Normiton - instructions for use, doses, side effects, contraindications

for tablets 5 mg: Lodipress [lactose monohydrate 93%, povidone 3.5%, crospovidone 3.5%] 181.0 mg; sodium carboxymethyl starch 10.0 mg; magnesium stearate 3.0 mg; silicon dioxide colloid 1.0 mg;

for tablets 10 mg: Ludistress [lactose monohydrate 93%, povidone 3.5%, crospovidone 3.5%] 363.0 mg; sodium carboxymethyl starch 20.0 mg; magnesium stearate 6.0 mg; silicon dioxide colloid 2.0 mg;

for tablets 15 mg: Ludistress [lactose monohydrate 93%, povidone 3.5%, crospovidone 3.5%] 264.0 mg; sodium carboxymethyl starch 15.0 mg; magnesium stearate 4.5 mg; silicon dioxide colloid 1.5 mg;

for tablets 20 mg: Lodipress [lactose monohydrate 93%, povidone 3.5%, crospovidone 3.5%] 352.0 mg; sodium carboxymethyl starch 20.0 mg; magnesium stearate 6.0 mg; Silica colloidal dioxide 2.0 mg.

Sheath:

for tablets 5 mg: Opaprai II white [polyvinyl alcohol 4.0 mg; titanium dioxide 2.5 mg; macrogol-3350 2.02 mg; talc 1.48 mg] 10.0 mg;

for tablets 10 mg: Opaprai II white [polyvinyl alcohol 8.0 mg; titanium dioxide 5.0 mg; macrogol-3350 4.04 mg; talc 2.96 mg] 20.0 mg;

for tablets 15 mg: Opadrai II yellow [polyvinyl alcohol 6.0 mg; titanium dioxide 3,051 mg; macrogol-3350 2.22 mg; talc 3.03 mg; dye quinoline yellow (E104) 0.615 mg; ferric iron oxide yellow (E172) 0.084 mg] 15.0 mg;

for tablets 20 mg: Opaprai II orange [polyvinyl alcohol 8.8 mg; titanium dioxide 3,418 mg; macrogol-3350 2.47 mg; talc 4.0 mg; lecithin 0.7 mg; dye quinoline yellow (E104) 0.002 mg; dye sunset yellow (E110) 0.610 mg] 20.0 mg.

Description:

For tablets 5 mg, 10 mg: round, biconcave tablets, covered with a film shell of white or almost white color, on a broken light yellow color with a greenish tinge.

For tablets 15 mg: oblong tablets, covered with a film coating of yellow color, on a broken light yellow color with a greenish tinge.

For tablets of 20 mg: oblong tablets, covered with a film shell of orange color, on a broken pale yellow color with a greenish tinge.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.03 Olanzapine

Pharmacodynamics:

Olanzapine is an antipsychotic agent (neuroleptic).

Pre-clinical studies have established an affinity for 5-NT₂_A/₂_FROM, 5-HT₃, 5-HT₆-serotonin receptors, D₁-, D₂-, D₃-, D₄-, D₅dopamine receptors, M-cholinoblocking effects due to blockade M_1-₅-choline receptors; also has an affinity for α₁-adreno- and H₁-histamine receptors.In animal experiments, antagonism was observed with respect to serotonin, dopamine and M-cholinergic receptors. In vivo and in vitro olanzapine has a more pronounced affinity and activity towards 5-NT₂serotonin receptors in comparison with D₂dopamine receptors. According to electrophysiological studies olanzapine selectively reduces the excitability of mesolimbic dopaminergic neurons, and at the same time has an insignificant effect on the striatial neural pathways involved in the regulation of motor functions.

Pharmacokinetics:

After oral administration olanzapine well absorbed, its maximum concentration in the plasma is achieved after 5-8 hours. Absorption of olanzapine does not depend on food intake. In studies with different doses in the range 1-20 mg, it is shown that the concentration of olanzapine in the plasma varies linearly and in proportion to the dose.

Olanzapine metabolized in the liver as a result of conjugation and oxidation. The main circulating metabolite is l0-N-glucuronide, which theoretically does not penetrate the blood-brain barrier. Isozymes CYP1A2 and CYP2D6 participate in education N-desmethyl- and 2-hydroxymethylmetabolites of olanzapine. Both metabolites in animal studies had significantly less pharmacological activity in vivo, than olanzapine. The main pharmacological activity of the drug is due to the initial compound - olanzapine, which has the ability to penetrate the blood-brain barrier.

