Composition, form of production and packaging
Lyophilizate for the preparation of a solution for the / m introduction of yellow color.
olanzapine 10 mg
Excipients: lactose monohydrate (50 mg), tartaric acid (3.5 mg).
Vials (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
Antipsychotic drug (neuroleptic) with a wide pharmacological spectrum of influence on a number of receptor systems.
In preclinical studies, the affinity of olanzapine for serotonin 5HT 2A / C -, 5HT 3 -, 5HT 6 receptors, dopamine D 1 -, D 2 -, D 3 -, D 4 -, D 5 receptors, muscarinic M1-5 -receptors, adrenergic? 1 receptors and histamine H 1 -receptors. In experimental studies, the presence of antagonism of olanzapine with respect to serotonin 5HT receptors, dopamine and cholinergic receptors was revealed. In vivo and in vitro, olanzapine has a more pronounced affinity and activity for serotonin 5HT 2 receptors compared to dopamine D 2 receptors. According to electrophysiological studies, olanzapine selectively decreases the excitability of mesolimbic dopaminergic neurons and at the same time has an insignificant effect on the striatal neural pathways involved in the regulation of motor functions. Olanzapine reduces the conditioned protective reflex (a test characterizing antipsychotic activity) at doses lower than the doses causing catalepsy (a disorder reflecting a side effect on the motor function). Unlike other antipsychotics (antipsychotics), olanzapine enhances the anti-anxiety effect during the anxiolytic test.
In two placebo-controlled and two out of three comparative controlled trials involving 2,900 schizophrenic patients, olanzapine has been shown to provide statistically significant reduction in both productive (including delirium, hallucinations) and negative disorders.
After the / m administration of C max in the plasma is achieved after 15-45 minutes. Cmax, with a / m administration of 5 mg of olanzapine is 5 times higher than the concentration achieved when administered in an equivalent dose. In the range of therapeutic doses, the pharmacokinetics are linear.
Metabolic characteristics in the / m administration are quantitatively and qualitatively similar to the metabolic characteristics of olanzapine after ingestion.
T 1/2 for IM is similar to T 1/2 observed after ingestion.
- for rapid arrest of agitation (psychomotor agitation) in patients with schizophrenia, bipolar affective disorders and dementia.
The drug can not be administered iv or s.
When agitating for schizophrenia and bipolar affective disorder, the recommended dose is 10 mg once per month. Depending on the clinical condition of the patient, the second injection in a dose up to 10 mg can be administered no earlier than 2 hours after the first, and the third injection in a dose of up to 10 mg - not earlier than 4 hours after the second injection.
The safety of a total daily dose of more than 30 mg in clinical trials has not been evaluated.
If there are indications for continuing treatment with olanzapine, you should stop the IM injection and prescribe olanzapine for oral administration at a dose of 5-20 mg.
When agitating for dementia, the recommended dose is 2.5 mg once per month. Depending on the clinical condition of the patient, the second injection in a dose of up to 5 mg is administered no earlier than 2 hours after the first injection.
Safety of the total daily dose of more than 12.5 mg for this category of patients in clinical trials was not evaluated.
For elderly patients and patients with other clinical risk factors, the drug is prescribed in a dose of 2.5-5 mg, with dementia - in a dose of 2.5 mg.
Rules for the preparation of solution
The contents of the vial should be dissolved in 2.1 ml of sterile water for injection. The prepared solution should be clear, yellow in color. Before administration, it is necessary to check the solution for presence of mechanical impurities, if the solution and the container allow it to be done.
To administer the drug in different doses, the following table should be used.
The dose of olanzapine (mg) The volume of the solution for the intravenous injection (ml)
10 select the entire contents of the vial
The prepared solution should be used within 1 hour after preparation.
Dispose of the unused solution of the solution.
Incompatibility in breeding
Olanzapine for injection should be dissolved only with sterile water for injection.
Olanzapine for injection should not be mixed in the same syringe with diazepam, because there is a precipitation when mixing these drugs.
A solution of lorazepam should not be used to dissolve olanzapine for injection, because this combination lengthens the dissolution time.
Olanzapine for injection should not be mixed in the same syringe with haloperidol, t. the resulting low pH of the solution weakens the effect of olanzapine over time.
Very often (? 10%): drowsiness, weight gain. In 34% of patients, the prolactin concentration in the blood plasma was observed, which was weakly expressed and transient (the mean value of maximum concentrations of prolactin did not reach ULN and statistically significantly differed from placebo). Clinical manifestations of hyperprolactinemia associated with taking olanzapine (ie, gynecomastia, galactorrhea, and enlargement of the mammary glands) were rare. In most patients normalization of prolactin levels was observed without the abolition of olanzapine.
