Composition, form of production and packaging
The tablets covered with a film shell of white color, round, biconcave, with engraving "N23" on one side.
1 tab.
olanzapine 2.5 mg
Excipients: crospovidone - 2 mg, microcrystalline cellulose (type 102) - 11.5 mg, microcrystalline cellulose (type 200) - 26.5 mg, lupus - 58.25 mg (lactose monohydrate - 93%, povidone 3.5%, crospovidone 3.5%), magnesium stearate - 1.259 mg.
Sheath composition: opedrail II white - 3 mg (polyvinyl alcohol - 45.52%, titanium dioxide - 32%, talc - 20%, soy lecithin - 2%, xanthan gum - 0.48%).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film membrane of white color, round, biconcave, with engraving "N24" on one side.
1 tab.
olanzapine 5 mg
Excipients: crospovidone - 4 mg, microcrystalline cellulose (type 102) - 23 mg, microcrystalline cellulose (type 200) - 53 mg, lupus - 116.5 mg (lactose monohydrate - 93%, povidone 3.5%, crospovidone 3.5%), magnesium stearate - 2.5 mg.
The composition of the shell: opedrai II white - 6 mg (polyvinyl alcohol - 45.52%, titanium dioxide - 32%, talc - 20%, soy lecithin - 2%, xanthan gum - 0.48%).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film shell of white color, round, biconcave, with engraving "N25" on one side.
1 tab.
olanzapine 7.5 mg
Excipients: Crospovidone - 6 mg, microcrystalline cellulose (type 102) - 34.5 mg, microcrystalline cellulose (type 200) - 79.5 mg, lupistine - 174.75 mg (lactose monohydrate - 93%, povidone 3.5%, crospovidone 3.5%), magnesium stearate - 3.75 mg.
The composition of the shell: opadrai II white - 9 mg (polyvinyl alcohol - 45.52%, titanium dioxide - 32%, talc - 20%, lecithin soy - 2%, xanthan gum - 0.48%).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film cover of white color, round, biconcave, with engraving "N26" on one side.
1 tab.
olanzapine 10 mg
Excipients: crospovidone - 8 mg, microcrystalline cellulose (type 102) - 34.5 mg, microcrystalline cellulose (type 200) - 106 mg, lupus-233 mg (lactose monohydrate - 93%, povidone 3.5%, crospovidone 3.5%), magnesium stearate - 5 mg.
The composition of the shell: opedrai II white - 12 mg (polyvinyl alcohol - 45.52%, titanium dioxide - 32%, talc - 20%, soy lecithin - 2%, xanthan gum - 0.48%).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film shell of white color, round, biconcave, with engraving "N27" on one side.
1 tab.
olanzapine 15 mg
Excipients: crospovidone - 6 mg, microcrystalline cellulose (type 102) - 34.5 mg, microcrystalline cellulose (type 200) - 72 mg, lupistine - 174.75 mg (lactose monohydrate - 93%, povidone 3.5%, crospovidone 3.5%), magnesium stearate - 3.75 mg.
The composition of the shell: opadrai II white - 9 mg (polyvinyl alcohol - 45.52%, titanium dioxide - 32%, talc - 20%, lecithin soy - 2%, xanthan gum - 0.48%).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film shell of white color, round, biconcave, with engraving "N28" on one side.
1 tab.
olanzapine 20 mg
Excipients: crospovidone - 8 mg, microcrystalline cellulose (type 102) - 46 mg, microcrystalline cellulose (type 200) - 96 mg, ludipress - 233 mg (lactose monohydrate - 93%, povidone 3.5%, crospovidone 3.5%), magnesium stearate - 5 mg.
The composition of the shell: opedrai II white - 12 mg (polyvinyl alcohol - 45.52%, titanium dioxide - 32%, talc - 20%, soy lecithin - 2%, xanthan gum - 0.48%).
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
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 brainstem formation; 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, H 1 -gistamine 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 and distribution
Absorption of olanzapine is high, it does not depend on food intake. Time to reach C max in the blood plasma after taking the drug inside - 5-8 hours.
When taken in the dose range of 1-20 mg, the concentration in the plasma changes linearly, in proportion to the dose.
At a plasma concentration of 7-1000 ng / ml, the association with proteins is 93%; mainly with albumin and alpha 1-acid glycoprotein. Penetrates through gistogematicheskie barriers, incl. GEB.
Metabolism and excretion
Metabolised in the liver by conjugation and oxidation, active metabolites are not formed, the main pharmacological activity of the drug is due to olanzapine. The main circulating metabolite is glucuronide, it does not penetrate the BBB. Isozymes CYP1A2 and CYP2D6 cytochrome P450 are involved in the formation of N-desmethyl and 2-hydroxymethyl metabolites of olanzapine.