In healthy volunteers after oral administration, the average half-life was 33 h (21-54 h for 5-95%), and the average clearance of olanzapine from plasma was 26 l / h (12-47 l / h for 5-95%).

The pharmacokinetic parameters of olanzapine vary depending on smoking, sex and age (see table):

Characteristics of patients	Half-life, (h)	Clearance in plasma (l / h)
Attitude towards smoking
Non-smokers	38,6	>18,6
Smokers	30,4	27,7
Floor
Women	36,7	18,9
Men's	32,3	27,3
Age
Elderly (65 years and over)	51,8	17,5
Younger than 65 years	33,8	18,2

However, the degree of changes in the half-life and clearance due to each of these factors is significantly inferior to the degree of difference between these indicators among individuals. The pharmacokinetics in adolescents (13-17 years) and adults are similar. According to clinical studies, the exposure rate in adolescents is 27% higher than in adults.The difference in demographic parameters between the adult and adolescent population was that there were fewer smokers among adolescents, and lower average body weights were also noted.

There were no significant differences between the mean values of the half-life and clearance of olanzapine in plasma in individuals with severe renal dysfunction compared to those with normal renal function. About 57% of radiolabeled olanzapine is excreted by the kidneys mainly in the form of metabolites.

In smokers with minor violations of liver function, the clearance of olanzapine is lower than that of non-smokers without impaired liver function.

With a plasma concentration of olanzapine of 7-1000 ng / ml, its association with plasma proteins is about 93%. Olanzapine mainly binds to albumin and α₁acid glycoprotein. In a study involving individuals of European, Japanese and Chinese origin, there are no differences in the pharmacokinetics of olanzapine associated with race. Isoenzyme activity CYP2D6 does not affect the metabolism of olanzapine.

Indications:

Schizophrenia.

Bipolar affective disorder type I. Olanzapine in the form of monotherapy or in combination with lithium or valproic acid preparations is indicated for the treatment of acute manic or mixed episodes in bipolar affective disorder with or without psychotic manifestations and with / without rapid phase change. Olanzapine It is shown to prevent relapse in patients with bipolar disorder who have olanzapine was effective in treating the manic phase. In combination with fluoxetine olanzapine is indicated for the treatment of a depressive episode in the structure of bipolar disorder.

Therapeutically resistant depression. In combination with fluoxetine olanzapine is indicated for the treatment of therapeutically-resistant depression in adult patients (major depressive episodes, history of ineffective use of two antidepressant doses and duration of therapy appropriate for this episode).

Contraindications:

Hypersensitivity to any of the components of the drug.

Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Lactation period.

Children under 18 years.

Carefully:

No information.

Pregnancy and lactation:

Because of insufficient experience with olanzapine during pregnancy, the drug should be administered during pregnancy only if the potential benefit to the patient is significantly greater than the potential risk to the fetus. Patients should be warned that in the event of the onset or planning of pregnancy during treatment with olanzapine, they need to inform their physician about it.

Very spontaneous reports were received that newborns whose mothers were taking olanzapine in the third trimester of pregnancy, there was tremor, muscle hypertension, lethargy, drowsiness.

The study found that olanzapine penetrates into breast milk. The average dose received by the child (mg / kg) 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 during therapy with olanzapine.

Dosing and Administration:

Inside. Olanzapine can be taken regardless of food intake, since food does not affect the absorption of olanzapine.

Schizophrenia

The recommended initial dose of olanzapine is 10 mg once daily.Therapeutic doses of olanzapine range from 5 mg to 20 mg per day. The daily dose must be selected individually depending on the clinical condition of the patient. Dose increase above the standard daily dose (10 mg) is recommended only after an assessment of the clinical picture. When using the drug, it is necessary to regularly evaluate the need for continued therapy.

Bipolar disorder

To treat a manic episode, the recommended initial dose of olanzapine is 15 mg once daily as monotherapy or 10 mg once daily in combination with lithium or valproic acid. Therapeutic doses of olanzapine range from 5 mg to 20 mg per day. The daily dose must be selected individually, depending on the clinical condition of the patient. Dose increase above the standard daily is recommended only after assessment of the clinical picture and with an interval of at least 24 hours.

