Patient characteristics	Half-life (hours)	Plasma clearance (l/h)
Non-smokers	38.6 /p>	18.6
Smokers	30.4	27.7
Women	36.7	18.9
Men	32.3	27.3
Age 65 and older		51.8	17.5
Younger than 65	33.8 /p>		18.2

However, the extent to which age, sex, or smoking affects olanzapine clearance and T1/2 is insignificant compared to the individual variability in pharmacokinetics among individuals.

Pharmacokinetics in Special Patient Groups

Renal Impairment

In patients with severe renal impairment, no significant differences were found between the mean T1/2 and plasma clearance of olanzapine compared to those with normal renal function

People with severe renal impairment had no significant differences between the mean T1/2 and plasma clearance of olanzapine

People with normal renal function/p>

Hepatic impairment

In patients with hepatic impairment and smokers, clearance of olanzapine is lower than in nonsmokers without hepatic impairment.

In a study involving persons of European, Japanese and Chinese descent, no differences in olanzapine pharmacokinetics related to race were found.

Indications

Schizophrenia. Olanzapine is indicated for the treatment of exacerbations, maintenance and long-term antiretroviral therapy of patients with schizophrenia and other psychotic disorders with pronounced productive (delirium, hallucinations, automatisms, etc.) and/or negative (emotional flatness, decreased social activity, impoverished speech) symptoms, as well as concomitant affective disorders.

Bipolar affective disorder. Olanzapine as monotherapy or in combination with lithium or valproic acid is indicated for the treatment of acute manic or mixed episodes of bipolar affective disorder with/without psychotic manifestations and with/without rapid phase change. Olanzapine is indicated for the prevention of recurrent mania in patients with bipolar disorder in whom olanzapine has been effective in treating the manic phase.

In combination with fluoxetine, olanzapine is indicated for the treatment of depression associated with bipolar disorder (and for therapy of resistant depression in adult patients).

Active ingredient

Olanzapine

Composition

1 tablet contains:

The active ingredient: olanzapine benzoate 6.95 mg, corresponding to olanzapine 5.0 mg,

Auxiliary substances: calcium hydrophosphate 141.05 mg, microcrystalline cellulose 40.00 mg, sodium carboxymethyl starch (type A) 10.00 mg, magnesium stearate 2.00 mg.

How to take, the dosage

Orally, once a day since food has no effect on absorption of the drug, tablets of the drug Olanzapine may be taken regardless of meals. In case of withdrawal of the drug, gradual reduction of the dose is recommended.

Schizophrenia: The recommended starting dose of the drug is 10 mg per day.

Therapeutic doses of olanzapine are indicated in the range of 5 mg to 20 mg per day. The daily dose should be adjusted individually depending on the clinical condition of the patient. Increasing the dose beyond the standard daily dose (10 mg) is recommended only after appropriate clinical examination of the patient.

Episode mania: the recommended starting dose of olanzapine is 15 mg once daily as monotherapy or 10 mg once daily in combination therapy with lithium or valproic acid.

Therapeutic doses of olanzapine are indicated in the range of 5 mg to 20 mg daily. The daily dose should be adjusted individually, depending on the clinical condition of the patient. Increasing the dose beyond the standard daily dose is recommended only after an appropriate clinical examination of the patient. The dose should be increased gradually, at intervals of at least 24 hours.

Prevention of relapses in bipolar disorder: the recommended starting dose of the drug in remission is 10 mg per day. For patients already receiving the drug for treatment of a mania episode, maintenance therapy is given in the same doses.

On background therapy with Olanzapine, if a new manic, mixed or depressive episode develops, the drug dose should be increased with additional treatment of mood disorders, if necessary, according to clinical indications.

Maintenance therapy for bipolar disorder. Patients who have taken olanzapine for the treatment of acute mania should continue maintenance therapy at the same dose. In patients in remission, the recommended initial dose of olanzapine is 10 mg once daily. Thereafter, the daily dose should be adjusted individually, depending on the clinical condition of the patient, ranging from 5 mg to 20 mg per day.

