Composition, form of production and packaging
Tablets from light yellow to yellow, cylindrical, biconvex, engraved "L" on one side.
1 tab.
olanzapine 2.5 mg
Excipients: microcrystalline cellulose - 85.6 mg, lactose monohydrate - 17.2 mg, crospovidone - 1.1 mg, magnesium stearate - 1.1 mg.
7 pcs. - packings cellular planimetric (4) - packs cardboard.
Tablets from light yellow to yellow, cylindrical, biconvex, engraved "FA20" on one side.
1 tab.
olanzapine 5 mg
Excipients: microcrystalline cellulose - 171.3 mg, lactose monohydrate - 34.3 mg, crospovidone - 2.2 mg, magnesium stearate - 2.2 mg.
7 pcs. - packings cellular planimetric (4) - packs cardboard.
Tablets from light yellow to yellow color, cylindrical, biconvex, engraved "F20C" on one side.
1 tab.
olanzapine 7.5 mg
Excipients: microcrystalline cellulose - 257 mg, lactose monohydrate - 51.6 mg, crospovidone - 3.2 mg, magnesium stearate - 3.2 mg.
7 pcs. - packings cellular planimetric (8) - packs cardboard.
Tablets from light yellow to yellow color, cylindrical, biconvex, engraved "N30C" on one side.
1 tab.
olanzapine 10 mg
Excipients: microcrystalline cellulose - 342.6 mg, lactose monohydrate - 68.8 mg, crospovidone - 4.3 mg, magnesium stearate - 4.3 mg.
7 pcs. - packings cellular planimetric (4) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
PHARMACHOLOGIC EFFECT
Antipsychotic drug (antipsychotic). It has an affinity for serotonin (5-HT 2A / 2C , 5-HT 3 , 5-HT 6 ), dopamine (D 1 , D 2 , D 3 , D 4 , D 5 ), muscarinic (M 1-5 ), adrenergic (? 1 ) and histamine (H 1 ) receptors.
In vitro antagonism to 5-HT, dopaminovym and cholinergic receptors was detected. It has more pronounced affinity and activity with respect to serotonin 5-HT 2receptors, in comparison with dopamine D 2 -receptors.
Selectively reduces the excitability of mesolimbic (A10) dopaminergic neurons, has an insignificant effect on the striatum (A9) nerve 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
Suction and distribution
Absorption is high, does not depend on food intake; the time to reach C max after oral administration is 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 1- acid glycoprotein).
Metabolism
Metabolised in the liver by conjugation and oxidation. The main circulating metabolite is 10-N-glucuronide, which does not penetrate the GEB.
Isozymes CYP1A2 and CYP2D6 are involved in the formation of 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.
Excretion
Clearance - 26 l / h (12-47 l / h), T 1/2 - 33 h (21-54 h). It is excreted by the kidneys - 57% (mainly in the form of metabolites).
Pharmacokinetics in special clinical cases
Non-smoking (18.6 liters per hour, T 1/2 - 38.6 hours), smoking (27.7 liters per hour, T 1/2 - 30.4 hours), women (ground clearance 18.9 liters per hour, T 1/2 - 36.7 hours), men (clearance 27.3 l / h, T 1/2 - 32.3 h), patients 65 years and older (ground clearance 17.5 l / h, T 1/2 -51.8 h), patients under the age of 65 years (ground clearance - 18.2 l / h, T 1/2 - 33.8 h).
Smoking people with minor impairments of liver function are lower than in non-smoking non-disturbed liver function.
INDICATIONS
- schizophrenia in adults (exacerbation, supporting and prolonged anti-relapse therapy), psychotic disorders 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;
- recurrence of bipolar disorder (with efficacy of the drug in the treatment of the manic phase);
- Depressive conditions associated with bipolar disorder (in combination with fluoxetine).
DOSING MODE
The drug is taken orally, regardless of food intake, at a dose of 5-20 mg / day.
In schizophrenia in adults, the recommended initial dose is 10 mg / day.
