Ketilept coated pills 200mg N60
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Active ingredients
Quetiapine
Release form
Pills
Composition
Quetiapine fumarate 230.26 mg,; which corresponds to the content of quetiapine 200 mg; Auxiliary substances: microcrystalline cellulose, lactose monohydrate, sodium carboxymethyl starch (type A), povidone, magnesium stearate, anhydrous colloidal silicon dioxide, anhydrous.; , macrogol 4000, triacetin (triacetylglycerol), iron dye yellow oxide, iron dye red oxide.
Pharmacological effect
Antipsychotic drug (neuroleptic). It exhibits a higher affinity for serotonin 5-HT2 receptors than for dopamine D1 and D2 receptors in the brain. It also has a higher affinity for histamine and 1-adrenergic receptors and less in relation to 2-adrenergic receptors. No detectable affinity of quetiapine for m-choline and benzodiazepine receptors was found. In standard tests, quetiapine exhibits antipsychotic activity. The results of a study of extrapyramidal symptoms (EPS) in animals revealed that quetiapine causes a weak catalepsy at a dose that effectively blocks dopamine D2-receptors that inhibit D2-receptors effectively blocking D-receptors. ; Quetiapine causes a selective decrease in the activity of mesolimbic A10 dopaminergic neurons in comparison with A9 by nigrostriatal neurons involved in motor function. During a clinical study (At a dose of 75-750 mg / day) did not reveal differences between the use of quetiapine and placebo in the incidence of cases of EPM and concomitant use of anticholinergic drugs;. Quetiapine does not cause prolonged increase prolactin concentration in the blood plasma. In numerous studies with a fixed dose, there were no differences in the concentration of prolactin when using quetiapine or placebo. In clinical studies, quetiapine showed efficacy in the treatment of both positive and negative symptoms of schizophrenia.; The effects of quetiapine on 5-HT2 and D2 receptors continue up to 12 h after taking the drug.
Pharmacokinetics
Absorption; When ingested, quetiapine is well absorbed from the gastrointestinal tract. Eating does not significantly affect the bioavailability of quetiapine.; Distribution; Plasma protein binding - approximately 83%; Metabolism; Quetiapine is extensively metabolized in the liver.It has been established that CYP3A4 is a key enzyme for the CYP-mediated metabolism of quetiapine.; The main metabolites found in plasma do not have pronounced pharmacological activity. Quetiapine and some of its metabolites have a weak inhibitory activity against the isoenzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, but only at a concentration 10-50 times higher than the concentration observed at the usual effective dose of 300-450 mg / day. ; T1 / 2 is about 7 hours. Approximately 73% of quetiapine is excreted in the urine and 21% in the feces. Less than 5% of quetiapine is not metabolized and excreted unchanged by the kidneys or feces; Pharmacokinetics in special clinical situations; The average plasma clearance of quetiapine is approximately 25% less in patients with severe renal failure (CC less than 30 ml / min / 1.73 m2) and in patients with liver damage (stabilized alcoholic cirrhosis), but individual clearance values are within the range of healthy people. In a study of the pharmacokinetics of quetiapine in various dosages when prescribing quete Iapina before taking ketoconazole or simultaneously with ketoconazole resulted in an increase in average Cmax and AUC of quetiapine by 235% and 522%, respectively, and also resulted in a decrease in clearance of quetiapine by an average of 84%. T1 / 2 of quetiapine increased, but the average time to reach Cmax did not change. Based on the results of in vitro, one should not expect the simultaneous administration of quetiapine with other drugs will lead to a clinically pronounced inhibition of the CYP-mediated metabolism of other drugs.; The average clearance of quetiapine in elderly patients are 30–50% less than in patients aged from 18 to 65.; Quetiapine pharmacokinetics is linear, there are no differences in pharmacokinetic parameters in men and women.
Indications
- acute and chronic psychosis, including schizophrenia; - treatment of manic episodes in the structure of bipolar disorder; - treatment of depressive episodes of moderate to severe severity in the structure of bipolar disorder.
Contraindications
- pregnancy; - lactation period (breastfeeding); - children's age (efficacy and safety have not been established); - Hypersensitivity to the components of the drug. With caution, use the drug in patients with liver failure, convulsive seizures in history, cardiovascular and cerebrovascular diseases or other conditions that predispose to arterial hypotension; in elderly patients.
