Instructions for Adagio film-coated tablets 2.5 mg No. 30
Composition
active ingredient: olanzapine;
1 tablet contains olanzapine 2.5 mg;
Excipients: lactose monohydrate; hydroxypropylcellulose; crospovidone; microcrystalline cellulose; magnesium stearate;
film coating: hypromellose, Opadry yellow 03B220084 (hypromellose, titanium dioxide (E 171), talc, macrogol, iron oxide yellow (E 172)), carnauba wax: beeswax (60:40).
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets with a biconvex surface, coated with a light yellow to yellow film coating.
Pharmacotherapeutic group
Antipsychotics. ATX code N05A H03.
Pharmacological properties
Pharmacodynamics.
Olanzapine is an antipsychotic, antimanic, mood-stabilizing drug that exhibits a broad pharmacological profile across multiple receptor systems. In preclinical studies, olanzapine has shown affinity for a number of receptors (Ki; 2A/2C, 5HT3, 5HT6; dopamine D1, D2, D3, D4, D5; cholinergic muscarinic receptors M1–M5; α1-adrenergic, histamine H1 receptors). Animal behavioral studies have shown 5HT, dopamine, and cholinergic antagonism, consistent with the binding profile of olanzapine to these receptors. Olanzapine has demonstrated greater affinity for serotonin 5HT2 than dopamine D2 receptors in vitro and greater 5HT2 than D2 activity in vivo. Electrophysiological studies have shown that olanzapine selectively reduces the excitability of mesolimbic (A10) dopaminergic neurons, while having little effect on striatal (A9) pathways involved in motor function. Olanzapine inhibits the conditioned avoidance reflex, indicating its antipsychotic activity at doses lower than those that cause catalepsy, which is a sign of motor side effects. Unlike some other antipsychotic drugs, olanzapine enhances responses to stimuli during anxiolytic testing.
In healthy volunteers, olanzapine had a higher binding to 5-HT2A receptors than to dopamine D2 receptors after a single oral dose of 10 mg olanzapine as measured by positron emission tomography (PET). In addition, analysis of single-photon emission computed tomography (SPECT) images of schizophrenic patients showed that olanzapine-responsive patients had lower binding to striatal D2 receptors than other antipsychotic- and risperidone-responsive patients, and comparable to clozapine-responsive patients.
Clinical efficacy: In two of two placebo-controlled and two of three comparator-controlled studies involving over 2900 patients with schizophrenia with positive and negative symptoms, olanzapine showed statistically significant improvement in patients' condition.
In an international double-blind comparative study of 1484 patients with schizophrenia, schizoaffective disorder, and related disorders of varying severity associated with depressive symptoms (16.6 points on the Montgomery-Asberg Depression Rating Scale), a prospective secondary analysis of baseline to end-of-life mood changes showed a statistically significant improvement (p = 0.001) after olanzapine treatment (–6.0) compared with haloperidol treatment (–3.1).
In patients with manic or mixed episodes in bipolar disorder, olanzapine was superior to placebo and divalproex in reducing manic symptoms over 3 weeks. Olanzapine was comparable to haloperidol in terms of the proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks of treatment. In a study, olanzapine 10 mg added to lithium or valproate for 2 weeks resulted in a significant reduction in manic symptoms compared with lithium or valproate alone after 6 weeks.
In a 12-month study of the prevention of recurrence of manic episodes in patients who achieved remission with olanzapine and were then randomized to olanzapine or placebo, olanzapine demonstrated a statistically significant advantage over placebo on the endpoint of recurrence of bipolar disorder. Olanzapine also demonstrated a statistically significant advantage over placebo in preventing recurrence of mania and depression.
In a subsequent 12-month study of the prevention of recurrence of manic episodes in patients who achieved remission with concomitant olanzapine and lithium and were randomized to receive olanzapine or lithium alone, olanzapine was not statistically inferior to lithium on the endpoint of recurrence of bipolar disorder (olanzapine 30%, lithium 38.3%; p = 0.055).
Children: Experience in adolescents (aged 13 to 17 years) is limited. There are studies of the efficacy of short-term treatment of schizophrenia (6 weeks) and mania associated with bipolar disorder (3 weeks) in less than 200 adolescents. The starting dose of olanzapine was 2.5 mg and was increased up to 20 mg/day. During treatment with olanzapine, adolescents gained significantly more weight than adults. In adolescents, increases in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and prolactin were observed compared with adults. Data on maintenance of treatment effect and long-term use are limited.
Pharmacokinetics.