It is excreted mainly by kidneys (60%) in the form of metabolites.
Pharmacokinetics in special clinical cases
Smoking, sex and age affect T 1/2 and plasma clearance: non-smokers (clearance - 18.6 l / h, T 1/2 - 38.6 h), smoking (clearance - 27.7 l / h, T 1/2 - 30.4 h) ; women (ground clearance - 18.9 l / h, T 1/2 - 36.7 h), men (ground clearance - 27.3 l / h, T 1/2 - 32.3 h). In patients older than 65 years, T 1/2 is 51.8 h and plasma clearance is 17.5 l / h; in patients younger than 65 years T 1/2 - 33.8 h and plasma clearance - 18.2 l / h. Plasma clearance is lower in patients with hepatic insufficiency, women and non-smokers compared to the corresponding groups of patients.
INDICATIONS
- schizophrenia in adults (exacerbation, sustained and prolonged anti-relapse therapy), psychotic disorders in schizophrenia with productive (including delirium, hallucinations, automatisms) and / or negative (emotional flatness, decreased social activity, impoverishment of speech), symptomatology and concomitant affective disorders;
- bipolar affective disorder in adults (monotherapy or in combination with lithium or valproic acid preparations): acute manic or mixed episodes with or without psychotic manifestations and with / without rapid phase change;
- prevention of recurrence of mania in bipolar disorder (with the effectiveness of the drug in the treatment of the manic phase).
DOSING MODE
The drug is taken orally, regardless of food intake, washed down with water.
In schizophrenia in adults, the recommended initial dose is 10 mg / day.
In a manic episode associated with bipolar disorders in adults , 15 mg / day (1 time) as monotherapy or 10 mg / day (1 time) in combination with lithium or valproic acid (maintenance therapy at the same dose).
Prevention of recurrence of mania in bipolar disorder: the recommended initial dose of the drug in a state of remission is 10 mg / day. For patients who have already received Parnasan В® for the treatment of manic episodes, maintenance therapy is administered in the same doses. Against the background of therapy with Parnasan В®in case of a new manic, mixed or depressive episode, if necessary, increase the dose of the drug with additional treatment of mood disorders, according to clinical indications.
The daily dose of the drug in the treatment of schizophrenia, manic episode or prevention of recurrence of bipolar disorder may 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. For moderate hepatic insufficiency (cirrhosis, grade A or B on the Child-Pugh scale), the initial dose is 5 mg / day, and further increase in the dose with caution.
Women do not need a correction of the dosing regimen 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 of the drug. If necessary, further increase in dose with caution.
SIDE EFFECT
The incidence of side effects noted with the administration of Parnasan В® is given in accordance with the WHO classification: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1 / 100), rarely (> 1/10 000 and <1/1000), very rarely (<1/10000, including individual messages).
From the nervous system: very often - drowsiness; often - dizziness, akathisia, parkinsonism, asthenia, dyskinesia; rarely - convulsive syndrome (more often in the background of convulsive syndrome in anamnesis); very rarely - malignant neuroleptic syndrome, dystonia (including oculogic crisis) and tardive dyskinesia. With the abrupt withdrawal of Parnasan В®, very rarely are symptoms such as increased sweating, insomnia, tremors, anxiety, nausea, or vomiting.
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 QTc on the ECG, ventricular tachycardia / fibrillation and sudden death; very rarely - thromboembolism (including pulmonary artery embolism and deep vein thrombosis).
From the side of the digestive system: often - transitory anticholinergic effects, incl. constipation and dryness of the oral mucosa; rarely - hepatitis; very rarely - pancreatitis.
From the side of metabolism: very often - an increase in body weight; often - increased appetite, hypertriglyceridemia; very rarely - hyperglycemia and / or decompensation of diabetes mellitus, sometimes manifested by ketoacidosis or coma, including death, hypercholesterolemia, hypothermia.
On the part of the digestive system: often - a transient, asymptomatic increase in the activity of hepatic transaminases (ALT, ACT), especially at the beginning of therapy; rarely - hepatitis (including hepatocellular, cholestatic or mixed liver damage).
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: rarely - skin rash; infrequently - photosensitization reactions; very rarely - alopecia.
Allergic reactions: rarely - skin rash; very rarely - anaphylactoid reactions, angioedema, skin itching or urticaria.
Other: often - asthenia, peripheral edema; very rarely - withdrawal syndrome.
On the part of 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; rarely - transient, asymptomatic increase in ALT activity, ACT;infrequently - increased activity of CK; very rarely - increased activity of AP and total bilirubin; in isolated cases, an increase in plasma glucose of more than 200 mg / dL (suspected diabetes mellitus), 160-200 mg / dL (suspected hyperglycaemia) in patients with baseline glucose concentrations of less than 140 mg / dl. There were cases of an increase in the level of triglycerides (by 20 mg / dl from the initial), cholesterol (by 0.4 mg / dl from the initial), asymptomatic eosinophilia (single cases).
