Description
Olanzapine Pharmacodynamics
Antipsychotic medicine (neuroleptic). It has affinity to serotonin 5-NT2A/C-, 5-NT3-, 5-NT6-receptors; dopamine D1-, D2-, D3-, D4-, D5-receptors; M1-5-cholinoreceptors; ?1-adrenoreceptors and histamine H1-receptors. It shows antagonism to serotonin 5-NT-, dopamine and choline receptors.
Under in vitro and in vivo conditions it has a more pronounced affinity and activity towards serotonin 5-HT2-receptors compared to dopamine D2-receptors. According to electrophysiological studies, olanzapine selectively decreases excitability of mesolimbic (A10) dopaminergic neurons and, at the same time, has little effect on striatal (A9) nerve pathways involved in the regulation of motor functions. Olanzapine reduces the conditioned protective reflex (the test that characterizes antipsychotic activity) at lower doses than are required to achieve catalepsy (a disorder reflecting a side effect on motor function). Unlike other neuroleptics, olanzapine enhances the antianxiety effects of the anxiolytic test.
The use of olanzapine reduces both productive (including delirium, hallucinations) and negative disturbances.
Indications
Treatment of exacerbations, maintenance and long-term contradictory therapy of schizophrenia and other psychotic disorders with pronounced productive (including delirium, hallucinations, automatism) and/or negative (including emotional flattening, decreased social activity, impoverished speech) symptoms, as well as concomitant affective disorders.
Treatment of acute manic or mixed seizures in bipolar affective disorder with/without psychotic manifestations and with/without rapid phase change.
Contraindications
Contraindications to use
Hypersensitivity to olanzapine.
Use during pregnancy and lactation
Adequate and strictly controlled clinical safety studies of olanzapine use in pregnancy have not been conducted. 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 currently no data on excretion of olanzapine in breast milk. Breast-feeding should be discontinued if it is necessary to use during lactation.
Use in liver dysfunction
In moderate hepatic impairment, the initial dose is 5 mg/day.
Administration in renal impairment
In severe renal insufficiency, the initial dose is 5 mg/day.
Administration in children
Safety and effectiveness of olanzapine in patients under 18 years of age has not been studied.
Use in elderly patients
For elderly patients, the starting dose is 5 mg/day.
Dosage and administration
- The initial dose is 10-15 mg/day. Daily dose should be adjusted individually depending on clinical condition of a patient. Therapeutic doses are 5-20 mg/day. Increasing the dose beyond the standard one (10-15 mg/day, depending on indications) is recommended only after an appropriate clinical examination of the patient. The dose should be increased gradually, at intervals of at least 24 hours.
- In elderly patients and in patients with severe renal insufficiency or moderate hepatic insufficiency, the initial dose is 5 mg/day.
- A reduction in the starting dose is recommended for patients with a combination of factors (female patients, elderly, nonsmokers) in which olanzapine metabolism may be delayed.
