Leponex

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Leponex: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Leponex

ATX code: N05AH02

Active ingredient: clozapine (Clozapine)

Manufacturer: Novartis Pharmaceuticals UK, Ltd. (Novartis Pharmaceuticals UK, Ltd.) (UK)

Description and photo update: 2019-09-07

Leponex is an antipsychotic drug that has antiserotonin, sedative, antihistamine effects.

Release form and composition

The drug is available in the form of tablets: yellow, round, with beveled edges, “SANDOZ” engraved on the flat side in a circle, the other side of the tablet is beveled towards the dividing line and bears the inscription “L / O” (dosage 25 mg) or “Z / A (dosage 100 mg) (10 pcs. In blisters, in a cardboard box of 5, 10, 12 or 25 blisters and instructions for the use of Leponex).

1 tablet contains:

active substance: clozapine - 25 or 100 mg;
auxiliary components: lactose monohydrate, colloidal silicon dioxide, corn starch, povidone, magnesium stearate, talc.

Pharmacological properties

Pharmacodynamics

Leponex is an antipsychotic drug. Its active ingredient, clozapine, is an atypical neuroleptic. Possessing antipsychotic and sedative effects, it practically does not affect the level of prolactin concentration in the blood, does not cause pronounced extrapyramidal reactions and catalepsy, does not suppress the stereotyped state caused by the administration of amphetamine or apomorphine.

Clozapine has a pronounced blocking effect on dopamine D4 receptors, weakly blocking D1-, D2-, D3- and D5-receptors. In addition, it has antiserotonergic properties, has a pronounced alpha-adrenergic blocking, antihistamine and anticholinergic effect, suppresses the activation reaction on the electroencephalogram (EEG).

Clozapine has a rapid and clinically significant sedative effect. Its antipsychotic effect is especially noticeable in the treatment of patients with schizophrenia resistant to the action of other antipsychotics.

Short-term or long-term use of clozapine is effective against negative and productive symptoms of schizophrenia, and there has been a positive trend in some cognitive impairments.

Compared with olanzapine, the risk of suicidal behavior in patients receiving clozapine is 24% lower. Clozapine is distinguished from other antipsychotics by the complete absence of an increase in prolactin concentration or a very slight increase in its level. Due to this, against the background of the use of the drug, such undesirable effects as impotence, gynecomastia, amenorrhea, galactorrhea do not occur. In addition, it almost does not cause pronounced extrapyramidal reactions, including acute dystonia and tardive dyskinesia; side effects such as parkinsonism and akathisia rarely occur.

Potentially dangerous adverse reactions of clozapine use include granulocytopenia and agranulocytosis, the incidence of which is 3% and 0.7%, respectively.

Pharmacokinetics

After oral administration, clozapine is almost completely absorbed (90–95%). Simultaneous food intake does not affect the rate and degree of absorption. The absolute bioavailability of clozapine during the first passage through the liver is 50-60%. The equilibrium state is ensured by regular intake of Leponex 2 times a day. It takes an average of 2.1 hours to reach the maximum concentration of clozapine in the blood.

Plasma protein binding is approximately 95%, the volume of distribution is 1.6 l / kg.

Clozapine is metabolized almost completely; only one metabolite, desmethyl derivative, has pharmacological activity. Its effect, similar to clozapine, is mild and shorter in duration.

Excretion is biphasic, the half-life (T _1/2) of the final phase is from 6 to 26 hours. After a single dose of Leponex at a dose of 75 mg, T _{1/2 of the} final phase averages 7.9 hours. When an equilibrium state is reached after 7 days of therapy, this value increases to 14.2 hours. Clozapine is excreted in the form of metabolites: through the kidneys - up to 50%, through the intestines - 30% of the dose taken. In urine and feces, clozapine is found unchanged only in trace amounts.

It was found that in an equilibrium state, an increase in the daily dose of the drug from 37.5 mg to 75 and 150 mg (divided into 2 doses) causes a linear dose-dependent increase in AUC (area under the concentration-time curve), maximum and minimum clozapine plasma concentration …

Indications for use

The use of Leponex is indicated for the treatment of schizophrenia that is resistant to therapy with typical antipsychotics or for their intolerance.

