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Olanzapine Actavis 2.5mg Film-coated Tablets Last Updated on eMC 14-Nov-2014 View changes | Actavis UK Ltd Contact details Name of the medicinal product Qualitative and quantitative composition Pharmaceutical form Clinical particulars - 4.1 Therapeutic indications - 4.2 Posology and method of administration - 4.3 Contraindications - 4.4 Special warnings and precautions for use - 4.5 Interaction with other medicinal products and other forms of interaction - 4.6 Fertility, pregnancy and lactation - 4.7 Effects on ability to drive and use machines - 4.8 Undesirable effects - 4.9 Overdose Pharmacological properties - 5.1 Pharmacodynamic properties - 5.2 Pharmacokinetic properties - 5.3 Preclinical safety data Pharmaceutical particulars - 6.1 List of excipients - 6.2 Incompatibilities - 6.3 Shelf life - 6.4 Special precautions for storage - 6.5 Nature and contents of container - 6.6 Special precautions for disposal and other handling Marketing authorisation holder Marketing authorisation number(s) Date of first authorisation/renewal of the authorisation Date of revision of the text Dosimetry - 12 Instructions for preparation of radiopharmaceuticals Excipient(s) with known effect:2.5mg film-coated tablet contains 58.3mg lactose anhydrous and 0.064mg lecithin soya (E322). For the full list of excipients, see section 6.1. AdultsOlanzapine is indicated for the treatment of schizophrenia. Olanzapine is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response. Olanzapine is indicated for the treatment of moderate to severe manic episode. In patients whose manic episode has responded to olanzapine treatment, olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder (see section 5.1). Posology AdultsSchizophrenia: The recommended starting dose for olanzapine is 10mg/day. Manic episode: The starting dose is 15mg as a single daily dose in monotherapy or 10mg daily in combination therapy (see section 5.1). Preventing recurrence in bipolar disorder: The recommended starting dose is 10mg/day. For patients who have been receiving olanzapine for treatment of manic episode, therapy for preventing recurrence should be continued at the same dose. If a new manic, mixed, or depressive episode occurs, olanzapine treatment should be continued (with dose optimisation as needed), with supplementary therapy to treat mood symptoms, as clinically indicated. During treatment for schizophrenia, manic episode and recurrence prevention in bipolar disorder, daily dosage may subsequently be adjusted on the basis of individual clinical status within the range 5-20mg/day. An increase to a dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours. Paediatric populationOlanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy. A greater magnitude of weight gain, lipid and prolactin alterations has been reported in short term studies of adolescent patients than in studies of adult patients (see sections 4.4, 4.8, 5.1 and 5.2). Elderly patientsA lower starting dose (5mg/day) is not routinely indicated but should be considered for those 65 and over when clinical factors warrant (see also section 4.4). Patients with renal and/or hepatic impairmentA lower starting dose (5mg) should be considered for such patients. In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh Class A or B), the starting dose should be 5mg and only increased with caution. GenderThe starting dose and dose range need not be routinely altered for female patients relative to male patients. SmokersThe starting dose and dose range need not be routinely altered for non-smokers relative to smokers. When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the starting dose. Dose escalation, when indicated, should be conservative in such patients. (See sections 4.5 and 5.2.) Method of administrationOlanzapine can be given without regards for meals as absorption is not affected by food. Gradual tapering of the dose should be considered when discontinuing olanzapine. Dementia-related psychosis and/or behavioural disturbancesOlanzapine is not approved for the treatment of dementia-related psychosis and/or behavioural disturbances and is not recommended for use in this particular group of patients because of an increase in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-12 weeks duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or disturbed behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated patients compared to patients treated with placebo (3.5% vs. 1.5%, respectively). The higher incidence of death was not associated with olanzapine dose (mean daily dose 4.4mg) or duration of treatment. Risk factors that may predispose this patient population to increased mortality include age > 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of these risk factors. In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischemic attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for CVAE in association with olanzapine treatment. The efficacy of olanzapine was not established in these trials. Parkinson's diseaseThe use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo (see section 4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In these trials, patients were initially required to be stable on the lowest effective dose of anti-Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian medicinal products and dosages throughout the study. Olanzapine was started at 2.5mg/day and titrated to a maximum of 15mg/day based on investigator judgement. Neuroleptic Malignant Syndrome (NMS)NMS is a potentially life-threatening condition associated with antipsychotic medicinal products. Rare cases reported as NMS have also been received in association with olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac 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 presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued. Hyperglycaemia and diabetesHyperglycaemia and/or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported uncommonly, including some fatal cases (see section 4.8). In some cases, a prior increase in body weight has been reported which may be a predisposing factor. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g. measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually thereafter. Patients treated with any antipsychotic agents, including olanzapine film-coated tablets, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly, e.g. at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter. Lipid alterationsUndesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled clinical trials (see section 4.8). Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders. Patients treated with any antipsychotic agents, including olanzapine film-coated tablets, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g. at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter. Anticholinergic activityWhile olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events. However, as clinical experience with olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, or paralytic ileus and related conditions. Hepatic functionTransient, asymptomatic elevations of hepatic aminotransferases, alanine transferase (ALT), aspartate transferase (AST) have been seen commonly, especially in early treatment. Caution should be exercised and follow-up organised in patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic medicines. In cases where hepatitis (including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, olanzapine treatment should be discontinued. NeutropeniaCaution should be exercised in patients with low leukocyte and/or neutrophil counts for any reason, in patients receiving medicines known to cause neutropenia, in patients with a history of drug-induced bone marrow depression/toxicity, in patients with bone marrow depression caused by concomitant illness, radiation therapy or chemotherapy and in patients with hypereosinophilic conditions or with myeloproliferative disease. Neutropenia has been reported commonly when olanzapine and valproate are used concomitantly (see section 4.8). Discontinuation of treatmentAcute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported rarely (≥0.01% and <0.01%) when olanzapine is stopped abruptly. QT intervalIn clinical trials, clinically meaningful QTc prolongations (Fridericia QT correction [QTcF] ≥500 milliseconds [msec] at any time post baseline in patients with baseline QTcF<500 msec) were uncommon (0.1% to 1%) in patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. However, as with other antipsychotics, caution should be exercised when olanzapine is prescribed with medicines known to increase QTc interval, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia. ThromboembolismTemporal association of olanzapine treatment and venous thromboembolism has been reported uncommonly (≥ 0.1% and < 1%). A causal relationship between the occurrence of venous thromboembolism and treatment with olanzapine has not been established. However, since patients with schizophrenia often present with acquired risk factors for venous thromboembolism all possible risk factors of VTE e.g. immobilisation of patients, should be identified and preventive measures undertaken. General CNS activityGiven the primary CNS effects of olanzapine, caution should be used when it is taken in combination with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism, olanzapine may antagonize the effects of direct and indirect dopamine agonists. SeizuresOlanzapine should be used cautiously in patients who have a history of seizures or are subject to factors which may lower the seizure threshold. Seizures have been reported to occur uncommonly in patients when treated with olanzapine. In most of these cases, a history of seizures or risk factors for seizures were reported. Tardive DyskinesiaIn comparator studies of one year or less duration, olanzapine was associated with a statistically significant lower incidence of treatment emergent dyskinesia. However the risk of tardive dyskinesia increases with long term exposure, and therefore if signs or symptoms of tardive dyskinesia appear in a patient on olanzapine, a dose reduction or discontinuation should be considered. These symptoms can temporally deteriorate