Properties
- Form
- tableti saghech i
- Dosage mg
- 2.5
- Pack
- 28
What is it?
FORMULA: Olanzapine 2.5 mg film-coated tablet contains 2.5 mg of olanzapine. It also contains 29.73875 mg of lactose monohydrate as excipients and titanium dioxide (E171) as coloring agent. Olanzapine 5 mg film-coated tablet contains 5 mg of olanzapine. It also contains 59.47775 mg of lactose monohydrate as excipients and titanium dioxide (E171) as coloring agent. Olanzapine 10 mg film-coated tablet contains 10 mg of olanzapine. It also contains 118.955 mg of lactose monohydrate as excipients and titanium dioxide (E171) as coloring agent. PHARMACOLOGICAL PROPERTIES: PHARMACODYNAMIC PROPERTIES: PHARMACOTHERAPEUTIC GROUP: PSYCHOLEPTICS, DIZEPINES, OXAZEPINES, THIAZEPINES AND OXEPINES. PHARMACODYNAMIC ACTION Olanzapine is an antipsychotic, antimanic, and mood-stabilizing agent with a broad pharmacological profile affecting multiple receptor systems. PHARMACOKINETIC PROPERTIES: ABSORPTION: Olanzapine is well absorbed following oral administration, reaching peak plasma concentrations within 5-8 hours. Food does not affect absorption. Absolute oral bioavailability has not been determined relative to intravenous administration. DISTRIBUTION: Olanzapine is approximately 93% bound to plasma proteins over the concentration range of 7 to 1,000 ng/mL. Olanzapine is primarily bound to albumin and α1-acid glycoprotein. METABOLISM: Olanzapine is metabolized in the liver by conjugative and oxidative pathways. The main circulating metabolite is 10-N-glucuronide, which does not cross the blood-brain barrier. Cytochromes P450-CYP1A2 and P450-CYP2D6 contribute to the formation of N-desmethyl and 2-hydroxymethyl metabolites. In animal studies, both showed significantly less in vivo pharmacological activity compared to olanzapine. The primary pharmacological activity is derived from the parent compound, olanzapine. EXCRETION: Following oral administration in healthy volunteers, the mean elimination half-life of olanzapine varied with age and sex. RENAL IMPAIRMENT In patients with renal impairment (creatinine clearance <10 mL/min), there was no significant difference in mean elimination half-life (37.7 vs 32.4 h) or clearance (21.2 vs 25.0 L/h) compared to healthy subjects. A mass balance study showed that approximately 57% of radiolabeled olanzapine was recovered in urine, primarily as metabolites. HEPATIC IMPAIRMENT A small study in 6 subjects with clinically significant (Child-Pugh class A (n=5) and B (n=1)) cirrhosis showed a minor impact of orally administered olanzapine on pharmacokinetic parameters (2.5 - 7.5 mg single dose): subjects with mild to moderate hepatic dysfunction had slightly increased systemic clearance and a faster elimination half-life compared to subjects without hepatic dysfunction (n=3). The cirrhotic group had more smokers (4/6; 67%) than the non-hepatic dysfunction group (0/3; 0%). SMOKING In non-smokers compared to smokers (males and females), the mean elimination half-life was prolonged (38.6 vs 30.4 h) and clearance was reduced (18.6 vs 27.7 L/h). Elderly subjects, females compared to males, and non-smokers compared to smokers have reduced plasma clearance of olanzapine. However, the magnitude of the effect of age, sex, or smoking status on olanzapine clearance and half-life is small compared to the overall inter-individual variability. Studies in Caucasians, Japanese, and Chinese showed no differences in pharmacokinetic parameters among the three populations. PEDIATRIC USE ADOLESCENTS (13-17 YEARS): Olanzapine pharmacokinetic parameters are similar between adolescents and adults. In clinical studies, the mean exposure to olanzapine was approximately 27% higher in the adolescent group. Demographic differences between adolescents and adults are due to the lower mean body weight and lower proportion of smokers in