Supportive therapy for bipolar disorder: patients receiving olanzapine for treatment of a manic episode, it is necessary to continue maintenance therapy in the same dose.In patients in remission, the recommended initial dose of olanzapine is 10 mg once daily. In the future, the daily dose must be selected individually; depending on the clinical state of the patient, ranging from 5 mg to 20 mg per day.

For the treatment of a depressive episode olanzapine should be administered in combination with fluoxetine 1 time per day, in the evening, regardless of food intake. Typically, the initial dose is 5 mg of olanzapine and 20 mg of fluoxetine: Antidepressant activity was confirmed with olanzapine at a dose of 6-12 mg (mean daily dose of 7.4 mg) and fluoxetine at a dose of 25-30 mg (mean daily dose of 39 , 3 mg). If necessary, you can change the dose of both olanzapine and fluoxetine. When using the drug, it is necessary to regularly evaluate the need for continued therapy.

Therapeutically resistant depression

Olanzapine should be prescribed in combination with fluoxetine 1 time per day, in the evening, regardless of food intake. Typically, the initial dose is 5 mg of olanzapine and 20 mg of fluoxetine. If necessary, you can change the dose of both olanzapine and fluoxetine. Antidepressant activity was confirmed with olanzapine in a dose of 6-12 mg and fluoxetine in a dose of 25-30 mg.When using the drug, it is necessary to regularly evaluate the need for continued therapy.

General rules for choosing a daily oral dose for specific groups of patients

Reduction of the initial dose to 5 mg per day is recommended for elderly patients or patients with other clinical risk factors, including severe renal failure or moderate-level liver failure.

A reduction in the initial dose may be recommended for patients with a combination of factors (female, elderly, non-smokers) who can slow the metabolism of olanzapine.

The use of olanzapine has not been studied in persons younger than 13 years.

Side effects:

The table below summarizes the main side effects and their frequency recorded during clinical trials and / or post-marketing periods.

Highly often (≥10%)	Often (<10 and ≥1%)	Infrequently (≥0.1 and <1%)	The frequency is unknown (the frequency can not be determined from the available data)
Violations of the blood and lymphatic system
	Eosinophilia Leukopenia Neutropenia		Thrombocytopenia
Immune system disorders
		Hypersensitivity
Violations	from the side of metabolism and nutrition
Weight gain¹	Increase concentrations cholesterol^2,3 Increase concentrations glucose⁴ Increase concentrations triglycerides^2,5 Glucosuria Increased appetite	Development or decompensation of sugar diabetes, in some cases accompanied by ketoacidosis and diabetic coma, including fatal cases	Hypothermia
Disturbances from the nervous system
Drowsiness	Dizziness Akathisia⁶ Parkinsonism⁶ Dyskinesia⁶	Amnesia Dysatria Seizures in patients with convulsions in the anamnesis or in the presence of factors risk of seizures Dystonia (including oculogic crisis)		Malignant antipsychotic syndrome Late dyskinesia Syndrome "cancellation"⁷
Heart Disease
		Bradycardia Interval lengthening QTC		Ventricular tachycardia / ventricular fibrillation, sudden death
Vascular disorders
Orthostatic hypotension		Thromboembolism, including number of pulmonary arteries Deep vein thrombosis
Disorders from the digestive system
	Short-term m-cholinoblocking effects, including constipation and dry mouth	Blowing belly		Pancreatitis
Disturbances from the liver and bile ducts
	The transient increase in the activity of "hepatic" transferases (ALT, ACT), especially in the early period of treatment			Hepatitis (including hepatocellular, hepatocellular and mixed)
Disturbances from the skin and subcutaneous tissues
	Rash	Reaction photosensitivity Alopecia
Musculoskeletal system disorders
	Arthralgia			Rhabdomyolysis
Disorders from the kidneys and urinary tract
		Urinary incontinence Retention of urine Delayed start urination
Violations of the genitals and mammary gland
	erectile disfunction Decreased sex drive men and women	Amenorrhea Increase of mammary glands in women Galactorrhea in women Gynecomastia and an increase of mammary glands in men		Priapism
General disorders
	Asthenia Fatigue Edema Hyperthermia
From the respiratory system
		Nasal bleeding
Pregnancy, prenatal and postnatal period
		The syndrome of cancellation in newborns
Laboratory data
Increase concentrations prolactin in plasma⁸	Increased activity alkaline phosphatase Increased activity creatine phosphokinase Increased activity gamma-glutamate transferase Increase in concentration uric acid	Increase concentrations the general bilirubin

¹ In all patient groups, regardless of body mass index, a clinically significant increase in body weight was observed.

