Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Antipsychotic agent (antipsychotic). Has an affinity for serotonin 5-HT 2A / C -, 5-HT 3 -, 5-HT 6 -receptors; dopaminovym D 1 -, D 2 -, D 3 -, D 4 -, D 5 -receptors; M1-5 -cholinoreceptors; ? 1- adrenoreceptors and histamine H 1 -receptors. It shows antagonism against serotonin 5-HT, dopamine and cholinergic receptors.
In vitro and in vivo conditions it has more pronounced affinity and activity for serotonin 5-HT 2 receptors, as compared to dopamine D 2 -receptors. According to electrophysiological studies, olanzapine selectively reduces the excitability of mesolimbic (A10) dopaminergic neurons and, at the same time, has an insignificant effect on the striatum (A9) nerve pathways involved in the regulation of motor functions. Olanzapine reduces the conditioned protective reflex (a test characterizing antipsychotic activity) at lower doses than is required to achieve catalepsy (a disorder reflecting a side effect on the motor function). Unlike other neuroleptics, olanzapine increases the anti-anxiety effect during an anxiolytic test.
When olanzapine is used, both productive (including delirium, hallucinations) and negative disorders decrease.
PHARMACOKINETICS
After oral administration of olanzapine is well absorbed from the gastrointestinal tract, Cmax in plasma is reached after 5-8 hours. Olanzapine concentrations in plasma have a linear dependence on the dose (in the range from 1 to 20 mg). Eating does not affect the absorption of olanzapine.
At a plasma concentration of 7 to 1000 ng / ml, binding to plasma proteins is about 93%.
Olanzapine is metabolized in the liver by conjugation and oxidation. The main circulating metabolite is 10-N-glucuronide, which theoretically does not penetrate the BBB. Isozymes CYP1A2 and CYP2D6 are involved in the formation of N-desmethyl and 2-hydroxymethyl metabolites of olanzapine. Experimental animal studieshave shown that these metabolites have significantly less pharmacological activity in vivo than olanzapine. The main pharmacological activity is due to unaltered olanzapine.
The activity of the CYP2D6 isoenzyme does not affect the level of metabolism of olanzapine.
In healthy volunteers after ingestion of T 1/2 olanzapine is 33 h (21-54 h), and the average plasma clearance is 26 l / h (12-47 l / h).
About 57% of olanzapine labeled with radioisotopes is excreted in the urine, mainly in the form of metabolites.
The pharmacokinetic parameters of olanzapine vary depending on sex, age, the presence of a predilection for smoking (table):
Characteristics of patients T 1/2 (h) Plasma clearance (l / h)
Non-smokers 38.6 18.6
Smokers 30.4 27.7
Women 36.7 18.9
Men 32.3 27.3
Elderly (65 years and over) 51.8 17.5
Younger than 65 years old 33.8 18.2
However, the degree of changes in T 1/2 and plasma clearance under the influence of each of these factors is significantly inferior to the degree of individual differences in these parameters.
There were no significant differences between mean T 1/2 values ​​and plasma clearance of olanzapine in patients with severe renal dysfunction, compared with those with normal renal function.
In smokers with minor violations of liver function, plasma clearance of olanzapine is lower than that of non-smokers without such disorders.
INDICATIONS
Treatment of exacerbations, supporting and long-term antiretroviral therapy of schizophrenia and other psychotic disorders with marked productive (including delirium, hallucinations, automatism) and / or negative symptoms (including emotional flatness, decreased social activity, impoverishment of speech) as well as concomitant affective disorders.
Treatment of acute manic or mixed seizures with bipolar affective disorder with / without psychotic manifestations and with / without rapid phase change.
DOSING MODE
The initial dose is 10-15 mg / day. The daily dose must be selected individually depending on the clinical condition of the patient. Therapeutic doses are 5-20 mg / day.An increase in the dose above the standard dose (depending on the indications) of 10-15 mg / day is recommended only after an appropriate clinical examination of the patient. Increase the dose should be gradual, with intervals of at least 24 hours.
For elderly patients, as well as with renal failure of severe or insufficient liver function of moderate severity, the initial dose is 5 mg / day.
A decrease in the initial dose is recommended for patients with a combination of factors (female, elderly, non-smokers), which may slow the metabolism of olanzapine.
SIDE EFFECT
From the side of the central nervous system: a gait disorder (in patients with Alzheimer's dementia), drowsiness, akathisia, dizziness; rarely convulsive seizures, ZNS.