or even arise after discontinuation of treatment. Postural hypotensionPostural hypotension was infrequently observed in the elderly in olanzapine clinical trials. As with other antipsychotics, it is recommended that blood pressure is measured periodically in patients over 65 years. Sudden cardiac deathIn postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in patients with olanzapine. In a retrospective observational cohort study, the risk of presumed sudden cardiac death in patients treated with olanzapine was approximately twice the risk in patients not using antipsychotics. In the study, the risk of olanzapine was comparable to the risk of atypical antipsychotics included in a pooled analysis. Paediatric populationOlanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic parameters and increases in prolactin levels. Long-term outcomes associated with these events have not been studied and remain unknown (see sections 4.8 and 5.1). LactoseOlanzapine Film-coated Tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Lecithin soyaIf a patient is hypersensitive to peanut or soya, this medicine should not be used. Paediatric populationInteraction studies have only been performed in adults. Potential interactions affecting olanzapineSince olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine. Induction of CYP1A2The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to reduced olanzapine concentrations. Only slight to moderate increase in olanzapine clearance has been observed. The clinical consequences are likely to be limited, but clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary (see section 4.2). Inhibition of CYP1A2Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of olanzapine. The mean increase in olanzapine Cmax following fluvoxamine was 54% in female non-smokers and 77% in male smokers. The mean increase in olanzapine AUC was 52% and 108 % respectively. A lower starting dose of olanzapine should be considered in patients who are using fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin. A decrease in the dose of olanzapine should be considered if treatment with an inhibitor of CYP1A2 is initiated. Decreased bioavailabilityActivated charcoal reduces the bioavailability of oral olanzapine by 50 to 60% and should be taken at least 2 hours before or after olanzapine. Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine. Potential for olanzapine to affect other medicinal productsOlanzapine may antagonise the effects of direct and indirect dopamine agonists. Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g. 1A2, 2D6, 2C9, 2C19, 3A4). Thus no particular interaction is expected as verified through in vivo studies where no inhibition of metabolism of the following active substances was found: tricyclic antidepressant (representing mostly CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 2C19). Olanzapine showed no interaction when co-administered with lithium or biperiden. Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is required after the introduction of concomitant olanzapine. General CNS activityCaution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression. The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with Parkinson's disease and dementia is not recommended (see section 4.4).QTc intervalCaution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc interval (see section 4.4). AdultsThe most frequently (seen in ≥ 1% of patients) reported adverse reactions associated with the use of olanzapine in clinical trials were somnolence, weight gain, eosinophilia, elevated prolactin, cholesterol, glucose and triglyceride levels (see section 4.4), glucosuria, increased appetite, dizziness, akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, anticholinergic effects, transient asymptomatic elevations of hepatic aminotransferases (see section 4.4), rash, asthenia, fatigue, pyrexia, arthralgia, increased alkaline phosphatase, high gamma glutamyltransferase, high uric acid, high creatine phosphokinase and oedema. Tabulated list of adverse reactionsThe following table lists the adverse reactions and laboratory investigations observed from spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency terms listed are defined as follows:Very common (≥1/10)Common (≥1/100 to <1/10)Uncommon (≥1/1,000 to <1/100)Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000) Not known (cannot be estimated from the available data)1 Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. Following short term treatment (median duration 47 days), weight gain ≥ 7% of baseline body weight was very common (22.2%), ≥ 15% was common (4.2%) and ≥ 25% was uncommon (0.8%). Patients gaining ≥ 7%, ≥ 15% and ≥ 25% of their baseline body weight with long-term exposure (at least 48 weeks) were very common (64.4%, 31.7% and 12.3% respectively). 2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline. 3Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (≥ 6.2 mmol/l). Changes in total fasting cholesterol levels from borderline at baseline (≥ 5.17-< 6.2 mmol/l) to high (≥ 6.2 mmol/l) were very common. 