Expiration date: 08/2025
Structure and Composition:
Tablets. 1 tablet contains Olanzapine 5 or 10 mg
Excipients: Cellactose (a spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose powder), starch pregelatinized corn starch colloidal anhydrous silica magnesium stearate
in blister 7 pcs. In the paper cartons 4 blisters.
Description pharmaceutical form:
Tablets 5 mg: round, slightly biconvex, light yellow color with the inscription "5". Valid blotches of darker hue.
Tablets 10 mg: Round slightly biconvex, light yellow color with the inscription "10". Valid blotches of darker hue.
Pharmacokinetics:
High absorption of olanzapine, is unaffected by food Tmax after oral administration - 5-8 hours Protein binding -. 93% in the concentration range of 7 to 1000 ng / ml. Olanzapine is bound mainly to albumin and glycoprotein & alpha1-. It penetrates through the blood-tissue barriers, including BBB. It is metabolized in the liver, the active metabolite is not formed, the main circulating metabolite - glucuronide - does not penetrate the blood-brain barrier. Smoking, age and gender affect the T1 / 2 and the plasma clearance. Persons older than 65 years of T1 / 2 of 51.8 hr and plasma clearance - 17.5 l / h in patients younger than 65 years old - 33.8 hours and plasma clearance - 18.2 l / h. The plasma clearance is lower in patients with hepatic insufficiency, women and non-smoking patients compared with the respective groups of individuals. However, the degree of influence of age, gender, or smoking on clearance and T1 / 2 of olanzapine is negligible compared with the individual pharmacokinetic variability between individuals. Excreted mainly by the kidneys (60%) in the form of metabolites.
Description of the pharmacological actions:
Olanzapine - antipsychotic (neuroleptic) with a wide spectrum of pharmacological action. Antipsychotic effect due to blockade of dopamine D2-receptor and the mesolimbic system Mesocortical sedative action - blockade of adrenergic receptors of the reticular formation of the brain antiemetic action - blockade of dopamine D2-receptor trigger zone of the vomiting center hypothermic action - blockade of dopamine receptors of the hypothalamus. In addition, the impact on muscarinic, adrenergic, histamine H1, and some subclasses of serotonin receptors.
Olanzapine significantly reduces the productive (delusions, hallucinations) and negative (hostility, suspiciousness, emotional and social withdrawal) symptoms of psychosis. Rarely causing extrapyramidal disorders.
Indications:
schizophrenia (treatment)
Zalasta effectively supports the improvement of clinical symptoms during long-term treatment of patients with initial positive response to the drug.
moderate or severe episodes of mania (treatment)
prevention of relapse of mania in bipolar disorder patients with manic episodes with good effect of olanzapine therapy.
Contraindications:
- Hypersensitivity to olanzapine or other ingredients
- angle-closure glaucoma
- rare hereditary problems of galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose
- lactation
- Children up to age 18 years (effectiveness and safety have been established).
Precautions: renal failure, liver failure, prostatic hyperplasia, paralytic ileus, epilepsy, convulsions in history, leukopenia and / or neutropenia of various origins, myelosuppression of various origins, including myeloproliferative disorders, hypereosinophilic syndrome, cardiovascular and cerebrovascular disease, or other conditions predisposing to hypotension, inherent increase in the QT interval on an electrocardiogram (increasing corrected interval QT (the QTc) on the ECG), or under the conditions with the potential to cause an increase in the QT interval (eg co-administration of drugs prolonging the QT interval, congestive heart failure, hypokalemia, hypomagnesemia), advanced age, and concomitant use of other drugs of the central action of the immobilization, pregnancy.
Application of pregnancy and breastfeeding:
Due to the limited experience of the drug in pregnant women, olanzapine should be used only if the expected benefit to the mother justifies the potential risk to the fetus. Women should be informed of the need to inform your doctor about the ensuing or planned pregnancy with olanzapine treatment. There are few reports of tremor, hypertension, lethargy and sleepiness in children born to mothers treated with olanzapine in the III trimester of pregnancy.
The study revealed that olanzapine is released in breast milk. Average dose (mg / kg) received by the child when the equilibrium concentration of the mother, was 1.8% of the dose of olanzapine mother (mg / kg). We do not recommend breastfeeding on the background of treatment with olanzapine.
Side effect:
Classification of the incidence of side effects (WHO): very often - & ge1 / 10 often - from & ge1 / 100 to <1/10 uncommon - from & ge1 / 1,000 to <1/100 rarely - from & ge1 / 10,000 to <1/1000 rarely - <1/10000, including isolated reports.