Resistance or lack of therapeutic effect is defined as a lack of clinical response to the use of adequate doses of at least two antipsychotics over a period.

The criterion of intolerance to typical neuroleptics is defined as the development of severe and uncorrected undesirable neurological reactions (extrapyramidal disorders, tardive dyskinesia), which does not allow achieving a sufficient clinical effect when using them.

In addition, Leponex is prescribed to reduce the risk of suicidal behavior in patients with schizophrenia or schizoaffective psychosis, whose current clinical picture and data from their medical history indicate a chronic nature of the recurrence of suicidal behavior.

Leponex is prescribed to correct psychotic disorders in Parkinson's disease with the ineffectiveness of standard treatment after the abolition of anticholinergic drugs (including tricyclic antidepressants) and attempts to reduce the dose of an antiparkinsonian drug with a dopaminergic effect.

Contraindications

Absolute:

the inability to conduct a regular clinical blood test with the determination of the leukocyte formula;
an indication of a history of agranulocytosis, idiosyncratic or toxic granulocytopenia (except for cases of granulocytopenia or agranulocytosis that developed after previously used chemotherapy);
epilepsy resistant to therapy;
dysfunction of the bone marrow;
oppression of the central nervous system of any etiology, collapse;
toxic psychoses (including alcoholic psychosis), drug intoxication, coma;
myocarditis and other severe heart pathologies;
active liver disease, accompanied by nausea, jaundice, or anorexia;
liver failure, progressive liver disease;
severe kidney disease;
paralytic intestinal obstruction;
the simultaneous use of long-release neuroleptics and other drugs with significant potential to cause agranulocytosis;
lactose intolerance, glucose-galactose malabsorption syndrome, lactase deficiency;
breast-feeding;
age up to 18 years;
hypersensitivity to the components of the drug.

Leponex tablets should be used with extreme caution in patients with an increased risk of cerebrovascular accidents, elderly patients with dementia; simultaneously with drugs that have a pronounced inhibitory effect on the function of the bone marrow; with a low number of leukocytes against the background of benign ethnic neutropenia; with prostatic hyperplasia, angle-closure glaucoma, a history of primary bone marrow disease.

It is recommended to avoid concomitant therapy with long-acting antipsychotics (depot form), which have a potential myelosuppressive effect.

The use of Leponex during pregnancy is indicated only in cases of obvious need, when the expected clinical effect of therapy for the mother outweighs the potential threat to the fetus.

Leponex, instructions for use: method and dosage

Leponex tablets are taken orally.

When prescribing Leponex, it is necessary to conduct a clinical blood test to determine the leukocyte formula, you can start taking the drug if its indicators are within the normal range: the number of leukocytes is 3500 / mm ³ (3.5 x 10 ⁹ / l) and above, the absolute number of neutrophils is 2000 / mm ³ (2 x 10 ⁹ / l) and above.

Leponex can cause the development of agranulocytosis, the manifestations of which can contribute to the appearance of severe infectious diseases and lead to death. Therefore, the use of the drug must be accompanied by regular monitoring of the number of leukocytes and the absolute number of neutrophils: during the first 126 days - 1 time in 7 days, then - at least 1 time in 28 days and 28 days after the end of treatment.

The selection of the daily dose is made individually, the minimum effective dose should be used.

To minimize the likelihood of sedation, hypotension and seizures, the daily dose should be divided into several doses.

In patients on concomitant therapy with benzodiazepines, selective serotonin reuptake inhibitors or other drugs that interact with clozapine, an adequate dose adjustment of Leponex is necessary.

Clozapine is not recommended in combination with other antipsychotics.

When switching from treatment with another oral antipsychotic, its dose should be reduced or canceled gradually. Based on clinical data, the attending physician should determine the need to discontinue therapy with another neuroleptic and switch to the use of Leponex.

