Azaleptin 25 mg instructions for use. Azaleptin - instructions for use. Release form, composition and packaging

Content

Mental disorders in the structure of diseases of the population of Russia and Europe occupy one of the first places. They not only bring suffering to the patients themselves, but also negatively affect the socio-economic situation. The number of patients diagnosed with schizophrenia runs into the millions. The use of modern antipsychotics is an urgent task of practical psychiatry. Azaleptin significantly outperforms many neuroleptic drugs in terms of effectiveness and is widely used in the treatment of mental disorders.

Instructions for use Azaleptin

The appointment of Azaleptin should take into account many factors of the patient's individual condition, which can only be assessed by a specialist. The dose, according to the instructions, may vary depending on the stage of the disorder and the tolerance of the components of the drug. It is recommended that you carefully read the sections on contraindications, side effects and drug interactions.

Composition and form of release

The drug Azaleptin is available in the form of yellow-greenish flat-cylindrical tablets, the active ingredient of which is clozapine. Tablets are packaged in blisters, which are placed in a cardboard box. The composition of one tablet of the drug:

Pharmacodynamics and pharmacokinetics

Azaleptin tablets are antipsychotics-neuroleptics, derivatives of dibenzodiazepine. They have a sedative effect, do not cause extrapyramidal disorders, do not affect the production of prolactin. The active substance of the composition clozapine belongs to atypical antipsychotics. The action of the drug is based on the blockade of dopamine receptors in the mesolimbic and mesocortical structures of the brain, the removal of aggressiveness, and the effect on dopamine stimulants.

After oral administration, the tablets are rapidly absorbed from the gastrointestinal tract, the substance reaches a maximum concentration in the body after 2.5 hours, and a constant one after 8-10 days of administration. The drug is metabolized during the first passage through the liver, forms metabolites with the participation of cytochrome isoenzymes. The half-life is 8 hours. Excretion occurs through the kidneys and intestines.

Indications for Azaleptin's use

The drug has a high therapeutic efficacy, which leads to a wide range of its use as an antipsychotic agent. Azaleptin is prescribed for:

schizophrenia;
bipolar disorder;
delusional psychoses;
psychopathy;
organic pathologies of the brain;
addictions (drug addiction, alcoholism, substance abuse).

The strong antipsychotic effect of the drug is combined with a pronounced anti-negative and sedative effect. The drug reduces the manifestations of productive disorders, reduces the degree of mental arousal and aggression, reduces the craving for suicide. Azaleptin is able to correct behavioral disorders and alleviate the symptoms of severe psychotic disorders.

Method of application and dosage

Therapy with Azaleptin begins with 25-50 mg and gradually increases the dose to 200-300 per day. The maximum daily dose is 600 mg. The tablets are intended for oral administration. The daily dose should be divided into 2-3 doses, which are carried out after meals. In some cases, according to the doctor's prescription, the daily dose can be taken at one time (before bedtime). After an acceptable therapeutic effect is achieved, maintenance therapy of 25-200 mg is prescribed (let's say a single daily dose in the evening hours).

special instructions

The drug can be used only under the supervision of the attending physician, who, before prescribing treatment and determining the dosage, can prescribe a general blood test, assess the state of the cardiovascular system, liver, kidneys and draw a conclusion about the current state of the patient's health. When correcting the regimen, it must be taken into account that a sharp increase in dose can cause hypotension and an epileptic seizure. The patient should be instructed to report symptoms of myocarditis to the physician, including:

chest pain;
dyspnea;
heartbeat;
weakness.

During treatment with Azaleptin, it is necessary to systematically carry out a blood test for the number of leukocytes and neutrophils in the blood. The first 6 months of treatment, the blood test should be weekly, then (up to a year) - once every two weeks, and after 12 months, the analysis is carried out on a monthly basis. Control of the level of leukocytes is necessary in order to prevent a decrease in their level under the influence of the drug to critical levels. Due to the risk during course treatment of weight gain, it is recommended:

activate lifestyle;
reduce calorie intake.

drug interaction

The simultaneous use of Azaleptin with drugs entails different effects. The most common combinations include:

The combination with antidepressants increases the inhibitory effect on bone marrow hematopoiesis. The drug enhances the anticholinergic effect of the drugs of the same name, reduces the effectiveness of drugs based on sulfonylurea.
The combination with Digoxin, Heparin, Phenytoin, Warfarin increases their plasma concentration. These drugs displace clozapine from protein binding.
The simultaneous use of the drug with valproic acid changes the concentration of clozapine in the blood plasma, but there are no clinical manifestations of the interaction.
The combination with Carbamazepine reduces the concentration of clozapine in plasma, can cause severe pancytopenia, neuroleptic malignant syndrome.
The combination with caffeine increases the concentration of clozapine in the blood, increases the incidence of side effects.
The combination with lithium carbonate can lead to psychosis, myoclonus, delirium, convulsions, neuroleptic malignant syndrome.
The simultaneous use of clozapine with risperidone increases the concentration of the first in the blood, inhibits its metabolism. With the rapid replacement of clozapine with risperidone, dystonia develops.
Rifampicin increases the metabolic rate of Azaleptin.
Phenytoin, gel-like antacids, cholestyramine, norepinephrine, adrenaline lower the concentration of the active substance, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Ciprofloxacin, Cimetidine, Erythromycin increase it, which leads to toxicity.

Azaleptin and alcohol

In combination with drugs that depress the central nervous system (benzodiazepine derivatives), as well as with alcohol and ethanol-containing drugs, the severity and frequency of manifestations of a depressant effect on the central nervous system increase. Possible depression of the respiratory center. Therefore, the drug Azaleptin can not be combined with alcohol and medicines based on it.

Azaleptin side effects

Therapy with Azaleptin sometimes does not go unnoticed. Many patients note its side effects from different body systems. Among them:

fever, drowsiness, tardive dyskinesia, headache, epileptic seizures, agitation, depression, akathisia, restless sleep, confusion, insomnia, tremor, muscle rigidity, anxiety, autonomic disorders, dizziness, fainting, anxiety, increased fatigue;
impulsiveness of actions;
arterial hypertension, arrhythmia, tachycardia, arterial or orthostatic hypotension;
heartburn, nausea, dry mouth, vomiting, increased salivation;
weight gain, increased sweating;
thrombocytopenia, eosinophilia, leukopenia, granulocytopenia, agranulocytosis, cholestasis;
disturbance of accommodation;
constipation;
hyperthermia;
violations of urine production, urination;
myasthenia gravis;
leukocytosis;
decrease in potency.

Overdose

Exceeding the dose of Azaleptin is manifested by depression of consciousness, anxiety, delirious disorders, epileptic seizures. Thermolability, tachycardia, hypotension, collapse may occur. Due to disruption of the heart, intestinal atony and respiratory depression, a fatal outcome is possible. Treatment of poisoning consists in washing the stomach, taking sorbents, supporting respiratory function and heart function. Delayed digestive complications are possible. Dialysis or hemodialysis is ineffective.

Contraindications

Caution should be exercised when prescribing the drug to patients with decompensated heart disease, severe hepatic or renal insufficiency, angle-closure glaucoma, prostatic hyperplasia, intestinal atony, epilepsy. Contraindications for the use of Azaleptin tablets are:

granulocytopenia or agranulocytosis in history;
oppression of bone marrow hematopoiesis;
myasthenia gravis;
respiratory disorders;
coma;
toxic alcoholic psychosis;
pregnancy, lactation;
children's age up to five years;
hypersensitivity to the constituent ingredients.

Terms of sale and storage

Azaleptin is available by prescription. The product is stored in a dark place at temperatures up to 30 degrees for five years.

Analogues

The active ingredient clozapine is also included in other drugs that are substitutes for the agent in question. Azaleptin's analogs:

Azaleptol - tablets with antipsychotic and sedative effects, used to treat schizophrenia;
Azapine - a tablet drug for the treatment of schizophrenia, psychotic disorders in Parkinson's disease;
Clozapine - the closest analogue of tablets, is a generic (it has a cheap price);
Klozasten - sedative tablets used for psychomotor agitation, manic states;
Azaleprol is a neuroprotective and antipsychotic in the form of tablets that eliminate emotional and behavioral disorders;
Leponex - neuroleptic tablets for the treatment of schizophrenia, not amenable to conventional therapy.

Azaleptin price

Azaleptin tablets are found on sale at a cost that is influenced by the concentration of the active substance in the preparation and the pricing policy of pharmacies. It is difficult to buy the drug, it is not presented in every network. Approximate Moscow and St. Petersburg prices.

