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Active ingredients
Olanzapine
Release form
Pills
Composition
1 tab. olanzapine 10 mg Auxiliary substances: microcrystalline cellulose, lactose monohydrate, crospovidone, magnesium stearate.
Pharmacological effect
Olanzapine is an antipsychotic (antipsychotic) drug. In preclinical studies, an affinity was established for 5-НТ2А / 2С-, 5-НТ3-, 5-НТ6-serotonin receptors, D1-, D2-, D3-, D4-, D5-dopamine receptors, m-antino-blocking effects are due to the blockade M1- 5-cholinergic receptors; also has affinity for α1-adreno and H1-histamine receptors. In animal experiments, antagonism was revealed in relation to serotonin, dopamine and m-cholinergic receptors. In vivo and in vitro, olanzapine has a more pronounced affinity and activity for 5-HT2-serotonin receptors compared with D2-dopamine receptors. According to electrophysiological studies, olanzapine selectively reduces the excitability of mesolimbic dopaminergic neurons, and at the same time has a slight effect on the striatal pathways involved in the regulation of motor functions. Olanzapine reduces the conditioned defensive reflex (a test that characterizes antipsychotic activity) at doses lower than the doses that cause catalepsy (a disorder reflecting a side effect on motor function). Unlike other neuroleptics, olanzapine enhances the anti-anxiety effect when conducting anxiolytic test. Olanzapine provides a statistically significant reaction as productive (delusions, hallucinations, etc.), and negative disorders. With a single dose of 10 mg of olanzapine by means of positron emission tomography (PET) on healthy volunteers, a greater affinity of olanzapine for 5 HT2A- than for D2-dopamine receptors was established. On tomograms of patients with schizophrenia, it was shown that in patients sensitive to treatment with olanzapine, affinity for striatal D2 receptors is comparable to the effect in patients sensitive to receiving clozapine and lower than in patients sensitive to treatment with other antipsychotic drugs and risperidone. Clinical efficacy: In an international, double-blind, comparative study of patients with schizophrenia,schizoaffective or similar disorders of varying severity of depressive symptoms (average baseline 16.6 on the Montgomery-Asberg scale for assessing depression), a prospective secondary analysis on the mood scale from baseline to end point of control showed a statistically significant (p = 0.001) improvement in taking olanzapine (- 6.0) compared with haloperidol (-3.1). Patients with a manic or mixed episode of bipolar disorder compared with placebo and valproic acid (divalproate) showed high efficacy in reducing manic symptoms for 3 weeks. Comparable results of the effectiveness of olanzapine and haloperidol were observed in patients with symptomatic remission of mania and depression after 6-12 weeks. In the therapy of patients who took lithium or valproic acid for at least 2 weeks, the additional intake of 10 mg of olanzapine (lithium or valproic acid) resulted in a significant reduction in the symptoms of mania compared to monotherapy with lithium or valproic acid for 6 weeks. A 12-month study on the prevention of relapses of manic episodes in patients who achieved remission while taking olanzapine and then randomly assigned to the group of the drug olanzapine showed a statistically significant advantage over placebo for the main criterion for controlling the occurrence of bipolar disorder recurrence and in terms of preventing relapse of mania or relapse of depression . In the second 12-month study on the prevention of relapses of manic episodes in patients who achieved remission when co-administering olanzapine with the lithium drug, and then randomly assigned to the olanzapine or lithium monotherapy group. The effectiveness of olanzapine intake was statistically insignificant compared with the lithium drug by the main criterion for the control of relapse of bipolar disorder (olanzapine 30.0%, lithium 38.3%, p = 0.055). In an 18-month study of manic or mixed episodes of cat therapy in patients stabilized with olanzapine and mood stabilizing drugs (lithium or valproic acid), long-term co-therapy with olanzapine with lithium or valproic acid was not statistically significant compared with lithium or valproic monotherapy acids in order to delay the onset of relapse of bipolar disorder, determined by diagnostic signs.