Recommended dosage:

schizophrenia resistant to therapy: the first day of therapy - 12.5 mg (1/2 tablet of 25 mg) 1-2 times a day; the second day - 25 mg 1-2 times a day. Further, subject to good tolerance, the dose is gradually increased by 25–50 mg with an interval of several days so that by the end of 21 days of therapy, a daily dose of up to 300 mg is reached. Then, if clinically necessary, the daily dose can be increased by 50–100 mg every 3–7 days. In most cases, the antipsychotic effect of the drug occurs with the use of 300-450 mg of clozapine per day, divided into several doses. In some patients, the clinical effect is achieved with a lower dose, others may require a dose of up to 600 mg per day. To achieve the full therapeutic effect, it is possible to use a higher dose of Leponex. An uneven division of the daily dose is shown, it is advisable to take most of the dose before bedtime. The maximum daily dose is 900 mg. It should be borne in mind that against the background of the use of a daily dose of more than 450 mg, the risk of more frequent seizures and other side effects increases. After reaching the maximum clinical effect, it is possible to transfer the patient to maintenance therapy using lower doses of clozapine. Dose reduction should be done with caution and slowly. If the maintenance dose does not exceed 200 mg, then it can be taken once in the evening. The duration of maintenance therapy is 180 days or more. Discontinuation of therapy should be carried out by gradually reducing the dose over 7-14 days. If a sudden withdrawal of Leponex is required, including with the development of leukopenia,it is necessary to provide the patient with careful observation in connection with the possible development of withdrawal syndrome or exacerbation of psychotic symptoms. Withdrawal symptoms can include profuse sweating, headache, nausea, vomiting, and diarrhea. If the treatment was interrupted for more than 2 days, then the use of Leponex should be resumed with a dose of 12.5 mg 1-2 times a day. Further, until the therapeutic effect is achieved, the dose increase in patients with good tolerance can be carried out more quickly than initially. With extreme caution, the dose should be titrated in those patients in whom respiratory arrest or cardiac arrest was noted during the initial dose selection;nausea, vomiting, diarrhea. If the treatment was interrupted for more than 2 days, then the use of Leponex should be resumed with a dose of 12.5 mg 1-2 times a day. Further, until the therapeutic effect is achieved, the dose increase in patients with good tolerance can be carried out more quickly than initially. With extreme caution, the dose should be titrated in those patients in whom respiratory arrest or cardiac arrest was noted during the initial dose selection;nausea, vomiting, diarrhea. If the treatment was interrupted for more than 2 days, then the use of Leponex should be resumed with a dose of 12.5 mg 1-2 times a day. Further, until the therapeutic effect is achieved, the dose increase in patients with good tolerance can be carried out more quickly than initially. With extreme caution, the dose should be titrated in those patients in whom respiratory arrest or cardiac arrest was noted during the initial dose selection;in whom, at the initial dose selection, respiratory arrest or cardiac arrest was noted;in whom, at the initial selection of the dose, respiratory arrest or cardiac arrest was noted;
Reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective psychosis: the dosing regimen and the selection of an individual dose are carried out in the same way as for patients with schizophrenia resistant to therapy. The duration of the course of treatment is at least two years. After a regular thorough assessment of the patient's condition for the recurrence of suicidal behavior, the doctor decides whether to stop treatment or continue it;
psychosis in Parkinson's disease (with the ineffectiveness of standard therapy): the initial daily dose is not more than 12.5 mg, taken in the evening. Further, the dose can be increased by 12.5 mg, observing an interval of at least 3-4 days. The maximum daily dose is 50 mg, it should be reached no earlier than 14 days after the start of treatment. The daily dose should be taken in 1 dose in the evening. The therapeutic dose range is variable, with the average effective dose being 25–37.5 mg per day. It is possible to exceed the daily dose of 50 mg in exceptional cases when its intake for 7 days does not provide a satisfactory therapeutic effect. A further increase in the daily dose is carried out with caution, no more than 12.5 mg per 7 days. Do not exceed 100 mg per day. During the first 14–28 days, treatment should be accompanied by regular monitoring of blood pressure (BP) in the supine and standing positions. If the patient develops a pronounced sedation, orthostatic hypotension or confusion, the dose increase should be limited or postponed. It is possible to increase the doses of antiparkinsonian drugs in patients with indications based on the assessment of motor status only 14 days after the complete relief of psychotic symptoms. If, after increasing the dose, psychotic symptoms re-develop, you can increase the dose of Leponex by 12.5 mg in 7 days to 100 mg per day and take it in 1 or 2 doses. It is recommended to discontinue therapy by gradually reducing the daily dose by 12.5 mg once every 14 days. Immediate discontinuation of treatment is indicated if agranulocytosis or neutropenia develops. In this case, it is necessary to ensure careful psychiatric monitoring of the patient's condition due to the high risk of recurrence of symptoms.

