Заласта® Ku-tab

General characteristics. Structure:

Active agent: olanzapine of 5 mg, 7,5 mg, 10 mg, 15 mg and 20 mg
Excipients: Mannitolum, cellulose microcrystallic, кросповидон, a gipromelloza the low-replaced LH-21, aspartame, calcium silicate, magnesium stearate.

Pharmacological properties:

Olanzapine – antipsychotic means (neuroleptic) with a wide pharmacological action spectrum. Antipsychotic action is caused by blockade dopamine D2 receptors of mesolimbic and mesocortical system; sedative action – blockade of adrenoceptors of a reticular formation of a trunk of a brain; antiemetic action – blockade dopamine D2 receptors of a trigger zone of the emetic center; hypothermal action – blockade of dopamine receptors of a hypothalamus. Besides, exerts impact on muskarinovy, adrenergic, H1-histamine and some subclasses of serotoninovy receptors.

Olanzapine authentically reduces productive (nonsense, hallucinations) and negative symptomatology (hostility, suspiciousness, emotional and social autism) of psychoses. Seldom causes extrapyramidal disturbances.

Pharmacokinetics. Olanzapine absorption high, does not depend on meal; time necessary for achievement of the maximum concentration of drug in a blood plasma (TCmax) after oral administration - 5-8 h. Gets through gistogematichesky barriers, including a blood-brain barrier (GEB). It is metabolized in a liver, active metabolites are not formed, the main circulating metabolite - a glucuronide, does not get through GEB.

Smoking, gender and age influence an elimination half-life (T1/2) and plasma clearance. At persons 65 years of T1/2 are more senior makes 51,8 h and plasma clearance – 17,5 l/hour; at persons 65 years – 33,8 h and plasma clearance – 18,2 l/hour are younger. The plasma clearance is lower at patients with a liver failure, women and non-smoking in comparison with the corresponding groups of persons. It is removed preferential by kidneys (60%) in the form of metabolites.

Indications to use:

Drug is shown for treatment of schizophrenia.

Заласта® Ku-tab effectively supports improvement of clinical symptomatology at prolonged treatment at patients with initial positive reaction to drug.

The drug Zalasta® of Ku-tab is shown for treatment of moderate or heavy episodes of a mania.

At patients with maniacal episodes at good effect of therapy by olanzapine drug is shown for prevention of a recurrence of a mania at bipolar disorder.

Route of administration and doses:

Tablets for a rassasyvaniye of Zalasta® of Ku-tab are quickly dissolved in an oral cavity under the influence of saliva then are easily swallowed. As tablets brittle, after extraction from the blister them it is necessary to accept immediately. As an alternative, just before reception the tablet can be dissolved in a full glass of water.

Tablets for a rassasyvaniye of Zalasta® of Ku-tab of a bioekvivalentna to the simple tablets Zalasta®, the speed and extent of absorption, a dose and the mode of dosing are also equivalent. Заласта® can be applied by Ku-tab as an alternative to the tablets Zalasta®.

Since food does not influence absorption of drug, a pill for a rassasyvaniye of Zalasta® of Ku-tab can be taken irrespective of meal. In case of drug withdrawal the gradual dose decline is recommended.

Schizophrenia: the recommended initial dose of drug – 10 mg a day.

Mania episode: the initial dose makes 15 mg in one step at monotherapy or 10 mg a day as a part of a combination therapy.

Prevention of a recurrence at bipolar disorder: the recommended initial dose of drug in a condition of remission - 10 mg a day. For the patients who are already receiving the drug Zalasta® of Ku-tab for treatment of an episode of a mania, the maintenance therapy is carried out in the same doses. Against the background of therapy by the drug Zalasta® of Ku-tab in case of development of the new maniacal, mixed or depressive episode if necessary it is necessary to increase a drug dose with additional treatment of disturbances of mood, according to clinical indications.

The daily dose of drug at therapy of schizophrenia, a maniacal episode or prevention of a recurrence of bipolar disorder can make 5 - 20 mg/days, depending on a clinical condition of the patient. Increase in a dose over recommended initial is possible only after adequate repeated clinical assessment of a condition of the patient and not less than 24 hours are usually spent with an interval.

Special groups of patients:

At elderly patients decrease in an initial dose (to 5 mg a day) usually is not recommended, but perhaps at patients 65 years with risk factors are more senior (see the section "Special Instructions").

Reduction of an initial dose to 5 mg/days is recommended to patients with diseases of a liver and/or kidneys. At a moderate liver failure (cirrhosis, a class A or B on classification Chayld – I Drink hepatocellular insufficiency at patients with cirrhosis) the initial dose makes 5 mg / cут, perhaps further increase in a dose with care.

Women do not need change in dosing in comparison with men.