Pharmacokinetics
After oral administration, olanzapine is well absorbed, Cmax in plasma is reached after 5–8 hours. The absorption of olanzapine does not depend on food intake. In studies with different doses in the range of 1–20 mg, it was shown that plasma olanzapine concentration varies linearly and proportionally to the dose. Olanzapine is metabolized in the liver as a result of conjugation and oxidation. The major circulating metabolite is 10-N-glucuronide, which theoretically does not penetrate the blood-brain barrier. CYP1A2 and CYP2D6 isoenzymes are involved in the formation of N-desmethyl- and 2-hydroxymethylmetabolites of olanzapine. Both metabolites in animal studies had a significantly less pronounced pharmacological activity in vivo than olanzapine. The main pharmacological activity of the drug is due to the parent compound, olanzapine, which has the ability to penetrate the blood-brain barrier. In healthy volunteers, after oral administration, the average T1 / 2 was 33 h (21–54 h for 5–95%), and the average clearance of olanzapine from plasma was 26 l / h (12–47 l / h for 5–95%). However, the degree of changes in the half-life and clearance under the influence of each of these factors is significantly inferior to the degree of differences in these indicators between individuals. Pharmacokinetics in adolescents (13-17 years) and in adults are similar. According to clinical studies, the amount of exposure in adolescents is 27% higher than in adults. The difference in demographic parameters between the population of adults and adolescents was that there were fewer smokers among adolescents, as well as lower average body weight. Significant differences between the mean half-life and plasma clearance of olanzapine in individuals with severe impaired renal function, compared with those with normal renal function, have not been established. About 57% of the radioactively labeled olanzapine is excreted in the urine mainly as metabolites. In smokers with minor hepatic impairment, olanzapine clearance is lower than in non-smokers without impaired liver function. With a plasma concentration of 7-1000 ng / ml of olanzapine, its association with plasma proteins is about 93%. Olanzapine is primarily associated with albumin and an acidic α1-glycoprotein. In a study involving people of European, Japanese and Chinese origin, differences in the pharmacokinetics of olanzapine related to race were not established. CYP2D6 isoenzyme activity does not affect olanzapine metabolism.
Indications
Adult schizophrenia (exacerbation, supportive and long-term anti-relapse therapy), psychotic disorders with productive (including delusions, hallucinations, automatisms) and / or negative (emotional flatness, decrease in social activity, impoverishment of speech) symptoms and associated affective disorders. Bipolar affective disorder in adults (monotherapy or in combination with lithium or valproic acid): acute manic or mixed episodes with / without psychotic manifestations and with / without fast change faz.Retsidiv bipolar disorder (with efficacy in the treatment of manic phases) .Depressivnye conditions associated with bipolar disorder (in combination with fluoxetine).
Contraindications
Lactation period. Children's age up to 18 years. Hypersensitivity to the drug. The drug should be prescribed with caution in liver failure, prostatic hyperplasia, angle-closure glaucoma, epilepsy, myelosuppression (including leukopenia, neutropenia), myeloproliferative diseases, hypereosinophilic syndrome, paralytic intestinal obstruction, pregnancy.
Use during pregnancy and lactation
Due to the lack of experience with olanzapine during pregnancy, the drug should be prescribed during pregnancy only if the potential benefit to the patient 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 by their attending physician. Newborns whose mothers took antipsychotics (including olanzapine) during the third trimester of pregnancy have a risk of adverse reactions, including extrapyramidal disorders and / or withdrawal syndrome, the symptoms of which may change in strength and duration after birth. Agitation, hypertension and hypotension, tremor, drowsiness, respiratory distress syndrome or an eating disorder have been reported. Therefore, it is necessary to carefully monitor the condition of newborns. The study found that olanzapine passes into breast milk.The average dose received by the child (mg / kg) when reaching the equilibrium concentration in the mother was 1.8% of the dose of mother olanzapine (mg / kg). Breast feeding during olanzapine therapy is not recommended.
Dosage and administration
Method of application The drug is taken inside, regardless of the meal, at a dose of 5-20 mg / day. For schizophrenia in adults, the recommended initial dose is 10 mg / day. In acute mania associated with bipolar disorders, in adults - 15 mg 1 time / day as monotherapy or 10 mg 1 time / day in combination with lithium preparations or valproic acid (maintenance therapy at the same dose). For depression associated with bipolar disorders, in adults - 5 mg 1 time / day in combination with 20 mg of fluoxetine (if necessary, changes in doses of drugs are allowed). Elderly patients, patients with risk factors (including severe CRF or moderately severe liver failure), with a combination of risk factors (female gender, old age, non-smokers) in whom olanzapine metabolism can be slowed down, it is recommended to lower the initial dose to 5 mg / day.
