Index of drugs

Treatment of schizophrenia. olanzapine is indicated in long-term supportive care for patients who have a good response to treatment in the early phase of therapy. Treatment of moderate to severe manic episodes. In patients who respond well to olanzapine in the treatment of a manic episode, it is indicated to prevent the recurrence of bipolar disorder.

1 tabl powl. contains 5 mg or 10 mg olanzapine; the preparation contains lactose and soya lecithin.

Antipsychotic, anti-manic and stabilizing mood. Olanzapine has affinity for numerous receptors: serotonin (5HT_{2A / 2C}, 5HT₃, 5HT₆), Dopamine (D.₁, D₂, D₃, D₄, D₅), cholinergic muscarinic receptors (M.₁-M₅), α₁-renergic and histamine H-receptors₁. It has greater affinity for the 5-HT receptor₂ than to the D-receptor₂. Olanzapin selectively reduces the stimulatory activity of dopaminergic neurons of the mesolimbic system (A10), while having little effect on the striatum (A9) involved in motor function. It weakens the conditioned avoidance response, which is a test of antipsychotic activity at doses lower than those required to induce catalepsy, a phenomenon indicating the occurrence of side effects associated with motor activity. Unlike other antipsychotics, olanzapine increases the answer in the "anxiolytic" test. After oral administration, olanzapine is well absorbed from the gastrointestinal tract, reaching a maximum plasma concentration within 5-8 h (food does not affect the absorption of the drug). The degree of binding to plasma proteins is approximately 93%. Olanzapine in plasma binds mainly to albumin and α₁acidic glycoprotein. It is metabolized in the liver via conjugation and oxidation. The main circulating metabolite of olanzapine is 10-N-glucuronide, which does not cross the blood-brain barrier. Cytochromes CYP1A2 and CYP2D6 are involved in the formation of N-desmethyl and 2-hydroxymethyl metabolites, which show significantly less activity than olanzapine. Pharmacological activity depends mainly on the parent compound. Medium T_0,5 in the elimination phase, olanzapine was slightly longer in women than in men (respectively 36.7 h and 32.3 h). In elderly patients, average T_0,5 it was extended (51.8 hours). In smokers, average T_0,5 in the elimination phase it is reduced - 30.4 h.

Hypersensitivity to the active substance or to any of the excipients. Patients at risk of narrow-angle glaucoma.

