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Instruction for use: Olanzapine 5mg

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International Nonproprietary Name (INN): Olanzapine

Pharmaceutic group: Antipsychotic (neuroleptic)

Presentation:

Tablets 5 mg, 10 mg. ¹30.

Available with prescription

Indications for Olanzapine

Olanzapine is a preparation, which is usually prescribed by specialists in the psychiatry or neurology. Main indications include: schizophrenia, maniac episodes, schizoaffective or bipolar disorders, depression (in combination with fluoxetine). The course of treatment with Olanzapine is usually prolonged. This medicine eliminates productive and negative symptoms of these diseases. In comparison with haloperidol, olanzapine shows better remission period (a state of absence of the main disease’s exacerbations) and improves scores in Montgomery–Åsberg Depression Rating Scale.

Olanzapine, a thienobenzodiazepine, is an antipsychotic agent that demonstrates a broad pharmacologic profile across a number of receptor systems. Olanzapine displays high receptor affinity binding in vitro at dopamine D2, D3, D4, 5-HT2A/C, 5-HT3, 5-HT6, muscarinic M1-M5, adrenergic α1, and histamine H1 receptor subtypes, while displaying a lower affinity at dopamine D1 and D5 receptor subtypes. In a behavioural paradigm predictive of antipsychotic activity, olanzapine reduced conditioned avoidance response in rats at doses lower than 4 times those required to produce catalepsy. In a single dose (10 mg) PET study in healthy subjects, olanzapine produced higher 5-HT2A than dopamine D2 receptor occupancy. The percent of D2 occupancy was less than the threshold value predictive of extrapyramidal events. Before prescribing this remedy, be sure to read carefully a specialist’s leaflet.

This preparation should be taken orally, usually once a day. It may be taken independently on meal as far as food doesn’t influence upon an absorbability of the drug. The dosage and treatment’s tactics depends on specific features of a concrete patient and/or indication. The dosage usually varies from 5 mg till 20 mg per day. Olanzapine is commonly administrated as the only psychotropic agent (monotherapy), but in some indications it may be combined with preparations of lithium or valproic acid; in the case of therapeutically resistant depression it can be used together with fluoxetine.

More information about Olanzapine’s medical usage you can find in the approved leaflet (in Russian language only), which is included in each carton box with the product.

Trade name of the drug – Olanzapine

Dosage Form: tablets

Active substance:

olanzapine 5 mg or 10 mg

Excipients: lactose monohydrate (milk sugar) 50,60 / 101,20 mg, microcrystalline cellulose, 51,40 / 102,80 mg, pregelatinised starch 51,40 / 102,80 mg colloidal silicon dioxide (Aerosil) 0.80 / 1.60 mg magnesium stearate 0.80 / 1.60 mg.

Description:

Round biconvex tablet form from light yellow to yellow. Valid blotches of darker color.

Pharmacotherapeutic group: Antipsychotic (neuroleptic)

ATX code: N05AH03

Pharmacological Properties of Olanzapine

Pharmacodynamics

Olanzapine is an antipsychotic (neuroleptic).

In pre-clinical studies have shown an affinity for 5-HT2A / 2S-, 5-NT3-, 5-HT6 serotonin receptors, D1-, D2-, D3-, D4-, D5-dopamine receptors, m-anticholinergic effects due to blockade of M1 5 nicotinic acetylcholine receptor; also it has an affinity for a1-adrenergic and H1 histamine receptors. In animal experiments, it was detected antagonism of serotonin, dopamine and m-holinoretseptorami. In vivo and in vitro, olanzapine has a more pronounced activity and affinity towards the 5-HT2 serotonin receptors compared to D2-dopamine receptors. According to electrophysiological studies olanzapine selectively reduces the excitability of the mesolimbic dopaminergic neurons, and at the same time has very little effect on striatal nerve pathways involved in the regulation of motor function. Olanzapine reduced a conditioned defensive reflex (test characterizes the antipsychotic activity) at a dose lower than the dose causing catalepsy (disorder, reflecting the spillover effect on motor function). Unlike other neuroleptics, olanzapine increases during antianxiety effect "anxiolytic" test.

