medicalmeds.eu Medicines Antipsychotic (antipsychotic) means. Заласта®

Заласта®

Producer: Krka Slovenia

Code of automatic telephone exchange: N05AH03

Release form: Firm dosage forms. Tablets.

Indications to use: Schizophrenia. Maniacal syndrome (Mania).

General characteristics. Structure:

Active agent: olanzapine of 2,5 mg 5 mg 7,5 mg 10 mg 15 mg 20 mg;
excipients: a tsellaktoza (the connection which is dried up by spraying consisting of 75% of alpha lactose of monohydrate and 25% of powder of cellulose) — 56,75/113,5/170,25/340,5/454 mg; starch prezhelatinizirovanny — 7,5/15/22,5/30/45/60 mg; starch corn — 2,25/4,5/6,75/9/13,5/18 mg; silicon dioxide colloid anhydrous — 0,25/0,5/0,75/1/1,5/2 mg; magnesium stearate — 0,75/1,5/2,25/3/4,5/6 mg

Description of a dosage form

Tablets of 2,5 mg: round, slightly biconvex, light yellow color. Impregnations of more dark shade are allowed.

Tablets of 5 mg: round, slightly biconvex, light yellow color with a text "5". Impregnations of more dark shade are allowed.

Tablets of 7,5 mg: round slightly biconvex, light yellow color with a text "7,5". Impregnations of more dark shade are allowed.

Tablets of 10 mg: round slightly biconvex, light yellow color with a text "10". Impregnations of more dark shade are allowed.

Tablets of 15 mg: round slightly biconvex, light yellow color with a text "15". Impregnations of more dark shade are allowed.

Tablets of 20 mg: round slightly biconvex, light yellow color with a text "20". Impregnations of more dark shade are allowed.

Pharmacological properties:

Pharmacodynamics. 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 (hostility, suspiciousness, emotional and social autism) symptomatology of psychoses. Seldom causes extrapyramidal disturbances.

Pharmacokinetics. Olanzapine absorption high, does not depend on meal; Tmax after oral administration is 5–8 h. Linkng with proteins — 93% in the range of concentration from 7 to 1000 ng/ml. Olanzapine contacts, generally albumine and α1-гликопротеином. Gets through gistogematichesky barriers, including 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 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/h; at persons 65 years — 33,8 h and plasma clearance — 18,2 l/h are younger. The plasma clearance is lower at patients with a liver failure, women and non-smoking patients in comparison with the corresponding groups of persons. Nevertheless, extent of influence of age, sex or smoking on clearance and T1/2 of olanzapine is insignificant in comparison with individual variability of pharmacokinetics between certain people. It is removed preferential by kidneys (60%) in the form of metabolites.

Indications to use:

Schizophrenia (treatment);

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

moderate or heavy episodes of a mania (treatment);

prevention of a recurrence of a mania at bipolar disorder at patients with maniacal episodes at good effect of therapy by olanzapine.

Route of administration and doses:

Inside, 1 time a day, irrespective of meal. In case of drug withdrawal the gradual dose decline is recommended.

Schizophrenia: the recommended initial dose of drug — 10 mg/days.

Mania episode: the initial dose makes 15 mg in one step — at monotherapy or 10 mg/days — 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/days. For the patients who are already receiving the drug Zalasta® for treatment of an episode of a mania, the maintenance therapy is carried out in the same doses. In case of development of the new maniacal, mixed or depressive episode against the background of therapy by the drug Zalasta® 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 p are usually carried out with an interval.

Special groups of patients

At elderly patients decrease in an initial dose (to 5 mg/days) 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 of Chayld-Pyyu of hepatocellular insufficiency at patients with cirrhosis) the initial dose makes 5 mg/days, 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") 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, development of ketoacidosis or the ketoatsidotichesky coma which sometimes was followed, 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. At patients with a diabetes mellitus and risk factors of development of this disease regular clinical control and control of level of glucose of blood is recommended.

