Ziprexa Zidis - instructions for use, doses, side effects, contraindications

Excipients: gelatin 5.25 mg, mannitol 4.50 mg, aspartame 0.60 mg, sodium methyl parahydroxybenzoate 0.1125 mg, sodium propyl parahydroxybenzoate 0.0375 mg.

For a dosage of 10 mg:

active substance: olanzapine 10.00 mg;

Excipients: gelatin 7.00 mg, mannitol 6.00 mg, aspartame 0.80 mg, methylparahydroxybenzoate sodium 0.15 mg, sodium propyl parahydroxybenzoate 0.05 mg.

Description:

Round tablets are yellow.

Pharmacotherapeutic group:Antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.03 Olanzapine

Pharmacodynamics:

Olanzapine is an antipsychotic agent (neuroleptic) with a broad pharmacological spectrum of influence on a number of receptor systems.

In preclinical studies, the affinity of olanzapine for 5-NT₂_{A /}_2C, 5HT₃, 5NT₆-serotonin receptors; D₁, D₂, D₃, D₄, D₅dopamine receptors; M₁_-₅-muscarinic receptors; α₁-adrenergic and H₁-histamine receptors. In animal experiments, olanzapine antagonism was identified with respect to serotonin, dopamine and cholinergic receptors. In vitro and in vivo conditions olanzapine has a more pronounced affinity and activity for 5HT₂-serotonin 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 striatal neural pathways involved in the regulation of motor functions. Olanzapine. reduces the conditioned protective reflex (a test characterizing antipsychotic activity) at doses lower than the doses that cause catalepsy (a disorder reflecting a secondary effect on motor function). Olanzapine increases the anti-anxiety effect during the "anxiolytic" test.

Olanzapine provides a statistically significant reduction in both productive (delirium, hallucinations, etc.) and negative symptoms.

Pharmacokinetics:

Dispersible olanzapine tablets are bioequivalent to coated tablets of olanzapine and have a similar rate and degree of absorption. Dispersible olanzapine tablets are used in the same amount and at the same frequency as the coated tablets of olanzapine. Dispersible olanzapine tablets can be used instead of coated tablets of olanzapine.

After oral administration olanzapine well absorbed, and its maximum concentration in the plasma is achieved after 5-8 hours. Absorption of olanzapine is not dependent on food intake. In studies with different doses ranging from 1 mg to 20 mg, it is shown that the plasma concentrations of olanzapine vary linearly and in proportion to the dose. Olanzapine metabolized in the liver as a result of conjugation and oxidation. The main circulating metabolite is 10-N-glucuronide, which theoretically does not penetrate the blood-brain barrier. Isozymes CYP1A2 and CYP2D6 cytochrome P450 are involved in education N-desmethyl- and 2hydroxy methyl metabolites 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 starting substance - olanzapine, which has the ability to penetrate the blood-brain barrier.

In healthy volunteers, after oral administration, the mean half-life was 33 hours (21-54 hours 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 (hours)	Clearance in plasma (l / h)
Non-smokers	38,6	18,6
Smokers	30,4	27,7

Women	36,7	18,9
Men's	32,3	27,3

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 (age from 13 to 17 years) and in 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% labeled radioisotopes of olanzapine is excreted in the urine 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.

At a plasma concentration of 7 to 1000 ng / ml with plasma proteins, about 93% of olanzapine binds. 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 cytochrome P450 does not affect the metabolism of olanzapine.

Indications:

Schizophrenia. Olanzapine is indicated for the treatment of exacerbations, sustained and prolonged anti-relapse therapy in patients with schizophrenia.

Bipolar affective disorder. 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 with a history of ineffective use of antidepressant doses and duration of therapy appropriate for this episode).

Contraindications:

Olanzapine is contraindicated in patients with established hypersensitivity to any of the components of the drug:

Contraindicated in the use of phenylketonuria.

Contraindicated for persons under 18 years.

Closed-angle glaucoma.

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 onset or planning-pregnancy during the treatment with olanzapine, they need to inform theirthe attending physician.

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:

Dispersible tablets of olanzapine dissolve rapidly in saliva and are easily swallowed. It is difficult to remove the tablet from the mouth undissolved. Take the tablet from the blister with dry hands. Because of the fragility, the tablet should be taken immediately after removal from the blister. In addition, immediately before taking the pill can be dissolved in a glass of water or other liquid (orange juice, apple juice, milk or coffee).