If the number of eosinophils in the blood exceeds 3000 / mm ³, treatment with Leponex is recommended to be temporarily discontinued, pills can be resumed only after the number of eosinophils has decreased to less than 1000 / mm ³.

Cancellation of the drug is carried out when the number of platelets is less than 50,000 / mm ³.

When prescribing Leponex, the patient should be informed about the need to immediately consult a doctor if the body temperature rises, a sore throat appears, or any symptoms of an infectious disease occur. The doctor should remind you of this during each visit.

If any symptoms of infection appear, immediate determination of the leukocyte blood count is required.

If, during the first 126 days of treatment, a clinical blood test shows a decrease in the number of leukocytes to 3500-3000 / mm ³ and / or the absolute number of neutrophils to 2000-1500 / mm ³, then these indicators begin to be monitored 2 times within 7 days. In the period after 126 days of therapy with Leponex, hematological control 2 times in 7 days is performed if the number of leukocytes is 3000-2500 / mm ³, the absolute number of neutrophils is 1500-1000 / mm ³… In addition, if during therapy there is a significant decrease in the number of leukocytes compared to the initial level, then the blood test should be repeated. A blood test 2 times every 7 days is continued while taking Leponex until the indicators stabilize or recover to their original level.

An immediate discontinuation of drug treatment is required if during the first 126 days the leukocyte count is less than 3000 / mm ³ or the absolute neutrophil count is less than 1500 / mm ³, and after 126 days of Leponex therapy, the leukocyte count will decrease to less than 2500 / mm ³ or the absolute number of neutrophils is less than 1000 / mm ³. In each of these cases, it is required to determine the number of leukocytes and leukocyte counts on a daily basis and carefully monitor the patient for the occurrence of flu-like symptoms and other signs of an infectious disease. Hematological control after discontinuation of drug treatment should be continued until the hematological parameters are completely normalized.

If, after discontinuation of Leponex, the process of reducing the number of leukocytes (below 2000 / mm ³) and / or the absolute number of neutrophils (below 1000 / mm ³) continues, the patient must be admitted to a specialized hematology department and treated under the guidance of an experienced hematologist.

You can not resume treatment with Leponex in patients in whom drug withdrawal is caused by the development of leukopenia and / or neutropenia.

In order to confirm the hematological parameters the next day, it is recommended to conduct a repeated blood test, but stop taking the pills based on the results of the first analysis.

If Leponex therapy lasted more than 126 days and was suspended for a period of 3 to 28 days, then the control of the number of leukocytes and neutrophils in the blood should be carried out regularly at intervals of 7 days for 42 days. In the absence of hematological changes, further monitoring of blood counts can be carried out once every 28 days. If therapy has been suspended for 28 days or more, in the next 126 days of therapy, hematological control is required every 7 days.

In patients aged 60 years and older, it is recommended to start treatment with a dose of 12.5 mg once a day on the first day, followed by an increase in the dose by no more than 25 mg per day.

It is necessary to start the use of Leponex in patients with a history of seizures, diseases of the cardiovascular system, impaired renal function with a single dose of 12.5 mg on the first day, and the subsequent increase in the dose should be carried out more slowly and gradually than indicated in the general recommendations.