Azaleptin: instructions for use and reviews

Azaleptin is a drug of a group of antipsychotics. Refers to neuroleptics, has sedative properties. Promotes muscle relaxation, enhances the effect of painkillers and sleeping pills. It has a peripheral and central anticholinergic effect.

Release form and composition

The drug is available in the form of tablets: loskotsilindricheskoy shape, greenish-yellow color (10 pcs. in blister packs and 50 pcs. in dark glass / polymer jars, in a carton box 5 packs or 1 jar and instructions for the use of Azaleptin).

Composition of 1 tablet:

active substance: clozapine (azaleptin) - 25 mg or 100 mg;
excipients: potato starch, calcium stearate, lactose monohydrate (milk sugar).

Pharmacological properties

Pharmacodynamics

Azaleptin is an antipsychotic agent (neuroleptic), which practically does not lead to the development of extrapyramidal disorders. Helps to enhance the action of analgesic and hypnotic drugs.

The main types of pharmacological efficacy of the drug and the mechanisms of action that determine them:

Antipsychotic: associated with blockade of dopamine D 2 receptors of the mesocortical and mesolimbic systems;
Antiemetic: based on the blockade of dopamine D 2 receptors of the trigger zone of the vomiting center;
Sedative: due to blockade of adrenoreceptors of the reticular formation of the brain stem;
Hypothermic: associated with blockade of dopamine receptors in the hypothalamus.

Clozapine also has a peripheral and central m-anticholinergic, α-adrenergic blocking effect. It does not affect the concentration of prolactin in the blood.

The antipsychotic effect of the drug is close to that of aliphatic phenothiazines, while the development of a submelancholic shade and unpleasant subjective sensations is not noted. Reduces the seizure threshold. It has no cataleptogenic effect. It has no effect on higher intellectual functions, practically does not lead to the development of extrapyramidal disorders.

Pharmacokinetics

Clozapine is well absorbed from the gastrointestinal tract. Its bioavailability is in the range of 27–60%. The time to reach the maximum concentration of the substance in the blood is 2.5 hours (from 1 to 6 hours). The average stable equilibrium concentrations are 319 ng / ml (from 102 to 771 ng / ml), they are achieved in 8-10 days. Contacts proteins of a blood plasma at the level of 95%.

In the body, clozapine is distributed rapidly, the accumulation of the substance is noted in the parenchymal organs - in the lungs, liver, kidneys.

The metabolism of clozapine occurs in the liver by the CYH1A2 enzyme system, the metabolites are inactive or have weak activity, they are excreted by the kidneys and with bile (50 and 35%, respectively). The elimination half-life is highly variable: after taking a single dose of 75 mg - 8 hours (from 4 to 12 hours); after taking 2 times a day, 100 mg - 12 hours (from 4 to 66 hours).

Indications for use

Azaleptin is used for the following diseases:

Acute and chronic form of schizophrenia;
Manic states (classic and atypical mania, unproductive mania with delirium);
Affective insanity;
Mental and motor excitement.

Contraindications

Granulocytopenia;
Agranulocytosis in history;
Coma;
myasthenia;
Violation of bone marrow hematopoiesis;
Pregnancy;
Lactation;
Hypersensitivity to the drug;
Children's age up to 5 years.

When prescribing Azaleptin, care must be taken in patients with angle-closure glaucoma, decompensated diseases of the cardiovascular system, severe hepatic / renal failure, prostatic hyperplasia, epilepsy, intercurrent diseases with febrile syndrome, intestinal atony.

Azaleptin, instructions for use: method and dosage

A single dose of the drug for adults is from 50 mg to 200 mg, daily - from 200 mg to 400 mg. In most cases, treatment begins with 25-50 mg, gradually increasing the dosage to 200 or 300 mg per day.

Azaleptin tablets should be taken after meals 2-3 times a day. In some cases, it is possible to prescribe a daily dose in one dose at bedtime. The maximum allowable oral dose is 600 mg.

The course of treatment is 1-2 weeks, depending on the severity and form of the disease.

For sleep disorders, the drug is prescribed in small quantities (no more than 50 mg).