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. Olanzapine can be taken regardless of the intake of food, because eating does not affect the absorption of the drug. 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 over the standard daily dose (10 mg) is recommended only after assessment of the clinical clinical picture:

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. An increase in the dose above the standard daily dose is recommended only after assessment of the clinical 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 should 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 by the use of olanzapine in a dose 6-12 mg (average daily dose - 7.4 mg) and fluoxetine in a dose of 25-30 mg (mean daily dose - 39.3 mg). If necessary, you can change the dose of both olanzapine and fluoxetine.

Therapeutically resistant depression. 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. If necessary, you can change the dose of both olanzapine and fluoxetine. Antidepressant activity was confirmed by the use of olanzapine in a dose 6-12 mg and fluoxetine in a dose of 25-30 mg.

General selection rulesand the daily dose at oral administration for specific patient groups

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.

Often (≥10%)	Often (<10% and ≥ 1%)	Infrequently (0.1% ≥ and <1%)	Frequency unknown (the frequency can not be determined from the available data)
Violations of the blood and lymphatic systems
	Eosinophilia	Leukopenia Neutropenia	Thrombocytopenia
Immune system disorders
			Allergic reactions
Disorders from the metabolism and nutrition
Weight gain¹	Increase concentrations cholesterol^2,3 Increase concentrations glucose⁴ Increase concentrations triglycerides^2,5 Glucosuria Decreased appetite		Development or decompensation of diabetes mellitus, in some cases accompanied by ketoacidosis and diabetic coma, including fatal outcome Hypothermia
Disturbances from the nervous system
Drowsiness	Dizziness Akathisia⁶Parkinsonism⁶Dyskinesia⁶		Convulsions in patients with a history of seizures or presence of risk factors for seizures Malignant antipsychotic syndrome Dystonia (including oculogic crisis) Late dyskinesia The syndrome of "cancellation"⁷
Heart Disease
		Bradycardia Interval prolongation QT_C	Ventricular tachycardia, ventricular fibrillation, sudden death
Vascular disorders
	Orthostatic hypotension		Thromboembolism of the pulmonary arteries Deep vein thrombosis
Disorders from the digestive system
	Short-term anticholinergic effects, including constipation and dry mouth		Pancreatitis
Disturbances from the liver and bile ducts
	Transient rise activity "hepatic" transferase (ALT, ACT), especially in the early period of treatment		Hepatitis (including hepatocellular, hepatocellular or mixed)
Disturbances from the skin and subcutaneous tissues
	Rash	Reaction photosensorof the Alopecia
Musculoskeletal system disorders
			Rhabdomyolysis
Disorders from the kidneys and urinary tract
		Urinary incontinence	Delayed onset of urination
Violations of the genitals and mammary gland
			Priapism
General disorders
	Asthenia Fatigue Edema
Laboratory data
Increase in prolactin concentration in plasma⁸		Increase in activity of creatine phosphokinase, increase in the concentration of total bilirubin	Increase activity alkaline phosphatases

¹For all groups of patients, 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 (mean 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 was infrequent (0,8%). In patients receiving long-term treatment (at least 48 weeks), an increase of ≥ 7%, ≥ 15% and ≥25% was very frequent (64.4%, 31.7%, 12.3%, respectively).

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

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

Changing the concentration of cholesterol from the fasting borderline (> 5.17- < 6,2 mmol / l) to increased (≥ 6,2 mmol / l) was very frequent.

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

The change in glucose concentration from fasting margins (> 5.56 - <7 mmol / l) to elevated (≥ 7 mmol / l) was very frequent.

⁵Often 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.

⁶In 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 cases of development of parkinsonism, akathisia, dystonia, were observed less often 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.

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

⁸In clinical studies of up to 12 weeks, plasma concentrations of prolactin exceeded the upper limit of normal in approximately 30% of patients with normal prolactin baseline values. In most of these patients, the increase in prolactin concentration was moderate, and less than 2 times the upper limit of the norm. In patients who took olanzapine, disorders of the genitals and mammary gland, possibly associated with taking olanzapine (amenorrhea, breast enlargement, galactorrhea in women, gynecomastia and breast enlargement in men) were infrequent.Sexual dysfunction, possibly associated with taking olanzapine (erectile dysfunction in men, decreased libido in men and women) were observed frequently.

Undesirable effects in specific patient groups

A very frequent (≥10%) undesirable effect with olanzapine in clinical trials in patients with psychosis associated with dementia was gait and fall disability.

Frequent (<10% and ≥ 1%) adverse effects with olanzapine in elderly patients with psychosis associated with dementia were incontinence and pneumonia.

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%) undesirable effects were weight gain, dry mouth, increased appetite, tremor and frequent (< 10% and ≥ 1%) speech disorder.