In comparison with the smoking patients (see the section "Interaction with Other Medicines") it is not required from non-smoking patients of dose adjustment.

In the presence at the patient more than one factor, capable to influence drug absorption (a female, advanced age, non-smoking), perhaps will be required decrease in an initial dose. If necessary perhaps further increase in a dose with care.

Features of use:

There are very rare messages on development of a hyperglycemia and/or decompensation of a diabetes mellitus which sometimes were followed by development of ketoacidosis or a ketoatsidotichesky coma including there are messages on several fatal cases. The increase in body weight preceding a decompensation which could become the contributing factor was in certain cases noted. Or with risk factors of development of this disease regular clinical control and control of level of glucose of blood is recommended to the patients suffering from a diabetes mellitus.

At change of level of lipids therapy correction is required.

At the sharp termination of reception of olanzapine very seldom (less than 0,01%) development of the following symptoms is possible: perspiration, sleeplessness, tremor, alarm, nausea or vomiting. At drug withdrawal the gradual dose decline is recommended.

Anticholinergic activity. As clinical experience of use of olanzapine for people with associated diseases is limited, patients should appoint drug with care with a prostate hyperplasia, paralytic intestinal impassability.

Experience of use of olanzapine for the patients with psychoses at Parkinson's disease called by reception of dofaminomimetik. Olanzapine is not recommended for treatment of the psychoses at Parkinson's disease caused by reception of dofaminomimetik. Symptoms of parkinsonism and hallucination amplify. At the same time olanzapine did not surpass placebo in efficiency of treatment of psychoses.

Olanzapine is not shown for treatment of psychoses and/or behavioural frustration at dementia, in connection with the increased mortality and increase in risk of cerebrovascular disturbances (a stroke, the tranzitorny ischemic attacks). Increase in mortality does not depend on a dose of olanzapine or duration of therapy. Treat the risk factors contributing to increase in mortality: the age is more senior than 65 years, a dysphagy, sedation, a hyponutrient and dehydration, diseases of lungs (for example, pneumonia, including aspiration), a concomitant use of benzodiazepines. Nevertheless, the increased death frequency in groups of olanzapine in comparison with placebo did not depend on these risk factors.

At therapy by anti-psychotics improvement of a clinical condition of the patient occurs during the period from several days to several weeks. During this period the patient needs careful observation.

Abnormal liver functions. At the beginning of therapy perhaps asymptomatic increase in transaminases of a liver (ALT and nuclear heating plant). At patients with initially increased levels of nuclear heating plant and/or ALT, with the liver failure and states which are potentially limiting functionality of a liver, and also accepting hepatotoxic medicines, it is necessary to be careful at purpose of olanzapine. At increase in ALT and/or nuclear heating plant against the background of therapy drug recommends medical observation of the patient and, perhaps, reduction of a dose of drug. When diagnosing hepatitis (including gepatokletochny, cholestatic or mixed) olanzapine needs to be cancelled.

Hematologic changes. Drug should be used with care at patients with a leukopenia and/or a neutropenia of any genesis, a miyelosupressiya of medicinal genesis, and also against the background of radiation or chemotherapy, owing to associated diseases, at patients with hyper eosinophilic states or myeloproliferative diseases. The neutropenia was often noted at simultaneous use of olanzapine and valproic acid (see the section "Side effect").

Malignant Antipsychotic Syndrome (MAS). ZNS - potentially life-threatening state connected with therapy by antipsychotic means (neuroleptics), including olanzapine. Clinical manifestations of ZNS: fever, muscle tension, consciousness disturbance, vegetative disturbances (unstable pulse or labile arterial pressure, tachycardia, the increased sweating, arrhythmias). Additional symptoms of ZNS: increase in KFK, a myoglobinuria (against the background of a rabdomioliz) and an acute renal failure. At development of symptoms of ZNS, and also fervescence without the visible reasons, it is necessary to cancel all neuroleptics, including olanzapine.

Convulsive syndrome. Patients should appoint olanzapine carefully with spasms in the anamnesis or existence of the factors reducing a threshold of convulsive readiness. Against the background of reception of olanzapine of a spasm were registered seldom.

Late dyskinesia. Therapy by olanzapine was followed considerably by the smaller frequency of development of late dyskinesia, in comparison with a haloperidol. The risk of development of late dyskinesia increases at increase in duration of treatment. At emergence of signs of this state in the patient accepting olanzapine it is necessary to cancel drug or to reduce its dose. Symptoms of dyskinesia can temporarily accrue after drug withdrawal.

The general activity concerning TsNS. It is necessary to be careful at simultaneous use of other medicines of the central action and alcohol.