Side effects

The drug is well tolerated due to the central anticholinergic action and a moderate effect on dopamine receptors. But in some cases, Azaleptin tablets can cause the following side effects:

Central nervous system: headache, drowsiness, less often - confusion, insomnia, depression, extrapyramidal disorders, epilepsy;
Cardiovascular system: lowering blood pressure, orthostatic hypotension with dizziness, tachycardia, sometimes arterial hypertension;
Gastrointestinal tract: increased salivation, vomiting, nausea, heartburn, feeling of dry mouth, constipation;
Metabolism: increased sweating, weight gain;
Circulatory system: granulocytopenia, eosinophilia, thrombocytopenia, leukopenia;
Other systems: violation of accommodation, problems with urination, decreased potency, myasthenia gravis.

Overdose

An overdose of Azaleptin may be accompanied by respiratory depression, drowsiness, anxiety, epileptic seizures, tachycardia, hypotension, collapse, coma. Treatment for overdose involves the appointment of sorbents, maintaining the function of the heart and respiration, symptomatic therapy. Hemodialysis or peritoneal dialysis in case of poisoning does not give the desired effect.

special instructions

The development of granulocytopenia requires immediate discontinuation of the drug.

At the time of use of this drug, the use of alcoholic beverages should be avoided.

Influence on the ability to drive vehicles and complex mechanisms

During the period of treatment, care must be taken when driving and working with complex mechanisms that require increased concentration.

Use during pregnancy and lactation

Azaleptin is contraindicated during pregnancy/lactation.

Application in childhood

Azaleptin is not prescribed to patients under 5 years of age.

For impaired renal function

In severe renal failure, Azaleptin should be used under medical supervision.

For impaired liver function

In severe liver failure, Azaleptin should be used under medical supervision.

drug interaction

Tricyclic antidepressants, antipsychotic drugs, drugs that damage blood cells (pyrazolone-containing, non-steroidal anti-inflammatory drugs), antidepressants, carbamazepine, gold preparations, thyreostatics and antimalarials: concomitant use is contraindicated;
Antiepileptic drugs, anticoagulants, antimicrobial and hypoglycemic drugs (sulfonylurea derivatives): combined use requires caution;
Drugs with hypnotic, hypotensive and sedative effects, general anesthesia, narcotic analgesics, monoamine oxidase inhibitors, ethanol: their effect is enhanced;
Gel antacids, cholestyramine: absorption of clozapine from the intestine is impaired;
Levodopa and other dopamine release stimulants: their effect is weakened;
Benzodiazepines: there may be a violation of consciousness, an excessive decrease in blood pressure, depression / respiratory arrest;
Lithium preparations: their neurotoxicity increases (manifested as delirium, convulsions, extrapyramidal disorders);
Pentetrazole: the risk of seizures increases;
Myelotoxic agents: manifestations of Azaleptin's hematotoxicity are intensified.

Analogues

Azaleptin's analogues are: Azaleprol, Clozapine, Clozapin-Pharmaplant, Clozasten, Leponex.

Terms and conditions of storage

The drug should be stored in a dry, protected from sunlight place at a temperature not exceeding 30 °C.

Schizophrenia resistant to therapy, that is, in the absence of the effect of the use of typical antipsychotics or their intolerance. No effect is defined as the absence of satisfactory clinical improvement despite treatment with at least two typical antipsychotics at adequate doses for the required period of time. Intolerance is defined as the inability to achieve sufficient clinical improvement with the use of typical antipsychotics due to the development of severe and unmanageable adverse neurological reactions (extrapyramidal side effects or tardive dyskinesia). Risk of recurrence of suicidal behavior in patients with schizophrenia or schizoaffective psychosis. The risk of recurrence of suicidal behavior is determined by the history of the disease and the current clinical picture. Suicidal behavior refers to the actions of the patient, as a result of which the risk of his / her death is high. Correction of psychotic disorders in patients with Parkinson's disease with the ineffectiveness of standard treatment. Standard treatment failure is defined as inadequate control of psychotic symptoms and/or deterioration in motor function following the following measures: discontinuation of anticholinergic drugs, including tricyclic antidepressants; attempts to reduce the dose of an antiparkinsonian drug that has a dopaminergic effect.