Use during pregnancy and lactation
Category C. The safety and efficacy of quetiapine during pregnancy has not been established.; Use of the drug Ketilept during pregnancy is possible only when the intended benefits to the mother outweigh the potential risk to the fetus. It is not known whether quetiapine is secreted in breast milk. If necessary, the use of the drug Ketilept during lactation (breastfeeding) should decide on the termination of breastfeeding.
Dosage and administration
Ketilept should be taken orally, regardless of the meal.; Adults with acute and chronic psychosis, including schizophrenia, are prescribed the drug twice a day. The total daily dose in the first 4 days of therapy is 50 mg (1st day), 100 mg (2nd day), 200 mg (3rd day) and 300 mg (4th day). Starting from the 4th day, the usual effective daily dose of Ketilept is from 300 mg to 450 mg. Depending on the clinical effect and tolerance in each patient, the dose can be adjusted (varied) from 150 mg to 750 mg / day. The maximum recommended daily dose of 750 mg. For the treatment of acute manic episodes in the structure of bipolar disorder, the drug is prescribed 2 times / day. The total daily dose in the first 4 days of therapy is 100 mg (1st day), 200 mg (2nd day), 300 mg (3rd day) and 400 mg (4th day). Further selection of the dose up to 800 mg / day by the 6th day is possible with an increase of no more than 200 mg / day. Depending on the clinical response and tolerability in each patient, the dose can be selected in the range of 200 mg to 800 mg / day; the usual effective dose is in the range from 400 to 800 mg / day; the maximum recommended daily dose is 800 mg; For the treatment of depressive episodes in the structure of bipolar disorder, the drug is prescribed 1 time per day for the night. The daily dose in the first 4 days of therapy is 50 mg (1st day), 100 mg (2nd day), 200 mg (3rd day) and 300 mg (4th day). The recommended dose is 300 mg / day. The maximum recommended daily dose is 600 mg.; Maintenance therapy; To maintain remission, it is advisable to use the lowest dose. Patients should be periodically examined to determine the need for maintenance therapy.; Resuming interrupted treatment in patients who have previously received quetiapine: With resumption of therapy less than 1 week after discontinuation of Ketilept, the drug can be continued at a dose adequate for maintenance therapy.When resuming therapy in patients who have not received Ketilept for more than 1 week, the initial dose selection rules should be followed and an effective dose should be established according to the patient's clinical response. The recommended initial dose in elderly patients is 25 mg / day, then the dose should be increased by 25-50 mg / day to achieve an effective dose, which is usually lower than in younger patients. Similarly, more careful dose selection and reduced doses are recommended for debilitated patients or those predisposed to antihypertensive reactions. Patients with renal and hepatic insufficiency are advised to start therapy with 25 mg / day, then daily increase the dose to 25-50 mg to achieve an effective dose depending on the patient's clinical response and individual tolerance.; The efficacy and safety of quetiapine in children and adolescents has not been established.
Side effects
The most common side effects of quetiapine are drowsiness, dizziness, dry mouth, moderate asthenia, constipation, tachycardia, orthostatic hypotension and dyspepsia. According to the summary data of clinical studies, the number of patients who stopped taking the drug due to side effects is approximately the same in the groups receiving placebo and quetiapine. As with other antipsychotics, fainting, neuroleptic malignant syndrome, leukopenia, neutropenia, and peripheral edema are noted while taking quetiapine. 1/10); often (less than 1/10 and> 1/100); infrequently (less than 1/100 and> 1/1000); rarely (less than 1/1000); very rarely (less than 1/10 000); From the hemopoietic system: often - leukopenia3; infrequently - eosinophilia; very rarely - neutropenia3.; On the part of the metabolism: often - an increase in body mass4, an increase in serum transaminases (ALT, ACT) 5; infrequently - increased levels of GGT5, total cholesterol, triglycerides after meals; very rarely - hyperglycemia1,7, diabetes mellitus1,7.; From the nervous system: very often - dizziness1,6, drowsiness2; often - headache, anxiety, psychomotor agitation, tremor, syncope1,6; infrequently - epileptic seizures 1.; From the side of the cardiovascular system: often - tachycardia1,6,orthostatic hypotension1,6.; On the part of the respiratory system: often - rhinitis, pharyngitis. On the part of the digestive system: often - dry mouth, constipation, diarrhea, dyspepsia, abdominal pain.; On the part of the reproductive system: rarely - priapism .; Allergic reactions: sometimes - hypersensitivity.; Other: often - mild asthenia, peripheral edema; lower back pain, chest pain, low-grade fever, myalgia, dry skin, decreased visual acuity; rarely, malignant neuroleptic syndrome. 1; 1 See the Specific Instructions section.; 2 Drowsiness is possible, especially during the first 2 weeks of the course of treatment, which usually takes place with continued use of the drug Ketilept. 3 No steady-state cases have been observed in controlled clinical studies of quetiapine severe neutropenia or agranulocytosis. During the observation period after the registration of the drug, leukopenia and / or neutropenia passed after stopping the administration of quetiapine. Potential risk factors for leukopenia and / or neutropenia include a pre-existing decrease in the number of white blood cells and a history of drug leukopenia and / or neutropenia.; 4 An increase in body weight is mainly observed during the first weeks of treatment.; 5 Some patients use quetiapine an asymptomatic increase in the activity of serum transaminases (ALT, ACT) or GGT, which usually occurs with continued treatment with quetiapine.; 6 Like other antipsychotics with alpha1-adreno-blocking s activity Ketilept can cause orthostatic hypotension with dizziness, tachycardia and (in some patients) syncope, particularly in the initial dose titration period;. 7 In very rare cases during quetiapine marked hyperglycemia, and worsening of pre-existing diabetes mellitus.