The cerebrovascular undesirable phenomena, including a stroke at elderly patients with dementia. At elderly people postural arterial hypotension is infrequently observed. At patients 65 years are more senior it is recommended to control the arterial pressure (AP) periodically. Patients should appoint olanzapine with care with the established increase in an interval of QTc, especially elderly, with an inborn syndrome of the extended QT interval, congestive heart failure, a myocardium hypertrophy, a hypopotassemia and a hypomagnesiemia.

At olanzapine reception very seldom (less than 0,01%) cases of development of thromboembolisms of veins are registered Relationship of cause and effect between therapy by olanzapine and a vein thrombosis is not established. As patients with schizophrenia often have acquired risk factors of venous thromboses, it is necessary to reveal all possible other factors (for example, an immobilization) and to take preventive measures.

The tablets Zalasta® of Ku-tab contain aspartame – a phenylalanine source. Drug can be unsafe for the people suffering from a fenilketonuriya.

Influence on ability to drive the car and other mechanisms

As olanzapine can cause drowsiness and dizziness, patients should show care during the work with technical devices, including when driving.

Side effects:

From central (TsNS) and a peripheral nervous system: very often – drowsiness; often - dizziness, an akathisia, parkinsonism, dyskinesia; seldom – a convulsive syndrome (is more often against the background of a convulsive syndrome in the anamnesis); very seldom - a malignant antipsychotic syndrome (see the section "Special Instructions"), dystonia (including okulogirny crisis) and late dyskinesia. At sharp cancellation of olanzapine such symptoms as perspiration, sleeplessness, a tremor, alarm, nausea or vomiting are very seldom noted.

From cardiovascular system: often - arterial hypotension (including orthostatic); infrequently - bradycardia with a collapse or without; very seldom - increase in an interval of QTS at an ECG (see the section "Special Instructions"), ventricular tachycardia / fibrillation and sudden death (see the section "Special Instructions"), thromboembolisms (including an embolism of pulmonary arteries and a deep vein thrombosis).

From the digestive tract (DT): often - tranzitorny anticholinergic effects, including locks and dryness in a mouth; very seldom - pancreatitis.

Disturbances of metabolism and food: very often - a weight increase; often - increase in appetite; very seldom - the hyperglycemia and/or a decompensation of a diabetes mellitus which sometimes is shown ketoacidosis or a coma including a fatal outcome; gipertriglitseridemiya, hypercholesterolemia, hypothermia.

Gepato-biliarnye disturbances: often - tranzitorny, asymptomatic increase in level of "hepatic" transaminases (alaninaminotranspherase (ALT), aspartate aminotransferase (nuclear heating plant)), especially in an initiation of treatment (see. "Special instructions"); seldom - hepatitis (including the gepatokletochny, cholestatic or mixed damage of a liver).

From bodies of a hemopoiesis and lymphatic system: often – an eosinophilia; seldom – a leukopenia; very seldom - thrombocytopenia, a neutropenia.

From bodies of a musculoskeletal system: very seldom – рабдомиолиз.

From bodies of urinogenital system: very seldom - an ischuria, a priapism.

From skin and hypodermic cellulose: infrequently - reactions of a photosensitization.

Allergic reactions: seldom - skin rash; very seldom - anaphylactoid reactions, a Quincke's disease, a skin itch or a small tortoiseshell.

Others: often - an adynamy, peripheral hypostases; very seldom – an alopecia.

Laboratory parameters: very often - a giperprolaktinemiya, but clinical manifestations (for example, a gynecomastia, a galactorrhoea and increase in mammary glands) it is rare. At most of patients the level of prolactin normalizovyvatsya spontaneously without therapy cancellation. Infrequently - increase in level of a kreatinfosfokinaza (KFK); very seldom - increase in level of the alkaline phosphatase (AP) and the general bilirubin.

At elderly patients with dementia the big frequency of death and cerebrovascular disturbances (a stroke, the tranzitorny ischemic attacks) is registered in researches. At this category of patients disturbances of gait and falling were very frequent. Pneumonia, fervescence, a lethargy, an erythema, visual hallucinations and an incontience of urine were also often observed.

Among patients with medicinal (against the background of reception of agonists of dopamine) psychoses against the background of Parkinson's disease deterioration in parkinsonichesky symptomatology and development of hallucinations often were registered.

There are neutropenias (4,1%) given about development against the background of a combination therapy with valproic acid at patients with a bipolar mania. Simultaneous therapy with valproic acid or lithium promotes increase in frequency (> 10%) a tremor, dryness in a mouth, increases in appetite and an increase of weight. Also often disturbances of the speech (from 1 to 10%) were registered. In the first 6 weeks of a combination therapy with lithium the frequency of development of an increase of weight increases. Long therapy by olanzapine (up to 12 months) for the purpose of prevention of a recurrence at patients with bipolar disorder was followed by increase in body weight.