Side effects
The frequency of side effects is determined as follows very often (≥ 10%), often (≥ 1% and less than 10%), infrequently (≥ 0.1% and less than 1%), rarely (≥ 0.01% and less than 0.1%), very rarely (less than 0 .01%). In clinical studies, drowsiness and weight gain were very often observed. in 34% - hyperprolactinemia (mild and transient). Clinical manifestations of hyperprolactinemia were rarely observed. Frequently dizziness, asthenia, akathisia, increased appetite, peripheral edema, orthostatic hypotension, dryness of the oral mucosa, constipation. 200 mg / dL (suspected diabetes mellitus), 160–200 mg / dL (suspected hyperglycemia) in patients with an initial glucose concentration of less than 140 mg / dL. There have been cases of increases in triglycerides ( and 20 mg / dL from baseline), cholesterol (0.4 mg / dL from baseline), asymptomatic eosinophilia (few cases) .u patients with psychosis on dementia very often - disturbance of gait and falling. often - urinary incontinence and pneumonia. In patients with psychosis,induced dopamine agonist in Parkinson's disease is very often - increased symptoms of parkinsonism and hallucinations. In patients with bipolar mania (receiving the drug in combination with lithium preparations or valproic acid) it is very common to increase body weight, dry oral mucosa, increase appetite, tremor . often a speech disorder. Side effects observed in clinical studies and in post-marketing experience of use are listed below. The cardiovascular system is often orthostatic hypotension. infrequently - bradycardia. very rarely - venous thromboembolism. On the part of the digestive system, often - constipation, dryness of the oral mucosa, increased appetite. rarely - hepatitis. very rarely - pancreatitis, jaundice. On the side of metabolism, it is often peripheral edema. very rarely, diabetic coma, diabetic ketoacidosis. hyperglycemia, hypercholesterolemia, hypertriglyceridemia. From the side of the musculoskeletal system it is very rare - rhabdomyolysis. From the nervous system it is very often - drowsiness. often - akathisia, dizziness, asthenia. rarely - convulsions. From the side of the skin rarely - rash. From the urogenital system is very rare - priapism. From the hematopoietic system often - eosinophilia, rarely - leukopenia, very rarely - thrombocytopenia. From laboratory indicators very often - hyperprolactinemia. often - increased activity of ALT, ACT, hyperglycemia. very rarely - hyperbilirubinemia, increased activity of alkaline phosphatus. Others very often - weight gain, infrequently - photosensitivity, very rarely - allergic reactions, withdrawal syndrome.
Overdose
Signs and symptoms of overdose: Very frequent (frequency ≥10%) symptoms of an overdose of olanzapine were tachycardia, agitation / aggressiveness, speech disorder, various extrapyramidal disorders and disorders of consciousness of varying severity (from sedation to coma). Other clinically significant effects of olanzapine overdose included delirium, convulsions, neuroleptic malignant syndrome, respiratory depression, aspiration, increased and decreased blood pressure, arrhythmias (less than 2% of overdose cases), and cardiac and respiratory arrest.The minimum dose for acute overdose with a fatal outcome was 450 mg, the maximum dose for an overdose with a favorable outcome (survival) is 2 g. Medical help for overdose: There is no specific antidote for olanzapine. It is not recommended provoking vomiting. Standard overdose procedures (gastric lavage, intake of activated carbon) may be indicated. The combined intake of activated carbon and olanzapine showed a decrease in the bioavailability of olanzapine when taken orally up to 50-60%. Symptomatic treatment is shown in accordance with the clinical condition and control of vital body functions, including the correction of low blood pressure, circulatory disorders and the maintenance of respiratory function. Epinephrine, dopamine and other adrenomimetics that are β-adrenoreceptor agonists should not be used, since stimulation of these receptors may exacerbate hypotension. Monitoring of cardiovascular activity is necessary in order to identify possible arrhythmias. The patient must be under continuous medical supervision until full recovery.