Olanzapine in combination with fluoxetine for the treatment of bipolar depression should be prescribed once daily, in the evening, regardless of meals. Typically, the starting dose is 5 mg of olanzapine and 20 mg of fluoxetine. Antidepressant activity has been 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, it is possible to change the dose of both olanzapine and fluoxetine.

Olanzapine in combination with fluoxetine for treatment-resistant depression should be administered once daily, in the evening, regardless of meals. Typically, the starting dose is 5 mg olanzapine and 20 mg fluoxetine. If necessary, it is allowed to change the doses of both olanzapine and fluoxetine. Antidepressant activity has been confirmed with olanzapine at a dose of 6-12 mg and fluoxetine at a dose of 25-30 mg.

Special patient groups

In elderly patients, reduction of the starting dose (to 5 mg daily) is not usually recommended, but is possible in patients over 65 years of age if risk factors are present (see section on “Special Precautions”).

The general rules for choosing a daily oral dose for patients in special groups. Reduction of the starting dose to 5 mg daily is recommended in patients with clinical risk factors, including severe renal insufficiency or moderate hepatic insufficiency. Reducing the starting dose may be recommended for patients with a combination of factors (female patients, elderly, nonsmokers) that may slow down olanzapine metabolism.

Interaction

Potential drug interactions affecting olanzapine metabolism: olanzapine is metabolized by CYP1A2 isoenzyme, therefore inhibitors or inducers of cytochrome P450 isoenzymes with specific activity against CYP1A2 isoenzyme may affect pharmacokinetic parameters of olanzapine.

CYP1A2 isoenzyme inducers: clearance of olanzapine may be increased in smoking patients or concomitant administration of carbamazepine, which leads to decreased plasma concentration of olanzapine. Clinical monitoring is recommended as some cases require increasing the dose of the drug.

Drug interactions affecting/not affecting bioavailability of olanzapine: activated charcoal reduces absorption of olanzapine when taken orally by 50-60%, so it should be taken at least 2 hours before or after taking olanzapine. A single dose of magnesium or aluminum-containing antacids or cimetidine has no effect on the pharmacokinetics of olanzapine.

Fluoxetine (CYP450 isoenzyme inhibitor), when co-administered (60 mg once or 60 mg daily for 8 days) causes increase in maximum concentration (Cmax) of olanzapine by 16% on average and decrease in clearance of olanzapine by 16% on average. The degree of influence of this factor is significantly inferior to the severity of individual differences in these parameters, so it is generally not recommended to change the dose of olanzapine when using it in combination with fluoxetine.

Potential ability of olanzapine to affect other medications

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

Under in vitro conditions olanzapine does not inhibit major CYP450 isoenzymes (e.g., 1A2, 2D6, 2C9, 2C19, WA4). In vivo inhibition of metabolism of the following active substances was not found: tricyclic antidepressants (CYP2D6 isoenzyme), warfarin (CYP2C9 isoenzyme), theophylline (CYP1A2 isoenzyme) and diazepam (CYP3A4 and 2C19 isoenzymes).

No interaction was found when used concurrently with lithium or biperidine. Therapeutic monitoring of valproic acid in plasma showed that when concomitantly administered with olanzapine no changes in valproic acid doses are required (see section “Side effects”).

CYP1A2 isoenzyme inhibitors: Fluvoxamine, a potent specific inhibitor of CYP1A2 isoenzyme, significantly reduces clearance of olanzapine. The mean increase in maximum concentration (Cmax) of olanzapine after fluvoxamine administration was 54% in nonsmoking women and 77% in smoking men. The mean increases in the area under the concentration-time curve (AUC) of olanzapine in these patient categories were 52% and 108%, respectively. In patients taking fluvoxamine or any other CYP1A2 isoenzyme inhibitor (e.g., ciprofloxacin), it is recommended to start therapy with olanzapine at lower doses. Decrease in dose of olanzapine may also be required in case of adherence to therapy with CYP1A2 isoenzyme inhibitors. Drug interactions affecting/not affecting the bioavailability of olanzapine. activated charcoal reduces the absorption of olanzapine when taken orally by 50-60%, so it should be taken at least 2 hours before or after taking olanzapine. A single dose of magnesium or aluminum-containing antacids or cimetidine has no effect on the pharmacokinetics of olanzapine.

