Zalasta-Ku tab d/rassas 10mg N28 (KRKA)

There are very rare reports of the development of hyperglycemia and/or decompensation of diabetes mellitus, sometimes accompanied by the development of ketoacidosis or ketoacidotic coma, including reports of several fatal cases. In some cases, there was an increase in body weight preceding decompensation, which could become a predisposing factor. For patients with diabetes mellitus or with risk factors for developing this disease, regular clinical monitoring and monitoring of blood glucose levels is recommended. If lipid levels change, adjustment of therapy is required. If you abruptly stop taking olanzapine, very rarely (less than 0.01%) the following symptoms may develop: sweating, insomnia, tremor, anxiety, nausea or vomiting. When discontinuing the drug, a gradual dose reduction is recommended. Anticholinergic activity. Since clinical experience with the use of olanzapine in people with concomitant diseases is limited, the drug should be prescribed with caution to patients with prostatic hyperplasia, paralytic ileus. Experience with olanzapine in patients with psychosis in Parkinson's disease caused by taking dopaminomimetics. Olanzapine is not recommended for the treatment of psychosis in Parkinson's disease caused by dopaminomimetics. Symptoms of parkinsonism and hallucinations increase. At the same time, olanzapine was not superior to placebo in the treatment of psychosis. Olanzapine is not indicated for the treatment of psychosis and/or behavioral disorders in dementia, due to increased mortality and an increased risk of cerebrovascular disorders (stroke, transient ischemic attacks). The increase in mortality was independent of olanzapine dose or duration of therapy. Risk factors predisposing to increased mortality include: age over 65 years, dysphagia, sedation, malnutrition and dehydration, lung diseases (for example, pneumonia, including aspiration), concomitant use of benzodiazepines. However, the increased incidence of death in the olanzapine groups compared with placebo was independent of these risk factors. With antipsychotic therapy, the patient's clinical condition improves over a period of several days to several weeks. During this period, the patient needs careful monitoring. Liver dysfunction. At the beginning of therapy, an asymptomatic increase in liver transaminases (ALT and AST) is possible. Caution should be exercised when prescribing olanzapine in patients with initially elevated AST and/or ALT levels, hepatic impairment and conditions potentially limiting liver function, and those taking hepatotoxic drugs. If ALT and/or AST increase during drug therapy, medical monitoring of the patient and, possibly, a reduction in the dose of the drug are recommended. When diagnosing hepatitis (including hepatocellular, cholestatic or mixed), olanzapine should be discontinued. Hematological changes. The drug should be used with caution in patients with leukopenia and/or neutropenia of any origin, myelosuppression of drug origin, as well as during radiation or chemotherapy, due to concomitant diseases, in patients with hypereosinophilic conditions or myeloproliferative diseases. Neutropenia was often observed with the simultaneous use of olanzapine and valproic acid (see section "Side effects"). Neuroleptic malignant syndrome (NMS). NMS is a potentially life-threatening condition associated with treatment with antipsychotic drugs (neuroleptics), incl. olanzapine. Clinical manifestations of NMS: fever, muscle rigidity, impaired consciousness, autonomic disorders (unstable pulse or labile blood pressure, tachycardia, increased sweating, arrhythmias). Additional symptoms of NMS: increased CPK, myoglobinuria (against the background of rhabdomyolysis) and acute renal failure. If symptoms of NMS develop, as well as an increase in body temperature for no apparent reason, it is necessary to discontinue all antipsychotics, incl. olanzapine. Convulsive syndrome. Olanzapine should be used cautiously in patients with a history of seizures or the presence of factors that lower the seizure threshold. While taking olanzapine, seizures were rarely recorded. Tardive dyskinesia. Olanzapine therapy was associated with a significantly lower incidence of tardive dyskinesia compared with haloperidol. The risk of developing tardive dyskinesia increases with increasing duration of treatment. If signs of this condition occur in a patient taking olanzapine, the drug should be discontinued or the dose reduced. Symptoms of dyskinesia may temporarily increase after discontinuation of the drug. General activity in relation to the central nervous system. Caution should be exercised when using other centrally acting drugs and alcohol simultaneously. Cerebrovascular adverse events, including stroke in elderly patients with dementia. Postural hypotension is uncommon in older adults. In patients over 65 years of age, it is recommended to periodically monitor blood pressure. Olanzapine should be prescribed with caution to patients with an established increase in the QTc interval, especially the elderly, with congenital long QT syndrome, congestive heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia. Cases of venous thromboembolism have been reported very rarely (less than 0.01%) when taking olanzapine . A cause-and-effect relationship between olanzapine therapy and venous thrombosis has not been established. Since patients with schizophrenia often have acquired risk factors for venous thrombosis, all possible other factors (for example, immobilization) should be identified and preventive measures taken. Zalasta Qu-tab tablets contain aspartame, a source of phenylalanine. The drug may be unsafe for people with phenylketonuria. Effects on the ability to drive a car and use other mechanical equipment: Since olanzapine may cause drowsiness and dizziness, patients should exercise caution when operating technical devices, incl. when driving a car.