Olanzapine is a statistically reliable response as productive (delusions, hallucinations, etc..) And negative disorders.

In single dose of 10 mg of olanzapine by positron emission tomography (PET) in healthy volunteers found a greater affinity of olanzapine 5 to NT2A- than the D2-dopamine receptors. On tomograms patients with schizophrenia demonstrated that in patients treated with olanzapine sensitive affinity for striatal D2-receptors comparable effect in patients receiving clozapine sensitive to, and lower than in patients susceptible to treatment by other antipsychotic drugs, and risperidone.

Clinical efficacy

The international, double-blind, comparative study in patients with schizophrenia, schizoaffective disorder or similar disorders of varying severity of depressive symptoms (mean initial value of 16.6 on the Montgomery-Asberg Scale for Depression), a prospective secondary analysis on the scale of mood from the initial to the final point of control a statistically significant (p = 0.001) improved with olanzapine (-6.0) compared to haloperidol (-3.1).

Patients with manic or mixed episode of bipolar disorder compared to placebo and drug valproic acid (divalproex) showed high effectiveness in reducing the symptoms of manic for 3 weeks. Comparable results efficacy of olanzapine and haloperidol were observed in patients with symptomatic remission of mania and depression in 6-12 weeks. In koterapii patients receiving lithium medication or valproate for a minimum of 2 weeks, supplementation with 10 mg of olanzapine (koterapiya with drugs lithium or valproate) resulted in a significant reduction in symptoms of mania, compared with monotherapy drugs lithium and valproic acid for 6 weeks.

The 12-month study of the prevention of recurrence of manic episodes in patients who achieved remission with olanzapine and then randomized into a group taking the drug olanzapine, a statistically significant advantage over placebo on the primary outcome monitoring of recurrence of bipolar disorder, and in terms of preventing recurrence of mania or depressive relapse.

In the second 12-month recurrence prevention study in manic episode patients who achieved remission with combined olanzapine with lithium medication, and then randomized to olanzapine monotherapy group or drug lithium. The efficacy of olanzapine was not statistically significant compared to lithium on the primary drug control criterion of recurrence of bipolar disorder (olanzapine 30.0%, lithium 38.3%, p = 0.055).

The 18 month study koterapii manic or mixed episode patients stabilized with olanzapine and drugs, stabilizing mood (drugs lithium or valproate), long-term collaboration with olanzapine therapy with drugs lithium or valproate was not statistically significant compared to a monotherapy drug lithium or valproic acid for the purpose of delaying the appearance of recurrence of bipolar disorder, defined by the diagnostic criteria.

Pharmacokinetics

After oral olanzapine is well absorbed, its maximum concentration in plasma is achieved in 5-8 hours. The absorption of olanzapine is independent of food intake. In studies with different doses in the range of 1-20 mg it was shown that the plasma concentration of olanzapine varies linearly and proportionally with dose.

Olanzapine is metabolized in the liver as a result of oxidation and conjugation processes. The major circulating metabolite is 10-N-glucuronide, which theoretically does not penetrate the blood-brain barrier. CYP2D6 and CYP1A2 isozyme involved in the formation of N-2-dezmetil- gidroksimetilmetabolitov olanzapine. Both metabolites in animal studies had significantly less pronounced pharmacological activity in vivo, than olanzapine. The main pharmacological activity of the drug due to the parent compound - olanzapine, having the ability to penetrate the blood-brain barrier.

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

However, the rate of change in half-life and clearance under the influence of each of these factors is significantly inferior to the degree of differences of these parameters between individuals.

Indicators pharmacokinetics in adolescents (13-17 years) and adults are similar. According to clinical studies, exposure adolescents 27% higher than in adults. The difference between the demographic parameters of the population of adults and adolescents was the fact that there were fewer smokers, and had lower average body weight among adolescents.

No significant differences between the mean values of clearance and half-life of olanzapine in plasma in patients with severe renal impairment compared to individuals with normal renal function, has not been established. About 57% of radiolabelled olanzapine excreted in the urine primarily as metabolites.