Fluoxetine (CYP450 isoenzyme inhibitor), when co-administered (60 mg once or 60 mg daily for 8 days) causes increase in maximum concentration (Cmax) of olanzapine by 16% on average and decrease in clearance of olanzapine by 16% on average. The degree of influence of this factor is significantly less than the severity of individual differences in these parameters, so it is generally not recommended to change the dose of olanzapine when using it in combination with fluoxetine.

Potential ability of olanzapine to influence other drugs Olanzapine may weaken the effects of direct and indirect dopamine agonists.
Under in vitro conditions, olanzapine does not inhibit major CYP450 isoenzymes (e.g., 1A2, 2D6, 2C9, 2C19, WA4). In vivo inhibition of metabolism of the following active substances was not found: tricyclic antidepressants (CYP2D6 isoenzyme), warfarin (CYP2C9 isoenzyme), theophylline (CYP1A2 isoenzyme) and diazepam (CYP3A4 and 2C19 isoenzymes).

No interaction was found when used concurrently with lithium or biperidine. Therapeutic monitoring of valproic acid in plasma showed that when concomitant administration with olanzapine no changes in valproic acid doses are required (see section “Side effects”).
Caution should be exercised when concomitantly administering other centrally acting drugs. Although a single dose of alcohol (45 mg/70 kg) has no pharmacokinetic effect, administration of alcohol together with olanzapine may be accompanied by an increased suppressive effect on the central nervous system.

Special Instructions

Hyperglycemia and diabetes mellitus

There is a higher prevalence of diabetes mellitus in patients with schizophrenia. There are very rare reports of the development of hyperglycemia and/or decompensation of diabetes mellitus, sometimes accompanied by the development of ketoacidosis or ketoacidotic coma, including reports of several fatal cases. In some cases there was an increase in body weight prior to decompensation, which may have been a predisposing factor. In patients with diabetes mellitus and risk factors of this disease, regular clinical control and monitoring of blood glucose concentration is recommended.

Change in lipid concentrations

In therapy with olanzapine, plasma lipid concentrations should be monitored in patients with dyslipidemia and in patients with risk factors for lipid metabolism disorders. Patients receiving olanzapine therapy require monitoring of lipidogram values. If lipid concentrations change, correction of therapy is required.

Anticholinergic activity

In clinical trials, therapy with olanzapine has rarely had adverse reactions due to M-cholinoreceptor blockade. Because clinical experience with olanzapine in subjects with comorbidities is limited, the drug should be used with caution in patients with clinically significant prostatic hyperplasia, paralytic ileus, closed-angle glaucoma and similar conditions.

The use of olanzapine in patients with Parkinson’s disease

Olanzapine is not recommended for the treatment of psychosis caused by dopamine mimetics in Parkinson’s disease. Parkinsonian symptoms and hallucinations are increased. However, olanzapine was not superior to placebo for the treatment of psychosis.

Dopaminergic antagonism

In vitro olanzapine is antagonistic to dopamine receptors and, like other antipsychotics (neuroleptics), can theoretically inhibit the effects of levodopa and other dopamine receptor agonists.

The experience of olanzapine in elderly patients with psychosis associated with dementia. Efficacy of olanzapine in elderly patients with psychosis associated with dementia has not been established. In placebo-controlled clinical trials (lasting 6-12 weeks) in elderly patients (mean age 78 years) with psychosis and behavioral disorders associated with dementia, increased mortality was observed in patients treated with olanzapine compared to the placebo group (3.5% versus 1.5%, respectively). The increase in lethality was independent of the dose of olanzapine or the duration of therapy. Risk factors predisposing to increased mortality include: age over 75 years, dysphagia, sedation, malnutrition and dehydration, lung disease (e.g., pneumonia, including aspiration), concurrent administration of benzodiazepines.

