Composition, form of production and packaging
Tablets of light yellow color, round, slightly biconcave; allowed blotches of a darker shade.
1 tab.
olanzapine 2.5 mg
Excipients: cellactose (spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose), pregelatinized starch, corn starch, silicon dioxide colloidal anhydrous, magnesium stearate.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
Tablets of light yellow color, round, slightly biconcave, with the inscription "5"; allowed blotches of a darker shade.
1 tab.
olanzapine 5 mg
Excipients: cellactose (spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose), pregelatinized starch, corn starch, silicon dioxide colloidal anhydrous, magnesium stearate.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
Tablets of light yellow color, round, slightly biconcave, with the inscription "7.5"; allowed blotches of a darker shade.
1 tab.
olanzapine 7.5 mg
Excipients: cellactose (spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose), pregelatinized starch, corn starch, silicon dioxide colloidal anhydrous, magnesium stearate.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
Tablets of light yellow color, round, slightly biconcave, with an inscription "10"; allowed blotches of a darker shade.
1 tab.
olanzapine 10 mg
Excipients: cellactose (spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose), pregelatinized starch, corn starch, silicon dioxide colloidal anhydrous, magnesium stearate.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
Tablets of light yellow color, round, slightly biconcave, with an inscription "15"; allowed blotches of a darker shade.
1 tab.
olanzapine 15 mg
Excipients: cellactose (spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose), pregelatinized starch, corn starch, silicon dioxide colloidal anhydrous, magnesium stearate.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
Tablets of light yellow color, round, slightly biconcave, with an inscription "20"; allowed blotches of a darker shade.
1 tab.
olanzapine 20 mg
Excipients: cellactose (spray-dried compound consisting of 75% alpha-lactose monohydrate and 25% cellulose), pregelatinized starch, corn starch, silicon dioxide colloidal anhydrous, magnesium stearate.
7 pcs. - blisters (4) - packs of cardboard.
7 pcs. - blisters (8) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
Antipsychotic drug (neuroleptic) with a broad pharmacological spectrum of action. The antipsychotic effect is due to the blockade of dopamine D 2 receptors in the mesolimbic and mesocortical systems; sedative effect - adrenoreceptor blockade of the reticular formation of the brainstem; antiemetic effect - blockade of dopamine D 2 receptors in the trigger zone of the vomiting center; hypothermic action - blockade of dopamine receptors of the hypothalamus. In addition, it affects muscarinic, adrenergic, histamine H 1 -receptors and some subclasses of serotonin receptors.
Olanzapine significantly reduces productive (delusions, hallucinations) and negative symptoms (hostility, suspicion, emotional and social autism) of psychoses. Rarely causes extrapyramidal disorders.
PHARMACOKINETICS
Suction
Absorption of olanzapine is high, it does not depend on food intake. T max in the blood plasma after oral administration - 5-8 h.
Distribution
Binding to proteins - 93% in the concentration range from 7 to 1000 ng / ml. Olanzapine binds, mainly, with albumin and? 1- glycoprotein. Penetrates through gistogematicheskie barriers, incl. GEB.
Metabolism
Metabolized in the liver, active metabolites are not formed, the main circulating metabolite is glucuronide, does not penetrate the GEB.
Excretion
It is excreted mainly by kidneys (60%) in the form of metabolites.
Smoking, sex and age affect T 1/2 and plasma clearance. In people older than 65 years, T 1/2 is 51.8 hours and plasma clearance is 17.5 l / h, for people younger than 65 years, 33.8 hours and a plasma clearance of 18.2 l / h.
Plasma clearance is lower in patients with hepatic insufficiency, women and non-smokers compared to the corresponding groups of individuals. However, the extent of influence of age, sex or smoking on clearance and T 1/2 of olanzapine is negligible compared to the individual variability of pharmacokinetics between individuals.
INDICATIONS
- for the treatment of schizophrenia (Zalasta В® effectively supports the improvement of clinical symptoms in long-term treatment in patients with 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).
DOSING MODE
The drug is administered orally, 1 time / day. Because food does not affect the absorption of the drug, the tablets can be taken regardless of food intake. In case of cancellation, a gradual dose reduction is recommended.
In schizophrenia, the recommended initial dose of the drug is 10 mg / day.
For episodes of mania, the initial dose is 15 mg per dose in monotherapy or 10 mg / day as part of a combination therapy.
For the prevention of recurrences in bipolar disorder, the recommended initial dose of the drug in a state of remission is 10 mg / day. For patients already receiving Zalast В® for the treatment of manic episodes, maintenance therapy is administered in the same doses. On the background of therapy with Zalast В® , if a new manic, mixed or depressive episode develops, if necessary, increase the dose of the drug with additional treatment of mood disorders, in accordance with clinical indications.
