimetric (3) - packs cardboard.
Tablets, film-coated 1 tab.
quetiapine 100 mg
10 pieces. - packings cellular planimetric (3) - packs cardboard.
Tablets, film-coated 1 tab.
quetiapine 150 mg
10 pieces. - packings cellular planimetric (3) - packs cardboard.
Tablets, film-coated 1 tab.
quetiapine 25 mg
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (6) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
PHARMACHOLOGIC EFFECT
Quetiapine is an atypical antipsychotic drug that exhibits a higher affinity for serotonin (hydroxytryptamine) receptors (5HT 2 ) than for the dopamine receptors D 1and D 2 of the brain. Quetiapine also has a more pronounced affinity for histamine and alpha 1- adrenoreceptors and less for alpha 2- adrenoreceptors. There was no significant affinity for quetiapine for muscarinic and benzodiazepine receptors. In standard tests, quetiapine displays antipsychotic activity.
PHARMACOKINETICS
When administered orally, quetiapine is well absorbed from the digestive tract and is actively metabolized in the liver. The main metabolites in the plasma do not have a pronounced pharmacological activity.
The intake of food does not significantly affect the bioavailability of quetiapine. T 1/2 is about 7 hours. Approximately 83% of quetiapine binds to plasma proteins.
The pharmacokinetics of quetiapine is linear, there is no difference in pharmacokinetic parameters in men and women.
The average clearance of quetiapine in elderly patients is 30-50% less than in patients aged 18 to 65 years.
The average plasma clearance of quetiapine is less than approximately 25% in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min / 1.73 m 2 ) and in patients with liver damage, but interindividual clearance rates are within the range corresponding to healthy volunteers. Approximately 73% of quetiapine is excreted in urine and 21% with feces. Less than 5% of quetiapine is not metabolized and is excreted unchanged by kidneys or feces. It was found that CYP3A4 is the key isoenzyme of quetiapine metabolism, mediated by cytochrome P450.
In a quetiapine pharmacokinetics study at a different dose, the use of quetiapine prior to administration of ketoconazole or concomitantly with ketoconazole resulted in an increase in mean C max and area under the concentration-time curve (AUC) of quetiapine by 235% and 522%, respectively, the decrease in clearance of quetiapine, on average, by 84%. T 1/2 of quetiapine increased, but T max did not change.
Quetiapine and some of its metabolites have weak inhibitory activity against cytochrome P450 1A2, 2C9, 2C19, 2D6 and 3A4 isoenzymes, but only at concentrations 10-50 times higher than the concentrations observed at the usual effective dose of 300-450 mg / day.
Based on in vitro results, simultaneous use of quetiapine with other drugs should not be expected to result in clinically significant inhibition of cytochrome P450-mediated metabolism of other drugs.
INDICATIONS
- Acute and chronic psychoses, including schizophrenia;
- Manic episodes in the structure of bipolar disorder.
DOSING MODE
Adults:
Acute and chronic psychoses, including schizophrenia
The daily dose for the first 4 days of therapy is: the 1st day - 50 mg, the second day - 100 mg, the third day - 200 mg, the 4th day - 300 mg. Starting from the 4th day, the dose should be selected up to a clinically effective dose, which usually ranges from 300 to 450 mg / day. Depending on the clinical effect and individual tolerability, the dose can vary from 150 to 750 mg / day.
Treatment of manic episodes in the structure of bipolar disorder
Quetiapine is used as a monotherapy or as adjuvant therapy for mood stabilization.
The daily dose for the first 4 days of therapy is: 1st day - 100 mg, Day 2 - 200 mg, Day 3 - 300 mg, Day 4 - 400 mg. In the future, by the 6th day of therapy, the daily dose of the drug can be increased to 800 mg. An increase in the daily dose should not exceed 200 mg per day.
Depending on the clinical effect and individual tolerability, the dose may vary from 200 to 800 mg / day. Usually the effective dose is from 400 to 800 mg / day.
For the treatment of schizophrenia, the maximum recommended daily dose of quetiapine is 750 mg, for the treatment of manic episodes in the structure of bipolar disorder the maximum recommended daily dose of quetiapine is 800 mg / day.
In elderly patients, the initial dose of quetiapine is 25 mg / day. The dose should be increased daily by 25-50 mg until an effective dose is obtained, which is likely to be less than in young patients.
In patients with renal or hepatic insufficiency, it is recommended to start quetiapine therapy with 25 mg / day. It is recommended to increase the dose daily by 25-50 mg until the effective dose is reached.
