Zalasta Ku-tab, 5 mg, tablets, dispersible in the oral cavity, 28 pcs.
Orally dispersible tablets Zalasta® Ku-tab quickly dissolve in the oral cavity under the influence of saliva, after which they are easily swallowed. Since the tablets are fragile, they should be taken immediately after removal from the blister. Alternatively, the tablet may be dissolved in a full glass of water immediately before use.
Orally dispersible tablets Zalasta® Ku-tab are bioequivalent to simple Zalasta® tablets, the rate and extent of absorption, dose and dosage regimen are also equivalent. Zalasta® Ku-tab can be used as an alternative to Zalasta® tablets.
Because food does not affect the absorption of the drug; Zalasta® Ku-tab tablets can be taken regardless of meals. If the drug is discontinued, a gradual dose reduction is recommended
Schizophrenia
. The recommended initial dose of the drug is 10 mg/day.
Episode of mania.
The initial dose is 15 mg in 1 dose for monotherapy or 10 mg/day as part of combination therapy.
Relapse prevention in bipolar disorder.
The recommended initial dose of the drug in remission is 10 mg/day. For patients already receiving Zalasta® Qu-tab for the treatment of an episode of mania, maintenance therapy is carried out in the same doses. During therapy with Zalasta® Qu-tab, in the event of a new manic, mixed or depressive episode, the dose of the drug should be increased, if necessary, with additional treatment of mood disorders, in accordance with clinical indications.
The daily dose of the drug for the treatment of schizophrenia, a manic episode, or the prevention of relapses of bipolar disorder can be 5–20 mg/day, depending on the clinical condition of the patient. Increasing the dose above the recommended initial dose is possible only after an adequate re-clinical assessment of the patient’s condition and is usually carried out at intervals of at least 24 hours.
Special patient groups
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.
Liver and/or kidney diseases.
For patients with liver and/or kidney diseases, it is recommended to reduce the initial dose to 5 mg/day. For moderate liver failure (cirrhosis, class A or B according to the Child-Pugh classification of hepatic cell failure in patients with liver cirrhosis), the initial dose is 5 mg/day, further dose increases are possible with caution.
Women
no change in dosage is required compared to men.
Smoking.
In non-smoking patients, no dose adjustment is required compared to smokers.
If the patient has more than one factor that can affect the absorption of the drug (female gender, elderly age, non-smokers), a reduction in the initial dose may be necessary. If necessary, further increase in dose is possible with caution.
Zalasta® Q-tab®
Clinical improvement with antipsychotic treatment may occur within a few days to several weeks. Careful monitoring of patients during this period is required.
Psychosis due to dementia and/or behavior disorder
Olanzapine is not indicated for the treatment of psychosis associated with dementia and/or behavioral disorders due to the increased mortality and risk of cerebrovascular accidents in these patients.
In placebo-controlled studies (lasting 6 to 12 weeks) in elderly patients (mean age 78 years) with dementia-related psychosis and/or behavioral disturbances, there was a two-fold increase in deaths in the olanzapine group compared with placebo (3. 5% and 1.5%, respectively). The higher mortality rate was not associated with the dose of olanzapine (mean dose 4.4 mg) or duration of treatment.
Risk factors that may predispose this group of patients to higher mortality when treated with olanzapine include age ≥ 65 years, dysphagia, sedation, malnutrition and dehydration, presence of pulmonary pathology (eg, pneumonia with or without aspiration), or concomitant use with benzodiazepines. However, the incidence of death was higher in patients treated with olanzapine compared with patients treated with placebo, regardless of these risk factors.
In the same clinical studies, cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatal cases, were observed. In placebo-controlled studies, there was a threefold higher incidence of cerebrovascular adverse events in patients in the olanzapine group compared with the placebo group (1.3% versus 0.4%, respectively). All patients with cerebrovascular events treated with olanzapine and placebo had preexisting risk factors for cerebrovascular adverse events.
Age >75 years and vascular or mixed dementia were identified as risk factors for cerebrovascular adverse events during treatment with olanzapine. The effectiveness of olanzapine was not established in these studies.
Parkinson's disease
The use of olanzapine is not recommended in the treatment of psychosis induced by dopamine receptor agonists in Parkinson's disease.
In clinical trials, worsening Parkinson's disease symptoms and hallucinations were reported very frequently and at a higher rate than placebo, and olanzapine was not superior to placebo in treating psychotic symptoms. In these clinical studies, patients were initially required to stabilize on the lowest effective dose of Parkinson's disease medications (dopamine agonists) and continue to take them at the same dose throughout the study. The starting dose of olanzapine was 2.5 mg per day and could be increased to a maximum of 15 mg per day at the discretion of the investigator.
Neuroleptic malignant syndrome (NMS)
Neuroleptic malignant syndrome is a potentially life-threatening condition that occurs during the use of antipsychotic drugs. Rare cases of NMS have also been reported with olanzapine. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and autonomic disturbances (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias).
Additional signs may include increased CPK activity, myoglobinuria (rhabdomyolysis), and acute renal failure. Clinical manifestations of NMS or a significant unexplained increase in body temperature without other symptoms of NMS require discontinuation of all antipsychotics, including olanzapine.
Hyperglycemia and diabetes mellitus
Cases of hyperglycemia and/or development or decompensation of diabetes mellitus, in some cases accompanied by ketoacidosis and diabetic coma, including death, have been reported infrequently.