adolescents. These factors likely contribute to the higher mean exposure observed in adolescents. INDICATIONS: ADULTS Olanzapine is indicated for the treatment of schizophrenia. Olanzapine is effective in maintaining clinical improvement during long-term therapy in patients who have responded to initial treatment. Olanzapine is indicated for the treatment of moderate to severe manic episodes. If a patient has responded to olanzapine treatment during manic episodes, olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder (see PHARMACODYNAMIC PROPERTIES section). CONTRAINDICATIONS: Hypersensitivity to the active substance or to any of the excipients. Patients at risk of angle-closure glaucoma. WARNINGS/PRECAUTIONS: During antipsychotic treatment, improvement in the patient's clinical condition may take several days or weeks. Patients should be adequately monitored during this period. PSYCHOSIS AND/OR BEHAVIORAL DISORDERS ASSOCIATED WITH DEMENTIA Olanzapine is not recommended for patients with psychosis and/or behavioral disorders associated with dementia due to an increased risk of mortality and cerebrovascular events. PARKINSON'S DISEASE The use of olanzapine for the treatment of psychosis associated with dopamine agonists in patients with Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology and hallucinations occurred more frequently than with placebo (see ADVERSE REACTIONS/SIDE EFFECTS section), and olanzapine was not more effective than placebo in treating psychotic symptoms. MALIGNANT NEUROLEPTIC SYNDROME (NMS) NMS is a potentially life-threatening condition associated with antipsychotic drugs. Rare cases of NMS have also been reported with olanzapine. The clinical presentation of NMS includes hyperpyrexia, muscle rigidity, altered mental status, and signs of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or has unexplained high fever without additional clinical signs of NMS, all antipsychotic drugs, including olanzapine, should be discontinued. HYPERGLYCEMIA AND DIABETES Hyperglycemia and/or development or exacerbation of diabetes, sometimes associated with ketoacidosis or coma, have been reported rarely, including a few fatal cases (see ADVERSE REACTIONS/SIDE EFFECTS section). In some cases, there was a prior increase in body weight, which may be a predisposing factor. Appropriate clinical monitoring is recommended according to existing antipsychotic guidelines, e.g., blood glucose determination at baseline, at 12 weeks of olanzapine treatment, and then annually. Patients on treatment with any antipsychotic drug, including olanzapine, should be screened for signs and symptoms of hyperglycemia (e.g., polydipsia, polyuria, polyphagia, and weakness), and patients with diabetes mellitus or risk factors for diabetes mellitus should have regular monitoring for worsening glucose control. Regular weight monitoring is also necessary, e.g., at baseline, at 4, 8, and 12 weeks of olanzapine treatment, and then quarterly. LIPID CHANGES Adverse changes in lipid levels have been reported in patients treated with olanzapine in placebo-controlled clinical trials (see ADVERSE REACTIONS/SIDE EFFECTS section). Lipid changes should be managed clinically, especially in patients with dyslipidemia and in patients with risk factors for the development of lipid disorders. Regular lipid monitoring is necessary in patients treated with any antipsychotic drug, including olanzapine, according to existing antipsychotic guidelines, e.g., at baseline, at 12 weeks of olanzapine treatment, and then once every 5 years. ANTICHOLINERGIC ACTIVITY While olanzapine exhibited anticholinergic activity in vitro, clinical experience during clinical trials showed a low incidence of related events. However, since clinical experience with olanzapine in patients with concomitant diseases is limited, caution is advised when prescribing