Smokers persons with minor violations of liver function clearance of olanzapine is lower than in non-smokers with no liver function abnormalities.

At plasma concentrations of olanzapine 7-1000 ng / ml its relation to plasma proteins is approximately 93%. Olanzapine is mainly bound to albumin and a1-acid glycoprotein. In a study of people of European, Japanese and Chinese origin, differences in the pharmacokinetics of olanzapine associated with race, it has been established. CYP2D6 isoenzyme activity does not affect the metabolism of olanzapine.

Indications for Olanzapine

Olanzapine is indicated for the treatment of schizophrenia. Olanzapine is effective to maintain clinical improvement in the ongoing treatment of patients with schizophrenia, responding to the original treatment.

Olanzapine is indicated for the treatment of manic episodes of moderate to severe.

Olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder, in which he was effective in the treatment of manic phase (see. "Pharmacodynamics" section).

Treatment-resistant depression. In combination with fluoxetine, olanzapine is indicated for the treatment of treatment-resistant depression in adults (major depressive episodes with a history of inefficient use of two antidepressants on dose and duration of therapy course, adequate this episode). Olanzapine monotherapy is not indicated for the treatment of treatment-resistant depression.

Contraindications for Olanzapine

Hypersensitivity to any component of the drug.

Contraindicated for persons under 18 years of age.

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Pregnancy and lactation

Due to insufficient experience with olanzapine during pregnancy, the drug should be used during pregnancy only if the potential benefit to the patient is much higher than the potential risk to the fetus. Patients should be warned that in the event or planning pregnancy during treatment with olanzapine they need to report it to your doctor.

Neonates whose mothers had taken antipsychotics (including olanzapine) during the third trimester of pregnancy, the risk of adverse reactions including extrapyramidal disorders and / or withdrawal symptoms that may change after the birth of the strength and duration. It was reported on agitation, arterial hyper-and hypotension, tremor, somnolence, respiratory distress, or feeding disorder. Therefore, you must carefully monitor the condition of the newborn.

The study revealed that olanzapine passes into breast milk. The average dose received by a child (mg / kg) when the equilibrium concentration of the mother was 1.8% of the dose of olanzapine mother (mg / kg). We do not recommend breast-feeding during treatment with olanzapine.

Olanzapine Dosage and Administration

Inside. Olanzapine can be administered independently from the meal, as food has no effect on the absorption of olanzapine.

Schizophrenia

The recommended starting dose of olanzapine is 10 mg once a day. Therapeutic doses of olanzapine range from 5 mg to 20 mg per day. The daily dose should be individualized according to the patient's clinical condition. Increasing the dose above the standard daily dose (10 mg) is recommended only after the evaluation of the clinical picture. In applying the drug should regularly assess the need for continued therapy.

Bipolar disorder

For the treatment of manic episodes of olanzapine recommended starting dose is 15 mg once daily in monotherapy or 10 mg once daily in combination with lithium or valproate preparations. Therapeutic doses of olanzapine range from 5 mg to 20 mg per day. The daily dose should be individualized depending on the clinical condition of the patient. Increasing the dose above the standard daily recommended only after the evaluation of the clinical picture and with an interval of not less than 24 hours.

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

For the treatment of depressive episodes, olanzapine should be used in combination with fluoxetine 1 times a day, in the evening, regardless of the meal. Typically, the initial dose of olanzapine 5 mg and 20 mg of fluoxetine. Antidepressant Activity confirmed with olanzapine at a dose of 6-12 mg (mean daily dose - 7.4 mg) and fluoxetine at a dose of 25-30 mg (mean daily dose - 39.3 mg). If necessary, the dose may be modified both olanzapine and fluoxetine. In applying the drug should regularly assess the need for continued therapy.