In elderly patients with dementia, a large incidence of deaths and cerebrovascular disorders (stroke, transient ischemic attacks) is documented in studies. Very frequent in this category of patients were violations 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 (more than 10%) of tremors, dryness of the oral mucosa, increase appetite or weight gain. Violations of speech (from 1 to 10%) were also recorded.
CONTRAINDICATIONS
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
- the period of lactation (breastfeeding);
- age under 18 years (effectiveness and safety not established);
- Hypersensitivity to the active substance and other components of the drug.
Caution should be applied to the drug with renal failure, liver failure, benign prostatic hyperplasia, closed-angle glaucoma, paralytic intestinal obstruction, epilepsy, convulsive syndrome in history, 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 of the QT interval on the ECG (increase of the QT interval corrected on the ECG) or in the presence of conditions potentially capable of causing an increase in the QT interval (for example , simultaneous use of drugs that extend the QT interval, chronic heart failure, hypokalemia, hypomagnesemia), elderly patients, and while concurrent administration of drugs of central action; at phenylketonuria, immobilization, during pregnancy.
PREGNANCY AND LACTATION
Due to the limited experience of using the drug in pregnant women, Parnasan В® should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus. Women should be informed of the need to inform the doctor about the pregnancy or planned pregnancy with Parnasan В® . 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.
Studies have shown that olanzapine is excreted in breast milk. The average dose (mg / kg) received by the child when the equilibrium concentration was reached in the mother was 1.8% of the dose of Parnasan В® mother (mg / kg). It is not recommended to breast-feed on the background of therapy with Parnasan В® .
APPLICATION FOR FUNCTIONS OF THE LIVER
Use with caution in case of impaired renal function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in case of impaired liver function.
APPLICATION FOR CHILDREN
Contraindicated in children under 18 years.
APPLICATION IN ELDERLY PATIENTS
Use with caution elderly people.
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 diabetic coma, incl. there are reports of several lethal cases. There is no causal relationship between antipsychotic agents and these conditions. In some cases, there was a previous decompensation of weight gain, which could become a predisposing factor. Patients with diabetes mellitus or with risk factors for the development of this disease are recommended regular clinical monitoring and control of the concentration of glucose in the blood.
When the lipid concentration changes, correction of therapy is required.
With a sharp discontinuation of Parnasan В®, very rarely (less than 0.01%) develop the following symptoms: sweating, insomnia, tremor, anxiety, nausea, or vomiting.With the withdrawal of the drug, a gradual dose reduction is recommended.
Anticholinergic activity
Since the clinical experience of using Parnasan В® in patients with concomitant diseases is limited, the drug should be used with caution in patients with benign prostatic hyperplasia, paralytic intestinal obstruction, closed-angle glaucoma.
Parnasan В® is not recommended for the treatment of psychosis in Parkinson's disease caused by dopaminomimetics. The symptoms of parkinsonism and hallucinations increase. At the same time, the Parnasan В® drug did not exceed the placebo by the effectiveness of psychosis treatment.
Parnasan В® is not indicated for the treatment of psychosis and / or behavioral disorders in dementia due to increased mortality and increased risk of cerebrovascular disorders (stroke, transient ischemic attacks). These patients had previous risk factors (cerebrovascular disorders (history), transient ischemic attack, hypertension, smoking), as well as concomitant diseases and / or drug administration associated with cerebrovascular disorders. The increase in mortality does not depend on the dose of Parnasan В® or the duration of therapy. Risk factors predisposing to an increase in mortality include age over 65 years, dysphagia, sedation, malnutrition and dehydration, lung diseases (for example, pneumonia, including aspiration), simultaneous reception of benzodiazepines. However, the increased mortality in the Parnasan В® group 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.
Impaired liver function
At the beginning of therapy, an asymptomatic increase in hepatic transaminase activity (ALT and ACT) is possible. In patients with initially elevated ACT and / or ALT activity, with hepatic insufficiency and conditions potentially limiting the functionality of the liver, as well as those taking hepatotoxic drugs, caution should be exercised when using Parnasan В® . When the activity of ALT and / or ACT is increased against the background of drug therapy, it is recommended to observe the patient and, possibly, reduce the dose of the drug. When diagnosing hepatitis (including hepatocellular, cholestatic or mixed), Parnasan В® should be discontinued.
Hematologic disorders
The drug should be used with caution in patients with leukopenia and / or neutropenia any genesis, myelosuppression drug origin, as well as the background radiation or chemotherapy, due to comorbidities giperezonofilnymi in patients with myeloproliferative disorders or states. Neutropenia often observed while taking the drug Parnasan В® and valproic acid.