Interaction with other drugs
The metabolism of olanzapine can be altered by the action of inhibitors or inducers of cytochrome P450 isoenzyme, showing specific activity against the CYP1A2 isoenzyme. The clearance of olanzapine is increased in smoking patients and in patients taking carbamazepine (due to an increase in the activity of the CYP1A2 isoenzyme). Potential inhibitors of the isoenzyme CYP1A2 can reduce the clearance of olanzapine. Olanzapine is not a potential inhibitor of CYP1A2 isoenzyme; therefore, when taking olanzapine, the pharmacokinetics of drugs, such as theophylline, which are mainly metabolized by the isoenzyme CYP1A2, do not change. In clinical studies have shown that a single administration of a dose of olanzapine to background following medications therapy was not accompanied by the suppression of metabolism of these drugs: imipramine or its metabolite desipramine (isoenzymes CYP2D6, CYP3A, CYP1A2), warfarin (isoenzyme CYP2C19), theophylline (isoenzyme CYP1A2) or diazepam (isoenzyme CYP3A4, CYP2C19). There were also no signs of drug interactions when using olanzapine in combination with lithium preparations or biperiden. Against the background of the equilibrium concentration of olanzapine, there was no change in the pharmacokinetics of ethanol.However, taking ethanol together with olanzapine may be accompanied by an increase in the pharmacological effects of olanzapine, for example, a sedative effect. Fluoxetine (60 mg once or 60 mg daily for 8 days) causes an increase in the maximum concentration (Cmax) of olanzapine by an average of 16% and a decrease in the clearance of olanzapine by an average of 16%. The degree of influence of this factor is significantly inferior to the severity of individual differences of these indicators, so it is usually not recommended to change the dose of olanzapine when it is used in combination with fluoxetine. Fluvoxamine, an inhibitor of CYP1A2 isofrementa, reduces the clearance of olanzapine. The result is an average Cmax increase in olanzapine with fluvoxamine administration by 54% in non-smoking women and 77% in male smokers, and the average AUC (area under the concentration – time curve) of olanzapine is 52% and 108%, respectively. Small doses of olanzapine should be administered to patients who are receiving fluvoxamine together. In vitro studies using human liver microsomes have shown that olanzapine slightly suppresses the formation of valproic acid glucuronide (the main metabolic pathway of valproic acid). Valproic acid also slightly affects the metabolism of olanzapine in vitro. Therefore, a clinically significant pharmacokinetic interaction between olanzapine and valproic acid is unlikely. The absorption of olanzapine does not depend on food intake. A single dose of aluminum- or magnesium-containing antacids or cimetidine did not violate the bioavailability of olanzapine when taken orally. The simultaneous use of activated carbon and olanzapine reduced the bioavailability of the latter when taken orally up to 50-60%. According to in vitro studies using human liver microsomes, olanzapine also demonstrated extremely low potential for inhibiting the activity of the following cytochrome P450 isoenzymes: CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A.v
special instructions
Suicide: The risk of suicidal attempts by patients with schizophrenia and bipolar disorder of the first type is due to self-indicated diseases. In this regard, against the background of pharmacotherapy requires careful monitoring of those patients who are particularly at risk of suicide.When prescribing olanzapine, one should strive to minimize the number of pills taken by the patient in order to reduce the risk of overdose. body, stiffness, change in mental status and vegetative e violation (unstable pulse or blood pressure, tachycardia, cardiac arrhythmias, increased sweating). Additional signs can include an increase in the activity of creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. Clinically, the manifestations of malignant neuroleptic syndrome or a significant increase in body temperature without other symptoms of a malignant neuroleptic syndrome require the withdrawal of all neuroleptics, including olanzapine. Late dyskinesia: In comparative studies, treatment with olanzapine was significantly less frequently accompanied by the development of dyskinesias requiring medical correction than the use of atypical and other atypical antipsychotics. However, the risk of tardive dyskinesia should be considered in case of long-term neuroleptic therapy. When signs of tardive dyskinesia develop, correction of neuroleptic doses is recommended. It should be borne in mind that when translating into nolanzapine, symptoms of tardive dyskinesias may develop as a result of one-time cancellation of previous therapy. Over time, the intensity of these symptoms may increase, moreover, these symptoms may develop after cessation of therapy. Experience with elderly patients with