An increase in body weight of 7% or more from the mean after a short course of treatment (average duration 47 days) was very frequent (22.2%), an increase of 15% or more was frequent (4.2%) and an increase of 25% or more were infrequent (0.8%).

In patients receiving long-term treatment (at least 48 weeks), an increase in ≥7, ≥ 15 and ≥ 25% was very frequent (64.4, 31.7, 12.3% respectively).

² The average increase in fasting lipids (cholesterol, low-density lipoprotein (LDL), triglycerides) was more pronounced in patients without initial signs of lipid metabolism disorders.

³ Often there was an increase in cholesterol concentration from normal fasting values (<5.17 mmol / L) to elevated (≥ 6.2 mmol / L).

Cholesterol concentration change from fasting fasting (≥ 5.17 - <6.2 mmol / l) to increased (≥ 6.2 mmol / l) was very frequent.

⁴ Often there was an increase in glucose concentration from normal fasting values (<5.56 mmol / l) to elevated (≥7 mmol / L).

Change in glucose concentration from fasting borderline≥ 5.56 - <7 mmol / l) to elevated (≥ 7 mmol / l) was very frequent.

⁵ Often there was an increase in the concentration of triglycerides from normal fasting values (<1.69 mmol / l) to elevated (≥ 2.26 mmol / l).

The change in the concentration of triglycerides from the fasting borderline≥ 1.69 - <2.26 mmol / l) to elevated (≥ 2.26 mmol / l) was very frequent.

⁶ In clinical trials, cases of parkinsonism and dystonia in patients taking olanzapine; were more frequent, but the difference with the placebo group was not statistically significant.

In patients who took olanzapine, parkinsonism, akathisia, dystonia were observed less frequently than in patients receiving titrated doses of haloperidol. In view of the lack of detailed information about the presence of acute and late dyskinesia in patients with an anamnesis, it is currently impossible to conclude that olanzapine to a lesser degree causes the development of late dyskinesias or other late extrapyramidal syndromes.

⁷ With a sharp abolition of olanzapine, symptoms such as sweating, insomnia, tremors, anxiety, nausea, and vomiting were observed.

⁸ In clinical studies of up to 12 weeks, the concentration of prolactin in the plasma exceeded the upper limit of the norm in approximately 30% of patients with normal baseline values of prolactin.

In most of these patients, the increase in prolactin concentration was moderate, and less than 2 times the upper limit of the norm.

Undesirable effects in specific patient groups

Very frequent (≥ 10%), the undesirable effect of olanzapine in clinical trials in patients with psychosis associated with dementia was a violation of gait and fall.

Frequent (<10 and ≥ 1%), unwanted effects with olanzapine in elderly patients with psychosis associated with dementia were urinary incontinence, pneumonia, erythema, visual hallucinations, lethargy.

In clinical studies in patients with psychosis induced by the drug (dopamine receptor agonist) in Parkinson's disease, the increase in Parkinsonian symptoms was very frequent (≥10%) and with a higher frequency than in the placebo group. Hallucinations were also noted very often (≥ 10%) and with a higher frequency than in the placebo group.

In patients with bipolar mania receiving olanzapine in combination with lithium or valproic acid, very frequent (≥10%), unwanted effects were weight gain, dry mouth, increased appetite, tremor and frequent (<10 and ≥ 1%) speech disorder, neutropenia.

With long-term treatment (at least 48 weeks), the incidence of clinically significant adverse effects (weight gain, increase in glucose concentrations, total cholesterol, triglycerides, and worsening of the ratio of low density cholesterol / high density cholesterol) increases with time.

Overdose:

Signs and Symptoms

Very frequent (frequency ≥10%) with symptoms of olanzapine overdose were tachycardia, agitation / aggressiveness, speech impairment, various extrapyramidal disorders and disorders of consciousness of varying severity (from sedation to coma). Other clinically significant effects of olanzapine overdose included delirium, seizures, malignant neuroleptic syndrome, respiratory depression, aspiration, elevation and lowering of arterial pressure, arrhythmias (<2% cases of overdose) and cardiac arrest and respiration.The minimum dose for acute overdose with a lethal outcome was 450 mg, the maximum dose for an overdose with a favorable outcome (survival) is 2 g.

