Zalasta® Ku-tab® (Zalasta® Q-tab®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Dosage form: & nbsptablets, dispersible in the oral cavity
Composition:

1 tablet, dispersible in the oral cavity, 5 mg contains:

aactive substance: olanzapine 5.00 mg;

Excipients: mannitol 41.50 mg, microcrystalline cellulose 6.00 mg, crospovidone 6.00 mg, hypromellose low-substituted LH-21 4.50 mg, aspartame 0.50 mg, calcium silicate 10.00 mg, magnesium stearate 1.50 mg.

1 tablet, dispersible in the oral cavity, 7.5 mg, contains:

active substance: olanzapine 7.50 mg;

Excipients: mannitol 62.25 mg, microcrystalline cellulose 9.00 mg, crospovidone 9.00 mg, hypromellose low-substituted LH-21 6.75 mg, aspartame 0.75 mg, calcium silicate 15.00 mg, magnesium stearate 2.25 mg.

1 tablet, dispersible in the oral cavity, 10 mg contains:

active substance: olanzapine 10.00 mg;

Excipients: mannitol 83.00 mg, cellulose microcrystalline 12.00 mg, crospovidone 12.00 mg, hypromellose low-substituted LH-21 9.00 mg, aspartame 1.00 mg, calcium silicate 20.00 mg, magnesium stearate 3.00 mg.

1 tablet, dispersible in the oral cavity, 15 mg contains:

active substance: olanzapine 15.00 mg;

atExcipients: mannitol 124,50 mg, microcrystalline cellulose 18,00 mg, crospovidone 18,00 mg, hypromellose low-substituted LH-21 13.50 mg, aspartame 1.50 mg, calcium silicate 30.00 mg, magnesium stearate 4.50 mg.

1 tablet, dispersible in the oral cavity, 20 mg contains:

active substance: olanzapine 20.00 mg;

Excipients: mannitol 166.00 mg, microcrystalline cellulose 24.00 mg, crospovidone 24.00 mg, hypromellose low-substituted LH-21 18.00 mg, aspartame 2.00 mg, calcium silicate 40.00 mg, magnesium stearate 6.00 mg.

Description:

Tablets 5 mg, 7, 5 mg, 10 mg, 15 mg, 20 mg: round, slightly biconcave tablets of yellow color. Insignificant individual inclusions and marbling are allowed.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)
Pharmacodynamics:

Olanzapine is an antipsychotic agent (neuroleptic) with a broad pharmacological spectrum of action. The antipsychotic effect is due to the blockade of dopamine D2-receptor mesolimbic and mesocortical system; sedative effect - adrenoreceptor blockade of the reticular formation of the brainstem; antiemetic effect - blockade of dopamine D2receptors of the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus. In addition, it affects muscarinic, adrenergic, H1-gastamine and some subclasses of serotonin receptors.

Olanzapine significantly reduces productive (delusions, hallucinations) and negative symptoms (hostility, suspicion, emotional and social autism) of psychoses. Rarely causes extrapyramidal disorders.

Pharmacokinetics:

Absorption of olanzapine is high, does not depend on the intake food; time needed to achieve the maximum concentration of the drug in the blood plasma (TSmOh) after oral administration - 5-8 hours Penetrates through the histohematic barriers, incl. blood-brain barrier (BBB). Metabolized in the liver, active metabolites are not formed, the main circulating metabolite is glucuronide, does not penetrate the GEB. Smoking, sex and age affect half-life (T1/2) and plasma clearance. In persons over 65 years of age, T1/2 is 51.8 h and plasma clearance is 17.5 l / h; in persons younger than 65 years, 33.8 hours and a plasma clearance of 18.2 liters / hour. Plasma clearance is lower in patients with hepatic insufficiency, women and non-smokers in comparison with the corresponding groups of individuals. It is excreted mainly by kidneys (60%) in the form of metabolites.

Indications:

The drug is indicated for the treatment of schizophrenia.

Zalasta® Ku-tab® effectively supports the improvement of clinical symptoms in long-term treatment in patients with initial positive reactions to the drug.Zalasta® Cu-tab® is indicated for the treatment of moderate or severe episodes of mania.