Another very frequent (? 10%) side effect associated with the use of olanzapine in clinical trials in patients with Alzheimer's dementia was gait disorders.
Often (<10% and? 1%): dizziness, asthenia, akathisia, increased appetite, peripheral edema, orthostatic hypotension, dry mouth, constipation. Occasionally, a transient, asymptomatic increase in hepatic transaminases (ALT, AST) was observed; in isolated cases, an increase in plasma glucose to в‰Ґ200 mg / dl (suspected diabetes), and в‰Ґ160 mg / dL, but <200 mg / dL (suspected hyperglycaemia) in patients with baseline glucose? 140 mg / dL, triglyceridemia; in some patients asymptomatic eosinophilia was noted.
The table below summarizes the main side effects and their frequency, recorded during clinical trials and / or post-marketing periods, when treated with various olanzapine dosage forms.
System / Side Effect Frequency (%)
10 <10 and? 1 <1 and? 0.1 <0.1 and? 0.01 <0.01
Organism as a whole
2 Asthenia +
2 Increased sensitivity to light +
1 Weight gain +
The cardiovascular system
2 Bradycardia +
1 Orthostatic hypotension +
2 Constipation +
2 Dry mouth +
3 Hepatitis +
2 Increased appetite +
3 Diabetic coma +
3.5 Diabetic ketoacidosis +
3 Hyperglycemia +
2 Peripheral edema +
4 Violation of gait +
2 Akathisia +
2 Dizziness +
3 Seizures convulsions +
2 Drowsiness +
Skin and appendages
3 Rash +
3 Priapism +
1 Increase in ALT +
1 Increase in AST +
1 Increased prolactin +
1 Single cases of elevated glucose levels of 160 mg / dL, but <200 mg / dL (suspected hyperglycemia) +
1 Single cases of increasing the level of glucose-200 mg / dl (suspected diabetes) +
Single cases of increasing triglyceride levels in? 2 times VGN +
1 Eosinophilia +
3 Lakopenia +
3 Thrombocytopenia +
1 Evaluation of indicators from the database of clinical trials.
2 Side effects recorded in the clinical trials database.
3 Side effects recorded spontaneously in post-marketing studies.
4 Side effects identified in clinical studies in patients with Alzheimer's dementia.
5 In the COSTART classification, it is referred to as diabetic acidosis.
- established hypersensitivity to the components of the drug.
PREGNANCY AND LACTATION
In case of onset or planning of pregnancy during therapy with olanzapine, patients should be advised to consult a doctor. Because of the limited use of olanzapine in pregnancy in humans, the drug should be prescribed during pregnancy only if the potential benefit of therapy for the mother is significantly greater than the potential risk to the fetus.
The study found that olanzapine is excreted in breast milk. During therapy with olanzapine, breastfeeding should be discontinued.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In the early stages of therapy, the administration of the drug was accompanied by a transient, asymptomatic increase in the levels of hepatic transaminases (AST and ALT). Particular caution is necessary when increasing levels of AST and / or ALT in patients with liver failure, with limited functional reserve of the liver or in patients receiving potentially hepatotoxic drugs. In the event of an increase in AST and / or ALT levels during the use of the drug, careful monitoring of the patient and, if necessary, a reduction in dose are required.
In the treatment of any neuroleptic, including olanzapine, can develop malignant neuroleptic syndrome (CNS) - a potentially fatal symptom complex. Clinical manifestations of CNS include a significant increase in body temperature, rigidity of the musculature, changes in mental status and autonomic disorders (unstable pulse or AD, tachycardia, cardiac arrhythmias, increased sweating). Additional signs may include increased levels of creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Clinical manifestations of CNS or a significant increase in body temperature without other symptoms of NSA require the abolition of all neuroleptics, including olanzapine.
In comparative studies lasting more than 6 weeks, treatment with olanzapine was significantly less often accompanied by the development of dyskinesia requiring drug correction than with haloperidol. However, the risk of tardive dyskinesia with prolonged therapy with neuroleptics should be considered. With the development of signs of tardive dyskinesia, a dose reduction or elimination of olanzapine is recommended. Symptoms of tardive dyskinesia may increase or manifest after the drug is discontinued.
In some cases, the use of olanzapine, usually in the early stages of therapy, was accompanied by a transient, asymptomatic increase in the levels of hepatic transaminases (AST and ALT). Particular caution is necessary when increasing levels of AST and / or ALT in patients with liver failure, with limited functional reserve of the liver or in patients receiving potentially hepatotoxic drugs. In the event of an increase in AST and / or ALT levels during the use of the drug, careful monitoring of the patient and, if necessary, a reduction in dose are required.