Medical assistance for overdose

There is no specific antidote for olanzapine. It is not recommended to provoke vomiting. Standard procedures for overdose can be shown (gastric lavage, activated charcoal reception). A joint reception of activated charcoal and olanzapine showed a decrease in the bioavailability of olanzapine upon ingestion of up to 50-60%. Symptomatic treatment is shown in accordance with the clinical condition and control of vital body functions, including correction of low blood pressure, circulatory disorders andmaintenance of respiratory function. Do not use epinephrine, dopamine and other adrenomimetics, which are β-adrenoreceptor agonists, since stimulation of these receptors can aggravate arterial hypotension.

Interaction:

The metabolism of olanzapine can be altered by inhibitors or inducers of the cytochrome P450 isoenzyme exhibiting specific isoenzyme activity CYP1A2.The clearance of olanzapine is increased in smokers and in patients taking carbamazepine (in connection with an increase in isoenzyme activity CYP1A2). Potential inhibitors of isoenzyme CYP1A2 can reduce the clearance of olanzapine. Olanzapine is not a potential inhibitor of isoenzyme CYP1A2, so when taking olanzapine, the pharmacokinetics of medicines, such as theophylline, mainly metabolized by isoenzyme CYP1A2, does not change.

In clinical studies, it was shown that a single application of a dose of olanzapine against the background of therapy with the following drugs was not accompanied by a suppression of the metabolism of these drugs: imipramine or its metabolite desipramine (isozymes CYP2D6, CYP3A, CYP1A2), warfarin (isoenzyme CYP2C19), theophylline (isoenzyme CYP1A2) or diazepam (isoenzyme CYP3A4, CYP2C19). There were no signs of drug interaction with olanzapine in combination with lithium or biperidin.

Against the background of an equilibrium concentration of olanzapine, there was no change in the pharmacokinetics of ethanol. However, taking ethanol with olanzapine may be accompanied by an increase in the pharmacological effects of olanzapine, for example, sedation.

Fluoxetine (60 mg once or 60 mg daily for 8 days) causes an increase in the maximum concentration (C_max) of olanzapine on average by 16% and a decrease in the clearance of olanzapine by an average of 16%. The degree of influence of this factor is significantly inferior to the severity of individual differences in these indicators, therefore, it is usually not recommended to change the dose of olanzapine when used in combination with fluoxetine.

Fluvoxamine, inhibitor of isoenzyme CYP1A2, decreases the clearance of olanzapine. The result is an average increase in C_max olanzapine with the administration of fluvoxamine by 54% in nonsmoking women and by 77% in male smokers, the mean increase AUC (area under the concentration-time curve) of olanzapine by 52% and 108% respectively. Small doses of olanzapine should be given to patients who are jointly receiving fluvoxamine treatment.

In studies in vitro Using human liver microsomes, it has been shown that olanzapine slightly suppresses the formation of valproic acid glucuronide (the main pathway of valproic acid metabolism). Valproic acid also slightly affects the metabolism of olanzapine in vitro. Therefore, clinically significant pharmacokinetic interaction between olanzapine and valproic acid is unlikely.

Absorption of olanzapine is not dependent on food intake.

A single dose of aluminum or magnesium-containing antacids or cimetidine did not interfere with the bioavailability of olanzapine when ingested. Simultaneous use of activated charcoal and olanzapine reduced the bioavailability of the latter when administered orally to 50-60%.

According to research in vitro using human liver microsomes, olanzapine also demonstrated an extremely low potential for inhibiting the activity of the following cytochrome P450 isoenzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A.

Special instructions:

Suicide

The risk of suicide attempts by patients with schizophrenia and bipolar disorder of the first type is due to the aforementioned diseases. In this regard, against the background of pharmacotherapy requires careful monitoring of those patients who have a risk of suicide is particularly high. When prescribing olanzapine, one should strive to minimize the number of tablets taken by the patient, so as to reduce the risk of overdose.