Zalasta tablets 10 mg 28 pcs. In Nizhniy Novgorod

Olanzapine is an antipsychotic, antimanic and mood-stabilizing agent with a wide pharmacological spectrum of effects on a number of receptor systems. Preclinical studies have established affinity (Ki < 100 nmol/l) for various receptors: 5-HT2A/2C-, 5-HT3-, 5-HT6-serotonin, D1-, D2-, D3-, D4-, D5-dopamine , M1-5-muscarinic cholinergic receptors, α1-adrenergic and H1-histamine receptors. In animal studies evaluating the behavioral effects of olanzapine, olanzapine exhibited antagonism at serotonin, dopamine and m-cholinergic receptors, consistent with its receptor binding profile.

In vitro

and
in vivo
, olanzapine has a more pronounced affinity and activity for 5-HT2-serotonin receptors than for D2-dopamine receptors. According to electrophysiological studies, olanzapine selectively reduces the activity of mesolimbic (A10) dopaminergic neurons, and at the same time has a slight effect on striatal nerve pathways (A9) involved in the regulation of motor (motor) functions. Olanzapine reduces the conditioned defense response (in a test for antipsychotic activity) at doses below those that cause catalepsy (an effect indicative of motor [motor] adverse reactions). Unlike some other antipsychotics, olanzapine increases response in the anxiolytic test.

In a study in healthy volunteers with a single dose (10 mg) followed by positron emission tomography, olanzapine was more likely to bind to 5-HT2A-serotonin receptors than to D2-dopamine receptors. In addition, a study using single photon emission computed tomography in patients with schizophrenia found that patients who responded to olanzapine had lower connectivity with striatal D2 receptors compared with patients who responded to other antipsychotics and risperidone, while comparable to patients who responded to clozapine.

Clinical effects

In two of two placebo-controlled clinical trials and two of three comparative clinical trials involving more than 2900 patients with schizophrenia who had both positive and negative symptoms, olanzapine resulted in statistically significant reductions in both types of symptoms.

In an international, double-blind, comparative study of 1,481 patients with schizophrenia, schizoaffective and related disorders, and associated depressive symptoms (mean Montgomery-Asberg Depression Rating Scale score 16.6) in a prospective secondary analysis of score changes Mood assessment at the end of the study compared to baseline values showed a statistically significant (p=0.001) improvement in the patients' condition while taking olanzapine (-6.0) compared to haloperidol (-3.1).

The use of olanzapine for 3 weeks in patients with a manic or mixed episode of bipolar disorder was more effective in reducing the severity of manic symptoms compared with placebo and a complex of sodium valproate and valproic acid in a 1:1 ratio. Olanzapine also showed comparable efficacy to haloperidol in the proportion of patients achieving symptomatic remission of mania and depression at 6 and 12 weeks of use. The use of olanzapine 10 mg as part of combination therapy in combination with lithium or valproic acid for at least 2 weeks led to a greater reduction in the severity of mania than monotherapy with lithium or valproic acid after 6 weeks of use of the latter.

In a 12-month relapse prevention clinical trial in patients with a manic episode who achieved remission on olanzapine and were subsequently randomized to olanzapine or placebo, olanzapine was statistically significantly superior to placebo in achieving the primary endpoint of relapse of bipolar disorder. Olanzapine has also been shown to be superior to placebo in preventing relapse of both manic and depressive episodes.

Another 12-month relapse prevention clinical trial in patients with a manic episode who achieved remission on olanzapine plus lithium and were subsequently randomized to olanzapine alone or lithium alone found that olanzapine was statistically noninferior to the drug. lithium in relation to achieving the primary endpoint - relapse of bipolar disorder (olanzapine group - 30%, lithium group - 38.23%; p = 0.055).

An 18-month clinical trial of combination therapy with olanzapine plus a mood stabilizer (lithium or valproic acid) in patients with manic or mixed episodes showed no statistically significant superiority of long-term combination therapy over lithium or valproic acid monotherapy in terms of time to relapse of bipolar disorder. disorder defined in accordance with diagnostic (syndromic) criteria.

Zalasta®

Improvement in the patient's clinical condition with antipsychotic therapy can take from several days to several weeks; this period requires careful monitoring of the patient.