From the central and peripheral nervous system: very often - drowsiness often - dizziness, akathisia, parkinsonism, dyskinesia rare - convulsions (often on a background of seizures in history), very rarely - neuroleptic malignant syndrome (see "Special Instructions" section.) dystonia (including oculogyric crisis), and tardive dyskinesia. With a sharp lifting of olanzapine it is rarely observed symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting.
From the CCC: often - hypotension (including orthostatic) infrequently - bradycardia with or without collapse is very rare - increase in the QTc interval on the ECG (see "Special Instructions" section.), Ventricular tachycardia / fibrillation and sudden death (see . "Special instructions" section), thromboembolism (including pulmonary embolism and deep vein thrombosis).
On the part of the digestive tract: often - transient anticholinergic effects including constipation, dry mouth, rarely - pancreatitis.
Disorders of metabolism and nutrition: very often - often weight gain - increased appetite rarely - hyperglycemia and / or decompensation of diabetes, sometimes manifesting ketoacidosis or coma, including fatal hypertriglyceridemia, hypercholesterolemia, hypothermia.
Hepatobiliary disorders: often - transient, asymptomatic increase in liver transaminases (ALT, the ACT), especially in early treatment (see "Special Instructions".) Rarely - hepatitis (including hepatocellular, cholestatic or mixed liver injury).
From the side of blood and lymphatic system: often - eosinophilia, rarely - leukopenia, rarely - thrombocytopenia, neutropenia.
From the side of the musculoskeletal system: very rarely - rhabdomyolysis.
From the urogenital system: very rarely - urinary retention, priapism.
Skin and subcutaneous tissue: rare - photosensitivity reactions.
Allergic reactions: seldom - skin rash, very rarely - anaphylactoid reactions, angioedema, urticaria and pruritus.
Other: often - fatigue, peripheral edema are very rare - alopecia.
Laboratory parameters: very often - hyperprolactinemia, but clinical manifestations (eg, gynecomastia, galactorrhea, and breast enlargement) - rare. The majority of patients to normalize prolactin levels spontaneously without discontinuation rarely - increase in creatine phosphokinase (CPK) is very rare - increase in alkaline phosphatase and bilirubin.
In elderly patients with dementia is registered in the studies a higher rate of death and cerebrovascular disorders (stroke, transient ischemic attack). Very often in these patients were abnormal gait and falls. It is also often observed Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence.
Among patients with drugs (in patients receiving dopamine agonist) psychosis against the backdrop of Parkinson's disease is often detected worsening parkinsonian symptoms and hallucinations development.
There are data on the development of neutropenia (4.1%) in the combined therapy with valproic acid in patients with bipolar mania. Concurrent therapy with lithium or valproic acid increases the frequency (> 10%) of tremor, dry mouth, increased appetite and weight gain. Also, speech disorders frequently recorded (1 to 10%). During the first 6 weeks of combination therapy with lithium increases the incidence of weight gain. Prolonged therapy olanzapine (up to 12 months) in order to prevent relapses in patients with bipolar disorder accompanied by weight gain.
Drug Interactions:
Potential drug interactions affecting olanzapine metabolism: olanzapine is metabolised by the enzyme CYP1A2, therefore, inhibitors or inducers of cytochrome P450 isoenzymes, exhibiting specific activity towards CYP1A2 may affect the pharmacokinetic parameters of olanzapine.
Inducers of CYP1A2: olanzapine clearance may be elevated in patients who smoke or simultaneous administration of carbamazepine that reduces olanzapine concentration in blood plasma. Recommended clinical observation, because Some cases require increasing doses of the drug.
Inhibitors of CYP1A2: Fluvoxamine - specific inhibitor of CYP1A2 - significantly reduces the clearance of olanzapine. The mean increase in olanzapine Cmax following fluvoxamine in nonsmoking women was 54%, and male smokers - 77%. The mean increase in olanzapine AUC in these categories of patients was 5 and 108%. Patients receiving fluvoxamine or any other inhibitor of CYP1A2 (eg ciprofloxacin), olanzapine therapy is recommended to start with smaller doses. Reduction of olanzapine dose may be required in the case of accession to the therapy CYP1A2 inhibitors.
Drug interactions that influence / do not affect the bioavailability of olanzapine. Activated charcoal reduces the absorption of olanzapine after oral administration of 50-60%, it should be taken at least 2 hours before or after administration of olanzapine.
