Zyprexa tablets 10mg, No. 28

• Treatment of exacerbations, supportive and long-term anti-relapse therapy of schizophrenia and other psychotic disorders with pronounced productive (including delusions, hallucinations, automatism) and / or negative (including emotional flattening, decreased social activity, impoverishment of speech) symptoms, as well as concomitant affective disorders.

• Treatment of acute manic or mixed attacks in bipolar disorder with / without psychotic manifestations and with / without rapid phase change.

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

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 over the standard, constituting (depending on the indications) 10-15 mg / day, is recommended only after an appropriate clinical examination of the patient. The dose should be increased gradually, at intervals of at least 24 hours.

For elderly patients, as well as with severe renal failure or moderate liver failure, the initial dose is 5 mg / day.

A reduction in the initial dose is recommended for patients with a combination of factors (female patients, elderly patients, nonsmokers), in which olanzapine metabolism may slow down.

White film-coated tablets , round, with imprinted identification lettering 'LILLY 4115' on one side.

1 tab.

Active ingredient: olanzapine - 5 mg

Excipients : lactose monohydrate, hyprolose (hydroxypropyl cellulose), crospovidone, microcrystalline cellulose, magnesium stearate.

Shell composition: hypromellose (methylhydroxypropyl cellulose), a mixture of white dye YS-1-18027-A, carnauba wax (for polishing), blue food ink (for applying an identification inscription).

• Hypersensitivity to olanzapine.

• Pregnancy

• Lactation period

• Children under the age of 18.

Clinical and pharmacological group: Antipsychotic drug (neuroleptic)

Pharmaco-therapeutic group: Antipsychotic (neuroleptic) agent

pharmachologic effect

Antipsychotic (neuroleptic). Has an affinity for serotonin 5-HT2A / C-, 5-HT3-, 5-HT6-receptors; dopamine D1-, D2-, D3-, D4-, D5-receptors; M1-5-cholinergic receptors; ? 1-adrenergic receptors and histamine H1 receptors. Shows antagonism against serotonin 5-HT, dopamine and cholinergic receptors.

In vitro and in vivo it has a more pronounced affinity and activity for serotonin 5-HT2 receptors, compared to dopamine D2 receptors. According to the data of electrophysiological studies, olanzapine selectively reduces the excitability of mesolimbic (A10) dopaminergic neurons and, at the same time, has an insignificant effect on the striatal (A9) nerve pathways involved in the regulation of motor functions. Olanzapine reduces the conditioned defense reflex (a test that characterizes antipsychotic activity) at lower doses than is required to achieve catalepsy (a disorder reflecting side effects on motor function). Unlike other antipsychotics, olanzapine enhances the anti-anxiety effect in an anxiolytic test.

When using olanzapine, both productive (including delusions, hallucinations) and negative disorders are reduced.

Pharmacokinetics

After oral administration, olanzapine is well absorbed from the gastrointestinal tract, Cmax in plasma is reached after 5-8 hours. Plasma concentrations of olanzapine have a linear dependence on the dose (in the range from 1 to 20 mg). Food intake has no effect on olanzapine absorption.

At a plasma concentration of 7 to 1000 ng / ml, plasma protein binding 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 cross the BBB. CYP1A2 and CYP2D6 isoenzymes are involved in the formation of N-desmethyl and 2-hydroxymethyl metabolites of olanzapine. Experimental studies on animals have shown that these metabolites have significantly less pronounced pharmacological activity in vivo than olanzapine. The main pharmacological activity is due to unchanged olanzapine.

The activity of the isoenzyme CYP2D6 does not affect the metabolic rate of olanzapine.

In healthy volunteers, after oral administration, T1 / 2 of olanzapine is 33 hours (21-54 hours), and the mean 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.

Indication of active substances

• Treatment of exacerbations, supportive and long-term anti-relapse therapy of schizophrenia and other psychotic disorders with pronounced productive (including delusions, hallucinations, automatism) and / or negative (including emotional flattening, decreased social activity, impoverishment of speech) symptoms, as well as concomitant affective disorders.

• Treatment of acute manic or mixed attacks in bipolar disorder with / without psychotic manifestations and with / without rapid phase change.

Dosage regimen

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

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 over the standard, constituting (depending on the indications) 10-15 mg / day, is recommended only after an appropriate clinical examination of the patient. The dose should be increased gradually, at intervals of at least 24 hours.

For elderly patients, as well as with severe renal failure or moderate liver failure, the initial dose is 5 mg / day.

