Olanzapine table. 10 mg. 30 table
Olanzapine is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response.
Olanzapine table. 10 mg. 30 table
Adults: Olanzapine 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.
Olanzapine is indicated for the prevention of recurrence of manic episodes in patients with bipolar disorder, in which during a manic episode was a clinical response to olanzapine.
Dosage and method of administration
Schizophrenia: The recommended starting dose for 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.
Preventing recurrence in bipolar disorder: The recommended starting dose is 10 mg / day. In patients who have been receiving olanzapine for treatment of manic episode, to prevent its recurrence, is recommended to continue treatment with the same dose. When a new episode of mania, mixed episode or an episode of depression, olanzapine treatment should be continued (with dose optimization as needed), with supplementary therapy to treat symptoms of mood, if 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 5-20 mg / day. Increasing the dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should be generally at intervals of not less than 24 hours. Olanzapine can be given without regards for meals as absorption is not affected by food. Upon discontinuation of olanzapine should be considered tapering.
Children and adolescents
Olanzapine is not recommended for use in children and adolescents under 18 - years of age due to insufficient data on safety and effectiveness. In short-term studies of adolescent patients reported a significant increase in body weight, changes in lipid levels and prolactin compared to studies in adult patients.
Usually not recommended lower starting dose (5 mg / day), but this dose may be considered in patients 65 years and over when clinical factors warrant.
Patients with renal and / or hepatic impairment
These patients should be considered a lower starting dose (5 mg). In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh Class A or B), the starting dose should be 5 mg and only increased with caution.
Gender: The starting dose and dose range need not be routinely altered for female patients relative to male patients.
Smokers: The starting dose and dose range need not be routinely altered for non-smokers relative to smokers.
When there is more than one, slowing metabolism factors (female gender, geriatric age, non-smoker) should be given to decreasing the starting dose. Dose escalation, when indicated, should be conservative in such patients.
Hypersensitivity to the active substance or to any of the excipients.
Patients known to be at risk of narrow-angle glaucoma.
Special precautions for use
During antipsychotic treatment, improvement in the patient's clinical condition may take several days to several weeks.
Patients should be closely monitored during this period.
Psychosis associated with dementia and / or behavioral disturbances
Olanzapine is not indicated for the treatment of psychosis associated with dementia and / or behavioral 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.
The use of olanzapine in the treatment of psychosis in patients with Parkinson's disease associated with dopamine agonist intake is not recommended. In clinical trials often and more frequently than with placebo were reported worsening of Parkinsonian symptomatology and hallucinations, and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In these studies, patients are required to be initially stabilized with the lowest effective dose of anti-product (dopamine agonist) and to remain on the same anti-Parkinsonian medicinal products and dosages throughout the study. Olanzapine was started at a dose of 2,5 mg / day and titrated up to 15 mg / day at the discretion of the physician.
Neuroleptic Malignant Syndrome (NMS)
NMS is a potentially life-threatening condition associated with antipsychotic medicinal product. Rarely reported cases of NMS associated 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 creatinine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.
Hyperglycemia and Diabetes
Hyperglycaemia and / or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma, including some fatal cases. In some cases reported prior increase in body weight, which may be a predisposing factor. Adequate clinical monitoring is used as guidance for the use of antipsychotics. Patients treated with any antipsychotic agents, including olanzapine, 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.
Changes in lipid
Undesirable alterations in lipids in patients treated with olanzapine in placebo-controlled clinical trials. Lipid alterations should be managed as clinically appropriate, particularly in patients with dyslipidemia in patients with risk factors for the development of lipids disorders. Patients treated with any antipsychotic agents, including olanzapine, should be monitored regularly lipid levels, used as guidelines for the use of antipsychotics.
Although in vitro studies, olanzapine demonstrated anticholinergic activity, experience during the clinical trials revealed a low incidence of related events. Since clinical experience with olanzapine in patients with concomitant illness is limited, it is recommended that it be administered with caution in patients with prostatic hypertrophy, or paralytic ileus and related conditions.
Often transient, asymptomatic elevations of hepatic transaminases, alanine transferase (ALT) and aspartate transferase (AST), especially in early treatment. Caution should be exercised in patients with elevated ALT and / or AST, in patients with signs and symptoms of hepatic impairment, and those with previous conditions associated with limited hepatic functional reserve, or who are being treated with potentially hepatotoxic drugs products. In the event of elevated ALT and / or AST during treatment, follow-up and possibly consideration of dose reduction. Where was diagnosed hepatitis (including hepatocellular, cholestatic or mixed liver injury), olanzapine treatment should be discontinued.
As with other antipsychotics, caution should be exercised in patients who for some reason have low leukocyte and / or neutrophil counts in patients who are known that they receive products that lead to neutropenia, in patients with a history of drug-induced bone marrow / bone marrow 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 is often reported with concomitant administration of olanzapine and valproate.
