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Active ingredients
Olanzapine
Release form
Pills
Composition
1 tablet contains: olanzapine 5 mg. Auxiliary substances: cellactose (spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose), pregelatinized starch, corn starch, anhydrous colloidal silicon dioxide, magnesium stearate.
Pharmacological effect
Olanzapine is an antipsychotic (neuroleptic) with a broad pharmacological spectrum of action. The antipsychotic effect is due to the blockade of the dopamine D2 receptors of the mesolimbic and mesocortical system; sedative action - blockade of adrenoreceptors of the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2-receptors of the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus. In addition, it affects the muscarinic, adrenergic, H1-histamine and some subclasses of serotonin receptors. Olanzapine reliably reduces the productive (delusions, hallucinations) and negative (hostility, suspicion, emotional and social autism) symptoms of psychosis. Rarely causes extrapyramidal disorders.
Pharmacokinetics
Olanzapine absorption is high, does not depend on food intake; Tmax after oral administration is 5–8 h. Protein binding is 93% in the concentration range from 7 to 1000 ng / ml. Olanzapine binds mainly albumin and α1-glycoprotein. Penetrates histohematogenous barriers, incl. BBB. Metabolized in the liver, active metabolites are not formed, the main circulating metabolite - glucuronide - does not penetrate through the BBB. Smoking, sex and age affect T1 / 2 and plasma clearance. In persons older than 65 years, T1 / 2 is 51.8 h and plasma clearance is 17.5 l / h; in persons younger than 65 years old - 33.8 h and plasma clearance - 18.2 l / h. Plasma clearance is lower in patients with hepatic insufficiency, women and non-smoking patients in comparison with the respective groups of individuals. However, the degree of influence of age, gender or smoking on clearance and T1 / 2 of olanzapine is insignificant compared with the individual variability of pharmacokinetics between individuals. Excreted mainly by the kidneys (60%) as metabolites.
Indications
For the treatment of schizophrenia (Zalasta effectively supports the improvement of clinical symptoms with prolonged treatment in patients with an initial positive reaction to the drug); for the treatment of moderate or severe episodes of mania; for the prevention of recurrence of mania in bipolar disorder (in patients with manic episodes with a good effect of olanzapine therapy).
Contraindications
Angle-closure glaucoma; children's age up to 18 years (efficiency and safety are not established); lactation period; galactose intolerance, lapp lactase deficiency or impaired glucose-galactose absorption; Hypersensitivity to olanzapine or other components of the drug.
Precautionary measures
With care: renal failure, liver failure, prostatic hyperplasia, paralytic intestinal obstruction, epilepsy, a history of convulsions, leukopenia and / or neutropenia of various genesis, myelosuppression of various genesis, including myeloproliferative diseases, hypereosinophilic syndrome, cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, congenital increase in the QT interval on an ECG (increase in QTc on an ECG), or in the presence of conditions potentially capable of causing an increase in the QT interval prolonged QT interval, congestive heart failure, hypokalemia, hypomagnesemia), old age, as well as the simultaneous use of other drugs central action; immobilization, pregnancy.
Use during pregnancy and lactation
Due to the limited experience of using 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 about the need to inform the doctor about the occurrence or planned pregnancy during olanzapine therapy. There are isolated reports of tremor, arterial hypertension, lethargy and drowsiness in children born to mothers who took olanzapine in the third trimester of pregnancy. The study revealed that olanzapine is released into breast milk.The average dosage (mg / kg) received by the child upon reaching the equilibrium concentration in the mother was 1.8% of the dose of mother olanzapine (mg / kg). Breast-feeding during olanzapine therapy is not recommended.
Dosage and administration
The drug is administered orally, 1 time / day. Since food does not affect the absorption of the drug, pills can be taken regardless of the meal. In case of drug withdrawal, a gradual dose reduction is recommended. In schizophrenia, the recommended initial dose of the drug is 10 mg / day. In episodes of mania, the initial dose is 15 mg per dose with monotherapy or 10 mg / day as part of combination therapy. The recommended initial dose of the drug in remission is 10 mg / day. For patients already receiving Zalasta for the treatment of an episode of mania, supportive therapy is carried out in the same doses. With Zalast treatment, if a new manic, mixed or depressive episode develops, the dose of the drug should be increased with additional treatment for mood disorders, in accordance with clinical indications. -20 mg / day, depending on the clinical condition of the patient. Increasing the dose over the recommended initial dose is possible only after an adequate re-clinical assessment of the patient’s condition and is usually performed at intervals of at least 24 hours. In elderly patients, a reduction in the initial dose (up to 5 mg / day) is usually not recommended, but it is possible in patients over 65 years of age with risk factors. Patients with liver and / or kidney diseases are recommended to reduce the initial dose to 5 mg / day. In moderate liver failure (cirrhosis, class A or B according to Child-Pugh hepatocellular insufficiency in patients with cirrhosis of the liver), the initial dose is 5 mg / day, a further increase in dose with caution is possible. Women do not need changes in dosing compared to men In non-smoking patients, dose adjustment is not required compared with smoking patients. If the patient has more than one factor that can affect the absorption of the drug (female, old age, non-smoker), it is possible buet lowering initial dosage. If necessary, a further dose increase with caution is possible.