In patients with manic episodes with a good effect of olanzapine therapy, the drug is indicated for the prevention of recurrence of mania in bipolar disorder.

Contraindications:

- Hypersensitivity to olanzapine or other components of the drug;

- angle-closure glaucoma;

- children under 18 years of age (efficacy and safety not established);

- lactation period.

Carefully:

Renal failure, hepatic insufficiency, prostatic hyperplasia, paralytic intestinal obstruction, epilepsy, history of convulsive syndrome, leukopenia and / or neutropenia of various genesis, myelosuppression of various genesis, incl. myeloproliferative diseases, hypereosinophilic syndrome, cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, congenital increase in the interval QT on an electrocardiogram (ECG) (increase in the corrected interval QT (QTc) on the ECG) or in the presence of conditions potentially capable of causing an increase in the interval QT (for example, simultaneous administration of drugs that extend the interval QT, congestive heart failure, hypokalemia, hypomagnesemia), elderly age, as well as simultaneous intake of other drugs of central action; phenylketonuria, immobilization, pregnancy.

Pregnancy and lactation:

Due to the limited experience of using the drug in pregnant women, olanzapine It should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus. Women should be informed of the need to inform the doctor about the onset or planned pregnancy on the background of olanzapine therapy. There are isolated reports of tremors, arterial hypertension, lethargy and drowsiness in children born to mothers who took olanzapine in the third trimester of pregnancy.

The study found that olanzapine excreted in breast milk. The average dosage (mg / kg) received by a child when the mother's equilibrium concentration reached equilibrium was 1.8% of the mother's olanzapine dose (mg / kg). It is not recommended to breast-feed on the background of olanzapine therapy.

Dosing and Administration:

Tablets for resorption Zalasta® Ku-tab® quickly dissolve in the mouth under the action of saliva, after which they are easily swallowed. Because the tablets are fragile, they should be taken immediately after removal from the blister. Alternatively, just before use, the tablet can be dissolved in a full glass of water.

The Zalast® Cu-tab® resorption tablets are bioequivalent to simple Zalast® tablets, the speed and degree of absorption, dosage and dosage regimen are also equivalent. Zalasta® Cu-tab® can be used as an alternative to Zalast® tablets.

Because foodand does not affect the absorption of the drug, Zalast® Cu-tab® resorption tablets can be taken regardless of food intake. In case of cancellation, a gradual dose reduction is recommended.

Schizophrenia: the recommended initial dose of the drug is 10 mg per day.

Episode of the Mania: the initial dose is 15 mg in one dose with monotherapy or 10 mg per day as part of a combination therapy.

Prevention of relapse in bipolar disorder: the recommended initial dose of the drug in a state of remission is 10 mg per day.For patients already receiving Zalast® Cu-tab® for the treatment of manic episodes, maintenance therapy is administered in the same doses. On the background of therapy with Zalast® Cu-tab®, if a new manic, mixed or depressive episode develops, if necessary, increase the dose of the drug with additional treatment of mood disorders, according to clinical indications.

The daily dose of the drug in the treatment of schizophrenia, a manic episode or the prevention of recurrence of bipolar disorder may be 5-20 mg / day, depending on the clinical state of the patient. An increase in the dose above the recommended initial dose is only possible after an adequate repeated clinical assessment of the patient's condition and is usually performed with an interval of at least 24 hours.

Special patient groups

In elderly patients a reduction in the initial dose (up to 5 mg per day) is usually not recommended, but it is possible in patients older than 65 years in the presence of risk factors (see section "Special instructions").

Patients with liver and / or kidney disease It is recommended to reduce the initial dose to 5 mg / day. With moderate hepatic insufficiency (cirrhosis,class A or B according to the Child-Pugh classification of hepatocellular insufficiency in patients with cirrhosis of the liver), the initial dose is 5 mg / day, a further dose increase with caution is possible.

Women There is no need to change the dosage in comparison with men.

Have non-smoking patients dosage adjustment with smokers (see section "Interaction with other drugs") is not required.

If the patient has more than one factor that can influence the absorption of the drug (female, elderly, non-smokers), it may be necessary to reduce the initial dose. If necessary, further increase in dose with caution.