In some cases, there was an increase in body weight, which could serve as a predisposing factor. Close clinical monitoring of patients with diabetes mellitus and patients with risk factors for developing diabetes mellitus is recommended according to the following guidelines: measurement of blood glucose concentrations at baseline, 12 weeks after starting olanzapine, and annually thereafter.
Patients taking antipsychotic drugs, including olanzapine, should be monitored for signs and symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, weakness).
Patients with diabetes mellitus or risk factors for diabetes mellitus require regular monitoring of blood glucose concentrations. Regular monitoring of body weight is necessary: before starting treatment, 4, 8 and 12 weeks after starting olanzapine, and subsequently every 3 months.
Change in lipid profile
In placebo-controlled studies, undesirable lipid changes were observed in patients receiving olanzapine. Changes in the lipid profile should be adjusted according to clinical need, especially in patients with dyslipidemia and in patients with risk factors for developing lipid disorders. Patients taking antipsychotic drugs, including olanzapine, should have their lipid profile checked regularly as recommended: before starting treatment, 12 weeks after starting olanzapine, and every 5 years thereafter.
Anticholinergic activity
Although olanzapine exhibited anticholinergic activity in in vitro
, the use of olanzapine in clinical studies revealed a low incidence of complications associated with it. However, since clinical experience with olanzapine in patients with underlying medical conditions is limited, caution should be exercised when prescribing olanzapine in patients with clinically significant prostatic hypertrophy, paralytic ileus, and similar conditions.
Liver dysfunction
Often, especially in the early stages of therapy, a transient asymptomatic increase in the activity of “liver” aminotransferases (AST and ALT) was noted. Particular caution is required when increasing serum AST and/or ALT activity in patients with symptoms of liver dysfunction, previously diagnosed conditions associated with limited liver functional reserve, or in patients receiving treatment with potentially hepatotoxic drugs. If hepatitis (including hepatocellular, cholestatic or mixed) is diagnosed, olanzapine should be discontinued.
Neutropenia
Olanzapine should be used with caution in patients with low white blood cell and/or neutrophil counts; in patients receiving drugs that can cause neutropenia; in patients with a history of drug suppression of bone marrow function; in patients with suppression of bone marrow function due to concomitant disease, radiation or chemotherapy; and in patients with eosinophilia or myeloproliferative diseases. Cases of neutropenia have been frequently reported with concomitant use of olanzapine and valproate.
Discontinuation of therapy
In rare cases (≥0.01% and <0.1%), the following acute symptoms were observed when olanzapine was abruptly stopped: increased sweating, insomnia, tremor, anxiety, nausea or vomiting.
QT interval
In clinical studies, clinically significant prolongation of the QTc interval (QTcF > 500 ms at any time after the start of treatment with a baseline QTcF < 500 ms) occurred infrequently (0.1%-1%) in patients receiving olanzapine. , with no significant differences in associated cardiac complications compared with placebo. However, caution should be exercised when prescribing olanzapine with drugs that increase the QTc interval, especially in elderly patients with congenital long QT syndrome, congestive heart failure, cardiac hypertrophy, hypokalemia and hypomagnesemia.
Thromboembolism
Infrequently (≥ 0.1% and < 1%) cases of a temporal association between the development of venous thromboembolism and olanzapine therapy have been reported. The presence of a cause-and-effect relationship between olanzapine and venous thromboembolism has not been established. However, given that patients with schizophrenia often have acquired risk factors for the development of thromboembolism, all possible risk factors for this complication, including immobilization of patients, should be identified and the necessary preventive measures should be taken.
General activity in relation to the central nervous system
Given the primary central nervous system effects of olanzapine, caution should be exercised when olanzapine is used in combination with other centrally acting drugs and alcohol. Because olanzapine can antagonize dopamine receptors in vitro, it may antagonize 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. Cases of seizures were uncommon in patients taking olanzapine, and most of these cases reported a history of seizures or risk factors for seizures.
Tardive dyskinesia
In comparative studies lasting up to a year, treatment with olanzapine was significantly less likely to be accompanied by the development of dyskinesia requiring drug correction. However, the increased risk of tardive dyskinesia should be taken into account with long-term therapy with antipsychotics. If signs of tardive dyskinesia develop, it is recommended to reduce the dose or discontinue olanzapine. Symptoms of tardive dyskinesia may increase or manifest after discontinuation of the drug.
Postural hypotension
Postural hypotension was observed infrequently in clinical studies of olanzapine in elderly patients. It is recommended to periodically measure blood pressure in patients over 65 years of age.
Sudden death from cardiovascular failure
A case of sudden death has been reported following post-marketing surveillance of olanzapine. In a retrospective observational study, the risk of suspected sudden cardiovascular death in patients receiving olanzapine was approximately twice that of patients not taking antipsychotics. In this study, the risk with olanzapine was comparable to the risk with 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
Zalasta® Ku-tab® contains aspartame, which is a source of phenylalanine. The drug may be unsafe for people suffering from phenylketonuria.
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
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, incl. there are reports of several fatal cases. In some cases, there was an increase in body weight preceding decompensation, which could become a predisposing factor. In patients with diabetes mellitus and risk factors for the development of this disease, regular clinical monitoring and monitoring of blood glucose levels is recommended.
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.