Side effects

Undesirable disorders of Leponex from systems and organs (classified as follows: very often - ≥ 1/10, often - ≥ 1/100 and <1/10, infrequently - ≥ 1/1000 and <1/100, rarely - ≥ 1 / 10,000 and <1/1000, very rarely - <1/10,000, including isolated cases):

on the part of the blood and lymphatic system: often - eosinophilia, leukopenia, leukocytosis, neutropenia; infrequently - agranulocytosis (after discontinuation of treatment, its manifestations are usually reversible, but can cause sepsis and death); rarely - lymphopenia, anemia; very rarely - thrombocytosis, thrombocytopenia;
on the part of metabolism and nutrition: often - increased body weight; rarely - impaired glucose tolerance, worsening of the course of diabetes mellitus, the development of diabetes mellitus; very rarely - ketoacidosis, hypercholesterolemia, severe hyperglycemia, hypertriglyceridemia, hyperosmolar coma;
from the nervous system: very often - dizziness, drowsiness or sedation; often - tremor, seizures (including fatal), muscle stiffness, seizures, headache, myoclonic seizures, akathisia, extrapyramidal symptoms; infrequently - neuroleptic malignant syndrome (the main symptoms are hyperthermia, muscle rigidity, cognitive changes, autonomic lability); rarely - delirium, confusion; very rarely - obsessive-compulsive disorder, tardive dyskinesia;
on the part of the organ of vision: often - blurred vision;
from the heart: very often - tachycardia (more often during the first weeks of therapy); often - changes in the ECG (electrocardiogram), including conduction abnormalities, depression of the ST segment, flattening and inversion of the T wave; rarely - arrhythmia, circulatory collapse, pericarditis (including with pericardial effusion), myocarditis (including with eosinophilia); very rarely - cardiac arrest, cardiomyopathy;
on the part of the vessels: often - orthostatic hypotension, fainting, arterial hypertension; rarely - shock (as a consequence of severe arterial hypotension, which arose with a significant increase in the dose of Leponex; cessation of blood circulation or respiration is not excluded), thromboembolism (including death or in combination with organ necrosis);
from the respiratory system, chest and mediastinal organs: rarely - lower respiratory tract infections (including fatal ones), pneumonia, food aspiration; very rarely - respiratory depression, respiratory arrest;
from the gastrointestinal tract: very often - constipation, hypersalivation; often - dry mouth, nausea, vomiting; rarely, dysphagia; very rarely - an increase in the parotid salivary gland, intestinal obstruction, blockage by coprolites or paralytic intestinal obstruction;
from the hepatobiliary system: often - an increase in the activity of liver enzymes; rarely - cholestatic jaundice, pancreatitis, hepatitis; very rarely - fulminant liver necrosis;
from the urinary system: often - urinary incontinence, urinary retention; very rarely - interstitial nephritis;
from the genitals and mammary gland: very rarely - priapism;
dermatological reactions: rarely - skin reactions;
mental disorders: often - dysarthria; infrequently - dysfemia; rarely - anxiety, agitation;
laboratory parameters: rarely - an increase in the activity of creatine phosphokinase; very rarely - hyponatremia;
general disorders: often - a feeling of fatigue, benign hyperthermia, impaired thermoregulation or sweating; very rarely - sudden death (reasons not established).

In addition to the adverse events reported during clinical studies of Leponex, there are reports of the following side effects, the frequency of which has not been established:

from the nervous system: changes in the EEG, cholinergic syndrome;
from the endocrine system: pseudopheochromocytoma;
from the heart: chest pain, angina pectoris, myocardial infarction (including fatal);
from the immune system: leukocytoclastic vasculitis, angioedema;
from the respiratory system, chest and mediastinal organs: nasal congestion, bronchospasm;
from the gastrointestinal tract: heartburn, diarrhea, dyspepsia, abdominal discomfort, colitis;
from the hepatobiliary system: hepatotoxicity, liver steatosis, liver fibrosis, liver necrosis, liver cirrhosis, severe liver failure requiring liver transplantation or leading to death, liver damage (including life-threatening conditions);
from the musculoskeletal system: muscle pain, muscle weakness, muscle spasms, systemic lupus erythematosus;
from the urinary system: bedwetting, renal failure;
dermatological reactions: pigmentation disorders.