Cerebrovascular adverse events, including stroke in elderly patients with dementia

Cerebrovascular adverse events (stroke, transient ischemic attack), including fatal outcomes, have been reported in studies of olanzapine in elderly patients with psychosis associated with dementia. In placebo-controlled trials, a higher incidence of cerebrovascular adverse events was noted in patients in the olanzapine group compared to the placebo group (1.3% vs. 0.4%, respectively). All patients had prior risk factors for cerebrovascular adverse events (smoking, arterial hypertension, a previous history of a cerebrovascular adverse event or transient ischemic attack), and comorbidities with drug intake that were temporally associated with cerebrovascular adverse events.

Postural hypotension

Postural hypotension was not frequently observed in elderly patients during clinical trials of olanzapine. As with therapy with other antipsychotics, periodic blood pressure monitoring is recommended in patients over 65 years of age.

The QT interval

In clinical trials, clinically significant prolongation of the QT interval (Friederick formula QT correction [QTcF] ≥500 milliseconds in patients with a baseline QTcF< 500 msec) only (0.1%-1%) in patients treated with olanzapine against the background of no significant difference with placebo for associated cardiac events. However, as with other neuroleptic drugs, caution should be exercised when prescribing olanzapine simultaneously with drugs that can prolong the QT interval, especially in elderly patients, patients with QT interval prolongation syndrome, congestive heart failure, cardiac hypertrophy, hypokalemia or hypomagnesemia. An electrocardiogram should be monitored during therapy with olanzapine.

Hepatic disorders

In the beginning of therapy there is often asymptomatic increase in liver transaminases activity (ALT and ACT) in serum. Rare cases of hepatitis have been noted. In addition, there have been isolated reports of cholestatic and mixed liver damage. In patients with initially elevated serum ACT and/or ALT activity in patients with liver failure and conditions potentially limiting liver function, as well as those taking hepatotoxic drugs, special caution should be exercised when prescribing olanzapine. In case of ALT and/or ACT increase during the drug therapy, medical monitoring of the patient is recommended and possibly decrease of the drug dose. If hepatitis (including hepatocellular, cholestatic or mixed) is diagnosed, olanzapine should be stopped.

Hematological changes

The drug should be used with caution in patients with leukopenia and/or neutropenia of any genesis, myelosuppression of drug genesis, as well as against the background of radiation or chemotherapy, due to concomitant diseases, in patients with hypereosinophilic states or myeloproliferative diseases. Neutropenia has often been noted with concomitant use of olanzapine and valproic acid (see section “Side effects”).

Malignant neuroleptic syndrome (MNS)

MNS is a potentially life-threatening condition associated with therapy with antipsychotics (neuroleptics), including olanzapine. Clinical manifestations of MNS: fever, muscle rigidity, impaired consciousness, autonomic disorders (unstable pulse or labile blood pressure, tachycardia, increased sweating, arrhythmias). Convulsive syndrome

Olanzapine should be cautiously prescribed in patients with a history of seizures or the presence of risk factors that reduce the seizure threshold. Seizures have rarely been reported on olanzapine.

Late dyskinesia

In comparative studies, therapy with olanzapine had a significantly lower incidence of tardive dyskinesia requiring medication correction than did the use of typical and other atypical neuroleptics. The risk of developing tardive dyskinesia increases with increasing duration of therapy. If signs of tardive dyskinesia develop in a patient taking olanzapine, a dose adjustment is recommended. Symptoms of dyskinesia may increase temporarily even after drug withdrawal.

General CNS activity

Cautious concomitant use of olanzapine and other centrally acting medications should be observed and alcohol should be avoided.

Thromboembolism

In the administration of olanzapine very rarely (less than 0.01%) cases of venous thromboembolism have been reported. A causal relationship between olanzapine therapy and venous thromboembolism has not been established. Because patients with schizophrenia often have acquired risk factors for venous thrombosis, all possible other factors (e.g., immobilization) should be identified and preventive measures taken.

Sudden death

The clinical experience with any neuroleptic, including olanzapine, has revealed a similar, dose-dependent increase in the risk of sudden death due to acute heart failure. In a retrospective observational cohort study, the risk of suspected sudden cardiac death was approximately doubled in patients treated with olanzapine compared with patients who were not using neuroleptics. In the study, the risk for olanzapine was comparable to the risk for the atypical neuroleptics included in the pooled analysis.