4 Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (≥ 7 mmol/l). Changes in fasting glucose from borderline at baseline (≥ 5.56 - < 7 mmol/l) to high (≥ 7 mmol/l) were very common. 5 Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (≥ 2.26 mmol/l). Changes in fasting triglycerides from borderline at baseline (≥ 1.69 mmol/l - < 2.26 mmol/l) to high (≥ 2.26 mmol/l) were very common. 6In clinical trials, the incidence of parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo. Olanzapine-treated patients had a lower incidence of parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol. In the absence of detailed information on the pre-existing history of individual acute and tardive extrapyramidal movement disorders, it can not be concluded at present that olanzapine produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes. 7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly. 8 In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal range in approximately 30% of olanzapine treated patients with normal baseline prolactin value. In the majority of these patients the elevations were generally mild, and remained below two times the upper limit of normal range. 9 Adverse event identified from clinical trials in the Olanzapine Integrated Database.10 As assessed by measured values from clinical trials in the Olanzapine Integrated Database.11 Adverse event identified from spontaneous post-marketing reporting with frequency determined utilising the Olanzapine Integrated Database.12 Adverse event identified from spontaneous post-marketing reporting with frequency estimated at the upper limit of the 95% confidence interval utilising the Olanzapine Integrated Database. Long-term exposure (at least 48 weeks)The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 6 months. Additional information on special populationsIn clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher incidence of death and cerebrovascular adverse reactions compared to placebo (see section 4.4). Very common adverse reactions associated with the use of olanzapine in this patient group were abnormal gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence were observed commonly. In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with Parkinson's disease, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo. In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine resulted in an incidence of neutropenia of 4.1%; a potential contributing factor could be high plasma valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (≥ 10%) of tremor, dry mouth, increased appetite, and weight gain. Speech disorder was also reported commonly. During treatment with olanzapine in combination with lithium or divalproex, an increase of ≥ 7% from baseline body weight occurred in 17.4% of patients during acute treatment (up to 6 weeks). Long-term olanzapine treatment (up to 12 months) for recurrence prevention in patients with bipolar disorder was associated with an increase of ≥ 7% from baseline body weight in 39.9% of patients. Paediatric populationOlanzapine is not indicated for the treatment of children and adolescent patients below 18 years. Although no clinical studies designed to compare adolescents to adults have been conducted, data from the adolescent trials were compared to those of the adult trials. The following table summarises the adverse reactions reported with a greater frequency in adolescent patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term clinical trials in adolescent patients. Clinically significant weight gain (≥ 7%) appears to occur more frequently in the adolescent population compared to adults with comparable exposures. The magnitude of weight gain and the proportion of adolescent patients who had clinically significant weight gain were greater with long-term exposure (at least 24 weeks) than with short-term exposure. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency terms listed are defined as follows:Very common (≥ 1/10)Common (≥ 1/100 to < 1/10).13 Following short term treatment (median duration 22 days), weight gain ≥ 7% of baseline body weight (kg) was very common (40.6%), ≥ 15% of baseline body weight was common (7.1%) and ≥ 25% was common (2.5%). With long-term exposure (at least 24 weeks), 89.4% gained ≥ 7%, 55.3% gained ≥ 15% and 29.1% gained ≥ 25% of their baseline body weight. 14 Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high (≥ 1.467 mmol/l) and changes in fasting triglycerides from borderline at baseline (≥ 1.016 mmol/l - < 1.467 mmol/l) to high (≥ 1.467 mmol/l). 15 Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high (≥ 5.17 mmol/l) were observed commonly. Changes in total fasting cholesterol levels from borderline at baseline (≥ 4.39 - < 5.17 mmol/l) to high (≥ 5.17 mmol/l) were very common.16 Elevated plasma prolactin levels were reported in 47.4% of adolescent patients. Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme website: www.mhra.gov.uk/yellowcard. Signs and symptomsVery common symptoms in overdose (>10% incidence) include tachycardia, agitation/aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness ranging from sedation to coma. Other medically significant sequelae of overdose include delirium, convulsion, coma, possible neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, cardiac arrhythmias (< 2% of overdose cases) and cardiopulmonary arrest. Fatal outcomes have been reported for acute overdoses as low as 450mg but survival has also been reported following acute overdose of approximately 2g of oral olanzapine. ManagementThere is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard procedures for management of overdose may be indicated (i.e. gastric lavage, administration of activated charcoal). The concomitant administration of activated charcoal was shown to reduce the oral bioavailability of olanzapine by 50 to 60%. Symptomatic treatment and monitoring of vital organ function should be instituted according to clinical presentation, including treatment of hypotension and circulatory collapse and support of respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-agonist activity since beta stimulation may worsen hypotension. Cardiovascular monitoring is necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue until the patient recovers. Clinical efficacyIn two of two placebo and two of three comparator controlled trials with over 2,900 schizophrenic patients presenting with both positive and negative symptoms, olanzapine was associated with statistically significantly greater improvements in negative as well as positive symptoms. In a multinational, double-blind, comparative study of schizophrenia, schizoaffective, and related disorders which included 1,481 patients with varying degrees of associated depressive symptoms (baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary analysis of baseline to endpoint mood score change demonstrated a statistically significant improvement (p=0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1). In patients with a manic or mixed episode of bipolar disorder, olanzapine demonstrated superior efficacy to placebo and valproate semisodium (divalproex) in reduction of manic symptoms over 3 weeks. Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of the proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks. In a co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition of olanzapine 10mg (co-therapy with lithium or valproate) resulted in a greater reduction in symptoms of mania than lithium or valproate monotherapy after 6 weeks. In a 12-month recurrence prevention study in manic episode patients who achieved remission on olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated statistically significant superiority over placebo on the primary endpoint of bipolar recurrence. Olanzapine also showed a statistically significant advantage over placebo in terms of preventing either recurrence into mania or recurrence into depression. In a second 12-month recurrence prevention study in manic episode patients who achieved remission with a combination of olanzapine and lithium and were then randomised to olanzapine or lithium alone, olanzapine was statistically non-inferior to lithium on the primary endpoint of bipolar recurrence (olanzapine 30.0%, lithium 38.3%; p = 0.055). In an 18-month co-therapy study in manic or mixed episode patients stabilised with olanzapine plus a mood stabiliser (lithium or valproate), long-term olanzapine co-therapy with lithium or valproate was not statistically significantly superior to lithium or valproate alone in delaying bipolar recurrence, defined according to syndromic (diagnostic) criteria. Paediatric populationThe experience in adolescents (ages 13 to 17 years) is limited to short term efficacy data in schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than 200 adolescents. Olanzapine was used as a flexible dose starting with 2.5 and ranging up to 20 mg/day. During treatment with olanzapine, adolescents gained significantly more weight compared with adults. The magnitude of changes in fasting total cholesterol, LDL cholesterol, triglycerides, and prolactin (see sections 4.4 and 4.8) were greater in adolescents than in adults. There are no data on maintenance of effect and limited data on long term safety (see sections 4.4 and 4.8). AbsorptionOlanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5 to 8 hours. The absorption is not affected by food. Absolute oral bioavailability relative to intravenous administration has not been determined DistributionThe plasma protein binding of olanzapine was about 93 % over the concentration range of about 7 to about 1000 ng/ml. Olanzapine is bound predominantly to albumin and a1-acid-glycoprotein. BiotransformationOlanzapine is metabolized in the liver by conjugative and oxidative pathways. The major circulating metabolite is the 10-N-glucuronide, which does not pass the blood brain barrier. Cytochromes P450- CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in animal studies. The predominant pharmacologic activity is from the parent olanzapine. EliminationAfter oral administration, the mean terminal elimination half-life of olanzapine in healthy subjects varied on the basis of age and gender. In healthy elderly (65 and over) versus non-elderly subjects, the