Zyprexa zidis dispersible pills 10mg №28

Packaging

Indications and usage

- Schizophrenia:
- For the treatment of exacerbations, supportive and long-term anti-relapse treatment of patients with schizophrenia and other psychotic disorders with severe productive (including delusions, hallucinations, automatisms) and / or negative (emotional flatness, decrease in social activity, impoverishment of speech) symptoms, and concomitant affective disorders.

- In the form of monotherapy or in combination with lithium or valproate - for the treatment of acute manic or mixed episodes in bipolar affective disorder with / without psychotic manifestations and with / without rapid phase change;
- To prevent relapse in patients with bipolar disorder in whom olanzapine was effective in the treatment of the manic phase.

Contraindications

Hypersensitivity to the drug.

Pregnancy and Breastfeeding

There is not enough clinical experience with olanzapine during pregnancy, so the prescription of the drug is possible only in cases where the expected benefit of therapy for the mother greatly exceeds the potential risk to the fetus.

Patients should be warned that in the event of the onset or planning of pregnancy during the period of treatment with olanzapine, they should be informed about this to their doctor.

The study found that olanzapine is excreted in breast milk. The average dose (mg / kg) received by the child when the mother reached C ss was 1.8% of the dose (mg / kg) of the mother. If necessary, the use of the drug during lactation breastfeeding is recommended to stop.

Dosage and administration

Olanzapia dispersible pills quickly dissolve in saliva and are easily swallowed. Remove the pill from the mouth undissolved difficult. Due to the fragility of the pill should be taken immediately after removal from the blister. In addition, immediately before taking the pill can be dissolved in a glass of water or other liquid (orange juice, apple juice, milk or coffee).

Olanzapine can be taken regardless of the meal, because food does not affect the absorption of the drug.

The daily dose must be selected individually, depending on the clinical condition of the patient.

- For the treatment of schizophrenia and similar psychotic disorders: The recommended starting dose of olanzapine is 10 mg 1 time / day. Therapeutic doses of olanzapine range from 5 mg to 20 mg / day. Increasing the dose of more than the standard daily dose of 10 mg is recommended only after an appropriate clinical examination of the patient.

For the treatment of acute mania with bipolar disorder: The recommended starting dose of olanzapine is 15 mg 1 time / day. as monotherapy or 10 mg 1 time / day. in combination with lithium or valproate. Olanzapine can be taken regardless of the meal, because the meal does not affect the absorption of the drug. Therapeutic doses of olanzapine range from 5 mg to 20 mg. It is recommended to increase the dose above the standard daily dose of 15 mg only after an appropriate clinical examination of the patient. The dose should be increased gradually, at intervals of at least 24 hours.

Supportive therapy for bipolar disorder: Patients who take olanzapine to treat acute mania need to continue supportive therapy at the same dose. In patients in remission, the recommended initial dose of olanzapine is 10 mg 1 time / day. In the future, the daily dose must be selected individually, depending on the clinical condition of the patient, ranging from 5 mg to 20 mg / day.

Olanzapine in combination with Fluoxetine should be administered 1 time / day, regardless of the meal. As a rule, the initial dose is 5 mg of olanzapine and 20 mg of fluoxetine. If necessary, changes in doses of both olanzapine and fluoxetine are allowed.

For elderly patients or patients with other clinical risk factors, including severe renal insufficiency or moderate hepatic insufficiency, it is recommended to reduce the initial dose of olanzapine to 5 mg / day.

For patients with a combination of factors that may cause a delay in the matabolism of olanzapine (female patients, old age, non-smokers) who may slow down the metabolism of olanzapine, a decrease in the initial dose of olanzapine may also be recommended.

Research data from olanzapine during therapy in children and adolescents under the age of 18 years is limited.

Also, for convenience of dosing, it is possible to use the drug: Zyprexa Zidis pl. 5 mg pack. 28 Eli Lilly and Company Ltd.

Adverse reactions

- Very often? 10% - drowsiness, weight gain; 34% - an increase in plasma prolactin concentration, which was mild and transient (the average value of the maximum concentration of prolactin did not reach VGN and was not statistically significantly different from placebo). Clinical manifestations of hyperprolactinemia associated with taking olanzapine (ie, gynecomastia, galactorrhea, and an increase in the mammary glands) were rarely observed. In most patients, normalization of prolactin levels was observed without discontinuing olanzapine.

- Often 3 times was not observed.

- Rarely - ranzitornoy, asymptomatic increase in hepatic transaminases (AST and ALT) in serum.

- In isolated cases Increased plasma glucose level up to? 200 mg / dL (suspected diabetes mellitus), as well as? 160 mg / dL, but up to

- In some cases, Asymptomatic eosinophilia.