Long-term therapy with the drug

Long-term therapy with olanzapine (up to 12 months), to prevent relapse in patients with bipolar disorders, showed an increase in body weight >7% of baseline (in 39.9% of patients). With longer therapy (more than 48 weeks), clinically significant changes – increases in body weight, glucose concentration, total cholesterol/LDL/HDL or triglyceride levels – were observed. In adult patients who completed 9-12 months of treatment, an increase in mean blood glucose concentration was observed after approximately 6 months. Patients with risk factors for comorbidities who are on long-term therapy with olanzapine should be monitored by a specialist for the duration of therapy.

Withdrawal syndrome

The following symptoms are very rare (less than 0.01%) if olanzapine is stopped abruptly: sweating, insomnia, tremors, anxiety, nausea, or vomiting. A gradual reduction in the dose is recommended when withdrawing the drug.

Pediatric use

Olanzapine is not recommended for use in children and adolescents under 18 years of age due to insufficient data on efficacy and safety. In short-term studies, a greater increase in body weight and changes in lipid and prolactin concentrations have been reported in patients 13 to 17 years old than in similar studies in adults, (see side effects section).

Influence on ability to drive trans. cf. and mech:

Patients taking olanzapine, during treatment, should be careful when driving motor vehicles and engaging in other, potentially dangerous activities that require increased concentration and rapid psychomotor reactions, as olanzapine may cause drowsiness and dizziness.

Contraindications

– Hypersensitivity to olanzapine or other drug components;

– Established risk of closed angle glaucoma;

– Closed-angle glaucoma;

– Childhood under 18 years of age (efficacy and safety not established).

With caution:

Renal failure, hepatic failure, prostatic hyperplasia, paralytic intestinal obstruction, epilepsy, seizure syndrome in the history, leukopenia and/or neutropenia of various genesis, myelosuppression of various genesis, including.ч. myeloproliferative diseases, hypereosinophilic syndrome, cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, congenital increased QT interval on electrocardiogram (ECG) (increased correlated QT interval (QTc) on ECG), or in the presence of conditions that may potentially cause QT interval prolongation (e.g., concomitant administration of QT interval prolongers, congestive heart failure, hypokalemia, hypomagnesemia), elderly age, as well as concomitant administration of other drugs of central action; immobilization.

Side effects

The table below summarizes the major adverse effects and their frequency that have been reported during spontaneous reports, clinical trials, and/or in the post-registration period. Within each group, adverse reactions are presented in descending order of significance.

Hypersensitivity

Bradycardia with or without collapse

QTc interval prolongation on ECG

Nosebleeds

Very common (≥10%)		Often (≥1 and < 10%)	Infrequent (≥0.1 and < 1%)	Frequency unknown (frequency cannot be determined from available data)
Disorders of the blood and lymphatic system
	Eosinophilia <	Leukopenia Neutropenia	Trombocytopenia
Immune system disorders

Metabolic and nutritional disorders
Increased body weight1	Increased cholesterol concentration2,3 Increased glucose concentration4 Increased concentration of triglycerides2,5 Glucosuria Elevated appetite	The development or decompensation of diabetes mellitus, sometimes accompanied by ketoacidosis and diabetic coma, including several deaths	Hypothermia
Nervous system disorders
Sleepiness	Dizziness Akathisia6 Parkinsonism6 Dyskinesia6	Seizures (with a history of seizures or risk factors for them) Amnesia Dysarthria Dystonia (including oculogyric crisis)	Malignant neuroleptic syndrome Late dyskinesia Drug withdrawal syndrome7
Cardiac disorders