Discontinuation of treatment
Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported very rarely (<0.01) when olanzapine is stopped abruptly.
In clinical trials, there were infrequent (0.1% to 1%) clinically significant prolongation of the QT-interval (QT corrected Fridericia [QTcF]> 500 milliseconds [msec] at any time post baseline ECG in patients with baseline QTcF <500 msec) in patients treated with olanzapine, with no significant differences in associated cardiac events compared to placebo. However, as with other antipsychotic drugs, olanzapine should be prescribed with caution in conjunction with medicinal products known to prolong the QTc-interval, especially in the elderly, in patients with the syndrome of congenital long QT congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia.
Very rare (<0.01%) reported Temporal association of olanzapine treatment and venous thromboembolism. There is no causal relationship between the occurrence of venous thromboembolism and treatment with olanzapine. However, since patients with schizophrenia often present with acquired risk factors for venous thromboembolism all possible risk factors of VTE eg. Immobilisation of patients, and to take preventive measures.
Given the main effects of olanzapine CNS Caution is advised when combining with other centrally acting drugs and alcohol. As exhibits in vitro antagonism of dopamine, you may antagonize the effects of direct and indirect dopamine agonists.
Seizures / Convulsions
Olanzapine should be used cautiously in patients with a history of seizures or are subject to factors that can reduce the seizure threshold. Rarely reported cases of seizures in such patients treated with olanzapine. Most of these cases have a history of seizures or risk factors for seizures.
In comparative studies with treatment duration up to one year, olanzapine was associated with a statistically significant lower incidence of treatment emergent dyskinesia unexpected. The risk of tardive dyskinesia increases with duration of exposure, so that in case of signs or symptoms of tardive dyskinesia appear in a patient on olanzapine should consider dose reduction or discontinuation. These symptoms can temporally deteriorate or even arise after discontinuation of treatment.
In clinical trials of olanzapine in elderly patients infrequently observed orthostatic hypotension. As with other antipsychotics, it is recommended that periodic monitoring of blood pressure in patients aged over 65 years.
Use in children and adolescents under the age of 18
Olanzapine is not indicated for the treatment of children and adolescents. Studies in patients aged between 13 and 17 years showed various adverse reactions, including weight gain, changes in metabolic parameters and increases in prolactin levels. Not studied the long-term consequences of these adverse events remain unknown.
Interaction studies have only been performed in adults.
Potential interactions affecting olanzapine
Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine.
Induction of CYP1A:
The 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. The clinical significance is likely to be limited, but clinical monitoring is recommended, and considering an increase of olanzapine dose if needed.
Inhibition of CYP-1A2:
Fluvoxamine, 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 nonsmokers and 77% in male smokers. The mean increase in AUC of olanzapine, respectively, 52% and 108%. In patients who are using fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin, should be given a lower initial dose. Reducing the dose of olanzapine should be considered if treatment with an inhibitor of CYP1A2.
Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60% and should be taken at least 2 hours before or after olanzapine. There is no evidence that fluoxetine (an inhibitor of CYP2D6), single doses of antacid (aluminum, magnesium) or cimetidine significantly affect the pharmacokinetics of olanzapine.
Potential for olanzapine to affect other medicinal products:
Olanzapine may antagonize the effects of direct and indirect dopamine agonists.
Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (eg, 1A2, 2D6, 2C9, 2C19, 3A4). The lack of interaction is confirmed in in vivo studies where no inhibition of metabolism of the following active ingredients: tricyclic antidepressant (representing mostly group CYR2D6), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 2C19).
No interaction of olanzapine with lithium or biperiden when co-administered. Therapeutic monitoring of valproate plasma levels did not indicate a need for dose adjustment of valproate after the introduction of concomitant olanzapine.
Should be exercised caution in patients who consume alcohol or receive medicinal products inhibiting effect on the central nervous system. Concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with Parkinson's disease and dementia.
Olanzapine should not be used concomitantly with medicinal products known to increase QTc-interval.
Use during pregnancy and lactation
There are no adequate and well-controlled studies in pregnant women. Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during treatment with olanzapine. Nevertheless, because human experience is limited, olanzapine should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
Very rarely reported spontaneous tremors, hypertonia, lethargy and sleepiness, in infants born to mothers who had used olanzapine during the third trimester of pregnancy. In a study in healthy, lactating women, olanzapine was excreted in breast milk. Mean infant exposure (mg / kg) at steady state was estimated to be 1.8% of the dose adopted by mother (mg / kg). Patients should be advised not to breast-feed if they are taking olanzapine.
Effects on ability to drive and use machines
No studies on the effects on ability to drive and use machines. Because olanzapine may cause more somnolence and dizziness, patients should be cautioned about operating machinery, including motor vehicles.