In acute mania associated with bipolar disorders, adults 15 mg once a day as monotherapy or 10 mg once a day in combination with lithium or valproic acid (maintenance therapy at the same dose).
In depression associated with bipolar disorders, in adults - 5 mg 1 time / day in combination with 20 mg fluoxetine (if necessary, changes in the doses of drugs).
Elderly patients , patients with risk factors (including severe CRF or moderate-level hepatic insufficiency), with a combination of risk factors (female, elderly, non-smokers) who have olanzapine metabolism may be slowed, a reduction in the initial dose to 5 mg / day.
SIDE EFFECT
The frequency of occurrence of side effects is determined as follows: very often (? 10%), often (? 1% and <10%), infrequently (? 0.1% and <1%), rarely (? 0.01% and <0.1%), very rarely (<0.01%).
In clinical studies, drowsiness and weight gain were very common; in 34% - giperprolaktinemiya (weakly expressed and transient). Clinical manifestations of hyperprolactinaemia were rare.
Often: dizziness, asthenia, akathisia, increased appetite, peripheral edema, orthostatic hypotension, dryness of the oral mucosa, constipation.
Rarely: transient, asymptomatic increase in ALT activity, ACT.
In isolated cases: an increase in plasma glucose levels of more than 200 mg / dl (suspected diabetes mellitus), 160-200 mg / dL (suspected hyperglycaemia) in patients with a baseline glucose concentration 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 patients with psychosis in the background of dementia: very often - a violation of gait and fall; often - incontinence of urine and pneumonia.
In patients with psychosis induced by the use of dopamine agonist in Parkinson's disease: very often - increased symptoms of parkinsonism and hallucinations.
In patients with bipolar mania (receiving the drug in combination with lithium or valproic acid): very often - weight gain, dryness of the oral mucosa, increased appetite, tremor; often - speech disorder.
The following side effects are observed in clinical trials and post-marketing experience.
From the cardiovascular system: often - orthostatic hypotension; infrequently bradycardia; very rarely venous thromboembolism.
From the digestive system: often - constipation, dryness of the oral mucosa, increased appetite; rarely - hepatitis; very rarely - pancreatitis, jaundice.
From the side of metabolism: often - peripheral edema; very rarely-diabetic coma, diabetic ketoacidosis. hyperglycemia, hypercholesterolemia, hypertriglyceridemia.
From the musculoskeletal system: very rarely - rhabdomyolysis.
From the nervous system: very often - drowsiness; often - akathisia, dizziness, asthenia; rarely convulsions.
From the skin: rarely - a rash.
From the genitourinary system: very rarely - priapism.
From the hemopoietic system: often - eosinophilia, rarely - leukopenia, very rarely - thrombocytopenia.
Laboratory indicators: very often hyperprolactinemia; often - increased activity of ALT, ACT, hyperglycemia; very rarely - hyperbilirubinemia, increased activity of alkaline phosphatase.
Other: very often - weight gain, infrequent - photosensitivity, very rarely - allergic reactions, withdrawal syndrome.
CONTRAINDICATIONS
- lactation period;
- children's age till 18 years;
- Hypersensitivity to the components of the drug.
With caution should prescribe the drug for liver failure, prostatic hyperplasia, zakratougolnoy glaucoma, epilepsy, myelosuppression (including leukopenia, neutropenia), myeloproliferative diseases, hypereosinophilic syndrome, paralytic intestinal obstruction, pregnancy.
PREGNANCY AND LACTATION
Caution should be prescribed during pregnancy.
If it is necessary to prescribe the drug during lactation, breastfeeding should be discarded.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution should prescribe the drug for liver failure.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
Elderly patients , patients with risk factors (including severe CRF or moderate-level hepatic insufficiency), with a combination of risk factors (female, elderly, non-smokers) who have olanzapine metabolism may be slowed, a reduction in the initial dose to 5 mg / day.