mean elimination half-life was prolonged (51.8 versus 33.8 hr) and the clearance was reduced (17.5 versus 18.2 l/hr). The pharmacokinetic variability observed in the elderly is within the range for the non-elderly. In 44 patients with schizophrenia > 65 years of age, dosing from 5 to 20mg/day was not associated with any distinguishing profile of adverse events. In female versus male subjects the mean elimination half life was somewhat prolonged (36.7 versus 32.3 hr) and the clearance was reduced (18.9 versus 27.3 l/hr). However, olanzapine (5-20mg) demonstrated a comparable safety profile in female (n=467) as in male patients (n=869). Renal impairmentIn renally impaired patients (creatinine clearance < 10 ml/min) versus healthy subjects, there was no significant difference in mean elimination half-life (37.7 versus 32.4 hr) or clearance (21.2 versus 25.0 l/hr). A mass balance study showed that approximately 57 % of radiolabelled olanzapine appeared in urine, principally as metabolites. SmokersIn smoking subjects with mild hepatic dysfunction, mean elimination half-life (39.3 hr) was prolonged and clearance (18.0 l/hr) was reduced analogous to non-smoking healthy subjects (48.8 hr and 14.1 l/hr, respectively). In non-smoking versus smoking subjects (males and females) the mean elimination half-life was prolonged (38.6 versus 30.4 hr) and the clearance was reduced (18.6 versus 27.7 l/hr). The plasma clearance of olanzapine is lower in elderly versus young subjects, in females versus males, and in non-smokers versus smokers. However, the magnitude of the impact of age, gender, or smoking on olanzapine clearance and half-life is small in comparison to the overall variability between individuals. In a study of Caucasians, Japanese, and Chinese subjects, there were no differences in the pharmacokinetic parameters among the three populations. Paediatric populationAdolescents (ages 13 to 17 years): The pharmacokinetics of olanzapine are similar between adolescents and adults. In clinical studies, the average olanzapine exposure was approximately 27% higher in adolescents. Demographic differences between the adolescents and adults include a lower average body weight and fewer adolescents were smokers. Such factors possibly contribute to the higher average exposure observed in adolescents. Acute (single-dose) toxicitySigns of oral toxicity in rodents were characteristic of potent neuroleptic compounds: hypoactivity, coma, tremors, clonic convulsions, salivation, and depressed weight gain. The median lethal doses were approximately 210mg/kg (mice) and 175mg/kg (rats). Dogs tolerated single oral doses up to 100mg/kg without mortality. Clinical signs included sedation, ataxia, tremors, increased heart rate, labored respiration, miosis, and anorexia. In monkeys, single oral doses up to 100mg/kg resulted in prostration and, at higher doses, semi-consciousness. Repeated-dose toxicityIn studies up to 3 months duration in mice and up to 1 year in rats and dogs, the predominant effects were CNS depression, anticholinergic effects, and peripheral haematological disorders. Tolerance developed to the CNS depression. Growth parameters were decreased at high doses. Reversible effects consistent with elevated prolactin in rats included decreased weights of ovaries and uterus and morphologic changes in vaginal epithelium and in mammary gland. Haematologic toxicityEffects on haematology parameters were found in each species, including dose-related reductions in circulating leukocytes in mice and non-specific reductions of circulating leukocytes in rats; however, no evidence of bone marrow cytotoxicity was found. Reversible neutropenia, thrombocytopenia, or anaemia developed in a few dogs treated with 8 or 10 mg/kg/day(total olanzapine exposure [area under the curve] is 12- to 15-fold greater than that of a man given a 12-mg dose). In cytopenic dogs, there were no adverse effects on progenitor and proliferating cells in the bone marrow. Reproductive toxicityOlanzapine had no teratogenic effects. Sedation affected mating performance of male rats. Estrous cycles were affected at doses of 1.1 mg/kg (3 times the maximum human dose) and reproduction parameters were influenced in rats given 3 mg/kg (9 times the maximum human dose). In the offspring of rats given olanzapine, delays in foetal development and transient decreases in offspring activity levels were seen. MutagenicityOlanzapine was not mutagenic or clastogenic in a full range of standard tests, which included bacterial mutation tests and in vitro and in vivo mammalian tests. CarcinogenicityBased on the results of studies in mice and rats, it was concluded that olanzapine is not carcinogenic. Tablet core:Lactose anhydrousMicrocrystalline celluloseCrospovidoneMagnesium stearate Tablet coat:Polyvinyl alcoholTitanium dioxide (E171)TalcLecithin soya (E322)Xanthan gum (E415) Pack sizes:In blisters: 7, 14, 28, 30, 35, 56 and 70 film-coated tablets. In containers: 100 and 250 film-coated tablets [250 tablets: Not available for 15 mg and 20 mg]. Not all pack sizes may be marketed. Actavis UK Ltd Whiddon Valley, Barnstaple, Devon, EX32 8NS, UK Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why? Active ingredients Legal categories This site uses cookies. By continuing to browse the site you are agreeing to our policy on the use of cookies. Continue