Overdose

Symptoms

The following symptoms may indicate an overdose of Leponex: drowsiness, confusion, hallucinations, agitation, revitalization of reflexes, areflexia, delirium, convulsions, extrapyramidal symptoms, fluctuations in body temperature, hypersalivation, dilated pupils, blurred vision, tachycardia, hypotension, arterial dyspnea respiratory depression or respiratory failure, aspiration pneumonia, lethargy, coma, collapse.

It should be noted that in adult patients who have not previously taken Leponex, a dose of 400 mg of the drug can cause the development of life-threatening coma, including those with a fatal outcome. In children, a 50–200 mg dose of clozapine is highly sedative and can lead to coma.

Treatment

There is no specific antidote. Therefore, urgent measures are required such as gastric lavage (if no more than six hours have passed since taking Leponex), taking activated charcoal. It is necessary to continuously monitor the function of the cardiovascular system, electrolytes and acid-base balance, to maintain the function of respiration.

The use of peritoneal dialysis and hemodialysis is ineffective.

Cholinesterase inhibitors, including physostigmine, pyridostigmine, and neostigmine, have been shown to correct anticholinergic effects. In case of arrhythmias, drugs should be prescribed depending on the symptoms (potassium and digitalis preparations, sodium bicarbonate), the use of procainamide and quinidine is contraindicated. In the case of arterial hypotension, the patient must intravenously (intravenously) inject any plasma replacement solution, including albumin. For stimulating blood circulation, the most effective agents are dopamine and angiotensin derivatives. Epinephrine and other beta-adrenergic agonists should not be used; they can cause additional vasodilation. With the development of seizures, a slow intravenous infusion of phenytoin or an intravenous injection of diazepam is prescribed. Long-acting barbiturates should not be used.

Careful medical observation of the patient's condition should be continued for at least 5 days in connection with the possible development of delayed reactions.

special instructions

Potentially dangerous side effects of Leponex are granulocytopenia and agranulocytosis, therefore, a prerequisite for using the drug is the regular determination of the leukocyte formula. This reduces the incidence of agranulocytosis and the death rate from it.

It is contraindicated to prescribe Leponex to patients who have had hematological disorders while using drugs in the past.

The appointment of Leponex should be made in strict accordance with clinical indications, and during the period of its use, compliance with all safety recommendations is required.

With the development of an infectious disease, antibiotic therapy should be started immediately due to the increased risk of developing septic shock in the patient.

It is necessary to ensure careful medical supervision of the patient for the occurrence of orthostatic hypotension at the stage of the initial dose selection. This complication often occurs with a rapid increase in the dose and against the background of the use of other psychotropic drugs, benzodiazepines. Orthostatic hypotension may be accompanied by fainting, circulatory and / or respiratory arrest, including death.

In rare cases, during the first 8 weeks and at later stages of treatment, the patient may experience resting tachycardia, accompanied by shortness of breath, arrhythmia, or signs of heart failure. If such symptoms occur, the necessary diagnostic measures should be taken to exclude myocarditis. The symptoms of clozapine-induced myocarditis may mimic those of myocardial infarction or flu. In case of suspicion of cardiomyopathy or myocarditis, Leponex should be immediately canceled and a cardiac examination should be performed.

It is not recommended to resume the use of the drug in patients in whom clozapine caused the development of myocarditis or cardiomyopathy.

It is recommended to use Leponex with caution for the treatment of patients with risk factors for stroke, diseases of the cardiovascular system, prolongation of the QT interval in the family history and simultaneously with drugs that can prolong the QTc interval.

It should be borne in mind that Leponex can lower the seizure threshold, therefore, during treatment, it is necessary to closely monitor patients with a history of epilepsy.

During the admission period, a temporary increase in body temperature up to 38 ° C and higher is possible (more often during the first three weeks of treatment). Such a fever is usually benign, but requires careful examination to exclude an infectious disease, agranulocytosis, or the development of neuroleptic malignant syndrome. If neuroleptic malignant syndrome is diagnosed, the pill should be stopped immediately.

