Egolanza - instructions for use, dose, side effects, contraindications

active substance: 5 mg, 7.5 mg, 10 mg, 15 mg and 20 mg of olanzapine (in the form of 7.03 mg, 10.55 mg, 14.06 mg, 21.09 mg and 28.12 mg of olanzapine dihydrochloride trihydrate, respectively;

Excipients: core: microcrystalline cellulose (40.99 / 61.48 / 81.97 / 122.96 / 163.94 mg), lactose monohydrate (40.98 / 61.47 / 81.97 / 122.95 / 163.94 mg ), giprolose (hydroxypropyl cellulose) (5.0 / 7.5 / 10.0 / 15.0 / 20.0 mg), crospovidone (5.0 / 7.5 / 10.0 / 15.0 / 20.0 mg), magnesium stearate (1.0 / 1.5 / 2.0 / 3.0 / 4.0 mg);

sheath: hypromellose (1.4 / 1.9 / 2.4 / 3.1 / 3.8 mg), dye quinoline yellow (0.014 / 0.019 / 0.023 / 0.031 / 0.038 mg), opadrai Y-1.7000 white (2.79 / 3.78 / 4.68 / 6.27 / 7.66 mg): hypromellose (62.5%), titanium dioxide (31.25%), macrogol 400 (6, 25% mg).

Description:

Tablets 5 mg: Oblong biconvex tablets covered with a film coat, yellow, without or almost odorless, with a risk on one side and engraved E 402 on the other side of the tablet.

Tablets 7.5 mg: Round, biconvex tablets, film-coated, yellow, without or almost odorless, with engraved E 403 on one side of the tablet.

Tablets 10 mg: Round biconvex tablets coated with a film coating, yellow, without or almost odorless, with engraved E 404 on one side of the tablet.

Tablets 15 mg: Round, biconvex tablets, film-coated, yellow, without or almost odorless, with engraved E 405 on one side of the tablet.

Tablets of 20 mg: Round biconvex tablets covered with a film coat, yellow, without or almost odorless, with engraved E 406 on one side of the tablet.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.03 Olanzapine

Pharmacodynamics:

Olanzapine is an antipsychotic agent (neuroleptic) with a broad pharmacological spectrum of influence on a number of receptor systems.

Has an affinity for serotonin (5-HT_{2а / с}, 5HT₃, 5NT₆), dopamine (D_1, D₂, D₃, D₄, D₅), muscarinic (M_1-5), adrenergic (alpha₁ and histamine (H₁) receptors.

Antagonism to serotonin (5HT), dopamine and cholinergic receptors was detected. Has a more pronounced affinity and activity with respect to serotonin 5HT₂-receptors, in comparison with dopamine D₂receptors.

Selectively reduces the excitability of mesolimbic (A10) dopaminergic neurons, has an insignificant effect on striatal (A9) neural pathways involved in the regulation of motor functions. Reduces the conditioned protective reflex in lower doses than the doses causing catalepsy. Strengthens the anti-anxiety effect during the "anxiolytic" test. Reliably reduces the productive (including delirium, hallucinations) and negative symptoms.

Pharmacokinetics:

Olanzapine is well absorbed after ingestion. FROM_mOh after oral intake is achieved after 5-8 hours. Food does not affect the absorption of the drug.

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 alpha₁acid glycoprotein.

Metabolised in the liver by conjugation and oxidation. The main circulating metabolite - 10-N-glucuronide, does not penetrate the blood-brain barrier (BBB). Isozymes CYP1A2 and CYP2D6 cytochrome P450 are involved in education N-desmethyl and 2-hydroxymethyl metabolites of olanzapine.

The main pharmacological activity of the drug is due to olanzapine, the activity of its metabolites is less pronounced.

It is excreted by the kidneys - 57% (mainly in the form of metabolites).

In healthy volunteers after oral administration, the half-life of T_1/2olanzapine is 33 h (21-54 h), and the average plasma clearance is 26 l / h (12-47 l / h).