the drug to patients with prostatic hypertrophy, paralytic ileus, or similar conditions. LIVER FUNCTION Transient, asymptomatic elevations of liver transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are common, especially in the early stages of treatment. Caution and further observation are required in patients with elevated alanine aminotransferase and/or aspartate aminotransferase, patients with signs and symptoms of liver dysfunction, patients with underlying conditions related to limited hepatic functional reserve, and patients treated with potentially hepatotoxic agents. In cases where hepatitis (including hepatocellular, cholestatic, or mixed liver injury) is diagnosed, olanzapine treatment should be discontinued. NEUTROPENIA Caution is advised in patients with low white blood cell count and/or neutrophil count of any cause, patients receiving drugs that cause neutropenia, patients with drug-induced bone marrow suppression/toxicity, patients with underlying diseases, bone marrow suppression due to radiation therapy or chemotherapy, and patients with hypereosinophilic syndrome or myeloproliferative disease. Neutropenia has been frequently reported with the concomitant use of olanzapine and valproate (see ADVERSE REACTIONS/SIDE EFFECTS section). DISCONTINUATION OF TREATMENT Sudden discontinuation of olanzapine treatment has rarely (≥0.01% and <0.1%) been associated with acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting. QT INTERVAL In clinical trials, clinically significant QTc prolongation was infrequent (0.1% to 1%) in patients treated with olanzapine, with no significant difference in associated cardiac events compared to placebo. However, caution is advised when administering olanzapine with drugs that prolong the QT interval, especially in the elderly, as well as in patients with congenital long QT interval syndrome, congestive heart failure, cardiac hypertrophy, hypokalemia, or hypomagnesemia. THROMBOEMBOLISM A temporal association between olanzapine treatment and venous thromboembolism has been reported infrequently (≥0.1% and <1%). A causal relationship between the development of venous thromboembolism and olanzapine treatment has not been established. However, since patients with schizophrenia often have acquired risk factors for venous thromboembolism, all possible risk factors for venous thromboembolism, such as patient immobilization, should be identified and preventive measures taken. GENERAL CNS ACTIVITY Given the primary CNS effects of olanzapine, caution is advised when used with other centrally acting agents and alcohol. Since olanzapine exhibits dopaminergic antagonism in vitro, it may antagonize the effects of direct and indirect dopaminergic agonists. SEIZURES Olanzapine should be used with caution in patients with a history of seizures or in whom there are factors that may lower the seizure threshold. Seizures have been reported rarely in patients treated with olanzapine. In most cases, a history of seizures or risk factors was present. TARDIVE DYSKINESIA In comparative studies of one year or less duration, olanzapine demonstrated a statistically significant lower incidence of treatment-emergent dyskinesia. However, the risk of tardive dyskinesia increases with prolonged use, and therefore, if signs or symptoms of tardive dyskinesia develop in patients treated with olanzapine, dose reduction or discontinuation of treatment should be considered. These symptoms may worsen temporarily or occur after discontinuation of treatment. POSTURAL HYPOTENSION Postural hypotension was reported not infrequently in elderly patients in clinical studies of olanzapine. Periodic monitoring of blood pressure is recommended in patients over 65 years of age. SUDDEN CARDIAC DEATH In post-marketing reports of olanzapine, cases of sudden cardiac death have been reported in patients