The anticholinergic activity of clozapine can lead to the development of undesirable effects on the part of various organs and body systems. Therefore, with an enlargement of the prostate, angle-closure glaucoma, diseases of the colon, or an indication in the anamnesis of surgical interventions on the organs of the lower abdomen, Leponex should be used under close supervision.

Possible disturbance of intestinal motility of varying severity, from constipation to intestinal obstruction, fecal obstruction or intestinal paresis. The situation can be aggravated by the simultaneous use of drugs with anticholinergic activity, including antipsychotic and antiparkinsonian drugs, antidepressants. It is imperative to recognize and actively treat constipation in time.

Against the background of the use of Leponex, metabolic disorders may occur, increasing the risk of complications from the cardiovascular system and cerebrovascular accidents. These include hyperglycemia, dyslipoproteinemia, and weight gain.

Patients with diabetes mellitus need to regularly monitor the concentration of glucose in the blood serum. If there are risk factors for diabetes mellitus (including a family history of diabetes mellitus and overweight), patients should have their fasting blood glucose measured both prior to initiation and periodically during treatment with an atypical antipsychotic drug.

For hyperglycemia that occurs with clozapine, symptoms such as weakness, polydipsia, polyuria, or polyphagia are characteristic. When they appear, the possibility of developing a glucose tolerance disorder in the patient should be taken into account and an appropriate examination should be carried out. Severe hyperglycemia that develops against the background of Leponex requires immediate withdrawal. In some cases, discontinuation of treatment with an atypical antipsychotic medication helped to restore normal glucose levels.

It is recommended to monitor lipid metabolism at the beginning and regularly during treatment.

With a sharp withdrawal of Leponex (including due to the development of leukopenia), the patient needs a thorough examination for the return of psychotic symptoms and rebound cholinergic symptoms, including increased sweating, headache, nausea, vomiting, diarrhea.

Influence on the ability to drive vehicles and complex mechanisms

Taking Leponex can lower the threshold of convulsive readiness and have a sedative effect, therefore, during the period of treatment, patients should not engage in potentially hazardous activities and drive vehicles and complex mechanisms.

Application during pregnancy and lactation

During gestation, the use of Leponex is allowed only in cases where, in the opinion of the doctor, the expected benefit from therapy for the mother outweighs the potential threat to the fetus.

It should be borne in mind that the effect of antipsychotic drugs on the fetus in the third trimester of pregnancy negatively affects the newborn. After birth, these children are at risk for withdrawal and / or extrapyramidal disorders. They may develop respiratory distress syndrome, agitation, hypotension, muscle hypertension, tremors, drowsiness, and eating disorders. The severity of the symptoms shown may require the use of intensive care in a hospital setting.

Cancellation of drug treatment during pregnancy should be done gradually.

The use of Leponex during lactation is contraindicated, therefore, if it is necessary to prescribe therapy with an antipsychotic drug, breastfeeding should be discontinued.

Since women of reproductive age with amenorrhea that have arisen during treatment with other antipsychotics, while taking the drug, the normal menstrual cycle can be restored, during the period of treatment with Leponex, it is recommended to use reliable methods of contraception.

Pediatric use

The appointment of Leponex is contraindicated for the treatment of patients under 18 years of age due to the lack of information on the safety and effectiveness of its use in children and adolescents.

With impaired renal function

It is contraindicated to use Leponex for the treatment of patients with severe kidney disease.

For violations of liver function

It is contraindicated to use Leponex for the treatment of patients with hepatic insufficiency, progressive liver disease, or during an exacerbation of liver disease accompanied by nausea, jaundice or anorexia.

In the presence of liver diseases, the use of Leponex is possible only with regular monitoring of hepatic function. If there is a clinically significant increase in liver function indicators or symptoms of jaundice appear, treatment should be suspended. It can be resumed only after the normalization of the functional parameters of the liver and under the close supervision of a doctor.

Use in the elderly

Leponex should be prescribed with caution in elderly patients with dementia.

