Zalasta pills 5mg n28

Latin name of the drug Zalasta®

Zalasta®

ATH

N05AH03 olanzapine

Pharmacological group

• Neuroleptics

Nosological classification (ICD-10)

• F20 Schizophrenia
• F30 Manic Episode
• F31.1 Bipolar affective disorder, current episode of mania without psychotic symptoms
• F31.2 Bipolar affective disorder, current episode of mania with psychotic symptoms

The composition and release form pills 1 tab. 5 mg 10 mg of excipients: cellactose (spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose powder), pregelatinized starch; corn starch; silica colloidal anhydrous; Magnesium stearate

in the blister 7 pcs.; in a pack of cardboard 4 blisters.

Description of the dosage form

Tablets 5 mg: round, slightly biconvex, light yellow in color with the inscription "5". Inserts of a darker shade are allowed.

Tablets 10 mg: round slightly biconvex, light yellow color with the inscription "10". Inserts of a darker shade are allowed.

pharmachologic effect

pharmachologic effect - neuroleptic, antipsychotic.

Pharmacodynamics

Olanzapine is an antipsychotic (neuroleptic) with a broad pharmacological spectrum of action. Antipsychotic action due to blockade of dopamine D2 receptorsmesolimbic and mesocortical system; sedative action - blockade of adrenoreceptors of the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2-receptors of the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus. In addition, it affects muscarinic, adrenergic, H1-histamine and some subclasses of serotonin receptors.

Olanzapine reliably reduces the productive (nonsense, hallucinations) and negative (hostility, suspicion, emotional and social autism) symptoms of psychosis. Rarely causes extrapyramidal disorders.

Pharmacokinetics

Olanzapine absorption is high, does not depend on food intake; Tmax after oral administration is 5–8 h. Protein binding is 93% in the concentration range from 7 to 1000 ng / ml. Olanzapine binds mainly albumin and α1-glycoprotein. Penetrates histohematogenous barriers, incl. BBB. It is metabolized in the liver, active metabolites are not formed, the main circulating metabolite - glucuronide - does not penetrate the BBB. Smoking, gender and age affect T1 / 2 and plasma clearance. In persons older than 65 years, T1 / 2 is 51.8 h and plasma clearance is 17.5 l / h; in persons younger than 65 years old - 33.8 h and plasma clearance - 18.2 l / h. Plasma clearance is lower in patients with hepatic impairment, women and non-smoking patients in comparison with the respective groups of individuals. However, the degree of influence of age, gender or smoking on clearance and T1 / 2 of olanzapine is insignificant compared with the individual variability of pharmacokinetics between individuals.Excreted mainly by the kidneys (60%) as metabolites.

Indications of the drug Zalasta®

schizophrenia (treatment);

Zalasta® effectively supports the improvement of clinical symptoms with long-term treatment in patients with an initial positive reaction to the drug.

mild to severe episodes of mania (treatment);

prevention of recurrence of mania in bipolar disorder in patients with manic episodes with a good effect of olanzapine therapy.

Contraindications

hypersensitivity to olanzapine or other components of the drug;

angle-closure glaucoma;

rare hereditary problems of galactose intolerance, Lappa lactase deficiency or impaired glucose-galactose absorption;

lactation period;

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

With care: renal failure, liver failure, prostatic hyperplasia, paralytic intestinal obstruction, epilepsy, a history of convulsions, leukopenia and / or neutropenia of various genesis, myelosuppression of various genesis, including myeloproliferative diseases, hypereosinophilic syndrome, cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, congenital prolongation of the QT interval on an ECG (increased QT interval (eg, co-administration of drugsprolonged QT interval, congestive heart failure, hypokalemia, hypomagnesemia), old age, and the simultaneous use of other drugs of central action; immobilization, pregnancy.

Use during pregnancy and lactation

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

The study found that olanzapine is secreted in breast milk. The average dosage (mg / kg) received by the child upon reaching the equilibrium concentration in the mother was 1.8% of the dose of mother olanzapine (mg / kg). Breast-feeding during olanzapine therapy is not recommended.

Side effects

Classification of the incidence of side effects (WHO): very often - ≥1 / 10; often from ≥1 / 100 to <1/10; infrequently - from ≥1 / 1000 to

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

From the CCC: often - arterial hypotension (including orthostatic); infrequently - bradycardia with or without collapse; 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 embolism and deep vein thrombosis).

On the part of the gastrointestinal tract: often - transient anticholinergic effects, including constipation and dry mouth; very rarely - pancreatitis.

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

Hepatobiliary disorders: often - transient, asymptomatic elevation of hepatic transaminase (ALT, ACT), especially at the beginning of treatment (see. "Special instructions"); rarely, hepatitis (including hepatocellular, cholestatic, or mixed liver damage).

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

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

On the part of the genitourinary system: very rarely - urinary retention, priapism.