Fluoxetine (an inhibitor of CYP450), a single dose of magnesium-aluminum containing antacids or cimetidine or no effect on the pharmacokinetics of olanzapine.
The potential ability of olanzapine to affect other medicinal products. Olanzapine may weaken the effect of direct and indirect dopamine agonists.
In in vitro conditions Olanzapine does not inhibit the CYP450 isoenzymes basic (eg 1A2, 2D6, 2C9, 2C19, ZA4). In vivo inhibition was detected following metabolic active substances: the tricyclic antidepressants (CYP2D6), warfarin (CYP2C9), theophylline (CYP1A2) and diazepam (CYP3A4 and 2C19).
There was no interaction during concomitant use with lithium or biperidenom. Therapeutic monitoring of the content of valproic acid in the plasma showed that it is not required (see. "Side effects" section), while the appointment with olanzapine dose valproic acid changes.
Caution must be exercised with concomitant use of other drugs of the central action. Despite the fact that a single dose of alcohol (45 mg / 70 kg) has no effect on pharmacokinetic, alcohol together with olanzapine may be accompanied by increased depressive effect on the central nervous system.
Dosage and administration:
Inside, 1 time a day, regardless of meals. In the case of withdrawal of the drug is recommended a gradual reduction in dose.
Schizophrenia: The recommended initial dose - 10 mg / day.
The episode of mania: the initial dose is 15 mg in one step - in monotherapy or 10 mg / day - as part of combination therapy.
Preventing recurrence in bipolar disorder: The recommended starting dose of the drug in clinical remission - 10 mg / day. For patients already receiving Zalasta® drug for the treatment of mania episodes, supportive therapy is conducted in the same doses. In the case of a new manic, mixed, or depressive episode during therapy with the drug Zalasta if necessary, increase the dose with additional treatment of mood disorders, according to the clinical indications.
The daily dose in the treatment of schizophrenia, manic episode or relapse prevention of bipolar disorder may be 5-20 mg / day, depending on the clinical condition of the patient. Increasing the dose over the recommended starting is possible only after appropriate clinical re-evaluation of the patient and is usually carried out at intervals of not less than 24 hours.
Special patient groups
Older patients are not usually recommended starting dose reduction (up to 5 mg / day), but it is possible in patients older than 65 years old with risk factors (see. "Special Instructions" section).
Patients with liver disease and / or kidney recommended initial dose reduction to 5 mg / day. In moderate hepatic insufficiency (cirrhosis, class A or B classification Child-Pugh hepatocellular insufficiency in patients with cirrhosis of the liver), the initial dose is 5 mg / day, may further increase the dose with caution.
Women do not need to change in dosing as compared to men.
In non-smokers dose adjustment for patients compared with smoking patients (see. Section "Interactions") is not required.
If a patient has more than one factor that can affect the absorption of the drug (female gender, older age, non-smoker), you may need to reduce the initial dose. If necessary, a further dose increase may with caution.
Overdose:
Symptoms: very common (> 10%) - tachycardia, agitation / aggression, dysarthria, various extrapyramidal symptoms, decreased level of consciousness by lethargy to coma less than 2% of cases - delirium, convulsions, coma, neuroleptic malignant syndrome (NMS), depression breathing, aspiration, increased or decreased blood pressure, cardiac arrhythmia in very rare cases - cardio-pulmonary insufficiency. The minimum dose of olanzapine in acute overdose fatalities - 450 mg, registered a maximum dose of an overdose of a favorable outcome (survival) - 1500 mg.
Treatment: gastric lavage, activated carbon (reduces the bioavailability of olanzapine by 60%), symptomatic treatment under the control of vital functions, including the treatment of arterial and vascular collapse gapotenzii, maintaining respiratory function. There is no specific antidote. It is not recommended to induce vomiting, to apply epinephrine, dopamine, or other beta-sympathomimetics Adrenomimeticalkie activity as the latter may worsen hypotension. To detect possible arrhythmias requires monitoring of cardiovascular activity. The patient should be under continuous medical supervision until complete recovery.
Special instructions:
There are very rare reports of the development of hyperglycemia and / or decompensation of diabetes, sometimes accompanied by the development of ketoacidosis or coma ketoatsidoticheskaya, including there are reports of a number of fatal cases. In some cases, it noted decompensation prior increase in body weight, which may be a predisposing factor. In patients with diabetes and risk factors for this disease is recommended clinical monitoring and regular blood glucose control.