From the side of metabolism: weight gain, peripheral edema.
On the part of the endocrine system: an increase in prolactin (clinical manifestations of hyperprolactinaemia were rare, in most cases normalization of prolactin levels occurred without the abolition of olanzapine); in isolated cases - hyperglycemia, diabetic coma, diabetic ketoacidosis.
From the cardiovascular system: orthostatic hypotension; rarely - aetiology.
From the digestive system: constipation, dry mouth, increased appetite, increased activity of ALT and AST; rarely - hepatitis.
Dermatological reactions: rarely - photosensitivity, rash.
From the genitourinary system: rarely - priapism.
From the hemopoietic system: eosinophilia; rarely - leukopenia, thrombocytopenia.
Other: asthenia.
CONTRAINDICATIONS
Hypersensitivity to olanzapine.
PREGNANCY AND LACTATION
Adequate and strictly controlled clinical studies of the safety of olanzapine during pregnancy have not been conducted. The use is possible only in cases when the expected benefit of therapy for the mother significantly exceeds the potential risk for the fetus.
There is currently no data on the isolation of olanzapine in breast milk. If it is necessary to use lactation, breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
In case of severe renal insufficiency, the initial dose is 5 mg / day.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
If the liver function is of moderate severity, the initial dose is 5 mg / day.
APPLICATION FOR CHILDREN
The safety and efficacy of olanzapine in patients under the age of 18 years have not been studied.
APPLICATION IN ELDERLY PATIENTS
For elderly patients, the initial dose is 5 mg / day.
SPECIAL INSTRUCTIONS
With extreme caution apply when increasing the activity of AST and ALT in patients with insufficient liver function, limited functional reserve of the liver or in patients receiving treatment with potentially hepatotoxic drugs. In the case of increased activity of AST and / or ALT during treatment with olanzapine, careful monitoring of the patient and, if necessary, a reduction in dose are required.
Use with caution in patients with epileptic seizures in the history or exposed to factors that reduce the threshold of convulsive readiness.
Use with caution in patients with a reduced number of leukocytes and / or neutrophils, due to various causes; with signs of oppression / toxic damage to bone marrow function under the influence of drugs in the anamnesis; with oppression of bone marrow function due to concomitant disease, radiotherapy or chemotherapy in history;with hypereosinophilia or myeloproliferative disease. In clinical studies, the use of olanzapine in patients with clozapine-dependent neutropenia or agranulocytosis in a history was not accompanied by relapses of these disorders.
Use with caution in patients with clinical manifestations of prostatic hyperplasia, paralytic intestinal obstruction, zakratougolnoy glaucoma and similar conditions.
In the treatment of neuroleptics, including olanzapine, ZNS development is possible. Clinical manifestations of CNS or a significant increase in body temperature without other symptoms of this syndrome require the withdrawal of all neuroleptics, including olanzapine.
With prolonged therapy with neuroleptics, there is a risk of developing tardive dyskinesia. With the development of signs of tardive dyskinesia, a dose reduction or elimination of olanzapine is recommended. Symptoms of tardive dyskinesia may appear or increase after the abolition of therapy.
Given the nature of the action of olanzapine on the central nervous system, caution should be used in combination with other central-action drugs and ethanol.
The safety and efficacy of olanzapine in patients under the age of 18 years have not been studied.
Influence on the ability to drive vehicles and work with mechanisms
During the treatment period, care should be taken in the activities associated with the need to concentrate attention and high speed of psychomotor reactions.
DRUG INTERACTION
With simultaneous use with drugs that exert a depressing effect on the central nervous system, with ethanol, the depressing effect on the central nervous system, antihypertensive effect is enhanced.
The metabolism of olanzapine can be altered by inhibitors or inducers of the isoenzyme CYP1A2. The plasma clearance of olanzapine is increased in smoking patients and in patients taking carbamazepine (due to an increase in activity of CYP1A2). Strong inhibitors of CYP1A2 can reduce plasma clearance of olanzapine.
Simultaneous reception of activated charcoal reduces the bioavailability of olanzapine by 50-60%.
With simultaneous application with fluvoxamine, the concentration of olanzapine in the blood plasma increases.
Admission of fluoxetine (60 mg once or 60 mg daily for 8 days) causes an increase in C max of olanzapine in blood plasma by an average of 16% and a decrease in plasma clearance of olanzapine by an average of 16%.
