Malignant neuroleptic syndrome. Malignant neuroleptic syndrome (CNS) can develop in the treatment of any neuroleptic, including olanzapine. Clinical manifestations of malignant neuroleptic syndrome include a significant increase in body temperature, stiff musculature,change in mental status and autonomic disorders (unstable pulse or blood pressure, tachycardia, arrhythmias, increased sweating). Additional signs may include increased levels of creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Clinical manifestations of malignant neuroleptic syndrome or a significant increase in body temperature without other symptoms of malignant neuroleptic syndrome require the removal of all antipsychotics, including olanzapine.
Late dyskinesia. In comparative studies lasting more than 6 weeks, treatment with olanzapine was significantly less often accompanied by the development of dyskinesia requiring drug correction than haloperidol. However, the risk of tardive dyskinesia with prolonged therapy with neuroleptics should be considered. 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.
Experience in elderly patients with psychotic disorders (delirium, hallucinations) against dementia. Cerebrovascular adverse events (for example, stroke, transient ischemic attack), including death, were noted in studies of olanzapine in elderly patients with psychotic disorders in the background of dementia. In placebo-controlled studies, a higher incidence of cerebrovascular adverse events was noted 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 the development of cerebrovascular adverse events (for example, the previously noted case of cerebrovascular undesirable phenomenon or transient ischemic attack, arterial hypertension, smoking), as well as concomitant diseases and / or medications associated with cerebrovascular undesirable events .
The effectiveness of olanzapine in elderly patients with psychotic disorders in the background of dementia is not established. In this category of patients in placebo-controlled clinical trials, the incidence of lethal cases in the olanzapine group was higher than in the placebo group (3.5% vs. 1.5%, respectively).The main risk factors for increased mortality for this group of patients in the treatment with olanzapine are age ≥80 years, sedation, concomitant use with benzodiazepines, or the presence of lung pathology (eg, pneumonia with or without aspiration).
There is insufficient evidence 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 inward and with intramuscular injection.
Olanzapine is not recommended for the treatment of patients with psychotic disorders on the background of dementia.
Dysfunction of the liver. In some cases, the use of olanzapine, usually in the early stages of therapy, was accompanied by a transient, asymptomatic increase in the parameters of hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) in the blood serum. There were rare cases of hepatitis. In very rare cases, hepatic cholestasis and other mixed liver damage were noted. A special precaution is necessary with an increase in aspartate aminotransferase and / or alanine aminotransferase in serum in patients withdeficiency of liver function, with limited functional reserve of the liver or in patients receiving potentially hepatotoxic drugs. In the case of an increase in aspartate aminotransferase and / or alanine aminotransferase levels during treatment with olanzapine, careful monitoring of the patient and, if necessary, a reduction in dose are required.
Hyperglycemia and diabetes mellitus. There is a higher prevalence of diabetes in patients with schizophrenia. As with some other antipsychotics, cases of hyperglycemia, diabetes mellitus, exacerbation of pre-existing diabetes mellitus, ketoacidosis and diabetic coma were very rare. There is no causal relationship between antipsychotic drugs and these conditions. A thorough clinical monitoring of patients with diabetes mellitus and patients with risk factors for developing diabetes is recommended.
Epileptic seizures. Olanzapine should be used with caution in patients with epileptic seizures in the history or exposed to factors that reduce the threshold of convulsive readiness.In such patients, seizures were rare in the treatment with olanzapine.
Hematologic changes. As with other antipsychotics, caution should be exercised when olanzapine is used in patients with reduced leukocyte counts and / or neutrophils in peripheral blood due to various causes; with signs of oppression 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, radiotherapy or chemotherapy in history; with hypereosinophilia or myeloproliferative disease.
In clinical studies, the use of olanzapine in patients with clozapine-dependent neutropenia or agranulocytosis in a history was not accompanied by relapses of these disorders.
Anticholinergic activity. In clinical trials, olanzapine therapy was rarely accompanied by anticholinergic side effects. However, clinical experience with olanzapine in patients with concomitant diseases is limited,therefore, caution should be exercised in prescribing olanzapine to patients with clinically significant prostatic hypertrophy, paralytic intestinal obstruction, occlusive glaucoma, and similar conditions.
Dopaminergic antagonism. In conditions in vitro olanzapine reveals antagonism against dopamine and, like other antipsychotic (neuroleptic) drugs, can theoretically suppress the action of levodopa and dopamine agonists.
Total activity against the central nervous system. Given the main effect of olanzapine on the central nervous system, caution should be exercised when using olanzapine in combination with other central-action drugs and alcohol.
Reductions in blood pressure and / or bradycardia were noted during intramuscular injection of olanzapine. Patients should be lying down when drowsiness and dizziness occur after the injection, until the examination shows no reduction in blood pressure, orthostatic hypotension, bradycardia and / or hypoventilation.
In connection with the possible development of bradycardia and / or lowering blood pressure after intramuscular injection of olanzapine,caution should be exercised in patients with severe cardiovascular disease, in which cases of fainting or lowering blood pressure and / or bradycardia may lead to an increased risk to the health of patients.
Care should be taken in patients receiving treatment with other drugs that can cause a decrease in blood pressure, bradycardia, and respiratory or central nervous system depression. The combined administration of olanzapine for intramuscular injections and benzodiazepines was not parenterally studied and therefore not recommended. In the case where intramuscular olanzapine is intended in combination with parenteral administration of benzodiazepines, a careful assessment of the clinical state of the patient with regard to excessive sedation and inhibition of cardiac and respiratory activity is recommended.