Side effects:

Classification of the incidence of adverse events (WHO): very often> 1/10; often from> 1/100 to <1/10; infrequently from> 1/1000 to <1/100; rarely from> 1/10000 to <1/1000; very rarely from <1/10000, including individual messages.

From the central (CNS) and peripheral nervous system: very often - drowsiness; often - dizziness, akathisia, parkinsonism, dyskinesia; rarely - convulsive syndrome (more often in the background of convulsive syndrome in anamnesis); very rarely - malignant neuroleptic syndrome (see section "Special instructions"), dystonia (including oculogic crisis) and tardive dyskinesia.With a sharp abolition of olanzapine, symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting are very rarely noted.

From the side of the cardiovascular system: often - arterial hypotension (including orthostatic); infrequently - a bradycardia with a collapse or without; very rarely - an increase in the QTc interval on the ECG (see section "Special instructions"), ventricular tachycardia / fibrillation and sudden death (see section "Special instructions"), thromboembolism (including pulmonary artery embolism and deep vein thrombosis).

From the gastrointestinal tract (GIT): often - transient anticholinergic effects, incl. constipation and dry mouth; very rarely - pancreatitis.

Metabolic and nutritional disorders: very often - weight gain; often - increased appetite; very rarely hyperglycemia and / or decompensation of diabetes mellitus, sometimes manifested by ketoacidosis or coma, including fatal outcome; hypertriglyceridemia, hypercholesterolemia, hypothermia.

Hepatobiliary disorders: often - transient, asymptomatic increase in the level of "liver" transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)), special at beginning of treatment (see"Special instructions"); rarely - hepatitis (including hepatocellular, cholestatic or mixed liver damage).

On the part of the organs of hematopoiesis and lymphatic system: often - eosinophilia; rarely - leukopenia; very rarely - thrombocytopenia, neutropenia.

From the organs of the musculoskeletal system: very rarely - rhabdomyolysis.

From the organs of the genitourinary system: very rarely - urinary retention, priapism.

From the skin and subcutaneous tissue: infrequently, photosensitization reactions.

Allergic reactions: rarely - skin rash; very rarely - anaphylactoid reactions, angioedema, skin itching or urticaria.

Other: often - asthenia, peripheral edema; very rarely - alopecia.

Laboratory parameters: very often hyperprolactinemia, but clinical manifestations (eg, gynecomastia, galactorrhea and breast enlargement) are rare. In most patients, the level of prolactin spontaneously normalized without the abolition of therapy. Infrequent - increase in the level of creatine phosphokinase (CK); very rarely - an increase in the level of alkaline phosphatase (APF) and total bilirubin.

In elderly patients with dementia, a large incidence of deaths and cerebrovascular disorders (stroke, transient ischemic attacks) is documented in studies.Very frequent in this category of patients were violations of gait and fall. Also often observed pneumonia, fever, lethargy, erythema, visual hallucinations and urinary incontinence.

Among patients with drug (against the background of dopamine agonists) psychoses on the background of Parkinson's disease often recorded worsening of parkinsonian symptoms and the development of hallucinations.

There are data on the development of neutropenia (4.1%) against a combination therapy with valproic acid in patients with bipolar mania. Simultaneous therapy with valproic acid or lithium helps to increase the frequency (> 10%) of tremors, dry mouth, increase appetite and weight gain. Violations of speech were often recorded (from 1 to 10%). In the first 6 weeks of combined therapy with lithium, the incidence of weight gain increases. Long-term therapy with olanzapine (up to 12 months) in order to prevent relapse in patients with bipolar disorder was accompanied by an increase in body weight.

Overdose:

Symptoms: very frequent (> 10%) with an overdose of olanzapine are: tachycardia, agitation / aggression, dysarthria, various extrapyramidal symptoms,a decrease in the level of consciousness from inhibition to coma; less than 2% of cases occur: delirium, convulsions, coma, malignant neuroleptic syndrome, respiratory depression, aspiration, hypertension or hypotension, cardiac arrhythmias; in very rare cases - cardiopulmonary insufficiency. The minimum dose of olanzapine for acute overdose with a lethal outcome is 450 mg, the maximum dose was recorded for an overdose with a favorable outcome (survival) of 1500 mg.