The 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 levels, cholesterol, glucose and triglyceride levels, glucosuria, increased appetite , dizziness, akathisia, parkinsonism, dyskinesia, orthostatic hypotension, anticholinergic effects, transient asymptomatic elevations of hepatic transaminases, rash, asthenia, fatigue and edema.
The following table lists the adverse reactions and laboratory research data from spontaneous reporting and in clinical trials. In each grouping frequency adverse reactions are presented in order of decreasing seriousness.
Blood and lymphatic system: eosinophilia, leukopenia, neutropenia, thrombocytopenia
Immune system disorders: allergic reaction
Metabolism and nutrition disorders: weight gain, elevated cholesterol levels, elevated glucose levels, elevated triglyceride levels, glucosuria, increased appetite, development or exacerbation of diabetes occasionally associated with ketoacidosis or coma, including some fatal cases.
Nervous System: somnolence, dizziness, akathisia, parkinsonism, dyskinesia, seizure, when in most cases have a history of seizures or risk factors for seizures, neuroleptic malignant syndrome
Dystonia (including oculogyration)
Cardiac disorders: bradycardia, prolongation of QTc, Not known, ventricular tachycardia / fibrillation, sudden death
Vascular disorders Orthostatic hypotension Thromboembolism (including pulmonary embolism and deep vein thrombosis)
Gastrointestinal disorders: Mild, transient anticholinergic effects including constipation and dry mouth
Pancreatitis Hepatobiliary disorders Transient, asymptomatic elevations of hepatic transaminases (ALT, AST), especially early in treatment, hepatitis (including active forms)
Urinary system disorders: Difficulty urinating, swelling
Skin and subcutaneous tissue disorders: Rash, photosensitivity reaction
Musculo-skeletal and connective tissue disorders: Alopecia, Rhabdomyolysis
Reproductive system and breast disorders
General disorders and administration site conditions: Asthenia
Research: High creatine phosphokinase increased total bilirubin, alkaline phosphatase increased Elevated plasma prolactin levels
Clinically significant weight gain was observed across all baseline categories of Body Mass Index (BMI).
Weight gain> 7% of baseline body weight was very common, and> 15% of baseline body weight was common. Gain> 25% of their baseline body weight was very common in patients with prolonged exposure.
In clinical trials, the incidence of Parkinsonism and dystonia in patients treated with olanzapine was 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 now be concluded that olanzapine causes in less tardive dyskinesia and / or other extrapyramidal symptoms sindromi.Ostri as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly.
Gynaecomastia, galactorrhoea, and breast augmentation are rare. In most patients, prolactin levels return to normal without discontinuation.
Long-term exposure (at least 48 weeks)
In patients who had adverse, clinically significant changes in weight gain, over time increased glucose, total / LDL / HDL cholesterol or triglycerides. In adult patients that completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 4-6 months.
Children and adolescents
Olanzapine is not indicated for use in children and adolescents under 18 years. Although no clinical studies designed to compare adolescents to adults, data from the adolescent trials were compared to those of the adult trials.
Slednaite data cover adverse reactions reported with a greater frequency in adolescent patients (aged 13 and 17 years) than in adult patients or adverse reactions only identified during short-term studies of adolescent patients. Clinically significant weight gain (> 7%) appears to occur more frequently in the adolescent population compared to adults with comparable exposures. The degree of weight gain and the proportion of adolescent patients who had clinically significant weight gain were greater with long exposure (at least 24 weeks) than with short-term exposure.
Adverse reactions in children and adolescents
Metabolism and nutrition
Very common: Weight gain, increased triglycerides, increased appetite.
Common: Elevated levels of cholesterol
Very common: Sedation (including: hypersomnia, lethargy, somnolence).
Common: Dry mouth
Very common: Elevations of hepatic transaminases - ALT / AST.
Decreased total bilirubin, elevated GGT, elevated plasma prolactin levels.
Weight gain> 7% of baseline body weight (kg) was very common and> 15% of baseline body weight was common. With long-term exposure (at least 24 weeks), approximately half of patients gained> 15%, and nearly a third gained> 25% of their baseline body weight. Among adolescent patients mean weight gain was greatest in patients who at baseline were overweight or obese.
Elevated plasma prolactin levels were reported in 47.4% of adolescent patients.
Signs and Symptoms: Very common symptoms in overdose (> 10% incidence) include tachycardia, agitation / aggressiveness, dysarthria, various extrapyramidal symptoms, and impairment 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 450 mg, but experience has also been reported following acute overdose of approximately 2 g of oral olanzapine.
Treatment of overdose: In no specific antidote for olanzapine. It is not recommended to induce vomiting. Can be displayed in standard care of overdose (ie 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 percent.