Malignant neuroleptic syndrome

Malignant neuroleptic syndrome (CNS) - a potentially lethal symptom complex, can develop in the treatment of any neuroleptic, including olanzapine. Clinical manifestations of malignant neuroleptic syndrome include a significant increase in body temperature, rigidity of the muscles, changes in mental status and autonomic disorders (unstable pulse or blood pressure, tachycardia, cardiac arrhythmias, increased sweating). Additional signs may include an increase in the activity of creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Clinical manifestations of malignant neuroleptic syndrome or a significant increase in body temperature without other symptoms of malignant neuroleptic syndrome require the removal of all antipsychotics, including olanzapine.

Late dyskinesia

In comparative studies, treatment with olanzapine was significantly less often accompanied by the development of dyskinesia requiring drug-induced correction than the use of typical and other atypical neuroleptics.However, the risk of tardive dyskinesia with prolonged therapy with neuroleptics should be considered. When developing signs of tardive dyskinesia, a dose adjustment of an antipsychotic is recommended. It should be borne in mind that when translated into olanzapine symptoms of tardive dyskinesia, may develop as a result of the simultaneous withdrawal of previous therapy. Over time, the intensity of this symptomatology may increase, moreover, these symptoms may develop after discontinuation of therapy.

Experience in elderly patients with psychosis associated with dementia The effectiveness of olanzapine in elderly patients with psychosis associated with dementia is not established. In this category of patients in placebo-controlled clinical trials, the incidence of lethal cases in the olanzapine group was higher than in the placebo group (3.5% vs. 1.5%, respectively). Risk factors that may predispose this group of patients to a higher mortality with olanzapine include age> 80 years, sedation, concomitant use with benzodiazepines, or the presence of lung pathology (eg, pneumonia with or without aspiration).There is insufficient data to establish differences in the incidence of cerebrovascular disorders and (or) mortality (compared to placebo) and in the risk factors for this group of patients with oral olanzapine and intramuscular injections.

Parkinson's disease

It is not recommended to use olanzapine in the treatment of psychoses induced by dopamine receptor agonists in Parkinson's disease. In clinical studies in patients with psychosis induced by the drug (dopamine receptor agonist) in Parkinson's disease, the increase in Parkinsonian symptoms was very frequent (≥ 10%) and with a higher frequency than in the placebo group. Hallucinations were also noted very often (≥10%) and with a higher frequency than in the placebo group.

Dysfunction of the liver

In some cases, the use of olanzapine, usually in the early stages of therapy, was accompanied by a transient, asymptomatic increase in the activity of "hepatic" transaminases (aspartate aminotransferase (ACT) and alanine aminotransferase (ALT)) in the blood serum. There were rare cases of hepatitis. In addition, there were isolated reports of cholestatic and mixed liver damage. Special caution is necessary when increasing activity ACT and (or) ALT in blood serum in patients with insufficient liver function, with limited functional reserve of the liver or in patients receiving potentially hepatotoxic drugs. In case of increased activity ACT and (or) ALT during treatment with olanzapine requires careful monitoring of the patient and, if necessary, a reduction in the dose. In case of serious violations of liver function caused by taking olanzapine, its use should be discontinued.

Hyperglycemia and diabetes mellitus

There is a higher prevalence of diabetes mellitus in patients with schizophrenia. As with some other antipsychotics, cases of hyperglycemia, decompensation of diabetes mellitus, in some cases accompanied by ketoacidosis and diabetic coma, including fatal cases, were rarely noted. A thorough clinical monitoring of patients with diabetes mellitus and patients with risk factors for the development of diabetes mellitus is recommended.

Change in lipid profile

In placebo-controlled trials, patients who received olanzapine, undesirable changes in the lipid spectrum were observed.Clinical observation is recommended (see section "Side effect").

Development of risk of sudden death

Experience in the clinical use of any antipsychotic, including olanzapine, found a similar, dose-dependent, double increase in the risk of death due to acute heart failure, compared with deaths due to acute heart failure in patients who did not use antipsychotics.