Treatment: there is no specific antidote. It is not recommended to provoke vomiting. It is necessary to carry out: gastric lavage, intake of activated charcoal (reduces the bioavailability of olanzapine by 60%), symptomatic treatment under the control of vital functions, including treatment of arterial hypotension and vascular collapse, maintenance of respiratory function. It is not recommended to use epinephrine, dopamine or other sympathomimetics with beta-adrenergic activity, the latter can aggravate arterial hypotension. To identify possible arrhythmias, monitoring of cardiovascular activity is necessary.The patient should be under continuous medical supervision until complete recovery.

Interaction:

Potential drug interactions affecting olanzapine metabolism: olanzapine is metabolized by the enzyme CYP1A2, therefore inhibitors or inducers of cytochrome P450 isoenzymes exhibiting specific activity against CYP1A2 may affect the pharmacokinetic parameters of olanzapine.

Inductors CYP1A2: The clearance of olanzapine can be increased in smokers or with the simultaneous administration of carbamazepine, which leads to a decrease in the concentration of olanzapine in the blood plasma. Clinical observation is recommended. some cases require an increase in the dose of the drug.

Inhibitors CYP1A2: fluvoxamine, a specific inhibitor CYP1A2 - significantly reduces the clearance of olanzapine. Average increase in maximum concentration (CmOh) of olanzapine after the administration of fluvoxamine in non-smokers was 54%, and for men who smoke, 77%. The average increase in the area under the "concentration-time" curve (AUC) of olanzapine in these categories of patients were 52% and 108%, respectively. In patients receiving fluvoxamine or any other inhibitor CYP1A2 (e.g., ciprofloxacin), therapy with olanzapine is recommended to begin with smaller doses. Reduction of the dose of olanzapine may also be required in case of adherence to therapy with inhibitors CYP1A2.

Drug interactions affecting / not affecting the bioavailability of olanzapine: Activated carbon reduces the absorption of olanzapine by oral intake by 50-60%, so it should be taken at least 2 hours before or after taking olanzapine.

Fluoxetine (inhibitor CYP450), a single dose of magnesium or aluminum-containing antacids or cimetidine do not affect the pharmacokinetics of olanzapine.

Potential ability of olanzapine to influence other drugs

Olanzapine may reduce the effects of direct and indirect dopamine agonists.

In conditions in vitro olanzapine does not suppress the main isoenzymes CYP450 (e.g., 1A2, 2D6, 2C9, 2C19, 3A4). In vivo There was no inhibition of the metabolism of the following active substances: tricyclic antidepressants (CYP2D6), warfarin (CYP2C9), theophylline (CYP1A2) and diazepam (CYP3A4 and 2C19).

No interaction was detected when used simultaneously with lithium or biperidene.Therapeutic monitoring of the content of valproic acid in plasma showed that with simultaneous administration with olanzapine, no changes in valproic acid doses are required (see the "Side effect" section).

Care should be taken when using other central-action drugs at the same time. Despite the fact that a single dose of alcohol (45 mg / 70 kg) does not have a pharmacokinetic effect, alcohol intake together with olanzapine may be accompanied by an increase in depressive effect on the central nervous system.

Special instructions:

There are very rare reports of development Hyperglycemia and / or decompensation of diabetes mellitus, sometimes accompanied by the development of ketoacidosis or ketoacidotic coma, including there are reports of several fatal cases. In some cases, there was a previous decompensation of weight gain, which could become a predisposing factor. Patients with diabetes or with risk factors for the development of this disease are recommended regular clinical control and monitoring of blood glucose levels.

When the level of lipids changes, correction of therapy is required.

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

Anticholinergic activity. Since clinical experience with olanzapine in people with concomitant diseases is limited, the drug should be used with caution in patients with prostatic hyperplasia, paralytic intestinal obstruction.