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Zalasta tablete (5/10mg) – Uputa o lijeku Proizvođač: Jadran Galenski laboratorij Samo na recept? DA Primjena: antipsihotik Skoči na: » opis » primjena » doziranje » mjere opreza » napomene Opis Što sadržava Zalasta Svaka tableta sadržava 5 mg odnosno 10 mg olanzapina. Pomoćne tvari: - laktoza monohidrat, celuloza, preželatinirani škrob, kukuruzni škrob, silicijev-dioksid koloidni (bezvodni), magnezij-stearat. Pakiranje Kutija sa 28 tableta (4 OPA/Al/PVC blistera s po 7 tableta) Način i mjesto izdavanja Izdaje se na liječnički recept , samo u ljekarnama. Rok valjanosti Otisnut je na pakiranju. Lijek se ne smije upotrebljavati nakon isteka roka valjanosti. Način čuvanja Čuvati na temperaturi do 25º, izvan dohvata djeci. Primjena Što je Zalasta Zalasta spada u skupinu antipsihotika. Zašto se Zalasta koristi Zalasta je namjenjena za liječenje duševnih smetnji, za koje je karakteristično da čujete, vidite ili osjećate stvari, kojih u stvarnosti nema, da pogrešno razmišljate, da ste neobično sumnjičavi i da se povlačite u sebe. Kod tih duševnih smetnji možete biti bezvoljni (depresivni), osjećati strah ili napetost. Zalasta je namjenjena i liječenju srednje teške do teške manične epizode te prevenciji ponovne pojave epizoda bipolarnog afektivnog poremećaja u bolesnika koji su dobro reagirali na početno liječenje. Doziranje Kako uzimati Zalastu Točno se pridržavajte liječnikovih uputa. Doze ne smijete mijenjati niti prekidati liječenje bez prethodnoga savjetovanja s liječnikom. Vaš će vam liječnik reći koliko tableta na dan morate uzeti i koliko ih dugo trebate uzimati. Lijek uzimajte jednom dnevno, prema uputama liječnika. Preporučuje se da uzimate lijek svaki dan u približno isto vrijeme. Nije važno da li lijek uzimate s hranom ili bez nje. Tablete progutajte cijele, s malo vode. Odrasli Preporučena je početna doza olanzapina u liječenju shizofrenije 10 mg na dan. Preporučena je početna doza olanzapina kao osnovnog liječenja (monoterapije) manične epizode 15 mg jednom na dan ili 10 mg olanzapina na dan ako se koristi u kombinaciji s drugim lijekovima. Preporučena je početna doza kod prevencije ponovne pojave epizode bipolarnog afektivnog poremećaja 10 mg na dan. U bolesnika koji su dobro regairali na početno liječenje olanzapinom, liječenje treba nastaviti istom dozom. U slučaju pojave nove manične, depresivne ili miješane epizode treba nastaviti s primjenom olanzapine (uz eventualnu prilagodbu doze) te ovisno o kliničkoj slici, dodatno liječiti prateće simptome poremećaja raspoloženja. Tijekom liječenja shizofrenije i manične epizode te prevencije ponovne pojave epizode bipolarnog afektivnog poremećaja dnevna se doza može postupno prilagođavati, ovisno o individualnom kliničkom statusu, u rasponu od 5 do 20 mg na dan. Povećanje doze iznad uobičajene početne dnevne doze od 10 mg preporučuje se samo nakon odgovarajuće kliničke procjene i to u intervalima koji ne bi smjeli biti manji od 24 sata. Djeca i adolescenti Učinkovitost i sigurnost primjene olanzapina u djece i adolescenata do 18 godina nije utvrđena. Stariji bolesnici Preporučuje se u bolesnika starijih od 65 godina, kod kojih opće kliničko stanje zahtijeva prilagođavanje doze započeti liječenje nižom dozom lijeka (5 mg na dan). Bolesnici s poremećenom funkcijom jetre ili bubrega Preporučuje se započeti liječenje nižom dozom lijeka (5 mg na dan) te se, po potrebi, doza oprezno povećava. Usporena razgradnja lijeka Poznato je da osobe ženskog spola i starije osobe, odnosno nepušači usporeno razgrađuju lijek u tijelu, zbog čega se povećava mogućnost nakupljanja lijeka i njegovog štetnog djelovanja. U prisustvu više čimbenika koji mogu utjecati na usporenu razgradnju lijeka, opravdano je započeti liječenje nižom dozom lijeka (5 mg na dan) te se, po potrebi, doza oprezno povećava. Ne prekidajte uzimanje lijeka samo zato što se osjećate bolje. Jako je važno da uzimate Zalastu toliko dugo koliko vam je liječnik propisao. Ako ste uzeli više Zalaste nego što ste trebali Ukoliko ste uzeli veću dozu lijeka nego što biste smjeli, odmah se posavjetujte s liječnikom ili ljekarnikom. Ako ste uzeli više tableta nego što je propisano, odmah se javite vašem liječniku ili najbližoj bolnici. Ako propustite uzeti Zalastu Ne uzimajte dvostruku dozu ukoliko ste zaboravili uzeti prijašnju dozu. Ako ste zaboravili uzeti lijek, samo nastavite uzimati lijek prema uobičajenom rasporedu. Mjere opreza Upozorite liječnika imate li kakvu kroničnu bolest, metabolički poremećaj, ako ste preosjetljivi ili uzimate kakve druge lijekove. Lijekovi ove vrste mogu uzrokovati neobične pokrete, prije svega lica i jezika. Ukoliko se to pojavi za vrijeme primjene Zalaste, obavijestite svog liječnika. Vrlo rijetko ova vrsta lijekova uzrokuje povišenu temperaturu, brže disanje, znojenje, krutost mišića, pospanost. U takvim slučajevima prestanite uzimati Zalastu i odmah se javite