treated with olanzapine. In a retrospective observational cohort study, the risk of probable sudden cardiac death in patients treated with olanzapine was approximately twice as high as in patients not receiving antipsychotic agents. In the study, the risk of olanzapine was similar to the risk of atypical antipsychotic agents considered in a meta-analysis. PEDIATRIC POPULATION Olanzapine is not indicated for the treatment of children and adolescents. Studies in patients aged 13-17 years showed various adverse events, including weight gain, changes in metabolic parameters, and increased prolactin levels (see ADVERSE REACTIONS/SIDE EFFECTS and PHARMACODYNAMIC PROPERTIES sections). LACTOSE Olanzapine 2.5 mg, 5 mg, and 10 mg film-coated tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product. FERTILITY, PREGNANCY AND LACTATION: PREGNANCY There are no adequate and well-controlled studies in pregnant women. If pregnancy occurs or is planned during olanzapine treatment, consult your doctor. However, due to limited experience in humans, olanzapine is used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates exposed to antipsychotic drugs (including olanzapine) during the third trimester of pregnancy are at risk of developing adverse reactions, including extrapyramidal or withdrawal symptoms, which may vary in severity and duration postpartum. Cases of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder have been reported. Therefore, neonates should be monitored carefully. BREAST-FEEDING In a study conducted in lactating, healthy women, olanzapine was excreted in breast milk. The mean infant exposure (mg/kg) at steady state was 1.8% of the maternal olanzapine dose (mg/kg). Patients are advised to discontinue breast-feeding during olanzapine treatment. FERTILITY The effect on fertility is unknown. EFFECTS ON ABILITY TO DRIVE AND USE MACHINES No studies have been conducted on the effect on the ability to drive and use machines. Since olanzapine may cause drowsiness and dizziness, caution should be exercised when operating machinery, including driving a vehicle. ADVERSE REACTIONS/SIDE EFFECTS SUMMARY OF SAFETY PROFILE Adverse reactions are listed in the table below. The table lists adverse events and laboratory analyses from clinical trials. Within each frequency group, adverse events are presented in decreasing order of severity. Frequency is defined as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); unknown (cannot be estimated from available data). VERY COMMON COMMON UNCOMMON RARE UNKNOWN DISORDERS OF THE BLOOD AND LYMPHATIC SYSTEM EOSINOPHILIA, LEUKOPENIA, NEUTROPENIA THROMBOCYTOPENIA DISORDERS OF THE IMMUNE SYSTEM HYPERSENSITIVITY METABOLISM AND NUTRITION DISORDERS WEIGHT GAIN INCREASED CHOLESTEROL LEVELS, INCREASED GLUCOSE LEVELS, INCREASED TRIGLYCERIDE LEVELS, GLYCOSURIA, INCREASED APPETITE DEVELOPMENT OR EXACERBATION OF DIABETES MELLITUS, RARELY ASSOCIATED WITH KETOACIDOSIS OR COMA, INCLUDING A FEW FATAL CASES (SEE WARNINGS/PRECAUTIONS SECTION) HYPOTHERMIA DISORDERS OF THE NERVOUS SYSTEM SOMNOLENCE DIZZINESS, AKATHISIA, PARKINSONISM, DYSKINESIA SEIZURES, WHERE MOST CASES HAD A HISTORY OF SEIZURES OR RISK FACTORS, DYSTONIA (INCLUDING OCULOGYRIC CRISIS), TARDIVE DYSKINESIA, AMNESIA, DYSARTHRIA, LINGUAL IMPAIRMENT, RESTLESS LEGS SYNDROME MALIGNANT NEUROLEPTIC SYNDROME (SEE WARNINGS/PRECAUTIONS SECTION), WITHDRAWAL SYNDROME DISORDERS OF THE HEART BRADYCARDIA, QTc PROLONGATION (SEE WARNINGS/PRECAUTIONS SECTION) VENTRICULAR TACHYCARDIA/FIBRILLATION, SUDDEN DEATH (SEE WARNINGS/PRECAUTIONS SECTION) DISORDERS OF THE VASCULAR SYSTEM ORTHOSTATIC HYPOTENSION THROMBOEMBOLISM (INCLUDING PULMONARY EMBOLISM AND DEEP VEIN THROMBOSIS) (SEE WARNINGS/PRECAUTIONS SECTION) DISORDERS OF THE RESPIRATORY SYSTEM, THORAX AND MEDIASTINUM EPISTAXIS DISORDERS OF THE GASTROINTESTINAL TRACT MILD, TRANSIENT ANTICHOLINERGIC