The half-life of olanzapine may vary depending on the age and sex, as well as the status of smoking: non-smokers (clearance - 18.6 l / h, T_1/2- 38.6 hours), smoking (clearance - 27.7 l / h, T_1/2 - 30.4 hours), women (ground clearance - 18.9 l / h, T_1/2- 36.7 hours), men (ground clearance - 27.3 l / h, T_1/2 - 32.3 hours), patients 65 years and older (ground clearance - 17.5 l / h, T_1/2 - 51.8 h), patients under 65 years of age (ground clearance - 18.2 l / h, T_1/2 - 33.8 h).

The degree of change 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 indicators. Reliable differences between the mean values of T_1/2 and plasma clearance of olanzapine in patients with severe renal dysfunction and in patients with normal renal function is not established.

Indications:

Schizophrenia (exacerbation, sustained and prolonged anti-relapse therapy). Bipolar affective disorder (monotherapy or in combination with drugs Li+ or valproic acid): acute manic or mixed episodes with / without psychotic manifestations and with / without rapid phase change.

Recurrence of bipolar disorder and prevention of recurrence of bipolar disorder (with efficacy of the drug in the treatment of the manic phase).

Contraindications:

Hypersensitivity to the active ingredient or any of the components of the drug.

Closed-angle glaucoma.

Psychoses and / or behavioral disorders associated with dementia.

Lactation period.

Children's age (under 18 years due to lack of clinical data).

Lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose).

Carefully:

Hepatic insufficiency, renal failure, prostatic hyperplasia, epilepsy, a history of convulsive syndrome, myelosuppression (including leukopenia, neutropenia), myeloproliferative diseases, hypereosinophilic syndrome, paralytic intestinal obstruction, pregnancy, cardiovascular and cerebrovascular diseases or other conditions predisposing to arterial hypotension, congenital increase in the interval QT on an electrocardiogram (ECG) (an increase in the corrected interval QT (QTc) on the ECG), or in the presence of conditions potentially capable of causing an increase in the interval QT (for example, simultaneous administration of drugs that extend the interval QT, congestive heart failure, hypokalemia, hypomagnesemia), elderly age, as well as simultaneous intake of other drugs of central action; immobilization.

Pregnancy and lactation:

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.

Olanzapine may be excreted in breast milk. It is not recommended to breast-feed on the background of therapy with EGOLANZA.

Dosing and Administration:

Inside, regardless of food intake, once - 5-20 mg / day.

With schizophrenia in adults, the recommended initial dose is 10 mg / day.

In acute mania associated with bipolar disorders in adults - 15 mg / day (1 time) as a monotherapy or 10 mg / day (1 time) in combination with drugs Li+ or valproic acid (maintenance therapy at the same dose).

Prevention of recurrence of bipolar disorder: the recommended initial dose is 10 mg per day. Patients who had previously received olanzapine to treat a manic episode, one should continue treatment at the same dose to prevent relapse. In the presence of a new manic, mixed or depressive episode, taking olanzapine should be continued (if necessary, specifying the dose); In the presence of clinical indications should additionally prescribe drugs to eliminate mood disorders.

In the treatment of schizophrenia, manic episode, as well as for the prevention of relapses of bipolar disorder, the daily dose can be subsequently adjusted in the range of 5 to 20 mg, taking into account the clinical state of the individual patient. Dose correction beyond the recommended dose as the initial dose is recommended only after careful clinical analysis, and should normally occur at intervals of at least 24 hours.

Before stopping taking olanzapine, you should gradually reduce the dose.

The maximum daily dose of olanzapine is 20 mg.

Elderly patients

A lower initial dose (5 mg per day) is not mandatory for all patients, but is possible for patients aged 65 years and older with clinical indications.

Impaired renal and / or liver function

For such patients, it may be necessary to reduce the initial dose (up to 5 mg per day). For moderate hepatic insufficiency (cirrhosis, class A or B by Child-Pugh), an initial dose of 5 mg should be given and increased with caution.

Floor

Women should be prescribed the drug in the same doses as men.