Neuroleptic malignant syndrome (CSN)
CSN - a potentially life threatening condition associated with therapy with antipsychotic drugs (neuroleptics), including: drug Parnasan В®. Clinical manifestations of NMS: fever, muscle rigidity, altered mental status, autonomic disorders (unstable heartbeat or labile blood pressure, tachycardia, sweating, arrhythmia). Additional symptoms of NMS: increased activity of CK, myoglobinuria (rhabdomyolysis on the background), and acute renal failure. With the development of NMS symptoms, as well as an increase in body temperature for no apparent reason, it is necessary to cancel all antipsychotics, including Parnasan preparation В® .
Writhing syndrome
drug Parnasan В® should be used with caution in patients with a history of seizures, or the presence of factors that lower the seizure threshold. In patients receiving the drug Parnasan В® seizures are rarely detected.
tardive dyskinesia
Drug therapy Parnasan В® accompanied by a significantly lower incidence of tardive dyskinesia as compared to haloperidol. The risk of developing tardive dyskinesia increases with the duration of therapy. When signs of the condition of the patient receiving the medication Parnasan В® , the drug should cancel or reduce the dose.Symptoms of tardive dyskinesia may increase or manifest after the drug is discontinued.
Overall activity in the CNS
should be careful while using other centrally acting agents, and alcohol.
Cerebrovascular adverse events, including stroke, in elderly patients with dementia
In elderly patients rarely observed postural hypotension. In patients older than 65 years should periodically monitor blood pressure. Preparation Parnasan В® should be used with caution in patients with established increased interval QT c , especially elderly patients with congenital syndrome increased interval QT, chronic heart failure, myocardial hypertrophy, hypokalemia and hypomagnesemia.
When receiving the preparation Parnasan В®very rarely (less than 0.01%) reported cases of venous thromboembolism. The causal relationship between the drug therapy Parnasan В® 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.
Under conditions in vitro olanzapine exhibits antagonism against dopamine and, like other neuroleptics, can theoretically suppress the action of levodopa and dopamine agonists.
Impact on the ability to drive vehicles and manage mechanisms
Because the drug Parnasan В® can cause drowsiness and dizziness, patients should be exercised when operating machinery requiring a high concentration, includingand road management.
OVERDOSE
Symptoms: very frequent (over 10%) with a drug overdose Parnasan В® 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, hypertension or hypotension, arrhythmias; in very rare cases - cardio-pulmonary insufficiency. Minimal dose of the drug Parnasan В® 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 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 is necessary to monitor cardiovascular activity. The patient should be under continuous medical supervision until complete recovery.
DRUG INTERACTION
Potential drug interactions affecting the metabolism of olanzapine
Olanzapine metabolized isoenzyme CYP1A2, however inhibitors or inducers of cytochrome P450 isoenzymes, exhibiting a specific activity against SYP1A2 can affect the pharmacokinetic parameters of olanzapine.
CYP1A2 inducers: 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 mean increase in olanzapine AUC in these categories of patients was, respectively, 52% and 108%. Patients taking fluvoxamine or any other inhibitor of isozyme CYP1A2 (e.g., ciprofloxacin), olanzapine therapy recommended to start with smaller doses. Reducing the dose of olanzapine may also be required in the case of adherence to therapy isoenzyme CYP1A2 inhibitors.
Drug interactions affecting / influencing the bioavailability not olanzapine
Activated charcoal reduces the absorption of olanzapine at intake by 50-60%, however it should be taken at least 2 hours before or after olanzapine.
Fluoxetine - inhibitor of isozyme CYP1A2 (60 mg or 60 mg once daily for 8 days) increases the C max of olanzapine by 16% and reduces the clearance of 16%, which is clinically value (correction doses of olanzapine required).
A single dose of magnesium- or aluminum-containing antacids or cimetidine did not affect the pharmacokinetics of olanzapine.
The potential ability of olanzapine to affect other medicinal products.
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 (SYP2S9), theophylline (SYP1A2) and diazepam (SYP3A4 and 2C19).
There were no interaction while the use of lithium or biperidenom. Olanzapine slightly suppresses the formation of valproic acid glucuronide (the main pathway of metabolism). Valproic acid is insignificant / affect the metabolism of olanzapine. Clinically significant pharmacokinetic interaction between olanzapine and valproic acid is unlikely. The therapeutic monitoring of the content of valproic acid in blood plasma showed that while the use of olanzapine, valproic acid changes doses are required.
Caution must be exercised while the use of other drugs central action. Despite the fact that a single dose of alcohol at a dose of 45 mg / 70 kg has no pharmacokinetic effect of alcohol intake with olanzapine may be accompanied by increased sedative action 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 out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 3 years.