Interaction with other medicines:

The potential medicinal interactions influencing olanzapine metabolism: olanzapine is metabolized by CYP1A2 enzyme therefore inhibitors or inductors of the isoenzymes of P450 cytochrome showing specific activity concerning CYP1A2 can influence pharmacokinetic parameters of olanzapine.

Inductors CYP1A2: the clearance of olanzapine can be increased at the smoking patients or at a concomitant use of carbamazepine that leads to decrease in concentration of olanzapine in a blood plasma. Clinical observation since some cases demand increase in a dose of drug is recommended.

CYP1A2 inhibitors: флувоксамин, specific CYP1A2 inhibitor - considerably reduces clearance of olanzapine. Average increase in the maximum concentration (Cmax) in olanzapine after reception of a fluvoksamin at non-smoking women made 54%, and the smoking men have 77%. Average increase in the area under a curve "concentration time" (AUC) of olanzapine in these categories of patients made respectively 52% and 108%. At the patients accepting флувоксамин or any other CYP1A2 inhibitor (for example, ciprofloxacin), olanzapine recommends to begin therapy with smaller doses. Reduction of a dose of olanzapine can be also required in case of accession to therapy of CYP1A2 inhibitors.

The medicinal interactions influencing influencing bioavailability of olanzapine: absorbent carbon reduces absorption of olanzapine at oral administration by 50-60% therefore it is necessary to accept it not less than in 2 hours prior to or after olanzapine reception.

Fluoxetine (CYP450 inhibitor), single dose magnesium or aluminum-bearing antacids or Cimetidinum do not influence olanzapine pharmacokinetics.

Potential ability of olanzapine to influence other medicines

Olanzapine can weaken action of direct and indirect agonists of dopamine.

In the conditions of in vitro olanzapine does not suppress the main isoenzymes of CYP450 (for example, 1A2, 2D6, 2C9, 2C19, 3A4). In vivo was not revealed oppressions of metabolism of the following active agents: tricyclic antidepressants (CYP2D6), warfarin (CYP2C9), theophylline (CYP1A2) and diazepam (CYP3A4 and 2C19).

Interaction at simultaneous use with lithium or Biperidinum is not revealed.

Therapeutic monitoring of the content of valproic acid in plasma showed what at co-administration with olanzapine of changes of doses of valproic acid is not required (see the section "Side effect").

It is necessary to be careful at simultaneous use of other medicines of the central action. In spite of the fact that the single dose of alcohol (45 mg / 70 kg) does not render pharmacokinetic effect, alcohol intake together with olanzapine can be followed by strengthening of depressive action on the central nervous system.

Contraindications:

Hypersensitivity to olanzapine.

Pregnancy and feeding by a breast

Due to the limited experience of use of drug for pregnant women, olanzapine should be applied at pregnancy, only if the expected advantage justifies potential risk for a fruit. Women have to be informed on need to report to the doctor about the occurred or planned pregnancy against the background of therapy by olanzapine. The children born from mothers accepting olanzapine in the third trimester of pregnancy have single messages on a tremor, an arterial hypertension, a lethargy and drowsiness.

In a research it was revealed that olanzapine is emitted in breast milk. The average dosage (mg/kg) received by the child at achievement of equilibrium concentration at mother made 1,8% of a dose of olanzapine of mother (mg/kg). Feeding by a breast against the background of therapy by olanzapine is not recommended.

Overdose:

Symptoms: very frequent (> 10%) at overdose olanzapine are: tachycardia, excitement/aggression, a dysarthtia, various extrapyramidal symptoms, decrease in level of consciousness from block to a coma; less than in 2% of cases arise: delirium, convulsions, coma, malignant antipsychotic syndrome, respiratory depression, aspiration, arterial hypertension or hypotension, cardiac arrhythmias; seldom or never - cardiopulmonary insufficiency. The minimum dose of olanzapine at acute overdose with a lethal outcome - 450 mg, is registered the maximum dose at overdose with a favorable outcome (survival) - 1500 mg.

Treatment: the specific antidote does not exist. It is not recommended to provoke vomiting. It is necessary to carry out: a gastric lavage, reception of absorbent carbon (reduces bioavailability of olanzapine by 60%), a symptomatic treatment under control of the vital functions, including treatment of arterial hypotension and vascular collapse, breath function maintenance. Use of Epinephrinum, dopamine or other sympathomimetics with a beta adrenomimeticheskoy activity since the last can aggravate arterial hypotension is not recommended. Monitoring of cardiovascular activity is necessary for detection of possible arrhythmias. The patient has to be under continuous medical observation to an absolute recovery.

Storage conditions:

Period of validity 2 years. Not to use drug after expiry date. To store at a temperature not above 30 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets for a rassasyvaniye of 5 mg, 7,5 mg, 10 mg, 15 mg and 20 mg.

On 7 tablets in the blister. On 4 or 8 blisters place in a pack cardboard together with the application instruction.