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

Antipsychotic agent (antipsychotic). The drug blocks serotonin 5-HT_2A and 5-HT_2C, 5-HT₃-, 5-HT₆ receptors, as well as dopamine D₁, D₂, D₃, D₄, D₅ in mesocortical and mesolimbic structures of the brain.

It also depresses M_1-5-cholinoreceptors; α₁-adrenoceptors and histamine H₁-receptors.

Olanzapine provides a reduction in both productive (including delusions, hallucinations), and negative symptoms of psychosis.

The anticholinergic effect is caused by a block of muscarinic M_1-5receptors.

Hypotensive - block α₁-adrenergic receptors of blood vessels.

Sedative, hypnotic - block H₁receptors, binding to GABA_Areceptors, β-adrenergic receptors.

Hyperprolactinaemia - blockade of dopamine D₅receptors.

Pharmacokinetics:

It is well absorbed from the gastrointestinal tract, the connection with plasma proteins is 93%. Biotransformation in the liver (CYP1A2, to a lesser extent - 2D6 and 2S19) with formation of inactive metabolites - 10-N-glucoronide and 4-N-desmethylolanzapine. The half-life is 33 hours. Excreted in the urine in the form of metabolites, to a lesser extent unchanged.

Indications:

- schizophrenia;

- treatment of manic episode from medium to severe;

- prevention of relapse in patients with bipolar disorder, in whom olanzapine proved effective in the treatment of the manic phase;

- therapeutically-resistant depression. In combination with fluoxetine olanzapine is indicated for the treatment of therapeutically-resistant depression in adult patients (major depressive episodes with a history of ineffective use of two antidepressants adequate for the dose and duration of therapy for this episode).

ICD-10

V.F20-F29.F20 Schizophrenia

V.F20-F29.F21 Chrysotile disorder

V.F20-F29.F22 Chronic delusional disorders

V.F20-F29.F23 Acute and transient psychotic disorders

V.F20-F29.F25 Schizoaffective disorder

V.F20-F29.F29 Inorganic psychosis, unspecified

V.F30-F39.F30 Manic episode

V.F30-F39.F31 Bipolar affective disorder

V.F30-F39.F32 Depressive episode

V.F30-F39.F33 Recurrent depressive disorder

Contraindications:

- hypersensitivity;

- age to 18 years;

- deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Carefully:

Diseases of the liver and kidneys, convulsive seizures, pregnancy and lactation, myeloproliferative diseases, prostatic hyperplasia, hypereosinophilic syndrome, myelosuppression.

Pregnancy and lactation:

Category FDA - C. Adequate and 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.

There are no data on the allocation of the drug with breast milk, during the treatment should stop breastfeeding.

Dosing and Administration:

Inside, regardless of food intake, since food does not affect the absorption of olanzapine.

The first dose is 10-15 mg per day. Further, the daily dose must be adjusted individually. Therapeutic dose - 5-20 mg per day.

Side effects:

From the nervous system: dizziness, gait disturbance, drowsiness, akathisia, parkinsonism, dyskinesia; infrequently - dystonia (including oculogic crisis), malignant neuroleptic syndrome, tardive dyskinesia; rarely - cramps, withdrawal syndrome; dysarthria, amnesia.

From the side of metabolism, nutrition and endocrine system: an increase in the concentration of prolactin, very often - weight gain; often - increased glucose concentration, increased cholesterol concentration,increased concentration of triglycerides, glucosuria, increased appetite; infrequently - development or decompensation of diabetes mellitus, in some cases accompanied by ketoacidosis or coma, including some deaths; rarely - hypothermia.

From the gastrointestinal tract: increased activity of hepatic transaminases, hepatitis, dry mouth, constipation, infrequently - bloating; rarely - pancreatitis.

From the skin and subcutaneous tissues: infrequently - the reaction of photosensitivity; rarely - a rash, alopecia.

From the side of musculoskeletal tissue: often - arthralgia; rarely rhabdomyolysis.

From the side of the kidneys and urinary tract: infrequent urinary incontinence; rarely - urine retention; very rarely - delay in the beginning of urination.

From the genitals and the breast: often - a decrease in libido in men and women, erectile dysfunction in men; infrequently - amenorrhea, gynecomastia, breast enlargement in women, galactorrhea; very rarely - priapism.

From the cardiovascular system: bradycardia, interval lengthening QT; rarely - ventricular tachycardia / ventricular fibrillation, sudden death, often - arterial hypotension, including orthostatic; rarely - thromboembolism of the pulmonary artery and deep vein thrombosis.