Overdose
Data on quetiapine overdose is limited. Symptoms: drowsiness, excessive sedation, tachycardia, decreased blood pressure. Extremely rare cases of quetiapine overdose have been reported, resulting in death or coma. Treatment: There is no specific antidote for quetiapine. Symptomatic therapy and measures aimed at maintaining the respiratory function, cardiovascular system, ensuring adequate oxygenation and ventilation are carried out. Medical observation should be continued until the patient is completely cured.
Interaction with other drugs
Particular caution is required when prescribing Ketilept in combination with other drugs acting on the CNS. In vitro results showed that quetiapine and its 9 metabolites in vivo are weak inhibitors of metabolic processes mediated by cytochrome P450 isoenzymes (1A2, 2C9, 2C19, 2D6 and 3A4). CYP3A4 is the main enzyme that mediates P450-mediated Quetiapine metabolism.; The effect of other drugs on Ketilept; Phenytoin: the simultaneous use of Ketilept with phenytoin leads to an increase in clearance of Quetiapine in plasma, because Phenytoin induces isoenzyme 3A4 cytochrome P450. The combination of quetiapine (250 mg 3 times / day) and phenytoin (100 mg 2 times / day) increased the average clearance of quetiapine 5 times after ingestion.; For the correction of symptoms of schizophrenia in patients receiving quetiapine and phenytoin at the same time, increased doses of Ketilept or other inducers of liver enzymes (including carbamazepine, barbiturates, rifampicin, GCS). In these cases, caution is required when discontinuing phenytoin and / or switching to valproate, which does not possess enzyme-inducing properties. Carbamazepine: simultaneous use of the drug Ketilept with carbamazepine significantly increases the clearance of quetiapine, which leads to a decrease in systemic exposure to quetiapine. Due to this interaction, it may be necessary to use higher doses of the drug Ketilept.; Inhibitors of CYP3A: simultaneous use of the drug Ketilept with ketoconazole (200 mg / day for 4 days), a strong inhibitor of the isoenzyme TIR3A, reduces the clearance of quetiapine after oral administration by 84%, As a result, Quetiapine plasma levels rise, on average, by 235%. Care must be taken when combining Ketilept with ketoconazole and other inhibitors of isoenzymes of the cytochrome P450 system, antifungal drugs from the azole group, and antibiotics from the macrolide group (including itraconazole, fluconazole, erythromycin); the dose of quetiapine should be reduced accordingly.; Cimetidine: daily regular administration of cimetidine (400 mg 3 times / day for 4 days), which is a nonspecific enzyme inhibitor, led to a 20% reduction in the average clearance of quetiapine (150 mg 3 times / day) from the plasma after oral administration.With simultaneous use of the drug Ketilept with cimetidine there is no need to change the dose of the first.; Thioridazine: thioridazine (200 mg 2 times / day) increased the clearance of quetiapine (300 mg 2 times / day) by 65% after ingestion; Risperidon and haloperidol: simultaneous use of quetiapine (300 mg 2 times / day) with the antipsychotic agent haloperidol (7.5 mg 2 times / day) or risperidone (3 mg 2 times / day) did not change the pharmacokinetics of quetiapine in an equilibrium state.; Fluoxetine and imipramine : simultaneous use of quetiapine (300 mg 2 ra a / d) with antidepressant and CYP3A4 and CYP2D6 inhibitor fluoxetine (60 mg 1 time / day) or the known CYP2D6 inhibitor imipramine (75 mg 2 times / day) did not change the equilibrium pharmacokinetics of quetiapine; Effect of Ketilept on other drugs; Antipyrine: repeated daily administration of quetiapine (up to 750 mg / day with a 3-fold dose) did not cause clinically significant changes in clearance of the antipyrine or its metabolites. This suggests that quetiapine does not have a significant inhibitory effect on hepatic enzymes involved in the metabolism of cytochrome P450-mediated antipyrine.; Lithium: simultaneous use of quetiapine (250 mg 3 times / day) with lithium did not affect any pharmacokinetic parameters lithium in equilibrium.; Lorazepam: the average clearance of lorazepam after oral administration (single dose of 2 mg) decreased by 20% while taking quetiapine (250 mg 3 times / day); Smoking did not affect the clearance of quetiapine from blood plasma .; Poskol ku clinical studies have demonstrated that quetiapine potentiate the cognitive and motor effects of ethanol in patients with psychosis, one should not drink alcohol during the course of treatment Ketilept.