Smokers

Smokers should be given the drug at the same doses as non-smokers.

In the presence of more than one factor that can cause a slowdown in metabolism (female, elderly, non-smokers), the need to reduce the initial dose to 5 mg / day should be considered. If necessary, further increase in dose with caution.

Side effects:

The frequency of side effects noted when taking the drug 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 (> 1/10000 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 - dystonia (including the oculogic crisis) and tardive dyskinesia. Very rarely malignant neuroleptic syndrome (CNS) can develop. Clinical manifestations of CNS are fever, rigidity of muscles, changes in mental state, instability of autonomic functions (unstable levels of heart rate and blood pressure, tachycardia, sweating, cardiac arrhythmia).Additional signs may be an increase in levels of creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. When the patient develops symptoms and signs of the CNS or the occurrence of unexplained fever without additional clinical manifestations of the NSA, all antipsychotics, including olanzapine.

With a sharp withdrawal of the drug, it is very rare to notice such symptoms as increased sweating, insomnia, tremor, anxiety, nausea, or vomiting.

From the cardiovascular system: often - arterial hypotension (including orthostatic); infrequently - a bradycardia with a collapse or without; very rarely - increasing the interval QTc on ECG, ventricular tachycardia / fibrillation and sudden death, very rarely - thromboembolism (including pulmonary artery embolism and deep vein thrombosis).

From the digestive system: often - transient anticholinergic effects, including constipation and dryness of the oral mucosa; rarely - hepatitis; very rarely - pancreatitis.

From the side of metabolism: very often - weight gain; often - increased appetite,hypertriglyceridemia; very rarely - hyperglycemia and / or decompensation of diabetes mellitus, sometimes manifested by ketoacidosis or coma, including death; hypercholesterolemia, hypothermia.

From the digestive system: often - a transient, asymptomatic increase in the activity of "liver" transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (ACT), especially at the beginning of therapy; rarely - hepatitis (including hepatocellular, cholestatic or mixed liver damage).

From the 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 - photosensitivity 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. 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, an increase in the activity of creatine phosphokinase (CKF); very rarely - an increase in the activity of alkaline phosphatase (APF) and total bilirubin. In isolated cases, there was an increase in the concentration of glucose in the blood plasma, triglycerides, cholesterol, asymptomatic eosinophilia.

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 drug (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 treatment with valproate or lithium increases the frequency (10%) of tremor, dryness of the oral mucosa, increased appetite or weight gain. Violations of speech (from 1 to 10%) were also recorded.

Overdose:

Symptoms: tachycardia, agitation / aggression, articulation disorder, extrapyramidal disorders, depression of consciousness of various severity (from sedation to coma), delirium, seizures, neuroleptic malignant syndrome, respiratory depression, aspiration, increase or decrease in blood pressure, arrhythmia, heart failure and respiratory depression.

The minimum dose for acute lethal overdose was 450 mg, the maximum dose with a favorable outcome (survival) - 1500 mg.

Treatment: gastric lavage, the appointment of activated charcoal, symptomatic treatment, maintenance of respiratory function.

Do not use sympathomimetics (including norepinephrine, dopamine) Which are agonists of the beta adrenergic receptors (stimulation of these receptors may worsen AD reduction). Careful medical supervision and monitoring should continue until the patient recovers.

Interaction:

Inductors or inhibitors of isoenzyme CYP1A2 can alter the metabolism of olanzapine. Inductors of isoenzyme CYP1A2: the clearance of olanzapine increases in smoking patients and with the simultaneous use of carbamazepine, which leads to a decrease in the concentration of olanzapine in the blood plasma. You may need to increase the dose of the drug.

Inhibitor inhibitors CYP1A2: fluvoxamine significantly suppresses the metabolism of olanzapine. Reducing the clearance of olanzapine, increases C_maxolanzapine in nonsmoking women by 54% and by 77% - among men who smoke, AUC - by 52% and 108% respectively, therefore in patients receiving fluvoxamine or any other isoenzyme inhibitor CYP1A2 (e.g., ciprofloxacin) should consider the possibility of using a lower initial dose of olanzapine.