Olanzapine is not approved for the treatment of patients with symptoms of psychosis and / or behavioral disorders due to dementia, due to increased mortality and the risk of cerebrovascular events, which is not recommended in these patients. Olanzapine is not recommended for the treatment of psychosis caused by the intake of dopamine agonists in patients with Parkinson's disease. Malignant neuroleptic syndrome (ZZN) is a potentially life threatening condition associated with the intake of antipsychotics. If the patient develops signs and symptoms indicative of RH or high fever with an unexplained cause, without other clinical symptoms of NMS, discontinue all antipsychotic medicinal products, including olanzapine. Due to the risk of hyperglycaemia and / or development or exacerbation of diabetes, appropriate monitoring of the clinical condition is recommended, in accordance with the applied antipsychotic guidelines (eg blood Glucose testing at the beginning of treatment, 12 weeks after the start of treatment, then every year). Patients should be monitored for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and asthenia), and patients with diabetes or risk factors for its development should regularly assess the level of diabetes mellitus alignment. The patient's weight should be checked systematically, e.g. at the beginning of treatment, 4, 8, 12 weeks.from the beginning of treatment, and then every quarter. In case of changes in lipid concentration, appropriate treatment should be used, especially in patients with dyslipidemia and in patients with risk factors for developing lipid disorders. In patients using olanzapine, lipid levels should be systematically checked in accordance with the current guidelines for antipsychotic treatment, e.g. at the beginning of treatment, 12 weeks after the start of treatment, and then every 5 years. Due to the anticholinergic activity of olanazapine and limited clinical experience in patients with co-morbidities, caution should be exercised when prescribing to patients with prostatic hyperplasia, paralytic ileus and similar diseases. Caution and control should be exercised in patients with elevated ALT and / or AST, and in patients with signs and symptoms of hepatic impairment, in patients with pre-existing limited functional reserve hepatic function, and in patients using medicines with potential hepatotoxic effects. In patients who have hepatitis (including hepatocellular and cholestatic liver damage, and a mixed form of liver injury), olanzapine should be discontinued. Caution should be exercised in patients with a small number of leukocytes and / or neutrophils for any reason, in patients taking neutropenic drugs, in patients with a history of drug-induced suppression and / or bone marrow toxicity, patients with myelosuppression caused by co-existing disease, radiation or chemotherapy and in patients with hypereosinophilia or myeloproliferative disease. Caution should be used when prescribing olanzapine and other QT prolonging agents, especially in elderly patients, patients with congenital long QT syndrome, congestive heart failure, cardiac hypertrophy, reduced potassium or Magnesium in the blood. During the treatment with olanzapine, transient occurrence of venous thromboembolism (VTE) has been very rarely reported. The causal relationship between this disease and the use of olanzapine has not been confirmed. However, since VTE risk factors are common in patients with schizophrenia, all possible VTE risk factors, such as immobilization of patients, should be diagnosed earlier and appropriate prophylactic measures should be taken. Caution should be used when taking the drug together with other centrally acting medicines and with alcohol. It is possible to antagonize olanzapine against direct and indirect dopamine agonists. Caution should be exercised when olanzapine is used in patients with a history of seizures or subjected to factors lowering the seizure threshold. If the patient receiving olanzapine develops signs and symptoms of tardive dyskinesia, a dose reduction or discontinuation should be considered. After discontinuation of the drug, these symptoms may temporarily worsen or only occur. Due to the risk of postural hypotension, it is recommended to periodically measure blood pressure in patients over 65 years of age. After the marketing of a product containing olanzapine, sudden cardiac deaths have been reported in patients using olanzapine. Olanzapine is not recommended for the treatment of children and adolescents under 18 years of age. In studies involving patients aged 13-17, there were various side effects, including weight gain, metabolic alteration and increased prolactin levels. The long-term effects of these side effects have not been studied and remain unknown. The product contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose. The preparation contains soybean lecithin - do not use in case of known hypersensitivity to peanut or soy.

During pregnancy, use only if the expected benefit to the mother outweighs the risk to the fetus.In newborns exposed to antipsychotics (including olanzapine) during the third trimester of pregnancy, there is a risk of side effects, including extrapyramidal symptoms and / or withdrawal symptoms of varying severity and duration. There have been reports of: agitation, increased tension, hypotonia, tremor, drowsiness, respiratory distress syndrome or feeding disorders. The condition of newborns should be carefully monitored. Olanzapine is excreted in breast milk - patients should be advised against breast-feeding while taking olanzapine.