special instructions
Cardiovascular diseases; Ketilept should be used with caution in patients with diagnosed cardiovascular diseases, vascular diseases of the brain or other conditions predisposing to arterial hypotension; Ketilept may cause orthostatic hypotension, especially in the initial period of dose adjustment; this occurs more often in the elderly than in younger patients. There is no relationship between Quetiapine and an increase in the QTc interval.However, when prescribing quetiapine at the same time as drugs prolonging the QТc interval, caution should be exercised, especially in elderly patients. Convulsive seizures; There are no differences in the incidence of seizures in patients taking Ketilept or placebo. However, just as with other antipsychotic medications, caution is advised when treating patients with a history of convulsive seizures.; Tardive dyskinesia; Ketilept, like other antipsychotics, can cause tardive dyskinesia with long-term use. In the event of signs and symptoms of tardive dyskinesia, the issue of dose reduction or drug withdrawal should be considered.; Malignant neuroleptic syndrome; Malignant neuroleptic syndrome may be associated with ongoing antipsychotic treatment. Clinical manifestations of the syndrome include hyperthermia, altered mental status, muscular rigidity, instability of the autonomic nervous system, increased levels of CPK. In such cases, Ketilept should be discontinued and appropriate treatment carried out.; Sudden withdrawal reactions; Acute withdrawal symptoms (including nausea, vomiting, insomnia) are described in very rare cases after abrupt cessation of antipsychotic drugs in high doses. Recurrence of symptoms of psychosis and the appearance of disorders associated with involuntary movements (akathisia, dystonia, dyskinesia) are possible. Therefore, if it is necessary to stop taking the drug, a gradual reduction of the dose is recommended.; Lactose intolerance; When drafting a diet for patients with lactose intolerance, it should be noted that pills coated with a film 25 mg, 100 mg, 150 mg, 200 mg and 300 mg contain lactose, respectively 4.42 mg, 17.05 mg, 25.47 mg, 34.1 mg and 50.94 mg. The drug should not be prescribed to patients with rare hereditary disorders of tolerance to galactose, hereditary deficiency of lactase lapp or glucose-galactose absorption disorder syndrome. Considering that quetiapine mainly affects the central nervous system, the drug should be used with caution in combination with other drugs which have a depressant effect on the central nervous system, or alcohol. A link has been established between the use of quetiapine in low doses and a decrease in thyroid hormone levels (T4 and free T4). The maximum reduction occurred during the first 2 or 4 weeks of quetiapine, but with a long course of treatment there was no further reduction.In almost all cases, discontinuation of quetiapine resulted in the restoration of T4 and free T4 levels, regardless of the duration of the course of treatment. A less significant decrease in T3 and reverse T3 was observed only with the use of quetiapine in higher doses. Levels of TSH and TSH (thyroxin-binding globulin) remained unchanged. Clinically pronounced hypothyroidism is not detected.; Like other antipsychotics, quetiapine may cause prolongation of the QTc interval, but this effect was not permanent in clinical trials. Therefore, in the first stages of treatment, for an individually determined period of time, the patient should be prohibited from driving a motor vehicle or dangerous machinery. In the future, the degree of restrictions is set individually.