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

Excipients: microcrystalline cellulose 85.6 mg, 171.3 mg, 257.0 mg or 342.6 mg,lactose monohydrate 17.2 mg, 34.3 mg, 51.6 mg or 68.8 mg, crospovidone 1.1 mg, 2.2 mg, 3.2 mg or 4.3 mg, magnesium stearate 1.1 mg, 2.2 mg, 3.2 mg or 4.3 mg, respectively.

Description:

Tablets are yellow, cylindrical, biconvex.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.H.03 Olanzapine

Pharmacodynamics:

Antipsychotic agent (antipsychotic). Has an affinity for serotonin (5-HT_{2A / C}, 5-HT₃, 5-HT₆), dopamine (D₁, D₂, D₃, D₄, D₅), muscarinic (M_l_-5), adrenergic (alpha1), and histamine (H₁) receptors.

In vitro antagonism to 5HT, dopamine and cholinergic receptors was revealed. Has a more pronounced affinity and activity with respect to serotonin 5HT₂ receptors in comparison with dopamine D₂ 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:

Absorption is high, it does not depend on food intake; TS_maxafter oral administration - 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.

Metabolised in the liver by conjugation and oxidation. The main circulating metabolite is a 10-N-glucuronide, not penetrating the 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.

Clearance - 26 l / h (12-47 l / h), T_1/2- 33 hours (21-54 hours). It is excreted by the kidneys - 57% (mainly in the form of metabolites). Non-smoking (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), up to 65 years (ground clearance - 18.2 l / h, T_1/2 - 33.8 h).

For smokers with minor violations of liver function, clearance is lower than for non-smokers without impaired liver function.

Indications:

Schizophrenia in adults (exacerbation, sustained and prolonged anti-relapse therapy), psychotic disorders with productive (incl.delusions, 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 drugs Li+ or valproic acid): acute manic or mixed episodes with / 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).

Contraindications:

Hypersensitivity, lactation period, children's age (under 18 years).

Carefully:

Hepatic insufficiency, prostatic hyperplasia, angle-closure glaucoma, epilepsy, myelosuppression (including leukopenia, neutropenia), myeloproliferative diseases, hypereosinophilic syndrome, paralytic intestinal obstruction, pregnancy.

Dosing and Administration:

Inside, regardless of food intake - 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 monotherapy or 10 mg / day (1 time) in combination with drugs Li+ or valproic acid (maintenance therapy at the same dose).

With depression associated with bipolar disorders in adults - 5 mg / day (1 time) 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 hepatic impairment), with a combination of risk factors (female, elderly, non-smokers) who can slow the metabolism of olanzapine, it is recommended that the initial dose be reduced to 5 mg / day.

Side effects:

Frequency: very often (more than 10%), often (more than 10% and less than 1%), infrequently (less than 1% and more than 0.1%), rarely (less than 0.1% and more than 0.01%), very rarely (less than 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 of more than 200 mg / dL (suspected diabetes mellitus), 160-200 mg / dl (suspected hyperglycaemia) in patients with baseline glucose concentrations less than 140 mg / dL.

There have been cases of elevation 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 on a background of dementia: very often - a violation of gait and fall; often - incontinence of urine and pneumonia.

In patients with psychosis induced by 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 drugs Li+ 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 in post-marketing experience.

On the part of the CAS: 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 side of 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 hematopoiesis: often - eosinophilia, rarely - leukopenia, very rarely - thrombocytopenia.

Laboratory indicators: very often hyperprolactinemia; often - increased ALT activity, ACT, hyperglycemia; very rarely - hyperbilirubinemia, increased activity of alkaline phosphatase.

Other: very often - weight gain, infrequent light sensitivity, very rarely allergic reactions, withdrawal syndrome.

Overdose:

Symptoms: tachycardia, agitation / aggressiveness, articulation disorder, extrapyramidal disorders,disorders of consciousness (from sedation to coma), delirium, seizures, malignant neuroleptic syndrome, respiratory depression, aspiration, increase or decrease in blood pressure, arrhythmias; heart and respiratory arrest.

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

Do not use sympathomimetics (incl. epinephrine, dopamine) Which are agonists of the beta adrenergic receptors (stimulation of these receptors may worsen AD reduction).

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

Interaction:

Inductors or inhibitors of the CYP1A2 isoenzyme may alter the metabolism of olanzapine.

The clearance of olanzapine increases in smokers and at simultaneous application carbamazepine (increased activity CYP1A2).

Ethanol did not affect the pharmacokinetics of olanzapine in the equilibrium state, but the administration of ethanol together 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 C_mOh olanzapine by 16% and reduces clearance by 16%, which has no clinical significance (no correction of the olanzapine dose is required).

Fluvoxamine (inhibitor CYP1A2), decreasing the clearance of olanzapine, increases C_mOh olanzapine in nonsmoking women at 54% and on 77% - at smoking men, 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.

Special instructions:

When treating with neuroleptics (including olanzapine), malignant neuroleptic syndrome (hyperthermia, muscular rigidity, changes in mental status, autonomic disorders, including unstable pulse or BP, tachycardia of cardiac arrhythmias, increased sweating, increased activity of CK, Myoglobinuria as a result of rhabdomyolysis, acute renal failure).

When revealing 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 drug use associated with cerebrovascular disorders. Olanzapine It is not recommended for the treatment of patients with psychosis on the background of dementia.

Particular caution is needed when increasing ALT activity 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.

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, 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 (in the 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 exhibits 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 drugs of central action 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:Tablets, 2.5 mg, 5 mg, 7.5 mg or 10 mg.

Packaging:

Tablets 2.5 mg or 5 mg or 10 mg. 7 tablets per contour cell package. 4 contour mesh packages together with instructions for use are placed in a pack of cardboard.

Tablets 7.5 mg. 7 tablets per contour cell package. 8 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the specified time on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000372

Date of registration:24.02.2011 / 19.05.2016

Expiration Date:Unlimited

The owner of the registration certificate:Kern Pharma S.L.Kern Pharma S.L. Spain

Manufacturer: & nbsp