The drug should be used with caution in patients with epileptic seizures in the history or exposed to factors that reduce the threshold of convulsive readiness. In such patients, seizures were rare in the treatment with olanzapine.
Caution should be exercised when prescribing olanzapine to patients with reduced leukocyte and / or neutrophil counts, patients with signs of oppression / toxic damage to bone marrow function under medical history, patients with bone marrow depression associated with concomitant disease, radiotherapy or chemotherapy in the anamnesis, patients 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.
In clinical trials, olanzapine therapy was rarely accompanied by anticholinergic side effects. However, clinical experience with olanzapine in patients with concomitant diseases is limited, and it is therefore advisable to use caution when administering olanzapine to patients with clinically significant prostatic hypertrophy, paralytic intestinal obstruction, occlusive glaucoma, and similar conditions.
In vitro, olanzapine exhibits antagonism against dopamine and, like other antipsychotics (neuroleptics), can theoretically suppress the action of levodopa and dopamine agonists.
Taking into account the main effect on the central nervous system, care should be taken when using the drug in combination with other central drugs and alcohol.
Use in Pediatrics
Olanzapine for IM injections in patients under the age of 18 years has not been studied.
Impact on the ability to drive vehicles and manage mechanisms
Since olanzapine may cause drowsiness, patients taking olanzapine should be careful in managing mechanical means, including the car.
Symptoms: very often (? 10%) - tachycardia, agitation, aggressiveness, articulation disorder, extrapyramidal disorders and disorders of consciousness of varying severity (from sedation to coma). Delirium, seizures, malignant neuroleptic syndrome, respiratory depression, aspiration, arterial hypertension or hypotension, cardiac arrhythmias (<2% of cases), cardiac arrest and respiration were also noted. The minimum dose for an overdose with a lethal outcome was 450 mg, the maximum dose for an overdose with a favorable outcome (survival) is 1.5 g.
Treatment: there is no specific antidote. Symptomatic therapy is shown in accordance with the clinical condition and control of the functions of vital organs (treatment of arterial hypotension, circulatory collapse, support of respiratory function). Do not use epinephrine, dopamine and other sympathomimetics, which are agonists of? -adrenoceptors, because stimulation of these receptors can aggravate arterial hypotension.
The metabolism of olanzapine can be altered by inhibitors or inducers of cytochrome P 450 isoenzymes exhibiting specific activity against CYP1A2. The clearance of olanzapine increases in smokers and in patients taking carbamazepine (due to an increase in activity of CYP1A2). Known potential inhibitors of CYP1A2 can reduce the clearance of olanzapine. Olanzapine is not a potential inhibitor of CYP1A2 activity, so when taking the drug, the pharmacokinetics of drugs such as theophylline, mostly metabolized with the participation of CYP1A2, does not change.
In clinical trials, it was shown that a single dose of olanzapine on the background of therapy with the following drugs was not accompanied by the suppression of the metabolism of these drugs: imipramine or its metabolite desipramine (CYP2D6, CYP3A4, CYP1A2), warfarin (CYP2S19), theophylline (CYP1A2), diazepam (CYP3A4, CYP2C19). There were no signs of drug interaction when using olanzapine in combination with lithium or biperiden.
Against the background of a stable concentration of olanzapine, there was no change in the pharmacokinetics of ethanol. However, the administration of ethanol with olanzapine may be accompanied by an increase in the pharmacological effects of olanzapine, for example, sedation.
Fluoxetine (60 mg once or 60 mg daily for 8 days) causes an increase in the maximum concentration of olanzapine by an average of 16% and a decrease in the clearance of olanzapine by an average of 16%. The degree of influence of this factor is significantly inferior to the severity of individual differences in these indicators, so it is usually not recommended to change the dose of olanzapine when it is prescribed in combination with fluoxetine.
In vitro studies using human liver microsomes showed that olanzapine slightly suppresses the process of formation of valproate glucuronide (the main pathway of valproate metabolism). Valproate also slightly affects the metabolism of olanzapine in vitro. Therefore, clinically significant interactions between olanzapine and valproate are unlikely.
According to in vitro studies using human liver microsomes, olanzapine also demonstrated an extremely low potential in inhibiting the activity of the following cytochrome P 450 isoenzymes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dark place at a temperature of 15 В° to 30 В° C; Do not freeze. Shelf life - 2 years.
The prepared solution should be used within 1 hour after dilution.