EFFECTS, INCLUDING CONSTIPATION AND DRY MOUTH ABDOMINAL DISTENSION PANCREATITIS HEPATOBILIARY DISORDERS TRANSIENT, ASYMPTOMATIC ELEVATION OF LIVER TRANSAMINASES (ALANINE AMINOTRANSFERASE, ASPARTATE AMINOTRANSFERASE), ESPECIALLY AT THE BEGINNING OF TREATMENT (SEE WARNINGS/PRECAUTIONS SECTION) HEPATITIS (INCLUDING HEPATOCELLULAR, CHOLESTATIC, OR MIXED LIVER INJURY) DISORDERS OF THE SKIN AND SUBCUTANEOUS TISSUE RASH PHOTOREACTION, ALOPECIA DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS SYNDROME) MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS ARTHRALGIA RHABDOMYOLYSIS RENAL AND URINARY DISORDERS URINARY INCONTINENCE, URINARY RETENTION, DIFFICULTY IN URINATION PREGNANCY, PUERPERIUM AND PERINATAL CONDITIONS DRUG WITHDRAWAL SYNDROME NEONATAL (SEE FERTILITY, PREGNANCY AND LACTATION SECTION) DISORDERS OF THE REPRODUCTIVE SYSTEM AND MAMMARY GLAND ERECTILE DYSFUNCTION IN MEN, DECREASED LIBIDO IN MEN AND WOMEN AMENORRHEA, BREAST ENLARGEMENT, GALACTORRHEA IN WOMEN, GYNECOMASTIA/BREAST ENLARGEMENT IN MEN GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS ASTHENIA, FATIGUE, EDEMA, PYREXIA INVESTIGATIONS INCREASED PLASMA PROLACTIN LEVELS INCREASED ALKALINE PHOSPHATASE, HIGH CREATINE PHOSPHOKINASE, HIGH GAMMA-GLUTAMYL TRANSFERASE, HIGH URIC ACID INCREASED TOTAL BILIRUBIN ADULTS In clinical trials, the most frequent (≥1% of patients) adverse events associated with olanzapine use were somnolence, weight gain, eosinophilia, increased prolactin, cholesterol, glucose, and triglyceride levels (see WARNINGS/PRECAUTIONS section), glycosuria, increased appetite, dizziness, akathisia, parkinsonism, leukopenia, neutropenia (see WARNINGS/PRECAUTIONS section), dyskinesia, orthostatic hypotension, anticholinergic effects, transient asymptomatic elevation of liver transaminases (see WARNINGS/PRECAUTIONS section), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma-glutamyl transferase, high uric acid, high creatine phosphokinase, and edema. LONG-TERM EXPOSURE (AT LEAST 48 WEEKS) The proportion of patients experiencing adverse events, clinically significant changes in weight, glucose, total/LDL/HDL cholesterol, or triglyceride levels increased over time. In adult patients who completed 9-12 months of treatment, the mean increase in blood glucose levels slowed down after approximately 6 months. PEDIATRIC POPULATION Olanzapine is not indicated for use in children and adolescents under 18 years of age. Although comparative clinical trials between adolescents and adults have not been conducted, data from adolescent studies have been compared to adult study results. The table below summarizes adverse reactions that were more frequently reported in adolescent patients (13-17 years of age) compared to adult patients, as well as adverse reactions reported only in short-term clinical studies in adolescent patients. Clinically significant weight gain (>7%), with comparable exposure, was reported more frequently in adolescents than in adults. The magnitude of weight gain and the proportion of adolescent patients experiencing clinically significant weight gain were higher with longer exposure (at least 24 weeks) than with short-term exposure. The frequency of adverse reactions is presented in decreasing order of severity. Frequency is defined as follows: very common (≥1/10), common (≥1/100, <1/10). METABOLISM AND NUTRITION DISORDERS VERY COMMON: WEIGHT GAIN, INCREASED TRIGLYCERIDE LEVELS, INCREASED APPETITE COMMON: INCREASED CHOLESTEROL LEVELS. NERVOUS SYSTEM DISORDERS VERY COMMON: SEDATION (INCLUDING: HYPERSOMNIA, LETHARGY, SOMNOLENCE). GASTROINTESTINAL DISORDERS COMMON: DRY MOUTH. HEPATOBILIARY DISORDERS VERY COMMON: ELEVATED LIVER TRANSAMINASE LEVELS (ALANINE AMINOTRANSFERASE/ASPARTATE AMINOTRANSFERASE; SEE WARNINGS/PRECAUTIONS SECTION) INVESTIGATIONS VERY COMMON: DECREASED TOTAL BILIRUBIN LEVELS, INCREASED GAMMA-GLUTAMYL