Contraindications Azaleptin tablets 25mg

Hypersensitivity to Azaleptin or any other components of the drug. The impossibility of a regular clinical blood test with the determination of the leukocyte formula. History of toxic or idiosyncratic granulocytopenia/agranulocytosis (with the exception of the development of granulocytopenia/agranulocytosis due to previous chemotherapy). Bone marrow dysfunction. Epilepsy resistant to therapy. Alcoholic or other toxic psychosis, drug intoxication, coma. Collapse and / or depression of the central nervous system (CNS) of any etiology. Severe kidney and heart disease (eg, myocarditis). Active liver disease with nausea, anorexia, or jaundice: progressive liver disease, liver failure. Simultaneous use of other drugs with a pronounced ability to cause agranulocytosis, including long-release antipsychotics: - paralytic ileus; -lactase deficiency, lactose intolerance, glucose-galactose malabsorption. The safety and efficacy of Azaleptin in children and adolescents under 18 years of age have not been established. With caution: Azaleptin should be used with caution in patients with a high risk of developing cerebrovascular accidents, as well as in elderly patients with dementia. Agranulocytosis: Due to the fact that azaleptin can cause the development of agranulocytosis, the following precautions must be observed: Simultaneously with azaleptin, drugs that have a pronounced inhibitory effect on bone marrow function should not be used. In addition, the concomitant use of long-acting antipsychotics in depot form, which have a potential myelosuppressive effect and cannot be rapidly eliminated from the body if necessary (for example, when granulocytopenia occurs), should be avoided. In patients with a history of primary bone marrow disease, the use of Azaleptin is possible only if the expected effect of therapy outweighs the risk of adverse reactions. Before starting treatment with Azaleptin, such patients should undergo a thorough examination by a hematologist. Particular attention should be paid to patients who have a low white blood cell count due to benign ethnic neutropenia. Azaleptin treatment in such cases can be started after obtaining the consent of the hematologist. Cholinolytic activity: Azaleptin has M-anticholinergic activity, and therefore careful monitoring is indicated for patients with prostatic hyperplasia and angle-closure glaucoma. Use during pregnancy and during breastfeeding. Pregnancy: There are no data on the use of Azaleptip during pregnancy. The drug should be used in pregnant women only if the expected benefit to the mother outweighs the risk to the fetus. If it is necessary to stop the use of the drug during pregnancy, the abolition of treatment with Azaleptin should be done gradually. Newborns exposed to antipsychotics during the third trimester of pregnancy are at risk for developing extrapyramidal disorders and/or withdrawal after birth. These neonates have developed agitation, muscular hypertension, hypotension, tremors, drowsiness, respiratory distress syndrome, and eating disorders. The severity of symptoms ranged from mild to severe, requiring intensive care and prolonged hospitalization. Breastfeeding: Azaleptin is excreted in breast milk and affects the newborn, and therefore, when using the drug, breastfeeding should be discontinued. Fertility: Amenorrhea may occur in some patients of reproductive age when using other antipsychotics. When transferring such patients to treatment with Azaleptin, it is possible to restore the normal menstrual cycle. In this regard, patients of reproductive age during treatment with Azaleptin should use reliable methods of contraception.