Patients over the age of 60, especially in the presence of impaired cardiovascular function, are at greater risk of developing orthostatic hypotension, tachycardia, anticholinergic effects (including urinary retention and constipation) than younger patients. It should be borne in mind that in people of this age group, against the background of the use of atypical antipsychotic drugs, the risk of death from psychosis or behavioral disorders caused by dementia increases.

Drug interactions

During the period of use of Leponex, concomitant therapy with drugs that have a significant inhibitory effect on the function of the bone marrow, long-acting antipsychotic drugs in the form of a depot, with a potential myelosuppressive effect, is contraindicated.

When taken together, clozapine can enhance the central action of ethanol, monoamine oxidase inhibitors, anesthetics, H ₁ -histamine receptor blockers, benzodiazepines and other drugs that depress the central nervous system (CNS). In addition, special care is required when prescribing clozapine to patients who have previously received or continue to receive therapy with benzodiazepines or other psychotropic drugs. This is associated with a high risk of collapse in patients, in some cases causing cardiac and / or respiratory arrest.

When taken simultaneously with lithium preparations or other agents that affect the function of the central nervous system, a possible increase in the risk of developing neuroleptic malignant syndrome should be taken into account.

When combined with drugs that depress respiration or have anticholinergic and hypotensive effects, an additive effect is possible.

The alpha-adrenergic blocking activity of clozapine can contribute to the weakening of the hypertensive effect of drugs with a predominant alpha-adrenomimetic effect, including norepinephrine, and paradoxically change the vasoconstrictor effect of epinephrine.

With concomitant therapy with antiepileptic drugs, dose adjustment may be required, since clozapine lowers the seizure threshold.

If it is necessary to simultaneously use Leponex with warfarin, digoxin or other drugs with a pronounced ability to bind to plasma proteins, their dose must be adjusted downward.

It is recommended with caution to combine clozapine with drugs that cause electrolyte disturbances or prolongation of the QT interval.

It is required to control the concentration of clozapine in blood plasma while using several drugs with an affinity for cytochrome CYP450 isoenzymes, including 1A2, 3A4, 2D6.

A possible increase in the level of tricyclic antidepressants, class 1C antiarrhythmic drugs and phenothiazine derivatives in blood plasma should be taken into account and, if necessary, their therapeutic doses should be reduced.

The combination of Leponex with drugs that affect the activity of isoenzymes of the cytochrome CYP450 system, including cimetidine, erythromycin, ciprofloxacin, clarithromycin, azithromycin, venlafaxine, fluvoxamine, paroxetine, fluoxapetine, citalopram, sertraline inhibitors, and other selective clotralin concentration plasma and lead to adverse reactions.

The change in the concentration of the drug in the blood plasma can be influenced by protease inhibitors and azole antimycotics.

Caffeine, being a substrate of the CYP1A2 isoenzyme, increases the plasma concentration of clozapine. When reducing the dose of consumed coffee or tea during the treatment period, a possible decrease in the content of clozapine in blood plasma should be taken into account.

Simultaneous administration of ciprofloxacin in a daily dose of 500 mg increases the plasma concentration of clozapine and N-desmethylclozapine. In addition, the risk of developing the interaction of Leponex with norfloxacin or enoxacin should be considered.

Carbamazepine and rifampicin, which are inducers of the isoenzyme CYP3A4 of the cytochrome P _{450 system}, as well as phenytoin, can cause a decrease in the concentration of clozapine in the blood plasma.

There are isolated reports of the interaction of clozapine with proton pump inhibitors, resulting in an increase in drug concentration.

It should be borne in mind that abrupt cessation of smoking during treatment in heavy smokers can potentiate an increase in the concentration of clozapine in blood plasma and the severity of its side effects.

Analogs

Leponex analogs are: Clozapine, Azaleprol, Azaleptin, Clozasten.

Terms and conditions of storage

Keep out of the reach of children.

Store at temperatures up to 30 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Leponex

There are no reviews of Leponex from patients or their caregivers.

Price for Leponex in pharmacies

The price for Leponex has not been set due to the lack of the drug in the pharmacy chain.

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!