Overdose:

Signs and Symptoms

Very frequent (frequency ≥ 10%) symptoms with olanzapine overdose were tachycardia, psychomotor 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, increased and decreased blood pressure, cardiac arrhythmias (< 2% of cases of overdose) and cardiac and respiratory arrest. The minimum dose - acute overdose with a lethal outcome was 450 mg, the maximum dose for an overdose with a favorable outcome (survival) - 2 in

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 treatment of arterial hypotension, circulatory disorders and maintenance of respiratory function. Do not use epinephrine, dopamine and other sympathomimetics, which are beta-adrenergic receptor 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 pharmacokinetics of medicines, such as theophylline, mainly metabolized by isoenzyme CYP1A2, does not change.

In clinical studies,that a single administration 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, the administration of ethanol along 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_mOh) 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, isofrene inhibitor CYP1A2, decreases the clearance of olanzapine. The result is an average increase in C_mOh olanzapine with the administration of fluvoxamine by 54% in nonsmoking women and by 77% in male smokers. Average increase AUC (area under the concentration-time curve) of olanzapine 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 olanzapine when administered up to 50-60%.

According to research in vitro using human liver microsomes, olanzapine also demonstrated an extremely low potential in 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) (potentially lethal symptom complex) can develop in the treatment of any neuroleptic, including olanzapine, however, to date, there is no evidence to confirm a reliable association of olanzapine with the development of this condition. 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 likely to be accompanied by the development of dyskinesia requiring medication correction; than the use of typical and other atypical antipsychotics. 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 due to 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 evidence 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 when taking olanzapine inward and with intramuscular injection.

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 activity - "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 the blood serum in patients with insufficient liver function, with limited functional reserve of the liver or patients receiving treatment with 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 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 in patients who received olanzapine, undesirable changes in the lipid spectrum were observed. Clinical observation is recommended (see "Side effect").

Development of the 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 (eg stroke, transient ischemic attack),including lethal outcomes, have been reported in studies of olanzapine in elderly patients with psychosis associated with dementia. In placebo-controlled studies, a higher incidence of cerebrovascular adverse events was noted in patients in the olanzapine group, compared with the placebo group (1.3% vs. 0,4% respectively).

All patients with cerebrovascular disorders had previous risk factors for the development of cerebrovascular adverse events (eg, a previously noted case of cerebrovascular undesirable phenomenon or transient ischemic attack, hypertension, smoking), as well as concomitant diseases and / or 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 convulsions or exposed to factors that reduce the threshold of convulsive readiness. In such patients, seizures were rare in the treatment with olanzapine.

Anticholinergic activity. In clinical trials, olanzapine therapy was rarely accompanied by anticholinergic side effects. However, the 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 the like.

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 low leukocyte and / or neutrophil count in the blood; receiving drugs that can cause neutropenia; with oppression of bone marrow function due to radiation or chemotherapy disease; 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.

Duration of the interval QT. In clinical studies, clinically significant lengthening of the interval QT (interval QT with the adjustment of Friederation [QTcF] ≥ 500 msec in patients with baseline. QTcF<500 msec) in patients who received olanzapine, on the background of absence, significant differences with placebo on the incidence of adverse cardiac events. However, as with other antipsychotics, caution should be exercised when prescribing olanzapine in combination with drugs that can lengthen the interval QT, especially in elderly patients, with congenital lengthening of the interval QT, congestive 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, given that 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.

General activity in relation to the central nervous system. Given the main effect of olanzapine on the central nervous system, caution should be exercised when using olanzapine in combination with other central-action drugs and alcohol.

Postural hypotension. Postural hypotension was rarely observed in clinical studies of olanzapine in the elderly. Just as with the use of other antipsychotics, in the case of olanzapine, patients older than 65 years are advised to periodically monitor blood pressure.

Phenylalanine. The composition of the drug is aspartame, which serves as a source of phenylalanine.

Children and teenagers under 18 years of age. Olanzapine is not recommended for use in children and adolescents under 18 years due to the lack of sufficient data on the effectiveness andsecurity. In short-term studies that were conducted in adolescents 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 are dispersible, 5 mg, 10 mg.

Packaging:

7 tablets in a blister pack.

For 4 blisters together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In dry, dark place at a temperature of 15-30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001165

Date of registration:07.10.2011

Expiration Date:Unlimited

The owner of the registration certificate:Eli Lilly East SAEli Lilly East SA Switzerland

Manufacturer: & nbsp

CATALENT UK SWINDON ZYDIS, Ltd. United Kingdom

Representation: & nbspELI LILLY EAST SA ELI LILLY EAST SA Switzerland

Information update date: & nbsp14.10.2017

Illustrated instructions

Instructions

Ziprex® Zidis ™ (Zyprexa® Zydis ™)