SIDE EFFECT
The most common adverse reactions associated with taking the drug: drowsiness (17.5%), dizziness (10%), constipation (9%), dyspepsia (6%), orthostatic hypotension and tachycardia (7%), dry mouth (7% ), an increase in the activity of "hepatic" enzymes in the blood serum (6%), an increase in the concentration of cholesterol and triglycerides in the blood plasma.
The intake of quetiapine may be accompanied by the development of moderate asthenia, rhinitis and dyspepsia, an increase in body weight (mainly in the first weeks of treatment). Quetiapine can cause orthostatic hypotension (accompanied by dizziness), tachycardia and in some patients - fainting; these adverse reactions mainly occur during the initial period of dose selection (see section "Special instructions"). Quetiapine therapy is associated with a small dose-dependent decrease in the concentration of thyroid hormones, in particular, total T4 and free T4. The maximum decrease in total and free T4 was recorded at the 2nd and 4th week of quetiapine therapy, without further reduction in the concentration of hormones in long-term treatment. Thereafter, there were no signs of clinically significant changes in the concentration of thyroid-stimulating hormone.
With prolonged use of quetiapine, there is a potential for the development of tardive dyskinesia. If symptoms of tardive dyskinesia occur, reduce the dose or stop further treatment with quetiapine. With a sharp cancellation of high doses of antipsychotic drugs, the following acute reactions (withdrawal syndrome) can occur: nausea, vomiting, rarely - insomnia.
There are cases of exacerbation of psychotic symptoms and the appearance of involuntary motor disorders (akathisia, dystonia, dyskinesia). In connection with this, it is recommended to gradually phase out the drug.
The following are the adverse reactions observed with the use of quetiapine and distributed among organs and systems:
From the nervous system : drowsiness, dizziness, headache, anxiety, asthenia, hostility, agitation, insomnia, akathisia, tremor, convulsions, depression, paresthesia, malignant neuroleptic syndrome (hyperthermia, muscle rigidity, changes in mental status, lability in the autonomic nervous system, increased activity of creatine phosphokinase), restless legs syndrome.
From the cardiovascular system: orthostatic hypotension, tachycardia, prolongation of the QT interval.
On the part of the digestive system: dryness of the oral mucosa, nausea, vomiting, abdominal pain, diarrhea or constipation, increased activity of "liver" transaminases, jaundice, hepatitis.
On the part of the respiratory system: pharyngitis, rhinitis.
Allergic reactions: to an internal rash, eosinophilia, angioedema, Stevens-Johnson syndrome, anaphylactic reactions.
Laboratory indicators: leukopenia, neutropenia, hypercholesterolemia, hypertriglyceridemia, decrease in T4 concentration (the first 4 weeks), hyperglycemia.
Other: back pain, chest pain, subfebrile condition, weight gain (mainly in the first weeks of treatment), myalgia, dry skin, impaired vision, incl. blurred vision, decompensation of existing diabetes, priapism, galactorrhea.
CONTRAINDICATIONS
- hypersensitivity to any of the components of the drug;
- simultaneous administration with inhibitors of CYP3A4, such as HIV protease inhibitors, azole antifungal drugs, erythromycin, clarithromycin, nefazodone;
- children's age till 18 years;
lactation period.
Use with caution in patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension; in old age; with hepatic insufficiency; convulsive seizures in the anamnesis; pregnancy.
PREGNANCY AND LACTATION
Use with caution in pregnancy. Contraindicated during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with renal insufficiency, it is recommended to start quetiapine therapy with 25 mg / day. It is recommended to increase the dose daily by 25-50 mg until the effective dose is reached.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with hepatic insufficiency , quetiapine therapy with 25 mg / day is recommended. It is recommended to increase the dose daily by 25-50 mg until the effective dose is reached.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
In elderly patients, the initial dose of quetiapine is 25 mg / day. The dose should be increased daily by 25-50 mg until an effective dose is obtained, which is likely to be less than in young patients.
SPECIAL INSTRUCTIONS
Quetiapine can cause orthostatic hypotension, especially in the initial period of dose selection (in elderly patients it is observed more often than in young patients).There was no correlation between the intake of quetiapine and the increase in QT with the -interval. However, when applying quetiapine concomitantly with drugs that extend the interval of QT c , care must be taken, especially in the elderly. During treatment with a decrease in the number of neutrophils less than 1000 / ОјL, quetiapine should be discontinued.