The daily dose of the drug in the treatment of schizophrenia, a manic episode or the prevention of recurrence of bipolar disorder can be 5-20 mg / day, depending on the clinical condition of the patient. An increase in the dose above the recommended initial dose is only possible after an adequate repeated 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 older than 65 years with risk factors.
Patients with liver and / or kidney disease are recommended to reduce the initial dose to 5 mg / day. With moderate hepatic insufficiency (cirrhosis, class A or B according to Child-Pugh classification of hepatic-cell insufficiency in patients with cirrhosis of the liver), the initial dose is 5 mg / day, possibly further dose increase with caution.
Women do not need a change in dosing compared to men.
In non-smoking patients, dose adjustments are not required compared to smokers.
If the patient has more than one factor that can influence the absorption of the drug (female, elderly, non-smokers), it may be necessary to reduce the initial dose. If necessary, further increase in dose with caution.
SIDE EFFECT
Classification of the incidence of adverse events (WHO): very often (> 1/10), often (> 1/100 to <1/10), infrequently (> 1/1000 to <1/100), rarely from (> 1/10 000 to <1/1000), very rarely from (<1/10 000, including individual messages).
From the side of the central nervous system and peripheral nervous system: very often - drowsiness; often - dizziness, akathisia, parkinsonism, dyskinesia; rarely - convulsive syndrome (more often in the background of convulsive syndrome in anamnesis); very rarely -cancer neuroleptic syndrome, dystonia (including oculogic crisis) and tardive dyskinesia. With a sharp abolition of olanzapine, symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting are very rarely noted.
From the side of the cardiovascular system: often - arterial hypotension (including orthostatic); infrequently - a bradycardia with a collapse or without; very rarely - an increase in the interval of QT c on the ECG, ventricular tachycardia / fibrillation and sudden death, thromboembolism (including pulmonary artery embolism and deep vein thrombosis).
From the side of the digestive system: often - transitory anticholinergic effects, incl. constipation and dry mouth, transient, asymptomatic elevation of hepatic transaminases (ALT, ACT), especially at the beginning of treatment; rarely - hepatitis (including hepatocellular, cholestatic or mixed liver damage); very rarely - pancreatitis, increased level of alkaline phosphatase and total bilirubin.
From the side of metabolism: 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 fatal outcome; hypertriglyceridemia, hypercholesterolemia, hypothermia.
On the part of the organs of hematopoiesis: often - eosinophilia; rarely - leukopenia; very rarely - thrombocytopenia, neutropenia.
From the musculoskeletal system: very rarely - rhabdomyolysis.
From the genitourinary system: very rarely - urinary retention, priapism.
From the skin and subcutaneous tissue: infrequently - the reaction of photosensitization.
Allergic reactions: rarely - skin rash; very rarely - anaphylactoid reactions, angioedema, skin itching or urticaria.
Other: often - asthenia, peripheral edema; very rarely - alopecia.
Laboratory indicators: very often hyperprolactinemia, but clinical manifestations (eg, gynecomastia, galactorrhea and breast enlargement) are rare. In most patients, the level of prolactin spontaneously normalized without the abolition of therapy. Infrequently, an increase in the level of creatine phosphokinase (CKF). In elderly patients with dementia, a large incidence of deaths and cerebrovascular disorders (stroke, transient ischemic attacks) is documented in studies. Very often in this category of patients there were abnormalities of gait and fall. Also often observed pneumonia, fever, lethargy, erythema, visual hallucinations and urinary incontinence.
Among patients with medicinal (against the background of dopamine agonists) psychoses on the background of Parkinson's disease often recorded worsening of parkinsonian symptoms and the development of hallucinations.
There are data on the development of neutropenia (4.1%) against a combination therapy with valproic acid in patients with bipolar mania. Simultaneous therapy with valproic acid or lithium helps to increase the frequency (> 10%) of tremors, dry mouth, increase appetite and increase body weight. Violations of speech were often recorded (from 1 to 10%). In the first 6 weeks of combined therapy with lithium, the frequency of weight gain increases. Long-term therapy with olanzapine (up to 12 months) in order to prevent relapse in patients with bipolar disorder was accompanied by an increase in body weight.
CONTRAINDICATIONS
- an angle-closure glaucoma;
- Children under 18 years of age (effectiveness and safety not established);
- lactation period;
- galactose intolerance, lactase deficiency lapp or impaired absorption of glucose-galactose;
- Hypersensitivity to olanzapine or other components of the drug.