- Adverse effects in special groups of patients. Patients with psychosis associated with dementia, very often (? 10%) had a gait disturbance and a fall.In elderly patients with dementia-related psychosis, often (

The table below summarizes the main side effects and their frequency, registered during clinical trials and / or in the post-registration period.

The main side effects in the treatment of various dosage forms of olanzapine are presented in the table.

1 Evaluation of indicators from the database of clinical studies.

2 Side effects registered in the database of clinical studies.

3 Side effects reported spontaneously in post-marketing research.

4 In the COSTART classification, referred to as diabetic acidosis.

5 In the classification, COSTART is referred to as hyperlipidemia.

6 For example, an anaphylactic reaction, angioedema, pruritus, or urticaria.

7 Ie. Sweating, nausea or vomiting.

Malignant neuroleptic syndrome (a potentially fatal symptom complex) can develop with any antipsychotic medication, including olanzapine, however, to date, there is no evidence to support a significant association of olanzapine intake with the development of this condition. Clinical manifestations of NMS include a significant increase in body temperature, muscle rigidity, changes in mental status, and autonomic disturbances (unstable pulse or blood pressure, tachycardia, cardiac arrhythmias, increased sweating). Additional signs may include increased levels of CPK, myoglobinuria (rhabdomyolysis), and acute renal failure.Clinical manifestations of malignant neuroleptic syndrome or a significant increase in body temperature without other symptoms of NNS require the elimination of all neuroleptics, including olanzapine.

In comparative studies, treatment with olanzapine was significantly less frequently accompanied by the development of dyskinesia requiring medical correction than the use of typical and other atypical antipsychotics. However, the risk of tardive dyskinesia during long-term neuroleptic therapy should be considered. If signs of tardive dyskinesia develop, a dose adjustment of the neuroleptic is recommended. It should be borne in mind that when transferred to olanzapine, symptoms of tardive dyskinesia may develop as a result of the simultaneous cancellation of previous therapy.

The efficacy of olanzapine in elderly patients with dementia-related psychosis has not been established. In this category of patients in placebo-controlled clinical trials, the frequency of fatal cases in the olanzapine group was higher than in the placebo group (3.5% versus 1.5%, respectively). Risk factors that may predispose this group of patients to higher mortality with olanzapine treatment include age> 80 years, sedation, concomitant use with benzodiazepines, or the presence of lung pathology (for example, pneumonia with or without aspiration).

There is not enough data to establish differences in the incidence of cerebrovascular disorders and / or mortality (compared with placebo), and in the risk factors for this group of patients when taking olanzapine by mouth and intramuscular injections.

In some cases, olanzapine intake, usually in the early stages of therapy, was accompanied by a transient, asymptomatic increase in serum levels of hepatic transaminases (AST and ALT). Rare cases of hepatitis have been reported. Special precaution is necessary when increasing levels of AST and / or ALT in the serum of patients with liver failure, with limited functional reserve of the liver, or in patients receiving treatment with potentially hepatotoxic drugs. In the event of an increase in AST and / or ALT levels during olanzapine treatment, careful monitoring of the patient and, if necessary, dose reduction are required.

There is a higher prevalence of diabetes in patients with schizophrenia. As with the use of certain other antipsychotic drugs, hyperglycemia, diabetes mellitus, exacerbation of pre-existing diabetes, ketoacidosis, and diabetic coma have been very rarely observed. The causal relationship between antipsychotic drugs and these conditions has not been established. Careful clinical monitoring of patients with diabetes mellitus and patients with risk factors for the development of diabetes is recommended.

Olanzapine should be used with caution in patients with a history of epileptic seizures or exposed to factors that reduce the threshold of seizure readiness. In these patients, olanzapine was rarely treated with olanzapine.

Cerebrovascular adverse reactions (for example, stroke, transient ischemic attack), including deaths, have been reported in olanzapine studies in elderly patients with dementia-related psychosis. In placebo-controlled studies, a higher incidence of cerebrovascular adverse events was observed in patients in the olanzapine group compared with the placebo group (1.3% vs. 0.4%, respectively).

All patients with cerebrovascular disorders had previous risk factors for developing cerebrovascular unwanted reactions (for example, a previously observed case of cerebrovascular unwanted reaction or transient ischemic attack, arterial hypertension, smoking), as well as concomitant diseases and / or medication associated with cerebrovascular unwanted reactions. Olanzapine is not indicated for the treatment of patients with psychosis associated with dementia.

As with the use of other antipsychotics, caution should be exercised in the treatment of olanzapine in the following groups of patients:

- Patients with a reduced number of leukocytes and / or neutrophils in the peripheral blood, due to various reasons.
- Patients with signs of depression / toxic impairment of bone marrow function under the influence of drugs in history.
- Patients with inhibition of bone marrow function due to concomitant disease, radiotherapy or Chemotherapy in history.
- Patients with hypereosinophilia or myeloproliferative disease.