On the part of the skin and subcutaneous tissue: infrequently - photosensitivity reactions.

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

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

Laboratory parameters: very often - hyperprolactinemia, but clinical manifestations (for example, gynecomastia, galactorrhea and enlargement of the mammary glands) - are rare. In most patients, prolactin levels spontaneously normalized without discontinuing therapy; infrequently - an increase in the level of creatine phosphokinase (CPK); very rarely - increased levels of alkaline phosphatase and total bilirubin.

In elderly patients with dementia, a high frequency of deaths and cerebrovascular disorders (stroke, transient ischemic attacks) was recorded in studies. Very frequent in this category of patients were gait disturbances and falls. Pneumonia, fever, lethargy, erythema, visual hallucinations and urinary incontinence have also been frequently observed.

Among patients with medicinal (against the background of dopamine agonist administration) psychoses against Parkinson's disease, worsening of parkinsonian symptoms and the development of hallucinations were often recorded.

There is evidence of the development of neutropenia (4.1%) on the background of combination therapy with valproic acid in patients with bipolar mania.Simultaneous therapy with valproic acid or lithium increases the frequency (> 10%) of tremor, dry mouth, increased appetite and weight gain. Speech disorders were also often recorded (from 1 to 10%). In the first 6 weeks of combination therapy with lithium, the frequency of development of weight gain increases. Long-term therapy with olanzapine (up to 12 months) to prevent relapse in patients with bipolar disorder was accompanied by an increase in body weight.

Interaction

olanzapine is metabolized by the CYP1A2 enzyme; therefore, inhibitors or inducers of cytochrome P450 isoenzymes, which show specific activity against CYP1A2, can affect the pharmacokinetic parameters of olanzapine.

Inductors CYP1A2: olanzapine clearance can be increased in patients who smoke or while taking Carbamazepine, which leads to a decrease in plasma olanzapine concentration. Clinical observation is recommended, since some cases require an increase in the dose of the drug.

CYP1A2 inhibitors: fluvoxamine - a specific inhibitor of CYP1A2 - significantly reduces the clearance of olanzapine. The average increase in Cmax of olanzapine after taking fluvoxamine in non-smoking women was 54%, and in smoking men, 77%. The average increase in olanzapine AUC in these categories of patients was 5 and 108%, respectively. In patients taking fluvoxamine or any other CYP1A2 inhibitor (for example, ciprofloxacin), olanzapine therapy is recommended to start with smaller doses.A reduction in the dose of olanzapine may also be required if CYP1A2 inhibitors are added to therapy.

Activated carbon reduces the absorption of olanzapine when taken orally by 50-60%, so it should be taken no less than 2 hours before or after taking olanzapine.

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

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

In vitro, olanzapine does not suppress the major CYP450 isoenzymes (for example, 1A2, 2D6, 2C9, 2C19, ZA4). In vivo metabolism of the following active substances was not detected: tricyclic antidepressants (CYP2D6), Warfarin (CYP2C9), theophylline (CYP1A2) and diazepam (CYP3A4 and 2C19).

No interaction was found when used simultaneously with lithium or biperiden. Therapeutic monitoring of plasma valproic acid showed that, while administering olanzapine at the same time, changes in valproic acid doses are not required (see the “Side Effects” section).

Caution should be exercised while using other drugs of central action. Despite the fact that a single dose of alcohol (45 mg / 70 kg) does not have a pharmacokinetic effect, taking alcohol with olanzapine may be accompanied by an increase in the depressive effect on the central nervous system.

Dosage and administration

Inside, 1 time per day, regardless of the meal. In case of drug withdrawal, gradual reduction of the dose is recommended.

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

Episode of mania: the initial dose is 15 mg in one dose - with monotherapy or 10 mg / day - as part of combination therapy.

Prevention of relapses with bipolar disorder: the recommended initial dose of the drug in remission is 10 mg / day. For patients already receiving Zalasta® for the treatment of an episode of mania, supportive therapy is carried out in the same doses. In the case of the development of a new manic, mixed or depressive episode during therapy with Zalasta®, if necessary, increase the dose of the drug with additional treatment of mood disorders, in accordance with clinical indications.

The daily dose of the drug in the treatment of schizophrenia, manic episode or prevention of relapses of bipolar disorder can be 5-20 mg / day, depending on the patient’s clinical condition. Increasing the dose over the recommended initial dose is possible only after an adequate re-clinical assessment of the patient’s condition and is usually performed at intervals of at least 24 hours.

Special patient groups

In elderly patients, a reduction in the initial dose (up to 5 mg / day) is usually not recommended, but it is possible in patients over 65 years of age with risk factors (see the section "Special Instructions").

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

Women do not need changes in dosing compared to men.

In non-smoking patients, dose adjustment in comparison with smoking patients (see the Interaction section) is not required.