With caution : renal insufficiency, hepatic insufficiency, prostatic hyperplasia, paralytic intestinal obstruction, epilepsy, history of convulsive syndrome, leukopenia and / or neutropenia of various genesis, myelosuppression of various genesis, incl. myeloproliferative diseases, hypereosinophilic syndrome, cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, congenital increase in the QT interval on the ECG (increase in QT c on the ECG), or in the presence of conditions potentially capable of causing an increase in the QT interval (eg simultaneous administration of drugs , QT prolonging interval, congestive heart failure, hypokalemia, hypomagnesemia), elderly age, as well as simultaneous intake of other drugs In Central action; immobilization, pregnancy.
PREGNANCY AND LACTATION
Due to the limited experience of the drug in pregnant women, olanzapine should be used during pregnancy only if the expected benefit for the mother justifies the potential risk to the fetus. Women should be informed of the need to inform the doctor about the onset or planned pregnancy on the background of olanzapine therapy.There are isolated reports of tremors, arterial hypertension, lethargy and drowsiness in children born to mothers who took olanzapine in the third trimester of pregnancy.
The study found that olanzapine is excreted in breast milk. The average dosage (mg / kg) received by a child at equilibrium concentration in the mother was 1.8% of the mother's olanzapine dose (mg / kg). It is not recommended to breast-feed on the background of olanzapine therapy.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution : kidney failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution : liver failure.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
In elderly patients, a reduction in the initial dose (up to 5 mg / day) is usually not recommended, but it is possible in patients older than 65 years with risk factors.
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, incl. there are reports of several fatal cases. In some cases, there was a previous decompensation of weight gain, which could become a predisposing factor. In patients with diabetes mellitus and risk factors for the development of this disease, regular clinical monitoring and monitoring of blood glucose levels are recommended.
When the level of lipids changes, correction of therapy is required.
With a sharp discontinuation of olanzapine, it is very rare (less than 0.01%) to develop the following symptoms: sweating, insomnia, tremor, anxiety, nausea, or vomiting. With the withdrawal of the drug, a gradual dose reduction is recommended.
Since clinical experience with olanzapine in people with concomitant diseases is limited, the drug should be used with caution in patients with prostatic hyperplasia, paralytic intestinal obstruction.
Experience with olanzapine in patients with psychoses in Parkinson's disease caused by dopaminomimetic therapy. Olanzapine is not recommended for the treatment of psychoses in Parkinson's disease caused by the intake of dopaminomimetics. The symptoms of parkinsonism and hallucinations increase. However, olanzapine was not superior to placebo in the treatment of psychoses.
Olanzapine is not indicated for the treatment of psychoses and / or behavioral disorders in dementia, due to increased mortality and increased risk of cerebrovascular disorders (stroke, transient ischemic attacks). The increase in mortality does not depend on the dose of olanzapine or the duration of therapy. Risk factors predisposing to increased mortality include: age over 65 years, dysphagia, sedation, malnutrition and dehydration, lung diseases (eg, pneumonia, including aspiration), simultaneous reception of benzodiazepines. However, the increased incidence of death in olanzapine compared with placebo did not depend on these risk factors
With antipsychotic therapy, the improvement in the clinical state of the patient occurs in the period from several days to several weeks. During this period, the patient needs careful observation.
At the beginning of therapy, an asymptomatic increase in liver transaminases (ALT and ACT) is possible. Patients with initially elevated levels of ACT and / or ALT, with hepatic insufficiency and conditions potentially limiting the functionality of the liver, as well as those taking hepatotoxic drugs, caution should be exercised when prescribing olanzapine. When ALT and / or ACT are increased against the background of drug therapy, it is recommended that medical supervision of the patient and, possibly, a reduction in the dose of the drug be recommended. When diagnosing hepatitis (including hepatocellular, cholestatic or mixed), olanzapine should be discarded.
The drug should be used with caution in patients with leukopenia and / or neutropenia of any genesis, myelosuppression of drug origin, as well as radiation or chemotherapy, due to concomitant diseases, in patients with hypereosinophilic conditions or myeloproliferative diseases. Neutropenia has often been observed with the simultaneous use of olanzapine and valproic acid.
ZNS is a potentially life-threatening condition associated with antipsychotic medication (neuroleptics), incl. olanzapine. Clinical manifestations of ZNS: fever, rigidity of muscles, impaired consciousness, vegetative disorders (unstable pulse or labile blood pressure, tachycardia, increased sweating, arrhythmias). Additional symptoms of ZNS: increased CK, myoglobinuria (against rhabdomyolysis) and acute renal failure. With the development of symptoms of the ZNS, as well as an increase in body temperature without apparent causes, it is necessary to cancel all neuroleptics, including. olanzapine.
Olanzapine should be carefully prescribed to patients with a history of seizures or the presence of factors that reduce the threshold of convulsive readiness. On the background of taking olanzapine, seizures were rarely recorded.