Method of application and dosage Azaleptin tablets 25mg

Tablets are taken orally. Azaleptin® should only be used if the white blood cell count and absolute neutrophil count are within normal limits prior to treatment, i.e. the number of leukocytes is 3.5x10 to the ninth degree / l, and the absolute number of neutrophils is 2x10 to the ninth degree / l. In addition, when using the drug, it is necessary to be able to regularly determine the number of leukocytes and the absolute number of neutrophils: weekly for the first 18 weeks, then at least 1 time in 4 weeks throughout the course of treatment, and also 4 weeks after the end of treatment. The dose of the drug should be selected individually. The minimum effective dose should be used in each patient. In order to minimize the risk of hypotension, seizures and sedation, the dose should be selected with caution, dividing the daily dose into several doses. In patients receiving drugs that interact with the drug Azaleptin® (such as benzodiazepines or selective serotonin reuptake inhibitors), an adequate dose adjustment of the drug is necessary. Switching from previous treatment with antipsychotics to therapy with azaleptin: The use of azaleptin in combination with other antipsychotics is not recommended. In the event that treatment with Azaleptin must be started in a patient already taking an antipsychotic by mouth, dose reduction or withdrawal of the previous drug should be done gradually. Based on clinical data, the attending physician should determine the need to stop taking another antipsychotic before starting therapy with Azaleptin. recommended doses. Schizophrenia resistant to therapy: On the first day, take 1 tablet of 25 mg 1 time per day. If it is necessary to start treatment with a dosage of 12.5 mg (1/2 tablet of 25 mg) 1 or 2 times a day, score tablets containing clozapine 25 mg should be used for dosing accuracy; on the second day - 1 or 2 tablets of the drug, 25 mg each. In the future, subject to good tolerance, the dose of the drug can be slowly increased by 25–50 mg so that within 2–3 weeks a daily dose of no more than 300 mg is reached. Then, if necessary, the daily dose can be increased by 50-100 mg every 3-4 days, or preferably every 7 days. In most patients, the onset of the antipsychotic effect of the drug should be expected when using a daily dose of azaleptin 300-450 mg (in divided doses). In some patients, a lower dose may be more effective, others may require a dose of up to 600 mg / day. The daily dose can be divided into separate doses unevenly, taking most of it at bedtime. To achieve the full therapeutic effect, some patients require the use of a higher dose of the drug. In this case, it is advisable to gradually increase the dose (each time by no more than 100 mg) until a maximum dose of 900 mg / day is reached. The possibility of a more frequent development of side effects (in particular, the appearance of seizures) should be taken into account when using a dose exceeding 450 mg / day. After reaching the maximum therapeutic effect, it is possible to use lower maintenance doses. Reduce the dose of the drug should be slow and with caution. Maintenance treatment should be continued for at least 6 months. If the daily dose of the drug does not exceed 200 mg, you can switch to a single evening dose of the drug. Termination of therapy: In the event of a planned discontinuation of treatment with the drug, a gradual dose reduction over 1 to 2 weeks is recommended. If it is necessary to suddenly discontinue the drug (for example, in the case of the development of leukopenia), the patient should be carefully monitored in connection with a possible exacerbation of psychotic symptoms and the development of a withdrawal syndrome associated with the cessation of the anticholinergic effect of the drug, manifested in the form of profuse sweating, headache, nausea, vomiting and diarrhea. Resumption of treatment: If more than 2 days have passed since the last use of the drug, treatment should be resumed, starting with a dose of 25 mg 1 time per day. If it is necessary to resume treatment with a dosage of 12.5 mg (1/2 tablet of 25 mg) 1 or 2 times during the first day, scored tablets containing clozapine 25 mg should be used for dosing accuracy. If this dose is well tolerated, subsequent dose increases to achieve a therapeutic effect can be carried out faster than recommended for starting treatment with the drug. However, if the patient had respiratory or cardiac arrest during the initial period of treatment, but then the dose of the drug was successfully brought to a therapeutic dose, increasing the dose with repeated use of the drug should be done with extreme caution. Reducing the risk of recurrent suicidal behavior in schizophrenia and schizoaffective psychosis: In the treatment of patients with schizophrenia and schizoaffective psychosis at risk of recurrence of suicidal behavior, the same recommendations for the method of administration and dosage as given for patients with schizophrenia resistant to therapy should be followed. To reduce the risk of suicidal behavior, it is recommended to use the drug for at least 2 years. After a two-year course of treatment, it is recommended to re-evaluate the risk of developing suicidal behavior. Further, the need to continue therapy with Azaleptin is determined on the basis of a regular thorough assessment of the risk of recurrence of suicidal behavior. Psychosis in Parkinson's disease (in cases of ineffective standard therapy): The initial dose of Azaleptin should not exceed 12.5 mg (1/2 tablet of 25 mg), it should be taken in the evening. Further, the dose should be increased by 12.5 mg, not more than 2 times a week, up to a maximum of 50 mg. For dosing accuracy, Azaleptin 25 mg tablets with a mark from another manufacturer should be used. A dose of 50 mg should be used no earlier than the end of the second week after the start of treatment. The entire daily dose is preferably taken in 1 dose in the evening. The average effective dose averages 25 - 37.5 mg per day. In the event that treatment with a daily dose of 50 mg for at least 1 week does not provide a satisfactory therapeutic effect, a further cautious dose increase of no more than 12.5 mg per week is possible. For dosing accuracy, Azaleptin 25 mg tablets with a mark from another manufacturer should be used. The dose of 50 mg per day may be exceeded in exceptional cases. Do not exceed a dose of 100 mg per day. Dose increases should be limited or delayed if orthostatic hypotension, marked sedation, or confusion develop. During the first weeks of treatment, blood pressure control is necessary. An increase in the dose of antiparkinsonian drugs, if indicated on the basis of an assessment of motor status, is possible no earlier than 2 weeks after complete relief of psychotic symptoms. If an increase in the dose of antiparkinsonian drugs causes a reappearance of psychotic symptoms, the dose of azaleptin can be increased by 12.5 mg / week to a maximum dose of 100 mg / day, taken in 1 or 2 divided doses (see above). Termination of therapy: At the end of therapy, it is recommended to gradually reduce the daily dose by 12.5 mg no more than once a week (preferably every 2 weeks). For dosing accuracy, Azaleptin 25 mg tablets with a mark from another manufacturer should be used. Treatment should be stopped immediately if neutropenia or agranulocytosis develops. In this situation, careful psychiatric monitoring is necessary, as symptoms can recur quickly. Use in patients 60 years of age and older: It is recommended to start treatment with very low doses (12.5 mg / day on the first day) and then increase the dose by no more than 25 mg per day. For dosing accuracy, Azaleptin 25 mg tablets with a mark from another manufacturer should be used. The experience of using Azaleptin in patients aged 60 years and older does not allow us to conclude that there are differences in the response to Azaleptin treatment in patients of different age groups. Use in patients with a history of seizures, diseases of the cardiovascular system (CVS) or kidney disease: in patients with a history of seizures, in the presence of cardiovascular disease or kidney disease, the dose of the drug on the first day should be 12.5 mg 1 time per day; further increase in dose should be carried out slowly and gradually. For dosing accuracy, Azaleptin 25 mg tablets with a mark from another manufacturer should be used. Severe cardiovascular disease and severe kidney disease are contraindications to the use of Azaleptin.