SPECIAL INSTRUCTIONS
When treating with neuroleptics (including olanzapine), malignant neuroleptic syndrome (hyperthermia, rigidity of the muscles, changes in mental status, vegetative disorders, including unstable pulse or BP, tachycardia, cardiac arrhythmias, increased sweating, increased activity of CKF , myoglobinuria as a result of rhabdomyolysis, acute renal failure).
When detecting clinical manifestations of malignant neuroleptic syndrome (including hyperthermia without other symptoms), the elimination of olanzapine is required.
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.
When taking olanzapine (in studies), in elderly patients with psychosis against a background of dementia, cerebrovascular disorders (stroke, transient ischemic attack), including fatal outcomes, were noted. These patients had previous risk factors (cerebrovascular disorders (history), transient ischemic attack, hypertension, smoking), as well as concomitant diseases and / or medication, associated with cerebrovascular disorders. Olanzapine is not recommended for the treatment of patients with psychosis on the background of dementia.
Particular caution is needed when increasing ALT and / or ACT activity in patients with hepatic impairment or receiving potentially hepatotoxic drugs. It is necessary to monitor the patient and, if necessary, reduce the dose.
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.
Olanzapine should be used with caution in patients with epileptic seizures in the history or in the presence of factors that reduce the threshold of convulsive readiness.
Olanzapine should be used with caution in patients with a decrease in the number of leukocytes and / or neutrophils, with signs of depression or toxic damage to bone marrow function under the influence of drugs (in the anamnesis), with oppression of bone marrow function due to concomitant disease, radio- or chemotherapy anamnesis); with hypereosinophilia or myeloproliferative disease.
The use of olanzapine in patients with clozapine-dependent neutropenia or agranulocytosis (in the anamnesis) was not accompanied by relapses of these disorders.
It is recommended to be cautious when prescribing olanzapine to patients with prostatic hypertrophy with clinical manifestations, paralytic intestinal obstruction, and closed-angle glaucoma.
Olanzapine shows antagonism against dopamine and, theoretically, can suppress the action of levodopa and dopamine agonists.
Caution should be exercised when using olanzapine in combination with other central-action drugs and ethanol.
Impact on the ability to drive vehicles and manage mechanisms
During the treatment period, care must be taken when driving vehicles and engage in potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
OVERDOSE
Symptoms: tachycardia, irritation / aggressiveness, articulation disorder, extrapyramidal disorders, disorders of consciousness (from sedation to coma), delirium, convulsions, malignant neuroleptic syndrome, respiratory depression, aspiration, increase or decrease in blood pressure, arrhythmias, cardiac arrest and respiration.
Treatment: gastric lavage, the appointment of activated charcoal, symptomatic treatment, maintenance of respiratory function.
Do not use sympathomimetics (including epinephrine, dopamine), which are beta-adrenergic receptor agonists (stimulation of these receptors can aggravate the decrease in blood pressure).
The minimum dose for acute overdose with a lethal outcome was 450 mg, the maximum dose with a favorable outcome (survival) is 1500 mg.
DRUG INTERACTION
Inducers or inhibitors of the CYP 1A2 isoenzyme may alter the metabolism of olanzapine.
The clearance of olanzapine is increased in smoking patients and with the simultaneous use of carbamazepine (the activity of CYP1A2 increases).
Ethanol did not affect the pharmacokinetics of olanzapine in an equilibrium state, however, ethanol administration in conjunction with olanzapine may be accompanied by an increase in the pharmacological effects of olanzapine (sedation).
Activated charcoal reduces the bioavailability of olanzapine to 50-60%.
Fluoxetine (60 mg once or 60 mg daily for 8 days) increases the C max of olanzapine by 16% and reduces the clearance by 16%, which is not clinically important (olanzapine dosage adjustment is not required).
Fluvoxamine (CYP 1A2 inhibitor) reduces the clearance of olanzapine, increases the C max of olanzapine in non-smokers by 54% and by 77% in men who smoke, AUC by 52% and 108%, respectively (a reduction in the dose of olanzapine is necessary).
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.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in dry, protected from light, out of the reach of children. temperature not higher than 25 В° РЎ. Shelf life - 2 of the year.