The therapy with olanzapine was accompanied by a significantly lower incidence of late dyskinesia, in comparison with haloperidol. The risk of developing tardive dyskinesia increases with increasing duration of treatment. If there are signs of this condition, the patient taking olanzapine should cancel the drug or reduce its dose.Symptoms of dyskinesia may temporarily increase after the drug is discontinued.
Caution must be exercised while the use of other drugs and central action of alcohol.
Older people rarely observed postural hypotension. In patients older than 65 years should periodically monitor blood pressure. Olanzapine should be used with caution in patients with established increasing the interval QT c , particularly the elderly, with a congenital syndrome elongate interval QT, congestive heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia.
With olanzapine very rarely (less than 0.01%) reported cases of venous thromboembolism. The causal relationship between olanzapine treatment and venous thrombosis has not been established. Since patients with schizophrenia often present acquired risk factors for venous thrombosis, should identify all possible other factors (for example, immobilization) and take preventive measures.
Zalasta Tablets В® contains lactose. The drug should not be taken in patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or malabsorption of glucose-galactose.
Impact on the ability to drive vehicles and manage mechanisms
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
OVERDOSE
Symptoms: very frequent (> 10%) with an overdose of olanzapine are tachycardia, agitation / aggression, dysarthria, various extrapyramidal symptoms, decreased level of consciousness from the retardation to coma; less than 2% of the cases arise: delirium, seizures, coma, neuroleptic malignant syndrome, respiratory depression, aspiration, increase or decrease in blood pressure, cardiac arrhythmias; in very rare cases - cardio-pulmonary insufficiency. The minimum dose of olanzapine in acute lethal overdose - 450 mg, maximum registered dose overdose with a favorable outcome (survival) - 1500 mg.
Treatment: there is no specific antidote. It is not recommended to provoke vomiting. It is necessary to gastric lavage, administration of activated charcoal (olanzapine reduced bioavailability by 60%), symptomatic treatment under the control of vital functions, including the treatment of hypotension and vascular collapse, the maintenance of respiratory function. We do not recommend the use of epinephrine, dopamine, or other sympathomimetic agents with beta-Adrenomimeticalkie activity because the latter may worsen hypotension. To detect possible arrhythmias requires monitoring of cardiovascular activity. The patient should be under continuous medical supervision until complete recovery.
DRUG INTERACTION
Olanzapine is metabolized by the enzyme CYP1A2, therefore, inhibitors or inducers of cytochrome P450 isoenzymes, exhibiting specific activity towards CYP1A2 can affect the pharmacokinetic parameters of olanzapine.
Inducers of CYP1A2: olanzapine clearance may be increased in patients who smoke or while taking carbamazepine, leading to a decrease in olanzapine plasma concentrations. Recommended clinical observation, because Some cases require increasing doses of the drug.
Inhibitors of CYP1A2: Fluvoxamine, a specific inhibitor of CYP1A2 - significantly reduces the clearance of olanzapine. The average increase in C maxolanzapine after administration of fluvoxamine in nonsmoking women was 54%, while male smokers - 77%. The average increase in AUC of olanzapine in these categories of patients was 52% and 108%. Patients taking fluvoxamine or any other inhibitors of CYP1A2 (eg, ciprofloxacin), olanzapine therapy is recommended to start with smaller doses. Reducing the dose of olanzapine may also be required in the case of adherence to therapy CYP1A2 inhibitors.
Activated charcoal reduces the absorption of olanzapine orally 50-60%, however it should be taken at least 2 hours before or after olanzapine.
Fluoxetine inhibitor (CYP450), a single dose of magnesium or aluminum containing antacids or cimetidine did not affect the pharmacokinetics of olanzapine.
Olanzapine may weaken the effect of direct and indirect dopamine agonists.
In the in vitro conditions did not suppress olanzapine major isoenzymes CYP450 (e.g., 1A2, 2D6, 2C9, 2C19, 3A4). In vivo it found no inhibition of metabolism of the following active substances: the tricyclic antidepressants (CYP2D6), warfarin (CYP2C9), theophylline (CYP1A2) and diazepam (CYP3A4 and 2C19).
There were no interaction while the use of lithium or biperidenom.
The therapeutic monitoring of valproic acid content in plasma showed that at a simultaneous administration with doses of olanzapine changes of valproic acid is required.
Caution must be exercised while the use of other drugs central action. Despite the fact that a single dose of alcohol (45 mg / 70 kg) has no effect pharmacokinetic, alcohol together with olanzapine may be accompanied by increased depressive effect on the central nervous system.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in reach of children at a temperature not higher than 30 В° C. The shelf life of the tablets 5 mg and 10 mg - 5 years, tablets of 2.5 mg, 7.5 mg, 15 mg and 20 mg - 3 years.