When you change the level of lipids required correction of therapy.
In a dramatic olanzapine very rarely (less than 0.01%) may develop the following symptoms: sweating, insomnia, tremor, anxiety, nausea, or vomiting. When the drug is recommended cancellation of a gradual reduction in dose.
Anticholinergic activity. Since clinical experience with olanzapine in people with underlying medical conditions is limited, the drug should be used with caution in patients with benign prostatic hyperplasia, paralytic ileus.
Experience with olanzapine in patients with psychosis in Parkinson's disease induced by administration Dofaminomimetiki. Olanzapine is not recommended for the treatment of psychosis in Parkinson's disease induced by administration Dofaminomimetiki. Increases the symptoms of Parkinson's disease and hallucinations. At the same time the effectiveness of olanzapine for the treatment of psychoses is not superior to placebo.
Olanzapine is not indicated for the treatment of psychosis and / or behavioral disturbances in dementia due to increased mortality and an increased risk of cerebrovascular disorders (stroke, transient ischemic attack). Increased mortality not dose of olanzapine or duration of therapy. Risk factors predisposing to increased mortality include age older than 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary diseases (such as pneumonia, including aspiration), concomitant use of benzodiazepines. However, the increased incidence of death in the groups of olanzapine compared with placebo did not depend on these risk factors.
If antipsychotic treatment improved the patient's clinical condition occurs in a period of several days to several weeks. During this period, the patient needs to be monitored closely.
Violations of the liver. At the beginning of therapy, possibly asymptomatic increase of liver transaminases (ALT and ACT). In patients with initially elevated levels of ACT and / or ALT, liver failure and states, potentially limiting the possibility of liver function, as well as those taking hepatotoxic drugs, caution should be exercised in the appointment of olanzapine. With an increase in ALT and / or ACT with treatment recommended drug medical patient monitoring and possibly reducing the dose of the drug. When diagnosing hepatitis (including hepatocellular, cholestatic or mixed) olazapin to cancel.
Hematologic changes. The drug should be used with caution in patients with leucopenia and / or neutropenia any genesis, myelosuppression medicinal origin, as well as on the background radiation or chemotherapy, due to concomitant diseases, in patients with hypereosinophilic conditions or myeloproliferative diseases. Neutropenia is often observed, while the use of olanzapine and valproate (see. "Side effects" section).
Neuroleptic malignant syndrome. Potentially life-threatening condition associated with antipsychotic therapy drugs (neuroleptics), including: olanzapine. It is characterized by the following clinical signs: fever, muscle rigidity, altered mental status, autonomic disorders (unstable heartbeat or labile blood pressure, tachycardia, sweating, arrhythmia). Additional symptoms of NMS: increased CPK, myoglobinuria (rhabdomyolysis in the background), and acute renal failure. With the development of NMS symptoms, as well as an increase in body temperature for no apparent reason, it is necessary to cancel all antipsychotics, including olanzapine.
Spastic syndrome. Olanzapine should be carefully administered to patients with a history of seizures, or in the presence of factors that reduce the seizure threshold. While taking olanzapine seizures rarely recorded.
Tardive Dyskinesia. Olanzapine was accompanied by a significantly lower incidence of tardive dyskinesia compared to haloperidol. The risk of developing tardive dyskinesia increases with the duration of treatment. If signs of this condition in patients taking olanzapine, should stop the drug or reduce the dose. The symptoms of psoriasis may temporarily increase after discontinuation of the drug.
Total activity against CNS. Caution must be exercised with concomitant use of other drugs of the central action and alcohol.
Cerebrovascular adverse events, including stroke, in elderly patients with dementia. Older people rarely observed postural hypotension. In patients older than 65 years is recommended to periodically monitor blood pressure. Olanzapine should be used with caution in patients with established increase QTc interval, especially the elderly, with a congenital syndrome of elongated interval QT, congestive heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia.
When olanzapine very rarely (less than 0.01%) reported cases of venous thromboembolism. The causal relationship between olanzapine treatment and venous thrombosis has not been established. Because patients with schizophrenia often present acquired risk factors for venous thrombosis, should identify all possible other factors (eg immobilization) and take preventive measures. Zalasta tablets contain lactose. The drug should not be taken in patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.
Effects on ability to drive a car or other mechanical means. During the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require high concentration and psychomotor speed reactions.