Risk of suicide

Patients with schizophrenia and bipolar disorder type 1 have a tendency to commit suicide; therefore, during pharmacotherapy, careful monitoring of patients at high risk of suicide is required. In order to reduce the risk of overdose, a minimum amount of the drug should be prescribed, sufficient to ensure the proper therapeutic effect.

Psychosis and/or behavioral disorders due to dementia

Olanzapine is not recommended for use in patients with psychosis and/or behavioral disorders due to dementia due to increased mortality and risk of cerebrovascular complications.

In placebo-controlled studies (6-12 weeks duration) in elderly patients (mean age 78 years) with psychosis and/or behavioral disturbance due to dementia, there was a two-fold increase in the incidence of death in patients receiving olanzapine compared with patients receiving olanzapine. from the placebo group (3.5% vs. 1.5%, respectively). The increased incidence of death was independent of the dose of olanzapine (mean daily dose 4.4 mg) and duration of treatment.

Risk factors that may predispose to increased mortality in this patient population include age over 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary disease (eg, pneumonia with or without aspiration), or concomitant use of benzodiazepines. However, the incidence of death was higher in patients receiving olanzapine compared with those receiving placebo, regardless of these risk factors.

Results from the same clinical trials indicate cerebrovascular adverse events (CVAEs) (eg, stroke, transient ischemic attack), including deaths. There was a threefold increase in the incidence of CVN in patients receiving olanzapine compared with patients receiving placebo (1.3% versus 0.4%, respectively). All patients receiving olanzapine and placebo who experienced cerebrovascular events had risk factors. Risk factors for the development of CVN associated with olanzapine treatment include age over 75 years and vascular/mixed dementia. Olanzapine was not effective in these studies.

Parkinson's disease

The use of olanzapine for the treatment of psychosis caused by the use of dopamine receptor agonists in Parkinson's disease is not recommended.

In clinical studies, worsening of parkinsonian symptoms and hallucinations was observed very often (and with a higher frequency than in the placebo group) (see section “Side effects”), the effectiveness of olanzapine for relieving psychotic symptoms was not greater than placebo. Inclusion criteria for these studies were: stable lowest effective dose of antiparkinsonian drugs (dopamine receptor agonist) and use of the same antiparkinsonian drugs and doses throughout the study. Olanzapine was started at 2.5 mg/day and increased at the discretion of the investigator to 15 mg/day.

Neuroleptic malignant syndrome (NMS)

NMS is a potentially lethal symptom complex caused by antipsychotic drugs. Rare cases of NMS have also been reported with the use of olanzapine. Clinical manifestations of NMS include hyperthermia, muscle rigidity, changes in mental status, and autonomic disturbances (unstable pulse or blood pressure, tachycardia, increased sweating, and arrhythmias). Additional signs may include: increased serum CPK activity, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms of NMS or has an unexplained high fever without additional manifestations of NMS, all antipsychotic medications, including olanzapine, should be discontinued.

Hyperglycemia and diabetes mellitus

Hyperglycemia and/or the development or decompensation of diabetes mellitus, sometimes accompanied by ketoacidosis or diabetic coma, have been reported infrequently, including several fatal cases (see section "Side effects").

In some cases, previous weight gain has been reported, which may be a predisposing factor. Close clinical monitoring is recommended in accordance with current antipsychotic treatment guidelines, such as measuring baseline blood glucose concentrations 12 weeks after initiation of olanzapine therapy and annually thereafter. Patients receiving any antipsychotic agents, including olanzapine, should be monitored for signs and symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness).

Patients with diabetes mellitus or risk factors for its development should regularly monitor blood glucose concentrations. Body weight should be checked regularly, for example before, 4, 8 and 12 weeks after starting olanzapine, and quarterly thereafter.

Lipid metabolic disorders

In placebo-controlled studies, undesirable changes in the lipid profile were observed in patients receiving olanzapine (see section "Side effects"). Lipid metabolic disorders should be corrected, especially in patients with dyslipidemia and patients with risk factors for developing lipid metabolic disorders.

Patients receiving any antipsychotic drugs, including olanzapine, should have their lipid profile monitored regularly in accordance with current antipsychotic treatment guidelines (eg, before starting treatment, after 12 weeks of starting therapy, and every 5 years thereafter).

Anticholinergic activity

Although olanzapine exhibited anticholinergic activity in vitro

In clinical studies, olanzapine therapy was rarely associated with anticholinergic side effects. However, clinical experience with olanzapine in patients with concomitant diseases is limited, so caution is recommended when prescribing the drug to patients with prostatic hypertrophy, paralytic ileus and similar conditions.