Very common: weight gain, drowsiness, increased plasma prolactin levels. Common: eosinophilia, increased cholesterol, increased Glucose, increased triglycerides, glucosuria, increased appetite, dizziness, akathisia, parkinsonism, dyskinesia, orthostatic hypotension, mild, transient anticholinergic effects (including constipation and dry mouth), transient, asymptomatic elevation of hepatic transaminases (especially in the initial phase of treatment), rash, erectile dysfunction in men and decreased libido in both sexes, asthenia, fatigue, edema. Uncommon: leukopenia, neutropenia, bradycardia, QTc prolongation, photosensitivity, alopecia, urinary incontinence, amenorrhea, breast enlargement, off milking, gynecomastia - breast enlargement in men, increased creatinine phosphokinase, increased total bilirubin. Not known: thrombocytopenia, allergic reactions, development or exacerbation of diabetes (sometimes with ketoacidosis or coma, including several deaths), hypothermia, convulsions (mainly in patients with a history of seizures or risk factors for convulsions), neuroleptic malignant syndrome, dystonia (in including rotational eye movements), tardive dyskinesia, withdrawal symptoms (sweating, insomnia, tremor, anxiety, nausea, vomiting), ventricular tachycardia, ventricular fibrillation, sudden death, thromboembolic events (including pulmonary embolism and deep vein thrombosis) ), pancreatitis, hepatitis (including hepatocellular, cholestatic or mixed liver damage), rhabdomyolysis, frequent urination, neonatal withdrawal syndrome, priapism, increased alkaline phosphatase. The percentage of patients with clinically significant adverse events such as weight gain, glucose concentration, total LDL and HDL cholesterol or triglycerides increased over time. In adult patients who completed treatment for 9 to 12 months, the rate of increase in mean glucose was released after about 4-6 months. In elderly patients diagnosed with dementia, olanzapine treatment was associated with an increased incidence of death and adverse vascular events. -cranial ones compared to placebo. Very common side effects in this group of patients were abnormal gait and falls; pneumonia, elevated body temperature, lethargy, erythema, visual hallucinations and urinary incontinence were frequently observed. In Parkinson's patients with drug-induced psychosis (after using dopamine agonists), parkinsonian symptoms and hallucinations have been reported very commonly. In patients diagnosed with a manic episode in the course of bipolar disorder, the combined use of olanzapine and valproate induced neutropenia in 4.1% of subjects. When using olanzapine with lithium or valproate, more frequent (> 10%) occurrence of tremor, dryness of the oral mucosa, increased appetite and weight gain were observed; Speech disorder was also commonly reported. When olanzapine was administered in combination with lithium or valproate during the active treatment phase (up to 6 weeks), 17.4% of patients had a weight gain of ≥7% relative to their initial body weight. Long-term (up to 12 months) use of olanzapine to prevent relapse in patients with bipolar disorder has been associated with an increase in body weight of ≥7% in relation to the initial body weight in 39.9% of patients. Children and youth. Olanzapine is not indicated for the treatment of children and adolescents under 18 years of age. There are no clinical trials comparing the effect of the drug on adolescents and on adults; data from studies with adolescents with adult results were compared.Adverse reactions reported more frequently in adolescents (13-17 years) than in adult patients and adverse reactions reported only in short-term clinical trials in adolescents: very common: weight gain, increased triglycerides, increased appetite, sedation (in hypersomnia, lethargy, somnolence), elevation of transaminases (ALAT, AST), reduction of total bilirubin, increased GGT activity, increased plasma prolactin (47.4% adolescent); common: dry mouth, increased cholesterol.

Orally. Adults. Schizophrenia: the recommended starting dose of olanzapine is 10 mg / day. Manic episode: the starting dose is 15 mg / day given as a single dose in monotherapy or 10 mg / day in combination therapy. Prevention of relapse of bipolar disorder: the recommended starting dose is 10 mg / day. In patients receiving olanzapine to treat a manic episode, to prevent relapse, treatment with the same dose should be continued. If a new mania, mixed episode or depression episode occurs, olanzapine should be continued (optimizing the dose if necessary) and if there are clinical indications, an additional treatment for mood disorders should be used. During the treatment of schizophrenia, manic episodes and for the prevention of recurrence of bipolar disorder, the daily dose may be set depending on the clinical condition of the patient in the range of 5-20 mg / day. Increasing the dose above the recommended starting dose is only recommended after a re-evaluation of the clinical condition and should be made no more frequently than every 24 hours. In elderly patients a lower starting dose (5 mg / day) is not routinely recommended, but should be considered if this is supported by clinical factors. In patients with impaired renal and / or hepatic function, a lower starting dose (5 mg) should be considered. In cases of moderate hepatic failure (cirrhosis, Child-Pugh class A or B) the starting dose should be 5 mg and be increased cautiously. If there is more than one factor that could slow down the metabolism of olanzapine (female gender, old age, non-tobacco use), a reduction of the starting dose should be considered. In these patients, increasing the dose, if indicated, should be performed with caution.
The preparation can be taken regardless of meals.