Treatment-resistant depression

Olanzapine should be used in combination with fluoxetine 1 times a day, in the evening, regardless of the meal. Typically, the initial dose of olanzapine 5 mg and 20 mg of fluoxetine. If necessary, the dose may be modified both olanzapine and fluoxetine. Antidepressant activity was confirmed when using olanzapina at a dose of 6-12 mg and fluoxetine dose 25-30 mg. In applying the drug should regularly assess the need for continued therapy.

General rules for daily dose selection for specific groups of patients with oral

Reduced initial doses up to 5 mg per day is recommended in elderly patients or patients with other clinical risk factors, including severe renal impairment or hepatic insufficiency of moderate severity. Reduction of initial dose to 5 mg can be recommended to patients with a combination of factors (female, aged and no smoking habits), which can reduce the metabolism of olanzapine (see. Table 1).

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

Side effect ofOlanzapine

system / Side effect (And footnote to the comment) The frequency of side effects
Very Often (≥ 1/10) Often (≥ 1/100 to <1/10) uncommon (≥ 1/1000 to <1/100) Rarely (≥ 1/10000 to <1/1000) very rare (<1/10000), or the frequency has not been established
1 2 3 4 5 6
Violations of the blood and lymphatic system
leukopenia (1, 3) ×
Neutropenia (3) ×
Thrombocytopenia (3) ×
Eosinophilia (1) ×
Violations by the immune system
Allergic reactions (Anaphylaxis, angioedema, urticaria or pruritus) (3) ×
Violations of the metabolism and nutrition
Increased body weight (2.4) ×
Increasing the concentration of glucose (3, 8) ×
Increasing concentrations of cholesterol (3, 9) ×
Increasing the concentration of triglycerides (3, 10) ×
Glycosuria (2) ×
Increased appetite ×
Decompensation or development of diabetes, in some cases coma or ketoacidosis accompanied, including some cases of death (3.8) ×
Hypothermia (3) ×
From the nervous system
Drowsiness (1) ×
Akathisia (1, 6) ×
Dizziness (1) ×
Parkinsonism (1, 6) ×
Dyskinesia (1, 6) ×
Dystonia (including oculogyric crisis) (2, 6) ×
Neuroleptic malignant syndrome (2, 3) ×
Tardive dyskinesia (3) ×
ataxiophemia
Amnesia
Cramps (2, 7)
"Cancellation" syndrome (3,5) ×
Violations from heart
Bradycardia (2) ×
The elongation QT (3) interval ×
Ventricular tachycardia / ventricular fibrillation, Sudden death (1, 3) ×
Violations by vessels
Hypotension including postural hypotension (1) ×
Pulmonary embolism and deep vein thrombosis (3) ×
Disorders of the respiratory system, organs, thoracic and mediastinal disorders
Nosebleeds (1) Disorders of the ×
gastrointestinal tract
Short m-anticholinergic effects including constipation and dry mouth ×
Bloating (2.3) ×
Pancreatitis (3) ×
Disorders of the liver and biliary tract
A transient increase in activity of "liver" transaminases (alaninaminotrans-ferazy (ALT), aspartate-ferazy (AST), especially in the early period of treatment (3) ×
Hepatitis (including hepatocellular, cholestatic or mixed liver injury) (3) ×
Disorders of the skin and subcutaneous tissue
Rash (3) ×
photosensitivity reaction (2) ×
Alopecia (3) ×
Violations of the musculoskeletal tissue
Arthralgia (2) ×
Rhabdomyolysis (3) ×
Violations of the kidney and urinary tract
Urinary incontinence ×
Delayed start of urination ×
Urinary retention (3) ×
Violations of the genital and breast
Amenorrhea (3) ×
Gynecomastia (1) ×
Increased breast cancer in women
galactorrhea ×
Priapism (1) ×
Decreased libido in men and women (3) ×
Erectile dysfunction in men (3) ×
Common disorders
Asthenia, fatigue (2) ×
Pyrexia (2) ×
Edema (2) ×
laboratory data
The increase in prolactin concentrations in the plasma (1.11) ×
Increased activity of alkaline phosphatase (2) ×
Increased activity of creatine phosphokinase (3) ×
Increased total bilirubin concentration (3) ×
Increased levels of uric acid (2) ×

Comments to the footnotes to Table 2:

1) The data collected during the placebo-controlled clinical trials, which were carried out to see "Schizophrenia, acute phase."