Liver dysfunction

Taking olanzapine was often, especially in the early stages of therapy, accompanied by a transient, asymptomatic increase in the activity of “liver” aminotransferases (AST and ALT) in the blood plasma. Caution and follow-up should be exercised in patients with increased plasma ALT and/or AST levels, symptoms of liver failure, conditions that cause decreased liver function reserve, or patients using potentially hepatotoxic drugs.

In patients with hepatitis (including hepatocellular, cholestatic and mixed liver disease), treatment with olanzapine should be discontinued.

Neutropenia

Olanzapine should be used with caution in patients with low white blood cell and/or neutrophil counts regardless of cause, a history of drug suppression/bone marrow toxicity, bone marrow suppression due to concomitant disease, radiation or chemotherapy, and in patients with hypereosinophilic conditions or myeloproliferative disease. Neutropenia has often been reported with concomitant use of olanzapine and valproic acid (see section "Side effects").

Discontinuation of therapy

Increased sweating, insomnia, tremor, anxiety, nausea and vomiting were reported rarely (≥0.01% and <0.1%) during abrupt discontinuation of olanzapine.

QT interval

In clinical studies, clinically significant prolongation of the QT interval (QT interval with Friederici correction [QTcF] ≥ 500 ms from a baseline QTcF < 500 ms) was observed infrequently (0.1-1%) in patients receiving olanzapine. differences with placebo in the incidence of adverse cardiac events. However, like other antipsychotics, caution should be exercised when prescribing olanzapine concomitantly with drugs that can prolong the QTc interval, especially in elderly patients, patients with congenital prolongation of the QT interval, chronic heart failure, myocardial hypertrophy, hypokalemia or hypomagnesemia.

Thromboembolism

Venous thromboembolism (VTE) has been reported infrequently (≥ 0.1% and < 1%) during olanzapine therapy. A cause-and-effect relationship between the use of olanzapine and VTE has not been established.

However, given that patients with schizophrenia often have acquired risk factors for the development of venous thromboembolism, it is necessary to identify all possible risk factors for VTE (for example, immobilization of patients) and take the necessary preventive measures.

General activity of the central nervous system (CNS)

Given the major effects of olanzapine on the central nervous system, caution should be exercised when using olanzapine concomitantly with other centrally acting drugs and ethanol. Because olanzapine exhibits dopamine receptor antagonism in vitro

, it can block the effects of direct and indirect dopamine receptor agonists.

Convulsions

Olanzapine should be used with caution in patients with a history of seizures or exposure to factors that lower the seizure threshold. Convulsions have been reported infrequently during treatment with olanzapine. In most cases, a history of seizures or risk factors for seizures were reported.

Tardive dyskinesia

In comparative studies lasting a year or less, treatment with olanzapine was statistically significantly less likely to be accompanied by the development of iatrogenic dyskinesia. However, the risk of developing tardive dyskinesia increases with long-term olanzapine therapy. Therefore, if signs or symptoms of tardive dyskinesia occur in a patient using olanzapine, dose reduction or discontinuation of olanzapine should be considered. After stopping therapy, these symptoms may temporarily worsen or even recur.

Postural hypotension

In clinical studies of olanzapine, postural hypotension was observed infrequently in elderly patients. As with other antipsychotics, periodic monitoring of blood pressure is recommended in patients over 65 years of age.

Sudden death from cardiovascular failure

According to post-registration experience with olanzapine, cases of sudden death from cardiovascular failure have been reported. In a retrospective observational cohort study, the risk of sudden sudden cardiovascular death in patients receiving olanzapine was approximately twice as high as in patients not receiving antipsychotics. The risk of olanzapine use in the study was comparable to that of the atypical antipsychotics included in the pooled analysis.

Use of olanzapine in children

Olanzapine is not recommended for use in children and adolescents. In studies in adolescents 13-17 years of age, various adverse reactions were reported, including weight gain, lipid metabolism disorders, and hyperprolactinemia.

Special information on excipients

The drug Zalasta® contains lactose and is therefore contraindicated in patients with lactase deficiency, lactose intolerance, and glucose-galactose malabsorption syndrome.

Zalasta

Use during pregnancy and breastfeeding

Due to limited experience with the drug in pregnant women, olanzapine should be used during pregnancy only if the expected benefit to the mother justifies the potential risk to the fetus.
Women should be informed of the need to inform their doctor about an existing or planned pregnancy during olanzapine therapy. There are isolated reports of tremor, arterial hypertension, lethargy and drowsiness in children born to mothers taking olanzapine in the third trimester of pregnancy. The study found that olanzapine is excreted into breast milk. The mean dosage (mg/kg) the child received when maternal steady-state concentrations were reached was 1.8% of the maternal olanzapine dose (mg/kg). Breastfeeding is not recommended during olanzapine therapy.