With the development of orthostatic hypotension against the background of drug treatment, it is necessary to reduce the dose or more slowly to titrate doses. The drug is not indicated for the treatment of psychoses associated with dementia. If the symptoms of tardive dyskinesia develop, the dose of the drug should be reduced or gradually canceled. Symptoms of tardive dyskinesia may increase or even appear after discontinuation of the drug.
In the case of malignant neuroleptic syndrome, the drug should be withdrawn.
Given that quetiapine mainly affects the central nervous system, the drug should be used with caution in combination with other drugs that depress the central nervous system, or alcohol. In children, adolescents and young people (under 24 years) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when assigning Quetiapine or any other antidepressants in children, adolescents and young people (younger than 24 years), the risk of suicide and the benefits of their use should be correlated. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. Any depressive disorder in itself increases the risk of suicide. Therefore, during treatment with antidepressants, all patients should be monitored for early detection of abnormalities or behavioral changes, as well as suicidal tendencies.
Impact on the ability to drive vehicles and manage mechanisms
Quetiapine can cause drowsiness, so during treatment, patients are advised to refrain from driving motor vehicles and engage in activities that require increased concentration and speed of psychomotor reactions.
OVERDOSE
Data on quetiapine overdose are limited. Cases of quetiapine have been reported in a dose exceeding 20 g, without fatal consequences and with complete recovery, but there are reports of extremely rare cases of quetiapine overdose leading to death or coma.
Symptoms may be due to the increase in known pharmacological effects of the drug, such as drowsiness and excessive sedation, tachycardia, and lowering blood pressure.
Treatment: There are no specific antidotes to quetiapine. In cases of overdose, gastric lavage may be possible (after intubation, if the patient is unconscious), taking activated charcoal and laxatives to excrete unabsorbed quetiapine, however, the effectiveness of these measures has not been studied. Symptomatic therapy and measures aimed at maintaining the function of respiration, cardiovascular system, providing adequate oxygenation and ventilation are shown. Medical supervision and surveillance should be continued until the patient is fully recovered.
DRUG INTERACTION
With the simultaneous use of drugs that have a potent inhibitory effect on the isoenzyme CYP3A4 (such as antifungal agents of the azole group and erythromycin, clarithromycin, nefazodone), the concentration of quetiapine in the plasma is increased, so the simultaneous administration of them with quetiapine is contraindicated.With simultaneous use of quetiapine with preparations inducing the liver enzyme system, such as carbamazepine, a decrease in the plasma concentration of the drug is possible, which may require an increase in the dose of quetiapine, depending on the clinical effect. In a study of the pharmacokinetics of quetiapine in various doses, when applied before or simultaneously with carbamazepine (inducer of hepatic enzymes) led to a significant increase in the clearance of quetiapine. This increase in quetiapine clearance reduced the AUC by an average of 13% compared with the use of quetiapine without carbamazepine. The simultaneous use of quetiapine with another inducer of microsomal liver enzymes - phenytoin, also led to an increase in clearance of quetiapine. With the simultaneous use of quetiapine and phenytoin (or other inducers of hepatic enzymes such as barbiturates, rifampicin), an increase in the dose of quetiapine may be required. It may also be necessary to reduce the dose of quetiapine when the phenytoin or carbamazepine or other inducer of the liver enzyme system is abolished or replaced with a drug that does not induce microsomal liver enzymes (eg, valproic acid).
The pharmacokinetics of lithium preparations does not change with the simultaneous use of quetiapine.
Quetiapine did not induce the induction of hepatic enzyme systems involved in the metabolism of antipyrine. The pharmacokinetics of quetiapine does not change significantly with simultaneous use with antipsychotic drugs - risperidone or haloperidol. However, simultaneous administration of quetiapine and thioridazine led to increased clearance of quetiapine. CYP3A4 is a key enzyme involved in cytochrome P450-mediated quetiapine metabolism. The pharmacokinetics of quetiapine does not change significantly with simultaneous use of cimetidine, which is an inhibitor of P450.
The pharmacokinetics of quetiapine did not change significantly with the simultaneous use of imipramine (CYP2D6 inhibitor) or fluoxetine (CYP3A4 and CYP2D6 inhibitor). Drugs that oppress the central nervous system, and ethanol increase the risk of side effects of quetiapine.
TERMS AND CONDITIONS OF STORAGE
Keep out of reach of children, dry, protected from light at a temperature of no higher than 25 В° C.
Shelf life - 2 years.