In this article, you can read the instructions for using the drug Azaleptin. Reviews of site visitors - consumers of this medicine, as well as opinions of doctors of specialists on the use of the neuroleptic Azaleptin in their practice are presented. A big request to actively add your reviews about the drug: did the medicine help or not help get rid of the disease, what complications and side effects were observed, perhaps not declared by the manufacturer in the annotation. Analogues of Azaleptin in the presence of existing structural analogues. Use for the treatment of schizophrenia, psychosis and sleep disorders in adults, children, and during pregnancy and lactation. The composition and interaction of the drug with alcohol.

Azaleptin- an antipsychotic agent (neuroleptic), a derivative of dibenzodiazepine. It has a pronounced antipsychotic and sedative effect. Practically does not cause extrapyramidal disorders; in this regard, clozapine belongs to the group of so-called "atypical" antipsychotics.

The antipsychotic effect is due to the blockade of dopamine D2 receptors in the mesolimbic and mesocortical structures of the brain.

The sedative effect is due to the blockade of alpha-adrenergic receptors of the reticular formation of the brain stem; antiemetic action - blockade of dopamine D2 receptors of the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus. It has a peripheral and central m-anticholinergic, alpha-adrenergic blocking effect. Does not affect the concentration of prolactin in the blood.

The antipsychotic effect is close to that of aliphatic phenothiazines, but without a "submelancholic shade" and unpleasant subjective sensations, does not have a cataleptogenic effect, and lowers the threshold for convulsive readiness.

Does not affect higher intellectual functions.

The development of the therapeutic effect is characterized by stages: the rapid onset of hypnotic and sedative effects; relief of anxiety, psychomotor agitation and aggressiveness (after 3-6 days); antipsychotic action (after 1-2 weeks); effect on the symptoms of negativism (after 20-40 days).

Compound

Clozapine + excipients.

Pharmacokinetics

When taken orally, it is absorbed from the gastrointestinal tract quickly and almost completely. Exposed to intensive metabolism during the "first pass" through the liver with the formation of metabolites of low activity or inactive. It is metabolized with the participation of the CYP1A2 isoenzyme. The distribution is intense and fast, penetrates the blood-brain barrier (BBB). Protein binding - 95%. Excreted by the kidneys - 50% and through the intestines - 30%.

Indications

acute and chronic forms of schizophrenia;
manic states;
affective insanity;
psychomotor agitation in psychopathy;
emotional and behavioral disorders (including in children);
sleep disorders.

Release form

Tablets 25 mg and 100 mg.

Instructions for use and dosage

Set individually. For oral administration, a single dose is 50-200 mg, daily - 200-400 mg. Treatment usually begins with a dose of 25-50 mg, then gradually increased by 25-50 mg per day to 200-300 mg per day for 7-14 days. The daily dose can be used once at bedtime or 2-3 times a day after meals. When treatment is discontinued, the dose should be gradually reduced over 1-2 weeks. After achieving a therapeutic effect, they switch to a maintenance course.

If necessary, clozapine can be administered intramuscularly.