2) Generalized data collected in the course of clinical trials.

3) Reported side effects spontaneously during post-marketing studies.

4) In all groups of patients, regardless of body weight, there was a clinically significant increase in body weight.

Increasing body weight by 7% or more from the average value after a short course of treatment (mean duration - 47 days) was observed very often (22.2%), an increase of 15% or more was common (4.2%) and an increase of 25% or more was infrequent (0.8%).

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

5) When the abrupt cancellation of olanzapine observed symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting.

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

In patients treated with olanzapine, parkinsonism, akathisia, dystonia were observed less frequently than in patients treated with titrated doses of haloperidol. Due to lack of detailed information about the presence of patients had a history of acute and tardive dyskinesias, it is currently impossible to conclude that olanzapine causes less development of tardive dyskinesia or other extrapyramidal syndromes later.

7) Convulsions mainly in patients with a history of seizures, or in the presence of risk factors for seizures.

8) It is often observed increase in the concentration of glucose from normal fasting values (<5.56 mmol / l) to high (³7 mmol / l).

Changing the concentration of glucose from borderline performance fasting (³5,56- <7 mmol / l) to high (³7 mmol / l) were very common.

9) of the increase in cholesterol concentration was observed from normal fasting values (<5.17 mmol / l) to high (³6,2 mmol / l).

Changing the concentration of cholesterol from the border indicators on an empty stomach (³5,17- <6,2 mmol / l) to high (³6,2 mmol / l) were very common.

10) increase the concentration of triglycerides was observed frequently on normal fasting values (<1.69 mmol / L) to high (³2,26 mmol / l).

Changing the concentration of triglycerides from borderline performance fasting (³1,69- <2,26 mmol / l) to high (³2,26 mmol / l) were very common.

11) In clinical studies, up to 12 weeks in plasma prolactin concentration exceeded the upper normal limit of approximately 30% of patients with normal baseline prolactin. The majority of these patients, an increase in prolactin concentrations was moderate, and less than 2 times the upper limit of normal.

Undesirable effects in specific groups of patients

Very common (³10%) undesirable effect of olanzapine in clinical trials in patients with psychosis associated with dementia, gait disturbance and was falling.

Frequent (<10 and ³1%) undesirable effects associated with the use of olanzapine in elderly patients with psychosis associated with dementia, incontinence and had pneumonia.

It is also often observed Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence.

In clinical studies in patients with psychosis induced by drug intake (dopamine receptor agonist) in Parkinson's disease, parkinsonism symptoms was strengthening too often (³10%) and a higher frequency than in the placebo group. Hallucinations have also been reported very common (³10%) and a higher frequency than in the placebo group.

In patients with bipolar mania, receiving olanzapine in combination with lithium preparations or valproic acid, is very common (³10%) undesirable effects were weight gain, dry mouth, increased appetite, tremor and frequent (<10 and ³1%) speech disorder.

overdose

Signs and symptoms of overdose

Very common (incidence ³10%) symptoms of an overdose of olanzapine were tachycardia, agitation / aggressiveness, impaired speech, various extrapyramidal disorder and disturbance of consciousness of varying severity (from sedation to coma). Other clinically relevant effects of olanzapine overdose include delirium, seizures, neuroleptic malignant syndrome, respiratory depression, aspiration, increase and decrease in blood pressure, arrhythmias (<2% of overdose cases) and heart failure and breathing. The minimum dose for acute overdose fatalities was 450 mg, the maximum dose of an overdose of a favorable outcome (survival) - 2 Years

Medical treatment for overdose

Specific antidote for olanzapine does not exist. Do not provoke vomiting. It can be shown standard procedures in overdose (gastric lavage, administration of activated charcoal). The joint administration of activated charcoal and olanzapine showed a decrease in the bioavailability of olanzapine at intake to 50-60%. Displaying symptomatic treatment according to the clinical condition and monitoring of vital body functions, including the correction of reduced blood pressure, circulatory disorders and maintain respiratory function. Do not use epinephrine, dopamine and other agonists that are b-adrenoceptor agonists as stimulation of these receptors may worsen hypotension.