Experience with olanzapine in patients with psychoses in Parkinson's disease caused by dopaminomimetic drugs. Olanzapine It is not recommended for the treatment of psychoses in Parkinson's disease caused by dopaminomimetic treatment. The symptoms of parkinsonism and hallucinations increase. Wherein olanzapine on the effectiveness of psychosis treatment did not exceed the placebo.

Olanzapine is not indicated for the treatment of psychoses and / or behavioral disorders in dementia, due to increased mortality and increased risk of cerebrovascular disorders (stroke, transient ischemic attacks). The increase in mortality does not depend on the dose of olanzapine or the duration of therapy.Risk factors predisposing to increased mortality include: age over 65 years, dysphagia, sedation, malnutrition and dehydration, lung diseases (eg, pneumonia, including aspiration), simultaneous reception of benzodiazepines. However, the increased incidence of death in olanzapine compared with placebo did not depend on these risk factors.

With antipsychotic therapy, the improvement in the clinical state of the patient occurs in the period from several days to several weeks. During this period, the patient needs careful observation.

Dysfunction of the liver. At the beginning of therapy, an asymptomatic increase in liver transaminases (ALT and ACT). Patients with initially elevated levels ACT and / or ALT, with hepatic insufficiency and conditions potentially limiting the functionality of the liver, as well as those taking hepatotoxic drugs, caution should be exercised when prescribing olanzapine. With increasing ALT and / or ACT on the background of drug therapy, it is recommended that medical supervision of the patient and, possibly, a reduction in the dose of the drug be recommended.When diagnosing hepatitis (including hepatocellular, cholestatic or mixed) olanzapine necessary cancel.

Hematologic 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 radiation or chemotherapy, due to concomitant diseases, in patients with hypereosinophilic conditions or myeloproliferative diseases. Neutropenia has often been noted with the simultaneous use of olanzapine and valproic acid (see the "Side effect" section).

Malignant neuroleptic syndrome (CNS). ZNS is a potentially life-threatening condition associated with antipsychotic medication (neuroleptics), incl. olanzapine. Clinical manifestations of ZNS: fever, rigidity of mytpc, impaired consciousness, autonomic disorders (unstable pulse or labile blood pressure, tachycardia, increased sweating, arrhythmias). Additional symptoms of ZNS: increased CK, myoglobinuria (against rhabdomyolysis) and acute renal failure.With the development of symptoms of the ZNS, as well as an increase in body temperature for no apparent reason, it is necessary to cancel all neuroleptics, including. olanzapine.

Convulsive Syndrome. Olanzapine should be cautiously prescribed to patients with a history of seizures or the presence of factors that reduce the threshold of convulsive readiness. On the background of taking olanzapine, seizures were rarely recorded.

Late dyskinesia. The therapy with olanzapine was accompanied by a significantly lower incidence of late dyskinesia, in comparison with haloperidol. The risk of developing tardive dyskinesia increases with increasing duration of treatment. When there are signs of this condition in the patient receiving olanzapine, you should cancel the drug or reduce its dose. Symptoms of dyskinesia may temporarily increase after the drug is discontinued.

Total activity against the central nervous system. Care should be taken when using other drugs of central action and alcohol.

Cerebrovascular adverse events, including stroke in elderly patients with dementia. In elderly people, postural arterial hypotension is not often observed. Have patients older than 65 years are recommended to periodically monitor blood pressure (BP). Olanzapine should be administered with caution to patients with an established interval QTc, especially the elderly, with a congenital syndrome of an elongated interval QT, congestive heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia.

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

Zalast® Cu-Tab® tablets contain aspartame - A source of phenylalanine. The drug may be unsafe for people suffering from phenylketonuria.

Effect on the ability to drive transp. cf. and fur:

Because the olanzapine may cause drowsiness and dizziness, patients should exercise caution when working with technical devices, incl. when driving.

Form release / dosage:

Tablets dispersible in the oral cavity, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg.

Packaging:

7 tablets per blister.

For 4 or 8 blisters are placed in a pack of cardboard along with instructions for use.

Storage conditions:

Store at a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription
Registration number:LSR-005803/09
Date of registration:17.07.2009
The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO
Manufacturer: & nbsp
Representation: & nbspKRKA KRKA Slovenia
Information update date: & nbsp16.08.2015
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