A reduction in the initial dose is recommended for patients with a combination of factors (female patients, elderly patients, nonsmokers), in which olanzapine metabolism may slow down.

Side effect

From the side of the central nervous system: gait disturbance (in patients with dementia of the Alzheimer's type), drowsiness, akathisia, dizziness; rarely - seizures, NNS.

From the side of metabolism: weight gain, peripheral edema.

From the endocrine system: an increase in the content of prolactin (clinical manifestations of hyperprolactinemia were rarely observed, in most cases, the normalization of prolactin levels occurred without canceling olanzapine); in isolated cases - hyperglycemia, diabetic coma, diabetic ketoacidosis.

On the part of the cardiovascular system: orthostatic hypotension; rarely - bradycardia.

From the digestive system: constipation, dry mouth, increased appetite, increased ALT and AST activity; rarely - hepatitis.

Dermatological reactions: rarely - photosensitization, rash.

From the genitourinary system: rarely - priapism.

From the hematopoietic system: eosinophilia; rarely - leukopenia, thrombocytopenia.

Others: asthenia.

Contraindications for use

• Hypersensitivity to olanzapine.

Application during pregnancy and lactation

There have been no adequate and well-controlled clinical studies of the safety of olanzapine during pregnancy. Application is possible only in cases where the expected benefit of therapy to the mother significantly outweighs the potential risk to the fetus.

There are currently no data on the excretion of olanzapine in breast milk. If necessary, use during lactation, breastfeeding should be discontinued.

Application for violations of liver function

In case of liver failure of moderate severity, the initial dose is 5 mg / day.

Application for impaired renal function

In severe renal failure, the initial dose is 5 mg / day.

Application in children

The safety and efficacy of olanzapine in patients under the age of 18 have not been studied.

Use in elderly patients

For elderly patients, the initial dose is 5 mg / day.

special instructions

Use with extreme caution with an increase in the activity of AST and ALT in patients with liver failure, limited liver functional reserve, or in patients receiving treatment with potentially hepatotoxic drugs. In the case of an increase in AST and / or ALT activity during olanzapine treatment, careful monitoring of the patient is required, and, if necessary, dose reduction.

Use with caution in patients with a history of epileptic seizures or exposed to factors that reduce the seizure threshold.

Use with caution in patients with a reduced number of leukocytes and / or neutrophils due to various reasons; with signs of depression / toxic dysfunction of the bone marrow under the influence of drugs in the anamnesis; with suppression 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 a history of clozapine-dependent neutropenia or agranulocytosis was not accompanied by relapses of these disorders.

Use with caution in patients with clinical manifestations of prostatic hyperplasia, paralytic intestinal obstruction, angle-closure glaucoma and similar conditions.

When treated with antipsychotics, including olanzapine, the development of ZNS is possible. Clinical manifestations of NMS or a significant increase in body temperature without other symptoms of this syndrome require the withdrawal of all antipsychotics, including olanzapine.

With prolonged therapy with antipsychotics, there is a risk of developing tardive dyskinesia. With the development of signs of tardive dyskinesia, a dose reduction or withdrawal of olanzapine is recommended. Symptoms of tardive dyskinesia may appear or worsen after discontinuation of therapy.

Given the nature of the action of olanzapine on the central nervous system, it should be used with caution in combination with other centrally acting drugs and ethanol.

The safety and efficacy of olanzapine in patients under the age of 18 have not been studied.

Influence on the ability to drive vehicles and work with mechanisms

During the period of treatment, care should be taken to engage in activities associated with the need for concentration of attention and high speed of psychomotor reactions.

Drug interactions

With simultaneous use with drugs that have a depressing effect on the central nervous system, with ethanol, the inhibitory effect on the central nervous system, antihypertensive effect, increases.

Olanzapine metabolism can be altered by inhibitors or inducers of the CYP1A2 isoenzyme. Plasma clearance of olanzapine is increased in smoking patients and in patients taking carbamazepine (due to an increase in CYP1A2 activity). Strong inhibitors of CYP1A2 can reduce the plasma clearance of olanzapine.

The simultaneous intake of activated carbon reduces the bioavailability of olanzapine by 50-60%.

With simultaneous use with fluvoxamine, the concentration of olanzapine in the blood plasma increases.

Taking fluoxetine (60 mg once or 60 mg daily for 8 days) causes an increase in the Cmax of olanzapine in blood plasma by an average of 16% and a decrease in the plasma clearance of olanzapine by an average of 16%.