liječniku. Primjena Zalaste u starijih bolesnika s demencijom se ne preporučuje radi mogućih ozbiljnih nuspojava. Ako patite od demencije, treba obavijestiti liječnika ako ste imali moždani udar ili »mali« moždani udar. Prije početka primjene Zalaste kažite svom liječniku ako imate bolest jetre ili bubrega, srčanu bolest, Parkinsonovu bolest, epilepsiju, tegobe s prostatom, ako imate zapletaj crijeva, bolesti krvi ili šećernu bolest. Iako nije utvrđena uzročna povezanost između pojave venske trombembolije i liječenja olanzapinom, preporučuje se u bolesnika sa shizofrenijom utvrditi prisutnost faktora rizika za nastanak trombembolije i poduzeti sve preventivne mjere. Ako ste stariji od 65 godina preporučuje se da liječnik kontrolira vaš krvni tlak. Tko ne bi trebao koristiti Zalastu Zalastu ne smijete uzimati ako ste preosjetljivi na olanzapin ili druge sastojke lijeka i ako imate glaukom uskog kuta. Trudnoća i dojenje Posavjetujte se s liječnikom ili ljekarnikom prije nego uzmete bilo koji lijek! Odmah obavijestite svoga liječnika ako ste trudni ili sumnjate na trudnoću. Ne smijete uzimati Zalastu za vrijeme trudnoće osim u slučaju kada ste se o tome posavjetovali s liječnikom. Ne uzimajte lijek za vrijeme dojenja. Utjecaj na sposobnost upravljanja vozilima i strojevima Zalasta može uzrokovati pospanost i tako utjecati na vaše psiho-fizičke sposobnosti. Ako se osjećate pospano, ne smijete upravljati motornim vozilima ili strojevima i morate o tome obavijestiti liječnika Nuspojave Kao svi lijekovi i Zalasta može imati nuspojave. Za vrijeme liječenja Zalastom mogu se pojaviti sljedeće nuspojave: - pospanost - povećanje tjelesne težine - vrtoglavica - porast apetita - zadržavanje vode u organizmu - povećana potreba za kretanjem - zatvor - suha usta - nemir - neobični pokreti - drhtanje ruku - krutost mišića - poteškoće pri govoru - promjena u koncentraciji nekih krvnih stanica i masnoća u krvotoku. Neki bolesnici mogu na početku primjene lijeka osjećati vrtoglavicu ili nesvjesticu, posebno kod ustajanja iz ležećeg ili sjedećeg položaja. U kliničkim ispitivanjima starijih bolesnika s demencijom, liječenje olanzapinom povezano je s povećanom učestalosti smrti i cerebrovaskularnih nuspojava u usporedbi s placebom. Vrlo česte nuspojave povezane s primjenom olanzapina u ovoj dobnoj skupini bile su abnormalan hod i padovi. Primjena Zalaste može pogoršati simptome Parkinsonove bolesti. Rijetko može Zalasta uzrokovati osip, ubrzani srčani ritam i reakciju preosjetljivosti na sunce. Vrlo rijetko uzrokuje bolest jetre, vensku trombemboliju, produljenu i/ili bolnu erekciju i tegobe pri mokrenju. Neki bolesnici imali su visoki šećer u krvi ili pogoršanje šećerne bolesti s ketoacidozom (ketoni u krvi i urinu) ili komom, koji su se javili vrlo rijetko. Vrlo rijetko su kod naglog prekida liječenjem olanzapinom opisani akutni simptomi kao što su: - znojenje - nesanica - tresavica - osjećaj tjeskobe - opća slabost s nagonom za povraćanje i povraćanje Liječnik će vam u tom slučaju predložiti postupno smanjenje doze prije prekida liječenja. Za vrijeme dugotrajne primjene ove vrste lijeka kod nekih je bolesnica došlo do istjecanja mlijeka iz prsiju, a također je došlo do neredovite ili izostanka menstruacije. Vrlo rijetko se mogu dojenčad, čije majke su uzimale olanzapin u zadnjem tromjesečju trudnoće tresti ili biti pospana. Rijetko se javljuju epileptički napadi. U većini slučajeva to se dogodilo u bolesnika koji su imali epileptičke napade u povijesti bolesti. Opazite li bilo koju nuspojavu, pa ako i nije spomenuta u ovoj uputi, obavijestite svoga liječnika ili ljekarnika. Koji lijekovi mogu dovesti do interakcija sa Zalastom Obavijestite svoga liječnika ili ljekarnika uzimate li ili ste prije kratkoga vremena uzimali bilo koji drugi lijek, pa i onda ako ste ga dobili bez recepta. Obavijestite svoga liječnika ako uzimate lijekove za liječenje Parkinsonove bolesti. Možete se osjećati pospano ako uzimate Zalastu u kombinaciji s antidepresivima ili s lijekovima koje koristite kada osjećate tjeskobu i strah odnosno lijekovima koji vam pomažu da lakše zaspete. Posebno je važno da obavijestite svoga liječnika ako uzimate fluvoksamin (antidepresiv), ketokonazol (antimikotik) ili ciprofloksacin (antibiotik), jer ti lijekovi mogu povećati koncentraciju olanzapina u krvi. Olanzapin nije pokazao interakcije pri istodobnoj primjeni s litijem ili biperidenom. Obavijestite svoga liječnika ako uzimate valproat (lijek koji se koristi u liječenju epilepsije). Istovremeno sa Zalastom možete koristiti samo lijekove koje vam je odobrio vaš liječnik. Uzimanje Zalaste zajedno s hranom i pićem Hrana ne utječe na prijelaz olanzapina iz probavnih organa u krvotok (apsorpcija). Potreban je oprez kod istovremene primjene Zalaste i alkohola jer može uzrokovati pospanost. Napomene Proizvođač “JADRAN”- Galenski laboratorij d.d., Pulac bb, Rijeka, Hrvatska u suradnji s KRKA d.d., Novo mesto, Slovenija Nositelj odobrenja za stavljanje lijeka u promet “JADRAN”-Galenski laboratorij d.d., Pulac bb, Rijeka, Hrvatska Amantilla Relax Značajno ublažava stres i tjeskobu. Tensilen Prirodno rješenje za stres, umor i iscrpljenost.