It requires monitoring of cardiovascular activity to identify possible arrhythmias. The patient should be under continuous medical supervision until complete recovery.

Interaction

The metabolism of olanzapine can vary under the influence of inhibitors or inducers of cytochrome P450 isoenzymes, exhibiting activity against particular isoenzyme CYP1A2. Clearance of olanzapine is increased in smokers and in patients taking carbamazepine (due to the increased activity of the isoenzyme CYP1A2). Potential inhibitors of CYP1A2 isoenzyme may decrease the clearance of olanzapine. Olanzapine is not a potent inhibitor of isozyme CYP1A2, so the pharmacokinetics of olanzapine drugs such as theophylline, mainly metabolized isoenzyme CYP1A2 is not changed.

In clinical studies have shown that a single application of a dose of olanzapine on the background of the following medications therapy was not associated with inhibition of metabolism of these drugs: imipramine or its metabolite desipramine (isoenzymes CYP2D6, CYP3A, CYP1A2), warfarin (isoenzyme CYP2C19), theophylline (isoenzyme CYP1A2) or diazepam (isoenzyme CYP3A4, CYP2C19). There were no drug interactions are also signs with olanzapine in combination with lithium or drugs biperidenom.

Against the background of the equilibrium concentration of olanzapine pharmacokinetics of ethanol changes were noted. However, reception of ethanol with olanzapine may be associated with increased pharmacological effects of olanzapine, such as sedation.

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

special instructions for Olanzapine

Suicide

The risk of committing suicide attempt patients with schizophrenia and bipolar disorder first type is caused by the mentioned diseases. In this regard, on the background of drug therapy requires careful monitoring for those patients who have particularly high risk of suicide. In the appointment of olanzapine should strive to minimilizatsii number of tablets taken by the patient in order to reduce the risk of overdose.

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome (NMS) (a potentially fatal symptom complex) can be developed for the treatment of any antipsychotics, including olanzapine. Clinical manifestations of neuroleptic malignant syndrome include a significant increase in body temperature, muscle rigidity, altered mental status, and autonomic disorders (unstable pulse or blood pressure, tachycardia, cardiac arrhythmias, sweating). Additional signs may include an increase in creatine kinase activity, myoglobinuria (rhabdomyolysis) and acute renal failure. Clinical manifestations of neuroleptic malignant syndrome or a significant increase in body temperature with no other symptoms of neuroleptic malignant syndrome require discontinuation of all antipsychotics, including olanzapine.

tardive dyskinesia

In comparative studies, olanzapine significantly less frequently accompanied by the development of dyskinesias requiring medical correction than the use of other typical and atypical antipsychotics. However, it should consider the risk of tardive dyskinesia after prolonged treatment with neuroleptics. With the development of symptoms of tardive dyskinesia is recommended that dose adjustment of neuroleptic. Note that when translated into the symptoms of tardive dyskinesia with olanzapine may develop due to the simultaneous cancellation of prior therapy. Over time, the intensity of said symptoms can be increased, moreover, the symptoms may develop after discontinuation of therapy.

Experience with elderly patients with psychosis associated with dementia

The efficacy of olanzapine in elderly patients with psychosis associated with dementia has not been established. In this group of patients in the placebo-controlled clinical trials, the frequency of deaths in the olanzapine group was higher than in the placebo group (3.5% vs. 1.5% respectively). Risk factors that may predispose this patient population to a higher mortality rate with olanzapine include age> 80 years, sedation, with the combined use of benzodiazepines, or presence of pulmonary disease (eg, pneumonia with or without aspiration it).

There is sufficient evidence to establish differences in the incidence of cerebrovascular disorders and (or) mortality (compared to placebo) and risk factors in this group of patients with olanzapine inside and intramuscular injections.