dementia-related psychosis: The efficacy of olanzapine in elderly patients with dementia-related psychosis has not been established. In this category of patients in place-controlled clinical trials, the frequency of lethal 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 in the treatment of lanzapine include more than 80 years of age, sedation, combined use with benzodiazepines, or the presence of lung disease (for example, pneumonia with or without aspiration).There is no sufficient data to establish differences in the incidence of cerebrovascular disorders and (or) mortality (compared with placebo) and risk factors in this group of patients with oral medication and intramuscular injections. Parkinson's disease. It is not recommended to use olanzapine in the treatment of psychoses induced by dopamine receptor agonists in Parkinson's disease. In clinical studies in patients with psychosis induced by taking the drug (dopamine receptor agonist) Parkinson's disease, an increase in the symptoms of parkinsonism was noted very often (≥10%) and with a higher frequency than in the group placebo. Hallucinations were also noted very often (≥10%) and with a higher frequency than in the placebo group. Liver dysfunction: In some cases, olanzapine, usually in the early stages of therapy, was accompanied by a transient, asymptomatic increase in liver transaminase activity (aspartate aminotransferase (ACT) and alanine aminotransferase (ALT)) in serum. There were rare cases of hepatitis. In addition, isolated reports of cholestatic and mixed liver damage were reported. Special caution is necessary when increasing the activity of ACT and / or ALT in serum blood in patients with insufficient liver function, with limited functional reserve of the liver or in patients receiving treatment with potentially hepatotoxic drugs. In case of an increase in ACT and / or ALT activity during olanzapine treatment, careful monitoring of the patient and, if necessary, dose reduction are required. For severe violations of liver function, due to the intake of olanzapine, its use should be discontinued. Hyperglycemia and diabetes mellitus: There is a higher prevalence of diabetes in patients with schizophrenia. As with some other antipsychotic drugs, hyperglycemia, decompensation of diabetes mellitus, and in some cases accompanied by ketoacidosis and diabetic coma, including death, have been rarely observed. A thorough clinical monitoring of patients with diabetes mellitus and patients with risk factors for the development of diabetes is recommended.Changes in the lipid profile: During the entry of a placebo-controlled study, unwanted changes in the lipid spectrum were observed in patients who received lolanzapine. Clinical observation is recommended. Development of risk of sudden death: The experience of clinical use of any neuroleptics, including olanzapine, revealed a similar, dose-dependent, twofold increase in the risk of death due to acute cardiac insufficiency compared with deaths due to acute heart failure in patients who did not use neuroleptics. Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including Lethal outcomes have been reported in olanzapine studies in elderly patients with psychosis associated with dementia. In the field-controlled studies, there was a higher incidence of cerebrovascular adverse events 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, a previously observed case of cerebrovascular adverse events or transient ischemic attack, arterial hypertension, smoking), as well as concomitant diseases and (or) taking medications associated with ceps, and with time-sensitive ceps. Olanzapine is not indicated for the treatment of patients with psychosis associated with dementia. Seizures Olanzapine should be used with caution in patients with a history of seizures or susceptibility to factors that reduce the threshold of seizure readiness. In these patients, olanzapine treatment was rarely followed by seizures. M-holinoblocking activity: In accompanying clinical studies, olanzapine therapy was rarely accompanied by undesirable reactions caused by blockade-cholinergic receptors. However, clinical experience with olanzapine patients with comorbidities is limited, so it is recommended to exercise caution when prescribing olanzapine to patients with clinically significant prostatic hyperplasia, paralytic intestinal obstruction, angle-closure glaucoma and similar conditions.The blockade of dopamine receptors: Under the conditions of invitro, olanzapine detects antagonism against dopamine receptors and, like other antipsychotics (neuroleptics), can theoretically suppress the action of levodopa and other agonistodofamine receptors. Hematologic changes: With caution, olanzapine should be used in patients with low levels of leukocytes and (or) neutrophils in the blood; receiving drugs that can cause neutropenia; with inhibition of bone marrow function due to radiation or chemotherapy; as well as in patients with eosinophilia and (or) myeloproliferative diseases. The development of neutropenia has been reported mainly in the combination of olanzapine with valproate. In clinical studies, the use of olanzapine in patients with clozapine-dependent neutropenia or agranulocytosis in a history of was not accompanied by a recurrence of these disorders. On neutropenia was reported glavnymobrazom, in combined therapy with olanzapine and valproic kislotoy.Interval QT: In clinical studies infrequently otmechalosklinicheski significant lengthening of the interval QT (QT interval korrektsieyFrideritsiya [QTcF] bolshe500 ms in patients with baseline pokazatelemQTcF less than 500 ms) in patients treated with olanzapine, in the absence of significant differences with placebo in the incidence of undesirable phenomena of the heart. However, as with the use of other antipsychotics, it is recommended to take caution when using olanzapine in combination with drugs that can lengthen the QT interval, especially in elderly patients with congenital lengthening of the QT interval, cardiac insufficiency, myocardial hypertrophy, hypokalemia, hypoglymia. Cancel therapy: In the case of a sharp withdrawal of olanzapine, it is extremely rare (less than 0.01%) that acute development of sweating, insomnia of tremor, anxiety, nausea and vomiting has been reported. Thromboembolism: It is extremely rare (less than 0.01%) that venous thromboembolism has been reported in olanzapine phonetherapy. The presence of a causal relationship between the intake of olanzapine and venous thromboembolism has not been established. However, considering that patients with schizophrenia often have acquired risk factors for venous thromboembolism, a cumulative assessment of all possible risk factors for the development of this complication, including immobilization of patients, and the necessary preventive measures are required.General activity in relation to the central nervous system: 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 and alcohol. Postural hypotension Postural hypotension has not often been observed in clinical studies of olanzapine in the elderly. As with the use of other antipsychotics, in the case of olanzapina patients over 65 years of age, it is recommended to periodically monitor blood pressure. Body weight: During treatment (up to 6 weeks) of the acute phase of schizophrenia, when the percentage of patients who experienced an increase in weight ≥7% of the baseline, the difference was statistically significant and amounted to 29% of olanzapine and only 3% in the placebo group. The average weight gain of these patients taking olanzapine in the acute phase was 2.8 kg. Body mass index (BMI) has always been clinically significant in the study group. With prolonged therapy for schizophreniaolanzapine, weight gain averaged 5.4 kg, in 56% of patients in the test group, body weight increased by more than 7% of the baseline. For patients who received long-term therapy for bipolar disorder, the average weight gain was 3.8 kg and the number of patients with an increase in weight of more than 7% was 31%. Hyperprolactinemia: During controlled clinical trials (no more than 12 weeks), an increase in the level of prolactin in the bloodstream was found in 30% of patients in the test group and 10.5% in the placebo group (control). The levels of increase in prolactin concentration were moderate. Identified clinical appearances included: menstrual dysfunction (often), sexual dysfunction (in particular, erectile dysfunction (in men), decreased or lostbido (in men and women), abnormal orgasm) and from the sternum gland (not often). Dysphagia: The occurrence of motility disorders of the esophagus and aspiration are associated with the use of antipsychotic drugs. Aspiration pneumonia is a common cause of morbidity and mortality in patients with severe Alzheimer's disease, which requires caution with regard to such patients. Body temperature regulation: An impaired ability of the body to control the internal temperature of the body is assigned to antipsychotic drugs.Appropriate care should be taken by patients who take olanzapine and are in conditions that increase the internal body temperature. For example, they perform vigorous physical exercises, are exposed to high environmental temperatures, take a drug with anticholinergic activity or are in dehydration conditions sweat). Children and adolescents under 18: Olanzapine is not recommended for use in children and adolescents under 18 due to the lack of sufficient efficacy and safety data. In short-term studies that were conducted in adolescents 13–17 years of age, a more significant increase in body weight and changes in lipid and prolactin concentrations were observed than in similar studies in adults. Impact on the ability to drive vehicles and other mechanisms Patients taking olanzapine should be warned of the dangers associated with the operation of the mechanisms, including the car, because olanzapine can cause drowsiness and dizziness.