Activated charcoal reduces the bioavailability of olanzapine by 50-60% and should be taken at least 2 hours before or 2 hours after olanzapine.

Fluoxetine (inhibitor CYP2D6), as well as a single dose of antacid preparations (aluminum or magnesium) or cimetidine, did not significantly affect the pharmacokinetics of olanzapine.

Ethanol did not affect the pharmacokinetics of olanzapine in the equilibrium state, however,the administration of ethanol together with olanzapine may be accompanied by an increase in the pharmacological effects of olanzapine (sedation).

Olanzapine slightly suppresses the formation of valproic acid glucuronide (the main pathway of metabolism). Valproic acid slightly affects the metabolism of olanzapine. Clinically significant pharmacokinetic interaction between olanzapine and valproic acid is unlikely.

Caution is needed when using olanzapine with drugs that extend the interval QTc (amitriptyline, chlorpromazine, droperidol, thioridazine, pimozide, quinidine, procainamide, sotalol, ephedrine, adrenaline, terbutaline, erythromycin, trimethoprim / sulfamethoxazole, ketoconazole, fluconazole, etc.) that disrupt the electrolyte balance or inhibit the metabolism of olanzapine in the liver.

The simultaneous use of olanzapine and antiparkinsonian drugs in patients with Parkinson's disease and dementia is not recommended.

Olanzapine exhibits antagonism against dopamine and, theoretically, can suppress the action of levodopa and dopamine agonists.

Olanzapine does not suppress major isoenzymes CYP450 in vitro (e.g., 1A2, 2D6, 2C9, 2C19, 3A4), clinically significant interaction is unlikely. There is no suppression of the metabolism of the following active substances: tricyclic antidepressants (representing mainly the pathway CYP2D6), warfarin (CYP2C9), theophylline (CYP1A2) or diazepam (CYP3A4 and 2C19).

No interaction was detected when used simultaneously with lithium or biperidene.

Special instructions:

During the administration of antipsychotics, the improvement of the clinical state of patients can occur within a few days or weeks. During this period, patients need careful monitoring.

Psychosis and / or behavioral disorders associated with dementia

Olanzapine is not approved for the treatment of psychosis and / or behavior disorders associated with dementia, and this drug is not recommended for use in such patients because of increased mortality and risk of impaired cerebral circulation.

With olanzapine in elderly patients with psychosis against a background of dementia, cerebrovascular disorders (stroke, transient ischemic attack), including lethal outcomes, were noted. These patients had previous risk factors (cerebrovascular disorders (history), transient ischemic attacks, hypertension, smoking),as well as concomitant diseases and / or drug use, associated with time-related cerebro-vascular disorders.

The use of olanzapine is not recommended for the treatment of psychoses associated with the administration of dopamine agonists in patients with Parkinson's disease.

Malignant neuroleptic syndrome (CNS)

When treating with neuroleptics (including olanzapine), a malignant neuroleptic syndrome can develop. Clinical manifestations of CNS are fever, rigidity of muscles, changes in mental state, instability of autonomic functions (unstable levels of heart rate and blood pressure, tachycardia, sweating, cardiac arrhythmia). Additional signs may be an increase in levels of creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. When the patient develops symptoms and signs of the CNS or the occurrence of unexplained fever without additional clinical manifestations of the NSA, all antipsychotics, including olanzapine.

Hyperglycemia and diabetes mellitus

There is a higher prevalence of diabetes mellitus in patients with schizophrenia.Very rarely there were cases of hyperglycemia, development of diabetes mellitus or exacerbation of pre-existing diabetes mellitus, ketoacidosis and diabetic coma. There is no causal relationship between antipsychotic drugs and these conditions. Clinical monitoring of patients with diabetes mellitus or with risk factors for its development is recommended.

Changes in lipid levels

When lipid levels change with olanzapine taking, appropriate treatment should be prescribed, especially in patients with dyslipidemia or risk factors for fat metabolism disorders.