Parkinson's disease

Olanzapine is not recommended to use in the treatment of psychosis induced by dopamine receptor agonists reception in Parkinson's disease. In clinical studies in patients with psychosis induced by drug intake (dopamine receptor agonist) in Parkinson's disease, parkinsonism symptoms was strengthening too often (³10%) and a higher frequency than in the placebo group. Hallucinations have also been reported very common (³10%) and a higher frequency than in the placebo group.

Disturbances of liver function

In some cases, olanzapine, usually in the early stages of therapy, accompanied by a transient, asymptomatic increase in the activity of "liver" transaminases (aspartate aminotransferase (ACT) and alanine aminotransferase (ALT)) in the blood serum. There have been rare cases of hepatitis. In addition, there have been isolated reports of cholestatic and mixed liver injury. Particular caution is required when increasing the ACT activity and (or) of ALT in blood serum in patients with failure of liver function, with limited functional reserve of the liver, or in patients treated with potentially hepatotoxic drugs. In the case of increasing the activity of ACT and (or) ALT during treatment with olanzapine requires careful monitoring of the patient and, if necessary, a dose reduction. In severe hepatic dysfunction caused by olanzapine and its use should be discontinued.

Hyperglycemia and diabetes

It noted a higher prevalence of diabetes mellitus in patients with schizophrenia. How and when taking certain other antipsychotic drugs are rarely observed cases of hyperglycemia, diabetes decompensation, in some cases accompanied by ketoacidosis and diabetic coma, including fatal. Recommended careful clinical monitoring of patients with diabetes and patients with risk factors for diabetes.

Changes in lipid profile

During the placebo-controlled studies, patients treated with olanzapine observed adverse lipid changes. Recommended clinical observation (see. "Side effects" section).

The development of sudden death risk

Experience of clinical application of all antipsychotics, including olanzapine showed similar dose-dependent, two-fold increase in the risk of death due to acute heart failure, compared with cases of death due to acute heart failure patients, do not use antipsychotics.

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

Cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, were observed in studies of olanzapine in elderly patients with psychosis related to dementia. In placebo-controlled studies observed a higher incidence of cerebrovascular adverse events in patients in the olanzapine group compared with the placebo group (1.3% vs. 0.4% respectively).

All patients with cerebrovascular disorders had preexisting risk factors for cerebrovascular adverse events (eg, previously noted the case of cerebrovascular adverse event or a transient ischemic attack, hypertension, smoking), as well as concomitant diseases and (or) administration of drugs, according to the time associated with cerebrovascular adverse phenomena.

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 convulsions in or exposed to factors that reduce the seizure threshold. In these patients with olanzapine seizures are rare.

M-anticholinergic activity

In clinical trials with olanzapine therapy is rarely accompanied by adverse reactions caused by blockade of m-cholinergic receptors. However, clinical experience with olanzapine in patients with concomitant illness is limited, therefore caution is advised in the appointment of olanzapine in patients with clinically significant prostate hyperplasia, paralytic ileus, narrow-angle glaucoma, and similar conditions.

Blockade of dopamine receptors

In in vitro conditions olanzapine detects antagonism of dopamine receptors, and, like other antipsychotic drugs (neuroleptics) can theoretically suppress the action of levodopa and other dopamine receptor agonists.

Hematologic changes

Caution should be used with olanzapine in patients with low white blood cells and (or) neutrophils in the blood; receiving drugs that can cause neutropenia; with inhibition of bone marrow function, disease caused by radiation or chemotherapy; as well as in patients with eosinophilia and (or) myeloproliferative diseases. On the development of neutropenia were reported mainly in combination with valproate olanzapine.

In clinical studies, the use of olanzapine in patients with neutropenia or agranulocytosis klozapinzavisimoy history was not associated with recurrence of these violations. On the development of neutropenia was reported mainly in combination therapy with olanzapine and valproate.