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 ACT). At patients with initially increased ACT and/or ALT levels, a liver failure and states which are potentially limiting functionality of a liver and also at accepting hepatotoxic medicines, it is necessary to be careful at purpose of olanzapine. At increase in ALT and/or ACT 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) олазапин it is necessary to cancel.

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. Potentially life-threatening state connected with therapy by antipsychotic means (neuroleptics), including olanzapine. It is characterized by the following clinical manifestations: fever, muscle tension, consciousness disturbance, vegetative disturbances (unstable pulse or labile the ABP, 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 ABP 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 a thromboembolism 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® contain lactose. Drug should not be accepted to patients with rare hereditary problems of intolerance of a galactose, deficit of lactase of Lapp or disturbance of absorption of glucose galactose.

Influence on ability to drive the car or to perform the works demanding the increased speed of physical and mental reactions. During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Classification of frequency of development of side effects (WHO): very often — ≥1/10; often — from ≥1/100 to <1/10; infrequently — from ≥1/1000 to <1/100; seldom — from ≥1/10000 to <1/1000; very seldom — <1/10000, including separate messages.

From TsNS and 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 CCC: often — arterial hypotension (including orthostatic); infrequently — bradycardia with a collapse or without; very seldom — increase in an interval of QTc 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 a GIT: often — tranzitorny anticholinergic effects, including locks and dryness in a mouth; very seldom — pancreatitis.

Disturbances of metabolism and diet: 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.

Gepatobiliarny disturbances: often — tranzitorny, asymptomatic increase in level of hepatic transaminases (ALT, ACT), 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 the ShchF level 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 Cmax of olanzapine after reception of a fluvoksamin at non-smoking women made 54%, and the smoking men have 77%. Average increase in AUC olanzapine at these categories of patients made respectively 5 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 take it not less than for 2 h 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, 2S9, 2S19, ZA4). In vivo was not revealed oppressions of metabolism of the following active agents: tricyclic antidepressants (CYP2D6), warfarin (CYP2C9), theophylline (CYP1A2) and diazepam (CYP3A4 and 2S19).

Interaction at simultaneous use with lithium or Biperidinum is not revealed. Therapeutic monitoring of 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 effects").

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 TsNS.

Contraindications:

Hypersensitivity to olanzapine or other components of drug;

closed-angle glaucoma;

rare hereditary problems of intolerance of a galactose, deficit of lactase of Lapp or disturbance of absorption of glucose galactose;

lactation period;

children's age up to 18 years (efficiency and safety are not established).

With care: a renal failure, a liver failure, a prostate hyperplasia, paralytic intestinal impassability, epilepsy, a convulsive syndrome in the anamnesis, a leukopenia and/or a neutropenia of various genesis, a miyelosupressiya of various genesis, including the myeloproliferative diseases, a hyper eosinophilic syndrome, cardiovascular and cerebrovascular diseases or other states contributing to arterial hypotension, inborn increase in an interval of QT at an ECG (increase in a korrigirovanny interval of QT (QTc) at an ECG) or in the presence of the conditions potentially capable to cause increase in an interval of QT (for example co-administration of drugs, extending QT interval, congestive heart failure, a hypopotassemia, a hypomagnesiemia), advanced age, and also a concomitant use of other medicines of the central action; immobilization, pregnancy.

Use at pregnancy and feeding by a breast

Due to the limited experience of use of drug for pregnant women olanzapine should be applied, only if the expected advantage for mother 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 III 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 often (> 10%) — tachycardia, excitement/aggression, a dysarthtia, various extrapyramidal symptoms, decrease in level of consciousness from block to a coma; less than in 2% of cases — a delirium, convulsions, a coma, the malignant antipsychotic syndrome (MAS), respiratory depression, aspiration, increase or decrease in the ABP, cardiac arrhythmia; 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: 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. The specific antidote does not exist. It is not recommended to induce vomiting, to apply Epinephrinum, a dopamine or other sympathomimetics with a beta adrenomimeticheskoy activity since the last can aggravate arterial hypotension. Monitoring of cardiovascular activity is necessary for detection of possible arrhythmias. The patient has to be under continuous medical observation to an absolute recovery.