Side effects
From the side of the central nervous system and peripheral nervous system: very often - drowsiness; often - dizziness, akathisia, parkinsonism, dyskinesia; seldom - a convulsive syndrome (more often against the background of a convulsive syndrome in the anamnesis); very rarely, malignant neuroleptic syndrome, dystonia (including oculogy crisis) and tardive dyskinesia. With abrupt cancellation of olanzapine, symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting are very rare. From the cardiovascular system: often - arterial hypotension (including orthostatic); infrequently - bradycardia with or without collapse; very rarely - an increase in the QTc interval on the ECG, ventricular tachycardia / fibrillation and sudden death, thromboembolism (including pulmonary artery embolism and deep vein thrombosis). On the part of the digestive system: often - transient anticholinergic effects, including constipation and dry mouth, transient, asymptomatic elevation of hepatic transaminase (ALT, ACT), especially at the beginning of treatment; rarely, hepatitis (including hepatocellular, cholestatic, or mixed liver damage); very rarely - pancreatitis, increased levels of alkaline phosphatase and total bilirubin. On the metabolic side: very often - an increase in body weight often - increased appetite; very rarely, hyperglycemia and / or decompensation of diabetes mellitus, sometimes manifested by ketoacidosis or coma, including a fatal outcome; hypertriglyceridemia, hypercholesterolemia, hypothermia. For the blood-forming organs: often - eosinophilia; rarely, leukopenia; very rarely - thrombocytopenia, neutropenia. From the musculoskeletal system: very rarely - rhabdomyolysis. From the urogenital system: very rarely - urinary retention, priapism. From the skin and subcutaneous tissue: rarely - photosensitization reactions. Allergic reactions: rarely - skin rash; very rarely - anaphylactoid reactions, angioedema, pruritus or urticaria. Other: often - asthenia, peripheral edema; very rarely - alopecia. Laboratory parameters: very often - hyperprolactinemia, but clinical manifestations (for example, gynecomastia, galactorrhea and an increase in the mammary glands) are rare. In most patients, the level of prolactin spontaneously normalized without discontinuation of therapy. Infrequently - an increase in the level of creatine phosphokinase (CPK).In elderly patients with dementia, a high frequency of deaths and cerebrovascular disorders (stroke, transient ischemic attacks) was recorded in studies. Very often, this category of patients had gait disturbances and falls. Pneumonia, fever, lethargy, erythema, visual hallucinations and urinary incontinence were also often observed. Among patients with medicinal (against the background of dopamine agonists) psychosis against Parkinson's disease, there was often a worsening of parkinsonian symptoms and hallucinations. There are data on the development of neutropenia ( 4.1%) in combination with valproic acid in patients with bipolar mania. Simultaneous therapy with valproic acid or lithium increases the frequency (> 10%) of tremor, dry mouth, increased appetite and increased body weight. Speech disorders were also often recorded (from 1 to 10%). In the first 6 weeks of combination therapy with lithium, the frequency of weight gain increases. Long-term therapy with olanzapine (up to 12 months) in order to prevent recurrence in patients with bipolar disorder was accompanied by an increase in body weight.
Overdose
Symptoms: very often (> 10%) - tachycardia, agitation / aggression, dysarthria, various extrapyramidal symptoms, a decrease in the level of consciousness from lethargy to coma; in less than 2% of cases, delirium, convulsions, coma, neuroleptic malignant syndrome (MNS), respiratory depression, aspiration, increased or decreased blood pressure, cardiac arrhythmia; in very rare cases, cardiopulmonary failure. The minimum dose of olanzapine for acute overdose with a fatal outcome is 450 mg, the maximum dose for overdose with a favorable outcome (survival) is 1500 mg. Treatment: gastric lavage, taking activated carbon (reduces the bioavailability of olanzapine by 60%), symptomatic treatment under the control is vital important functions, including the treatment of arterial hypotension and vascular collapse, maintaining respiratory function. There is no specific antidote. It is not recommended to induce vomiting, use epinephrine, dopamine or other sympathomimetics with beta-adreno-mimetic activity, since the latter may aggravate hypotension.To identify possible arrhythmias, monitoring of cardiovascular activity is necessary. The patient must be under continuous medical supervision until full recovery.
special instructions
There are very rare reports of the development of hyperglycemia and / or decompensation of diabetes mellitus, sometimes accompanied by the development of ketoacidosis or ketoacidotic coma, including There are reports of several fatal cases. In some cases, an increase in body weight preceding decompensation was noted, which could become a predisposing factor. Patients with diabetes mellitus and risk factors for the development of this disease are recommended to have regular clinical monitoring and control of blood glucose levels. If you change lipid levels, therapy must be adjusted. If you suddenly stop taking olanzapine, very rarely (less than 0.01%) may develop the following symptoms: insomnia, tremor, anxiety, nausea or vomiting. With the abolition of the drug is recommended gradual dose reduction.