Anticholinergic activity

Despite the fact that olanzapine in vitro has anticholinergic activity, due to the limited clinical experience of olanzapine in patients with concomitant diseases, caution is recommended when prescribing this drug to patients with prostatic hypertrophy, paralytic intestinal obstruction and other similar conditions.

Liver function

Particular caution is necessary when the activity of hepatic transaminases, ALT and / or ACT in patients with hepatic insufficiency or receiving potentially hepatotoxic drugs. It is necessary to monitor the patient and, if necessary, reduce the dose. If hepatitis is detected (including hepatocellular, cholestatic or mixed liver damage), olanzapine should be discontinued.

Neutropenia

Olanzapine should be used with caution in patients with a decrease in the number of leukocytes including neutrophils; with signs of oppression or toxic impairment of bone marrow function under the influence of drugs (in the anamnesis); with oppression of bone marrow function due to concomitant disease, radio or chemotherapy (in history); with hypereosinophilia or myeloproliferative disease. Neutropenia is often observed with the combined use of olanzapine and valproate.

The use of olanzapine in patients with clozapine-dependent neutropenia or agranulocytosis (in the anamnesis) was not accompanied by relapses of these disorders.

Discontinuation of the drug

With a sharp discontinuation of olanzapine in very rare cases (<0.01%), acute symptoms were noted, for example, insomnia, tremors, anxiety, nausea, or vomiting.

Interval QT

As with other antipsychotics, care should be taken during treatment with olanzapine if this drug is administered simultaneously with drugs that extend the interval QTc, especially in elderly patients, patients with congenital lengthening syndrome QT, congestive heart failure, cardiac hypertrophy, hypokalemia, hypomagnesia, or lengthening QT in a family history.

It should avoid the simultaneous use of other antipsychotics or drugs that also extend the interval QT or causing hypokalemia.

Thromboembolism

Coincidence of olanzapine and venous thromboembolism was recorded in rare cases (less than 0.01%). The causal relationship between symptoms of venous thromboembolism and the administration of olanzapine has not been established. However, because schizophrenia patients often have acquired risk factors for venous thromboembolism, all possible risk factors for venous thromboembolism, for example, patient immobility, should be identified and preventive measures taken.

Convulsive seizures

Olanzapine should be used with caution in patients,who have a history of convulsive seizures or are exposed to factors that reduce the threshold of convulsive readiness. Convulsive seizures in patients receiving olanzapine, are rare. In most of these cases, convulsive seizures in the history or risk factors of convulsive seizures are recorded.

Late dyskinesia

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.

Orthostatic hypotension

In clinical trials of olanzapine, orthostatic hypotension was rarely observed in elderly patients. As in the case of taking other antipsychotics, it is recommended to periodically measure blood pressure in patients older than 65 years.

Pediatric Use

Olanzapine is not recommended for the treatment of children and adolescents. Studies conducted in patients aged 13-17 years, revealed various adverse reactions, including weight gain, changes in metabolism parameters and increased prolactin levels. Long-term outcomes of these phenomena have not been studied and remain unknown.

Lactose

This drug contains lactose, so it should not be administered to patients with rare hereditary disorders of tolerance to galactose, a hereditary deficiency of Sami lactase or glucose-galactose malabsorption.

Caution should be exercised when using olanzapine in combination with other central-action drugs and ethanol.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Film-coated tablets, 5 mg, 7.5 mg, 10 mg, 15 mg and 20 mg.

Packaging:

For 7 tablets in a blister of the combined film "cold"(polyamide / aluminum foil / PVC) // aluminum foil.

4 or 8 blisters together with instructions for use are packed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep the drug out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000897

Date of registration:18.10.2011

The owner of the registration certificate:Egis Pharmaceutical Plant OJSCEgis Pharmaceutical Plant OJSC Hungary

Manufacturer: & nbsp

EGIS PHARMACEUTICALS, Plc Hungary

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp16.08.2015

Illustrated instructions

Instructions

Egolans® (Egolanza®)