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

Overdose

Symptoms: very often (> 10%) - tachycardia, agitation / aggression, dysarthria, various extrapyramidal symptoms, a decrease in the level of consciousness from lethargy to coma; in less than 2% of cases, delirium, convulsions, coma, neuroleptic malignant syndrome (MNS), respiratory depression, aspiration, increased or decreased blood pressure, cardiac arrhythmia; in very rare cases, cardiopulmonary failure. The minimum dose of olanzapine in acute overdose with a fatal outcome is 450 mg, the maximum dose in case of overdose with a favorable outcome (survival) is 1500 mg.

Treatment: gastric lavage, taking Activated carbon (reduces the bioavailability of olanzapine by 60%), symptomatic treatment under the control of vital functions, including the treatment of arterial hapotension and vascular collapse, maintaining respiratory function. There is no specific antidote.It is not recommended to induce vomiting, use epinephrine, dopamine or other sympathomimetics with beta-adreno-mimetic activity, since the latter may aggravate hypotension. To identify possible arrhythmias, monitoring of cardiovascular activity is necessary. The patient must be under continuous medical supervision until full recovery.

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, including There are reports of several fatal cases. In some cases, an increase in body weight preceding decompensation was noted, which could become a predisposing factor. In patients with diabetes mellitus and risk factors for the development of this disease, regular clinical monitoring and control of blood glucose is recommended.

At change of level of lipids correction of therapy is required.

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

Anticholinergic activity. Since clinical experience with olanzapine in people with comorbidities is limited, the drug should be carefully prescribed to patients with prostatic hyperplasia, paralytic intestinal obstruction.

Experience of using olanzapine in patients with psychosis in Parkinson's disease, caused by taking dopaminomimetik. Olanzapine is not recommended for the treatment of psychosis in Parkinson's disease caused by taking dopaminomimetic. Symptoms of parkinsonism and hallucinations are increasing. At the same time, olanzapine did not exceed placebo in terms of the effectiveness of treatment of 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 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 an increase in mortality include: age over 65, dysphagia, sedation, malnutrition and dehydration, lung diseases (for example, pneumonia, including aspiration), simultaneous administration of benzodiazepines. However, the increased frequency of death in the olanzapine groups compared with placebo did not depend on these risk factors.

With antipsychotic therapy, an improvement in the patient’s clinical condition occurs in a period from several days to several weeks. During this period, the patient needs careful observation.

Liver dysfunction. At the beginning of therapy, an asymptomatic increase in liver transaminases (ALT and ACT) is possible. In patients with initially elevated levels of ACT and / or ALT, liver failure 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 during drug therapy, medical observation of the patient is recommended, and possibly a reduction in the dose of the drug. When diagnosing hepatitis (including hepatocellular, cholestatic or mixed), olazapine should be canceled.

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 during radiation or Chemotherapy, due to concomitant diseases, in patients with hypereosinophilic conditions or myeloproliferative diseases. Neutropenia has often been observed with the simultaneous use of olanzapine and valproic acid (see the “Side Effects” section).

Malignant neuroleptic syndrome. Potentially life-threatening condition associated with therapy with antipsychotics (neuroleptics), incl. olanzapine. It is characterized by the following clinical manifestations: fever, muscle stiffness, impaired consciousness, autonomic disturbances (unstable pulse or labile blood pressure, tachycardia, increased sweating, arrhythmias). Additional symptoms of NNS: increased CPK, myoglobinuria (against the background of rhabdomyolysis) and acute renal failure.With the development of symptoms of ZNS, as well as an increase in body temperature for no apparent reason, it is necessary to cancel all antipsychotics, including olanzapine.

Convulsive syndrome. Olanzapine should be carefully prescribed to patients with a history of convulsions or the presence of factors that reduce the threshold of convulsive readiness. With olanzapine, seizures were rarely recorded.

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

Total activity against the central nervous system. Caution should be exercised while using other drugs of central action and alcohol.

Cerebrovascular adverse events, including stroke in elderly patients with dementia. Older people rarely observed postural hypotension. In patients older than 65 years, it is recommended to periodically monitor blood pressure. Olanzapine should be used with caution in patients with an established increase in the QTc interval, especially the elderly, with congenital syndrome of prolonged QT interval, congestive heart failure, myocardial hypertrophy, hypokalemia and hypomagnesia.

When taking olanzapine very rarely (less than 0.01%), cases of venous thromboembolism have been reported. 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 (such as immobilization) should be identified and preventive measures taken. Zalasta® pills contain lactose. The drug should not be taken in patients with rare hereditary problems of intolerance to galactose, Lappa lactase deficiency or impaired glucose-galactose absorption.

Influence on the ability to drive a car and other mechanical means. During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and psychomotor reactions.

Pharmacy sales terms

On prescription.

Storage conditions of the drug Zalasta®

At temperatures not above 25 ° C.

Keep out of the reach of children.

Expiration date of the drug Zalasta®

5 years.