TRANSFERASE, INCREASED PLASMA PROLACTIN LEVELS. If you notice any side effects, consult your doctor for advice. DRUG INTERACTIONS: INTERACTION STUDIES HAVE BEEN CONDUCTED ONLY IN ADULTS. POTENTIAL INTERACTIONS AFFECTING OLANZAPINE Since olanzapine is metabolized by CYP1A2, substances that can induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine. CYP1A2 INDUCTION Stimulation of olanzapine metabolism may be caused by smoking and carbamazepine, which can lead to a decrease in olanzapine concentration. Only mild to moderate increases in olanzapine clearance have been observed. Clinical data are likely limited, but clinical monitoring is recommended, and an increase in olanzapine dose may be considered if necessary (see DOSAGE AND ADMINISTRATION section). CYP1A2 INHIBITION Fluvoxamine, a specific inhibitor of CYP1A2, significantly inhibits the metabolism of olanzapine. The mean increase in olanzapine Cmax due to fluvoxamine was 54% in non-smoking women and 77% in smoking men. The mean increase in olanzapine AUC was 52% and 108%, respectively. A lower starting dose of olanzapine should be considered in patients taking fluvoxamine or any other CYP1A2 inhibitor, such as ciprofloxacin. If treatment with a CYP1A2 inhibitor is initiated, a reduction in olanzapine dose should be considered. REDUCED BIOAVAILABILITY Activated charcoal reduces the bioavailability of oral olanzapine by 50-60% and should be taken at least 2 hours before or 2 hours after olanzapine. Single doses of fluoxetine (CYP2D6 inhibitor), antacids (aluminum, magnesium), or cimetidine have not been shown to significantly affect olanzapine pharmacokinetics. OLANZAPINE'S POTENTIAL TO AFFECT OTHER MEDICINAL PRODUCTS Olanzapine may antagonize the effects of direct and indirect dopaminergic agonists. Olanzapine does not inhibit major CYP450 isoenzymes (e.g., 1A2, 2D6, 2C9, 2C19, 3A4) in vitro. Therefore, no specific interactions are expected, which was confirmed in in vivo studies where no inhibition of the metabolism of the following active substances was observed: tricyclic antidepressants (mainly CYP2D6 metabolism), warfarin (CYP2C9), theophylline (CYP1A2), or diazepam (CYP3A4 and 2C19). Olanzapine does not interact when used with lithium or biperiden. Therapeutic monitoring of valproate plasma levels has not shown that dose adjustment of valproate is necessary when co-administered with olanzapine. GENERAL CNS ACTIVITY Caution is advised in patients who consume alcohol or take medicinal products that can depress the central nervous system. In patients with Parkinson's disease and dementia, the use of olanzapine with antiparkinsonian medicinal products is not recommended (see WARNINGS/PRECAUTIONS section). QT INTERVAL Caution is advised when olanzapine is used with medicinal products that prolong the QT interval (see WARNINGS/PRECAUTIONS section). DOSAGE AND ADMINISTRATION: ADULTS SCHIZOPHRENIA: The recommended starting dose of olanzapine is 10 mg/day. MANIC EPISODE: The starting dose is 15 mg as a single daily dose in monotherapy or 10 mg daily in combination therapy (see PHARMACODYNAMIC PROPERTIES section). PREVENTION OF RECURRENCE IN BIPOLAR DISORDER: The recommended starting dose is 10 mg/day. For patients receiving olanzapine for the treatment of manic episodes, treatment for the prevention of recurrence continues at the same dose. If a new manic, mixed, or depressive episode develops, olanzapine treatment should be continued (with dose optimization if necessary) with additional therapy to treat mood symptoms, as clinically indicated. Subsequent daily dose adjustments in schizophrenia, manic episode, or prevention of recurrence in bipolar disorder can be made within the dose range of 5-20 mg/day based on individual clinical status. Increasing the initial recommended dose should only be done after appropriate clinical evaluation