The maximum oral dose is 600 mg per day.

In mild forms of the disease, for maintenance therapy, as well as in patients with hepatic and / or renal insufficiency, chronic heart failure, cerebrovascular disorders, it is prescribed in lower daily doses (25-200 mg).

Side effect

drowsiness;
headache;
confusion;
extrapyramidal disorders (akinesia, hypokinesia, muscle rigidity, tremor);
insomnia;
restless sleep;
depression;
epileptic seizures;
temperature increase of central genesis;
tachycardia;
arterial hypotension;
orthostatic hypotension, accompanied by dizziness;
arterial hypertension;
hypersalivation;
nausea, vomiting;
dry mouth;
heartburn;
weight gain;
increased sweating;
eosinophilia, granulocytopenia up to agranulocytosis, leukopenia, thrombocytopenia;
dry mouth;
constipation;
urination disorders;
myasthenia gravis;
decrease in potency;
disturbance of accommodation.

Contraindications

history of granulocytopenia or agranulocytosis (with the exception of the development of granulocytopenia or agranulocytosis due to previously used chemotherapy);
oppression of bone marrow hematopoiesis;
myasthenia gravis;
coma;
toxic psychosis (including alcoholic);
pregnancy;
lactation period;
children's age up to 5 years;
hypersensitivity to clozapine.

Use during pregnancy and lactation

Azaleptin is contraindicated during pregnancy and lactation (breastfeeding).

Use in children

Contraindicated in children under 5 years of age. The safety and efficacy of clozapine in children and adolescents under 16 years of age have not been established.

special instructions

Use with caution in severe diseases of the cardiovascular system, severe renal and / or liver failure, angle-closure glaucoma, prostatic hyperplasia, intestinal atony, epilepsy, intercurrent diseases with febrile syndrome.

During the period of treatment, systematic monitoring of the picture of peripheral blood is necessary.

When using Azaleptin, alcohol should be excluded.

Influence on the ability to drive vehicles and control mechanisms

Patients taking clozapine should refrain from potentially hazardous activities associated with the need for concentration and increased speed of psychomotor reactions.

drug interaction

With simultaneous use with drugs that have a depressant effect on the central nervous system (including benzodiazepine derivatives), ethanol-containing drugs, ethanol (alcohol), the severity and frequency of manifestations of a depressant effect on the central nervous system increases, and respiratory center depression increases.

With simultaneous use with agents that cause arterial hypotension, an additive hypotensive effect is possible.

With simultaneous use with agents that cause myelodepression, it is possible to increase the inhibitory effect on bone marrow hematopoiesis; with anticholinergic agents - it is possible to increase the anticholinergic effect.

With simultaneous use with digoxin or with drugs characterized by high protein binding (including heparin, warfarin, phenytoin), their plasma concentrations may increase, and Azaleptin may also be displaced by these drugs from its protein binding sites.

With simultaneous use with valproic acid, a change in the concentration of clozapine in the blood plasma is possible, while the clinical manifestations of the interaction were practically absent.

With simultaneous use with carbamazepine, the concentration of clozapine in the blood plasma decreases. Cases of severe pancytopenia and neuroleptic malignant syndrome have been described.

With simultaneous use with caffeine, the concentration of clozapine in the blood plasma increases and an increase in the incidence of side effects is possible.

With simultaneous use with lithium carbonate, myoclonus, convulsions, neuroleptic malignant syndrome, delirium, psychosis are possible.

With simultaneous use with risperidone, an increase in the concentration of Azaleptin in the blood plasma is possible, due, apparently, to a competitive effect on the CYP2D6 isoenzyme, which leads to inhibition of the metabolism of clozapine. With the rapid replacement of clozapine with risperidone, dystonia may develop.

Rifampicin may increase the metabolic rate of clozapine by inducing CYP1A2 and CYP3A isoenzymes.

With simultaneous use with phenytoin, a decrease in the concentration of clozapine in the blood plasma is possible; with fluoxetine, paroxetine, sertraline, fluvoxamine, an increase in the concentration of clozapine in the blood plasma is possible, which in some patients is accompanied by manifestations of toxicity. This action is especially pronounced with the simultaneous use of clozapine with fluvoxamine.

With simultaneous use with ciprofloxacin, an increase in the concentration of clozapine in the blood plasma is possible.

Analogues of the drug Azaleptin

Structural analogs of the active substance.