Cerebrovascular adverse events, including stroke, in elderly patients with dementia

Cerebrovascular adverse events (for example, stroke, transient ischemic attack), including death, were noted in studies of olanzapine in elderly patients with psychosis associated with dementia. In placebo-controlled studies, there was a higher incidence of cerebrovascular adverse events in patients in the olanzapine group than in the placebo group (1.3% vs. 0.4%, respectively). All patients with cerebrovascular disorders had previous risk factors for developing cerebrovascular adverse events (for example,previously noted case of cerebrovascular undesirable phenomenon or transient ischemic attack, arterial hypertension, smoking), as well as concomitant diseases and (or) taking medications associated with cerebrovascular undesirable events. Olanzapine is not indicated for the treatment of patients with psychosis associated with dementia.

Convulsions

Olanzapine should be used with caution in patients with a history of seizures or exposed to factors that reduce the threshold of convulsive readiness. In such patients, seizures were rare in the treatment with olanzapine.

M-holinoblocking activity

When conducting clinical trials, olanzapine therapy was rarely accompanied by undesirable reactions caused by blockade of m-cholinergic receptors. However, clinical experience with olanzapine in patients with concomitant diseases is limited, so caution should be exercised in prescribing olanzapine to patients with clinically significant prostatic hyperplasia, paralytic intestinal obstruction, occlusive glaucoma, and similar conditions.

Blockade of dopamine receptors

In conditions in vitro olanzapine exhibits antagonism against dopamine receptors and, like other antipsychotics (antipsychotics), theoretically can suppress the action of levodopa and other dopamine receptor agonists.

Neutropenia

Caution should be applied olanzapine in patients with a low content of leukocytes and (or) neutrophils in the blood; receiving drugs that can cause neutropenia with oppression of bone marrow function due to concomitant disease, radiation or chemotherapy; as well as in patients with eosinophilia and (or) myeloproliferative diseases. The development of neutropenia has been reported, mainly, when olanzapine is combined with valproate

Interval QT

In clinical studies, clinically significant lengthening of the interval QT (interval QT with the correction of Friederation [QTcF]> 500 ms in patients with baseline, QTcF <500 ms) in patients who received olanzapine, in the absence of significant differences with placebo in the frequency of occurrence of adverse events from the heart. However, as with other antipsychotics, caution should be exercised when using olanzapine in combination with drugs that can lengthen the interval QT, especially in elderly patients, with congenital lengthening of the interval QT, chronic heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia.

Abolition of therapy

In the case of a sharp abolition of olanzapine, extremely rarely (<0.01%) was reported on the acute development of sweating, insomnia, tremor, anxiety, nausea and vomiting.

Thromboembolism

Very rarely (<0.01%) reported on the development of venous thromboembolism in the background of olanzapine therapy.The presence of a causal relationship between the administration of olanzapine and venous thromboembolism has not been established. However, whatthe patients with schizophrenia often have acquired risk factors for venous thromboembolism, it is required to conduct an overall assessment of all possible risk factors for the development of this complication, including immobilization of patients, and to take the necessary preventive measures.

Total activity against the central nervous system

Taking into account the main effect of olanzapine on the central nervous system, caution should be exercised when using olanzapine in combination with other central drugs and alcohol.

Postural hypotension

Postural hypotension was rarely observed in clinical studies of olanzapine in the elderly.As with other antipsychotics, in patients with olanzapine, it is recommended that patients who are older than 65 years have periodic monitoring of blood pressure.

Children and teenagers under 18 years of age

Olanzapine is not recommended for use in children and adolescents under 18 years due to lack of sufficient data on efficacy and safety. In short-term studies that were conducted in adolescents aged 13-17 years, there was a greater increase in body weight and a change in the concentration of lipids and prolactin than in similar studies in adults.

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

Patients receiving olanzapine, care should be taken when controlling mechanical means, including a vehicle, because olanzapine may cause drowsiness and dizziness.

Form release / dosage:Tablets, film-coated, 5 mg, 10 mg, 15 mg, 20 mg.

Packaging:

6 or 10 tablets per foil blister Al/ OPA / Al/ PVC.

5 blisters for 6 tablets or 3 blisters for 10 tablets together with instructions for use are placed in a cardboard box.

Storage conditions:At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001725

Date of registration:02.07.2012

The owner of the registration certificate:Pharmaceutical factory "POLFARMA" JSCPharmaceutical factory "POLFARMA" JSC Poland

Manufacturer: & nbsp

POLPHARMA PHARMACEUTICAL WORKS, S.A. Poland

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp16.08.2015

Illustrated instructions

Instructions

Normiton (Normiton)