Index of drugs

Treatment of schizophrenia. olanzapine is effective in long-term supportive care for patients who have responded well to treatment early in treatment. Treatment of moderate to severe manic episodes. In patients with a good response to olanzapine therapy in the treatment of a manic episode, olanzapine is indicated for the prevention of relapse of bipolar disorder.

1 tabl contains 5 mg or 10 mg of olanzapine.

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 (m₁-m₅), α₁-renergic and histamine H-receptors₁. It has greater affinity for the 5-HT receptor₂ than to the D-receptor₂. The detailed mechanism of action is unknown, probably related to the 5-HT dopamine and serotonin receptor antagonists₂. 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. After oral administration, olanzapine is well absorbed from the gastrointestinal tract, reaching a maximum concentration in the blood within 5-8 h (food does not affect the absorption of the drug). 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 P-450 CYP1A2 and 2D6 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 - olanzapine. Olanzapine is approximately 93% bound to plasma proteins. The half-life and clearance of olanzapine may vary depending on age and sex, and smoking. The drug is excreted in about 57% in the urine, mainly in the form of metabolites.

Hypersensitivity to olanzapine or other components of the preparation. 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. 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. Patients receiving any antipsychotic medication, including those containing olanzapine, should be monitored for signs and symptoms of hyperglycaemia, and patients with diabetes or risk factors predisposing to diabetes should be regularly screened to detect deterioration of glycemic control; weight gain may be a predisposing factor - body weight should be monitored regularly. In case of changes in lipid concentration, appropriate treatment should be applied, in particular in patients with impaired lipid metabolism and in patients who are at risk of developing such disorders. For patients receiving any antipsychotic medication, including those containing olanzapine, lipid levels should be monitored regularly in accordance with accepted guidelines for antipsychotic treatment. Clinical experience associated with the use of olanzapine in patients with co-morbid conditions is limited - caution should be exercised when prescribing to patients with prostatic hyperplasia, intestinal paralysis and similar diseases.Caution should be exercised in patients with elevated ALT and / or AST, in patients with signs and symptoms of hepatic impairment, in patients with pre-existing limited hepatic reserve function, and in patients using drugs with potential hepatotoxic effects. When increased ALT and / or AST levels develop during treatment, a check-up should be performed and a dose reduction should be considered. 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 drugs that prolong the QTc interval, especially in elderly patients, patients with congenital long QT syndrome, congestive heart failure, hypertrophy of the heart, reduced potassium or Magnesium in the blood. During treatment with olanzapine, there is a risk of a transient thrombus with blockages in the venous system. In patients with schizophrenia, there are often risk factors for a blood clot in the venous system, all possible risk factors for blood clots with embolisms, eg immobilization, should be diagnosed earlier and appropriate preventive 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 indicated for the treatment of children and adolescents. 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.

During pregnancy, use only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. In newborns whose mothers took olanzapine in the third trimester of pregnancy, there was observed: tremor, increased tension, significant slowdown and drowsiness. Olanzapine is excreted in breast milk - patients should be advised against breast-feeding while taking olanzapine.

Very common: weight gain, drowsiness, increased plasma prolactin (accompanying clinical symptoms associated with breast and menstruation, e.g. amenorrhea, breast enlargement, milking outside the feeding period, gynecomastia - breast enlargement in men was uncommon; with sexual functions eg erectile dysfunction in men and decreased libido in both sexes were common). Common: eosinophilia, increased cholesterol, increased Glucose, increased triglycerides, glycosuria, increased appetite, dizziness, akathisia, parkinsonism, dyskinesias, 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, asthenia, fatigue, edema.Uncommon: leukopenia, neutropenia, bradycardia, QTc prolongation, photosensitivity, alopecia, incontinence, high creatinine phosphokinase, increased total bilirubin. Not known: thrombocytopenia, allergic reaction, development or worsening of diabetes (occasionally associated with ketoacidosis or coma, including fatal cases), hypothermia, seizures (in most cases, patients with seizures or risk factors for their occurrence), malignant syndrome neuroleptic, dystonia (including ocular rotation), tardive dyskinesia, withdrawal symptoms (eg: sweating, insomnia, tremor, anxiety, nausea, vomiting), ventricular tachycardia or ventricular fibrillation, sudden death, thromboembolism (including embolism) pulmonary artery and deep vein thrombosis), pancreatitis, hepatitis (including hepatocellular carcinoma, cholestatic liver injury or mixed form of liver injury), rhabdomyolysis, bladder feeling, priapism, increased alkaline phosphatase.
The proportion of patients with clinically significant changes associated with weight gain, glucose, total cholesterol, LDL, HDL or triglycerides increased over time. In adult patients after 9-12 months of treatment, the rate of increase in mean blood Glucose decreased after approx. 6 months. In elderly patients diagnosed with dementia, an increased incidence of death and adverse cerebrovascular events was observed. 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 (dopamine agonists), Parkinson's 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.
Olanzapine is not indicated for the treatment of children and adolescents under 18 years of age. There are no clinical trials comparing the effects of the drug on adolescents and adults. However, data from studies with adolescents with adult results were compared. Side effects reported more frequently in adolescents (13-17 years old) than in adult patients and adverse reactions reported only in short-term clinical trials in adolescents: very common: weight gain, increased triglyceride levels, increased appetite, sedation ( including: excessive need for normal sleep, lethargy, drowsiness), increase in liver transaminases (ALAT, AST), decrease in total bilirubin, increase in GGT, increase in plasma prolactin; often: increase in cholesterol, dryness of the oral mucosa.

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. In the case of a new mania, mixed episode or depression episode, olanzapine should be continued (if necessary optimizing the dose) and if there are clinical indications - additional treatment of affective symptoms.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.