From the respiratory system, chest and mediastinum: infrequently - epistaxis.

General disorders: often - asthenia, fatigue, pyrexia, edema.

Overdose:

Symptoms: Tachycardia, agitation / aggressiveness, speech impairment, various extrapyramidal disorders and disorders of consciousness of varying severity (from sedation to coma) were very frequent symptoms of olanzapine overdose. Other clinically significant effects of olanzapine overdose included delirium, seizures, malignant neuroleptic syndrome, respiratory depression, aspiration, increased or decreased blood pressure, arrhythmias and cardiac and respiratory arrest. The minimum dose for acute overdose with a lethal outcome was 450 mg, the maximum dose for an overdose with a favorable outcome (survival) is 2 g.

Treatment: a specific antidote of olanzapine does not exist. It is not recommended to induce vomiting. Standard procedures for overdose can be shown (gastric lavage, activated charcoal reception). A joint reception of activated charcoal and olanzapine showed a decrease in the bioavailability of olanzapine upon ingestion of up to 50-60%.Symptomatic therapy is shown in accordance with the clinical condition and control of vital body functions, including correction of low blood pressure, impaired blood circulation and maintenance of respiratory function. Do not use epinephrine, dopamine and other adrenomimetics, which are β-adrenoreceptor agonists, since stimulation of these receptors can aggravate arterial hypotension. It is necessary to monitor cardiovascular activity in order to identify possible arrhythmias. The patient should be under continuous medical supervision until complete recovery.

Interaction:

The drug enhances the effect of drugs that depress CNS.

Activated carbon reduces the bioavailability of the drug.

Fluoxetine increases the concentration of the drug in the blood plasma and reduces its plasma clearance.

Fluvoxamine, inhibitor of isoenzyme CYP1A2, reduces the clearance of olanzapine. The result is an average increase C_max olanzapine with the administration of fluvoxamine by 54% in nonsmoking women and by 77% in male smokers, the mean increase AUC olanzapine - by 52 and 108% respectively.Small doses of olanzapine should be given to patients who are jointly receiving fluvoxamine treatment.

The metabolism of the drug can change with simultaneous administration with drugs that modulate the activity of liver enzymes.

The clearance of olanzapine is increased in smokers and recipients carbamazepine (in connection with an increase in isoenzyme activity CYP1A2).

Special instructions:

The risk of suicide attempts by patients with schizophrenia and bipolar disorder of the first type is due to the aforementioned diseases. In this regard, against the background of pharmacotherapy requires careful monitoring of those patients who have a risk of suicide is particularly high. When prescribing olanzapine, one should strive to minimize the number of tablets taken by the patient to reduce the risk of overdose.

Malignant neuroleptic syndrome (potentially lethal symptom complex) can develop in the treatment of any neuroleptic, including olanzapine. Clinical manifestations malignant neuroleptic syndrome include a significant increase in body temperature, rigidity of the musculature,change in mental status and autonomic disorders (unstable pulse or blood pressure, tachycardia, cardiac arrhythmias, increased sweating). Additional signs may include increased activity creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. Clinical manifestations malignant neuroleptic syndrome or a significant increase in body temperature without other symptoms malignant neuroleptic syndrome require the removal of all antipsychotics, including olanzapine.

When developing signs of tardive dyskinesia, a dose adjustment of an antipsychotic is recommended. It should be borne in mind that when translated into olanzapine symptoms of tardive dyskinesia may develop due to the simultaneous withdrawal of previous therapy. Over time, the intensity of this symptomatology may increase, moreover, these symptoms may develop after discontinuation of therapy.

In the case of a sharp abolition of olanzapine, the acute development of sweating, insomnia, tremor, anxiety, nausea, and vomiting was very rarely reported.

Very rarely reported on the development of venous thromboembolism in the background of olanzapine therapy.The presence of a causal relationship between the administration of olanzapine and venous thromboembolism has not been established. However, given that patients with schizophrenia often have acquired risk factors for venous thromboembolism, an overall assessment of all possible risk factors for the development of this complication is required, including immobilize patients, and take the necessary preventive measures.

Impact on the ability to drive vehicles and manage mechanisms

Do not drive a car or perform work that requires increased attention during taking the drug.

Patients receiving olanzapine, the danger associated with the operation of machinery, including a vehicle, should be olanzapine may cause drowsiness and dizziness.

Instructions

Olanzapine (Olanzapinum)