and generally should occur at intervals of at least 24 hours. Olanzapine administration is not dependent on food, as food does not affect absorption. When discontinuing olanzapine, gradual dose reduction should be considered. SPECIAL POPULATIONS ELDERLY Generally, a lower starting dose (5 mg/day) is not routinely indicated, but should be considered in patients aged 65 and over, taking into account identified clinical factors (see WARNINGS/PRECAUTIONS section). RENAL AND/OR HEPATIC IMPAIRMENT A lower starting dose (5 mg) is used in such patients. In cases of moderate hepatic impairment (cirrhosis, Child-Pugh class A or B), the starting dose should be 5 mg and increased with caution. SMOKERS The starting dose and dose range should not be routinely changed for non-smokers compared to smokers. Olanzapine metabolism may be induced by smoking. Clinical monitoring is recommended, and an increase in olanzapine dose may be considered if necessary (see DRUG INTERACTIONS section). When more than one factor is present that may cause slowed metabolism (female gender, geriatric age, non-smoking status), a reduction in the starting dose should be considered. In such patients, dose increases, if necessary, should be done conservatively. In cases where a dose increase of 2.5 mg is considered necessary, olanzapine film-coated tablets should be used (see DRUG INTERACTIONS and PHARMACOKINETIC PROPERTIES sections). PEDIATRIC POPULATION Olanzapine is not recommended for children and adolescents under 18 years of age due to limited safety and efficacy data. Short-term studies in adolescent patients showed greater changes in weight gain, lipid and prolactin levels than in adult patient studies (see WARNINGS/PRECAUTIONS, ADVERSE REACTIONS/SIDE EFFECTS, PHARMACODYNAMIC PROPERTIES, and PHARMACOKINETIC PROPERTIES sections). OVERDOSE: SIGNS AND SYMPTOMS: Very common symptoms of overdose (>10% incidence) include tachycardia, agitation/aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness from sedation to coma. Other medically significant consequences of overdose include delirium, convulsions, coma, possible malignant neuroleptic syndrome, respiratory depression, aspiration, hypertension or hypotension, arrhythmias (in <2% of overdose cases), and cardiac arrest. Fatal outcome has been reported with acute overdose of 450 mg, but survival has been described with approximately 2 g of orally administered olanzapine in acute overdose. TREATMENT There is no specific antidote for olanzapine. Induction of vomiting is not recommended. Standard procedures for managing overdose are indicated (e.g., gastric lavage, administration of activated charcoal). Co-administration of activated charcoal reduces the oral bioavailability of olanzapine by 50-60%. Symptomatic treatment and monitoring of vital organ functions should be initiated according to clinical manifestations, including treatment of hypotension and circulatory collapse, and support of respiratory function. Epinephrine, dopamine, or other sympathomimetic agents with beta-agonist activity should not be used, as beta stimulation may worsen hypotension. Cardiovascular monitoring is necessary to detect possible arrhythmias. Appropriate medical supervision and monitoring should continue until the patient has fully recovered. STORAGE CONDITIONS Store at a temperature not exceeding 25°C, in its original packaging. Keep out of reach of children. PACKAGING: Olanzapine 2.5 mg film-coated tablet; presented in Al-Al blisters with 28 film-coated tablets. Olanzapine 5 mg film-coated tablet; presented in Al-Al blisters with 28 film-coated tablets. Olanzapine 10 mg film-coated tablet; presented in Al-Al blisters with 28 film-coated tablets. EXPIRY DATE: 2 YEARS DISPENSING CATEGORY: Pharmaceutical Product Group II, dispensed with prescription form №3. Consult your doctor before using this medication.