In clinical studies, the use of olanzapine in patients with clozapine-dependent neutropenia or agranulocytosis in history has not been accompanied by a relapse of these disorders.

In clinical studies, olanzapine therapy was rarely accompanied by anticholinergic side effects. However, clinical experience with olanzapine in patients with comorbidities is limited, so caution is advised when prescribing olanzapine in patients with clinically significant prostatic hypertrophy, paralytic ileus, angle-closure glaucoma, and similar conditions.

Taking into account the main effect of olanzapine on the central nervous system, care should be taken when using olanzapine in combination with other drugs of central action, as well as with alcohol.

- Impact on the ability to drive vehicles and control mechanisms Patients taking olanzapine, should be careful in the management of mechanical means, including vehicles, because olanzapine can cause drowsiness.

The metabolism of olanzapine can be altered by the action of inhibitors or inducers of isoenzymes of the cytochrome P450 system, which show specific activity against CYP1A2. The clearance of olanzapine is increased in smoking patients and in patients taking Carbamazepine (due to increased activity of CYP1A2).Known potential inhibitors of CYP1A2 can reduce the clearance of olanzapine. Olanzapine is not a potential inhibitor of CYP1A2 activity; therefore, when taking olanzapine, the pharmacokinetics of drugs, such as theophylline, that are mainly metabolized with CYP1A2, do not change.

In clinical studies it was shown that a single dose of olanzapine during the treatment with the following drugs was not accompanied by suppression of the metabolism of these drugs: imipramine or its metabolite desipramine (CYP2D6, CYP3A, CYP1A2), Warfarin (CYP2C19), theophylline (CYP1A2) or diazepamum CYP2C19). There are also no signs of drug interactions when using olanzapine in combination with lithium or biperidine.

There was no change in the pharmacokinetics of ethanol against the background of a stable concentration of olanzapine. However, taking ethanol together with olanzapine may be accompanied by an increase in the pharmacological effects of olanzapine, for example, a sedative effect.

A single dose of an aluminum- or magnesium-containing antacid or cimetidine did not violate the bioavailability of olanzapine when taken orally. Co-administration of Activated carbon reduced the bioavailability of olanzapine when administered orally to 50-60%. Fluoxetine (60 mg once or 60 mg daily for 8 days) causes an increase in C max of olanzapine by an average of 16% and a decrease in clearance of olanzapine by an average of 16%. The degree of influence of this factor is significantly inferior to the severity of individual differences in these indicators, so it is usually not recommended to change the dose of olanzapine when it is prescribed in combination with fluoxetine.

Fluvoxamine, an inhibitor of CYP1A2, reduces the clearance of olanzapine. The result is a moderate increase in C max of olanzapine when fluvoxamine is administered by 54% in non-smoking women and 77% in male smokers. The average increase in olanzapine AUC is 52% and 108%, respectively. Small doses of olanzapine should be prescribed to patients who are receiving fluvoxamine together.

In vitro studies using human liver microsomes have shown that olanzapine slightly inhibits the formation of valproate glucuronide (the main metabolic pathway of valproate). Valproate also slightly affects the metabolism of olanzapine in vitro. Therefore, a clinically significant pharmacokinetic interaction between olanzapine and valproate is unlikely.

In vitro, olanzapine detects antagonism against dopamine and, like other antipsychotics (neuroleptics), can theoretically suppress the effects of levodopa and dopamine agonists.

The absorption of olanzapine does not depend on food intake.

According to in vitro studies using human liver microsomes, olanzapine also demonstrated extremely small potential in suppressing the activity of the following cytochrome P450 isoenzymes: CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A.

- Symptoms: very often (? 10%) - tachycardia, agitation / aggressiveness, articulation disorder, various extrapyramidal disorders and disorders of consciousness of varying severity (from sedation to coma).Other clinically significant symptoms are seizures, neuroleptic malignant syndrome, respiratory depression, aspiration, arterial hypertension or hypotension, cardiac arrhythmias (- Treatment: there is no specific antidote for olanzapine. Vomiting is not recommended. Standard procedures for overdose are not recommended (gastric lavage, purpose of activated carbon.) The joint appointment of activated carbon showed a decrease in the bioavailability of olanzapine when administered orally to 50-60%. Symptom Athemic therapy in accordance with the clinical condition and control of the functions of vital organs, including the treatment of arterial hypotension, circulatory disorders and maintenance of respiratory function. Epinephrine, dopamine and other sympathomimetics that are agonists of? -drenoreceptors should not be used, since stimulation of these receptors may aggravate hypotension.

The drug should be stored at a temperature of 15 ° to 30 ° C.
Keep out of reach of children.

2 years.