		Ventricular tachycardia/fibrillation Sudden death
Vascular disorders
Arterial hypotension (incl.ч. orthostatic)		Thromboembolism (including pulmonary embolism and deep vein thrombosis)
Digestive system disorders
		Transient, transient anticholinergic effects, including.ч. Constipation and dry mouth	Abdominal bloating	Pancreatitis
Hepatic and biliary tract disorders
	Asymptomatic, temporary elevation of “liver” transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)), especially at the beginning of treatment				Hepatic transaminases/p>	Hepatitis (including hepatocellular, cholestatic, or mixed liver damage)
Skin and subcutaneous tissue disorders
	Rash	Reaction of photosensitivity Alopecia
Renal and urinary tract disorders
			Purinary incontinence Urinary retention
Genital and breast disorders
		Erectile dysfunction Decreased libido in men and women /td>	Amenorrhea Breast enlargement in women Galactorrhea in women /p> Gynecomastia and breast enlargement in men
Musculoskeletal disorders
	Arthralgia
General disorders
	Asthenia Fatigue Peripheral edema Hyperthermia
Respiratory system side

Pregnancy, prenatal and postnatal period
			Newborn “withdrawal” syndrome	td>
Laboratory indicators				/tr>
Increased plasma prolactin concentration8	Increased alkaline phosphatase activity Elevated creatine phosphokinase activity Elevated uric acid concentration	Elevated total bilirubin concentration

1In all patient groups, regardless of BMI, there was a clinically significant increase in body weight.

A 7% or greater increase in body weight from the mean after a short course of therapy (median duration of 47 days) was observed very frequently (22.2%), an increase of 15% or greater was frequent (4.2%), and an increase of 25% or greater was infrequent (0.8%). With a prolonged course of olanzapine therapy (more than 48 weeks), increases of ≥7%, ≥15%, and ≥25% of baseline body weight were very frequent (64.4%), 31.7%, and 12.3%, respectively).

2 Mean increases in fasting lipid concentrations (total cholesterol, low-density lipoproteins (LDL), and triglycerides) were most pronounced in patients without baseline signs of lipid metabolism disorders.

3Often there was an increase in cholesterol concentration from normal fasting (< 5.17 mmol/L), to high values (≥6.2 mmol/L). Changes in cholesterol concentration from borderline fasting (≥5.17 to < 6.2 mmol/L) to elevated (≥6.2 mmol/L) were very frequent.

4Frequent increases in glucose concentration from normal fasting (< 5.56 mmol/L), to elevated (≥7 mmol/L) were observed. Changes in glucose concentration from borderline fasting values (≥5.56 to < 7 mmol/L) to elevated values (≥7 mmol/L) were very frequent.

5Frequent increases in triglyceride concentration from normal fasting (< 1.69 mmol/L) to elevated values (≥2.26 mmol/L) were observed. Changes in triglyceride concentration from borderline values (≥1.69 to < 2.26 mmol/L) to elevated (≥2.26 mmol/L) were very frequent.

6In typical studies, cases of parkinsonism and dystonia were observed in patients receiving olanzapine therapy, but the rate was not statistically significantly different from the placebo group. Cases of Parkinson’s disease, akathisia and dystonia were registered less frequently in patients receiving olanzapine than in patients receiving titrated doses of haloperidol. Because of the lack of detailed information regarding patients’ history of acute and tardive dyskinesias, it cannot be concluded at this time that olanzapine is less likely to cause the development of tardive dyskinesias or other tardive extrapyramidal syndromes.

7Symptoms such as sweating, insomnia, tremors, anxiety, nausea, and vomiting have been observed with abrupt withdrawal of olanzapine.

8In clinical trials lasting up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal in approximately 30% of patients with normal baseline prolactin values. In the majority of such patients, the increase in prolactin concentrations was moderate, and less than 2 times the upper limit of the norm. There were also cases where patients’ prolactin concentrations spontaneously normalized without withdrawal of therapy.

Indesirable Effects in Special Patient Groups

In clinical trials, gait disturbances and falls have been reported as a very frequent (≥10%) adverse effect of olanzapine therapy in elderly patients with psychosis with dementia. Pneumonia, lethargy, erythema, visual hallucinations, and urinary incontinence were observed frequently (< 10% and ≥1%).