Use for liver dysfunction

With caution: liver failure.

Use for renal impairment

With caution: renal failure.

Use in children

Contraindicated in children and adolescents under 18 years of age.

Use in elderly patients

In elderly patients, a reduction in the initial dose (to 5 mg/day) is usually not recommended, but is possible in patients over 65 years of age if there are risk factors.

special instructions

If lipid levels change, therapy adjustments are required.

With abrupt cessation of olanzapine, very rarely (less than 0.01%) the following symptoms may develop: sweating, insomnia, tremor, anxiety, nausea or vomiting. When discontinuing the drug, a gradual dose reduction is recommended.

Since clinical experience with olanzapine in people with concomitant diseases is limited, the drug should be prescribed with caution to patients with prostatic hyperplasia or paralytic ileus.

Experience with the use of olanzapine in patients with psychosis in Parkinson's disease caused by taking dopaminomimetics. Olanzapine is not recommended for the treatment of psychosis in Parkinson's disease caused by dopaminomimetics. Symptoms of parkinsonism and hallucinations increase. However, olanzapine was not superior to placebo in treating psychosis.

Olanzapine is not indicated for the treatment of psychosis and/or behavioral disorders in dementia due to increased mortality and increased risk of cerebrovascular events (stroke, transient ischemic attack). The increase in mortality was independent of olanzapine dose or duration of therapy. Risk factors predisposing to increased mortality include: age over 65 years, dysphagia, sedation, malnutrition and dehydration, lung diseases (for example, pneumonia, including aspiration), concomitant use of benzodiazepines. However, the increased incidence of death in the olanzapine groups compared with placebo was independent of these risk factors

With antipsychotic therapy, improvement in the patient's clinical condition occurs within a period of several days to several weeks. During this period, the patient needs careful monitoring.

At the beginning of therapy, an asymptomatic increase in liver transaminases (ALT and AST) is possible. Caution should be exercised when prescribing olanzapine in patients with initially elevated AST and/or ALT levels, hepatic impairment and conditions potentially limiting liver function, and those taking hepatotoxic drugs. If ALT and/or AST increase during drug therapy, medical monitoring of the patient and, possibly, a reduction in the dose of the drug are recommended. When diagnosing hepatitis (including hepatocellular, cholestatic or mixed), olanzapine should be discontinued.

The drug should be used with caution in patients with leukopenia and/or neutropenia of any origin, myelosuppression of drug origin, as well as during radiation or chemotherapy, due to concomitant diseases, in patients with hypereosinophilic conditions or myeloproliferative diseases. Neutropenia has often been observed with concomitant use of olanzapine and valproic acid.

NMS is a potentially life-threatening condition associated with treatment with antipsychotic drugs (neuroleptics), incl. olanzapine. Clinical manifestations of NMS: fever, muscle rigidity, impaired consciousness, autonomic disorders (unstable pulse or labile blood pressure, tachycardia, increased sweating, arrhythmias). Additional symptoms of NMS: increased CPK, myoglobinuria (against the background of rhabdomyolysis) and acute renal failure. If symptoms of NMS develop, as well as an increase in body temperature for no apparent reason, it is necessary to discontinue all antipsychotics, incl. olanzapine.

Olanzapine should be used cautiously in patients with a history of seizures or the presence of factors that lower the seizure threshold. Seizures were rarely reported while taking olanzapine.

Olanzapine therapy was associated with a significantly lower incidence of tardive dyskinesia compared with haloperidol. The risk of developing tardive dyskinesia increases with increasing duration of treatment. If signs of this condition occur in a patient taking olanzapine, the drug should be discontinued or the dose reduced. Symptoms of dyskinesia may temporarily increase after discontinuation of the drug.

Caution should be exercised when using other centrally acting drugs and alcohol simultaneously.

Postural hypotension is uncommon in older adults. In patients over 65 years of age, it is recommended to periodically monitor blood pressure. Olanzapine should be administered with caution to patients with established QTc prolongation, especially the elderly, with congenital long QT syndrome, congestive heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia.

When taking olanzapine, very rarely (less than 0.01%) cases of venous thromboembolism have been reported. A cause-and-effect relationship between olanzapine therapy and venous thrombosis has not been established. Because patients with schizophrenia often have acquired risk factors for venous thrombosis, all possible other factors (eg, immobilization) should be identified and preventive measures taken.

Zalasta® tablets contain lactose. The drug should not be taken by patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.