The QT interval

In clinical studies rarely noted clinically significant prolongation of the interval QT (QT interval corrected Fridericia [QTcF]> 500 ms in patients with baseline QTcF <500 msec) in patients treated with olanzapine, against the background of the lack of significant differences from placebo in the incidence of adverse events from the heart. However, as well as the use of other antipsychotics, it is recommended to be careful with the use of olanzapine in combination with drugs capable of extending the interval the QT, especially in elderly patients with congenital prolongation of the interval QT, chronic heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia .

Cancel therapy

In the case of abrupt withdrawal of olanzapine rarely (<0.01%) reported the development of acute sweating, insomnia, tremor, anxiety, nausea and vomiting.

Thromboembolism

Very rarely (<0.01%) reported on the development of venous thromboembolism in the background with olanzapine treatment. The presence of a causal relationship between the intake of olanzapine and venous thromboembolism has been established. However, given that patients with schizophrenia often have acquired venous thromboembolism, a collective assessment is required to carry out all possible risk factors risk factors for this complication, including immobilization of patients and to take the necessary prevention measures.

Total activity against CNS

Given the primary CNS action of olanzapine, caution should be exercised when olanzapine in combination with other centrally acting drugs and alcohol.

postural hypotension

Postural hypotension is infrequently observed in clinical trials of olanzapine in elderly. As well as the use of other antipsychotics, olanzapine in the case of patients over 65 years of age it is recommended to carry out periodic blood pressure control.

Body mass

During treatment (up to six weeks) acute phase of schizophrenia, when during the placebo-controlled trials of olanzapine, percentage of patients who have had a weight gain of ≥ 7% from baseline, the difference was statistically significant and was 29% for taking olanzapine, and only 3% in the placebo group. The average weight gain of these patients treated with olanzapine, in the acute phase was 2.8 kg. Body mass index (BMI) is always clinically significantly increased in the study group. If long-term treatment of schizophrenia olanzapine weight gain averaged 5.4 kg, 56% of patients in the test group, the body weight increased by more than 7% from baseline. For patients who were long-term treatment of bipolar disorder, the mean weight gain was 3.8 kg, while the number of patients with an increase in weight of more than 7% was 31%.

hyperprolactinemia

During controlled clinical trials (less than 12 weeks) increase the level of prolactin in the blood has been found in 30% of patients of the test group and 10.5% in the placebo group (control). Sami increasing levels of prolactin concentrations were moderate. These clinical appearances include: violation of menstruation (often), sexual dysfunction (including erectile dysfunction (males), decreased or loss of libido (men and women), abnormal orgasm) and by the mammary glands (uncommon).

Dysphagia

The appearance of esophageal dysmotility and aspiration associated with antipsychotic drugs. Aspiration pneumonia is a common cause of morbidity and mortality in patients with severe Alzheimer's disease that requires care for such patients.

Body Temperature Regulation

Antipsychotic drugs are generally attributed to an impaired ability of the body to control the internal temperature of the body. Appropriate caution should be exercised in patients who are taking olanzapine, and thus are in conditions that increase internal body temperature. For example, performing vigorous exercise, exposed to high temperature environment, taking olanzapine together with any drug with anticholinergic activity, or are in the dehydration conditions (intense sweating).

Children and adolescents up to 18 years

Olanzapine is not recommended for use in children and adolescents under 18 years of age due to a lack of sufficient efficacy and safety data. In short-term studies, which were carried out in adolescents aged 13-17, it was observed a greater increase in body weight change and lipids and prolactin concentrations than in similar studies in adults.

Effects on ability to drive vehicles and other mechanisms

Patients taking olanzapine should be warned about the dangers associated with the operation of mechanisms, including car as olanzapine may cause drowsiness and dizziness.

Release form of Olanzapine

Tablets of 5 mg or 10 mg.

10 tablets in blisters of PVC film and aluminum foil printed patent.

1, 2, 3, 4 or 5, the contour of cellular packaging together with instructions for use are placed in a pile of cardboard.

Storage conditions of Olanzapine

In a dry, dark place at a temperature no higher than 30 ° C.

Keep out of the reach of children.

Shelf life of Olanzapine

3 years.

Do not use beyond the expiration date printed on the package.

Conditions of supply of Olanzapine from pharmacies

With prescription.

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