In clinical studies in patients with drug-induced (dopamine agonist-induced) Parkinsonian psychosis, an increase in Parkinsonian symptoms was observed very frequently (≥10%) and with a higher frequency than in the placebo group. Hallucinations were also very common in this group of patients.

In patients with bipolar mania, on combination therapy with valproic acid, the incidence of neutropenia was (4.1%), a contributing factor being the high plasma concentration of valproate. Long-term therapy

In long-term therapy with olanzapine (at least 48 weeks), the incidence of clinically significant adverse effects (increased body weight, increased glucose concentration, total cholesterol/LDL/LDL or triglycerides) increases over time. In adult patients who completed 9-12 months of treatment, an increase in mean blood glucose concentrations was observed after approximately 6 months.

Long-term therapy with olanzapine (up to 12 months) for relapse prevention in patients with bipolar disorder was also accompanied by an increase in body weight.

The use of olanzapine in children is not recommended.

The use of olanzapine in children and adolescents younger than 18 years is not recommended.

In a short-term efficacy study in patients 13-17 years old (the study included less than 200 adolescents), olanzapine was used in a range of doses starting at 2.5 and up to 20 mg/day. – The development of various adverse reactions has been reported. The long-term effects associated with these events have not been studied. In comparable olanzapine exposures, clinically significant weight gain (≥7%) was more common in adolescents compared to adult patients.

The degree of change in fasting total cholesterol, LDL, triglyceride, and prolactin concentrations was greater in adolescents than in similar studies in adult patients. Efficacy and safety data are limited.

Overdose

Symptoms. Very common (>10%) in olanzapine overdose are: tachycardia, agitation/aggressiveness, speech impairment, various extrapyramidal disorders and impaired consciousness of varying severity (from sedation to coma); in less than 2% of cases occur: Delirium, convulsions, coma, malignant neuroleptic syndrome, respiratory depression, aspiration, increased or decreased blood pressure, cardiac arrhythmias; in very rare cases, cardiopulmonary failure. The minimum dose of olanzapine in acute fatal overdose is 450 mg; a maximum dose in benign overdose (survival) of 2 g has been reported.

Treatment. There is no specific antidote for olanzapine. It is not recommended to induce vomiting. Symptomatic treatment in accordance with the clinical condition and monitoring of vital functions of the body, including treatment of arterial hypotension, arrhythmias, circulatory disorders and maintenance of respiratory function, gastric lavage, administration of activated charcoal (reduces bioavailability of olanzapine to 50-60%). Epinephrine, dopamine, and other sympathomimetics that are beta-adrenoreceptor agonists should not be used, as these drugs may aggravate arterial hypotension. The patient should be under continuous medical observation until full recovery.

Pregnancy use

Due to limited experience with the drug in pregnant patients, olanzapine should be used in pregnancy only if the expected benefit to the mother justifies the potential risk to the fetus.

In studies on rats it was found that olanzapine has no carcinogenic and teratogenic effects and has no mutagenic properties. However, olanzapine has been found to cause delayed fetal development. It temporarily reduces fertility in sexually mature individuals.

Women should be informed about the need to inform the doctor about the occurred or planned pregnancy during therapy with olanzapine. Newborn children whose mothers took antipsychotics in the third trimester of pregnancy are at risk of developing extrapyramidal disorders and/or withdrawal syndrome of varying severity and duration. There have been isolated reports of tremor, arterial hypertension, lethargy and somnolence in children born to mothers who took olanzapine in the third trimester of pregnancy. Such children should be monitored by a physician after birth.

Studies have found that olanzapine is excreted into breast milk. The average dose (mg/kg) received by the infant when reaching equilibrium concentration in the mother was 1.8% of the mother’s olanzapine dose (mg/kg). Breastfeeding during therapy with olanzapine is not recommended.

Similarities

Zyprexa, Zalasta, Zalasta Ku-tab, Olanzapine

Additional information

Weight	0.013 kg
Shelf life	3 years Do not use after the expiration date.
Conditions of storage	In the dark place at a temperature not exceeding 25 °С. Store out of the reach of children.
Manufacturer	Ozon, Russia
Medication form	pills
Brand	Ozon