Absorption. The drug is well absorbed after oral administration, with Cmax in plasma reached after 5–8 hours. Food intake does not affect the absorption of olanzapine. The absolute bioavailability of olanzapine when administered orally compared to intravenously has not been established.
Distribution: The plasma protein binding of olanzapine was approximately 93% over a concentration range of 7 ng/mL to 1000 ng/mL. Olanzapine binds primarily to albumin and α1-acid glycoprotein.
Biotransformation. Olanzapine is metabolized in the liver by conjugation and oxidation. The major circulating metabolite is the 10-N-glucuronide, which does not cross the blood-brain barrier. Cytochromes P450-CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl metabolites, which have shown significantly less pharmacological activity in vivo than olanzapine in animal studies. The major pharmacological activity is due to the parent olanzapine.
Elimination: After oral administration, the mean elimination half-life of olanzapine in volunteers varied with age and gender.
In healthy elderly volunteers (65 years of age and older), the mean half-life was longer (51.8 vs. 33.8 hours) and plasma clearance was reduced (17.5 vs. 18.2 L/h) compared to younger volunteers. Pharmacokinetic variations observed in elderly volunteers were within the range of younger volunteers. In 44 schizophrenic patients >65 years of age, dosing from 5 to 20 mg/day was not associated with any distinctive adverse event profile.
In women, the mean half-life was longer (36.7 vs. 32.3 hours) and plasma clearance was reduced (18.9 vs. 27.3 L/h) compared to men. However, the safety profile of olanzapine (5–20 mg) was comparable in women (N = 467) and men (N = 869).
Patients with renal insufficiency. In patients with renal insufficiency (creatinine clearance
Patients with hepatic impairment. A small study of the effect of hepatic impairment in 6 patients with clinically significant cirrhosis (Child-Pugh class A (n = 5) and B (n = 1)) found little effect on the pharmacokinetics of oral olanzapine (2.5–7.5 mg). Patients with mild to moderate hepatic impairment had slightly increased systemic clearance and a shorter half-life compared with patients without hepatic impairment (n = 3). There were more smokers in the cirrhotic group (4/6; 67%) than in the non-cirrhotic group (0/3; 0%).
Patients who smoke. In non-smokers compared to smokers (men and women), the mean half-life was longer (38.6 vs. 30.4 hours) and plasma clearance was reduced (18.6 vs. 27.7 L/h).
Olanzapine plasma clearance is lower in elderly patients compared to young patients, in women compared to men, and in non-smokers compared to smokers. However, factors such as age, gender, and smoking status may have little effect on olanzapine plasma clearance and half-life compared to the variability in these parameters between individuals.
No differences in the pharmacokinetics of olanzapine were found in studies involving European, Japanese, and Chinese patients.
Children. The pharmacokinetics of olanzapine are similar in adolescents and adults. In clinical trials, the mean exposure to olanzapine was approximately 27% higher in adolescents. Demographic differences between adolescents and adults include lower mean body weight and fewer smokers among adolescent patients. These factors likely contribute to the higher mean exposure to olanzapine observed in adolescents.
Indication
Olanzapine is indicated for the treatment of schizophrenia.
Olanzapine is effective in maintaining the achieved clinical effect during long-term therapy in patients who have responded to initial therapy.
Olanzapine is indicated for the treatment of moderate to severe manic episodes.
Olanzapine is indicated for the prevention of recurrent attacks in patients with bipolar disorder who have responded to olanzapine treatment of mania.
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the medicinal product. Known risk of angle-closure glaucoma.
Interaction with other medicinal products and other types of interactions
Drug interaction studies have only been conducted in adults.
CYP1A2 inducers. Olanzapine metabolism may be induced by smoking and carbamazepine, which may result in decreased olanzapine concentrations. Only a mild to moderate increase in olanzapine clearance has been observed. Its clinical consequences are likely to be limited, but clinical monitoring and, if necessary, an increase in the olanzapine dose are recommended.
CYP1A2 inhibitors. Fluvoxamine, a specific CYP1A2 inhibitor, significantly reduces the metabolism of olanzapine. This results in a mean increase in Cmax after fluvoxamine of 54% in non-smoking women and 77% in smoking men. The mean increase in olanzapine AUC is 52% and 108%, respectively. A lower starting dose of olanzapine should be considered for patients taking fluvoxamine or any other CYP1A2 inhibitor, such as ciprofloxacin. A dose reduction of olanzapine should be considered if treatment with a CYP1A2 inhibitor is considered.
Reduced bioavailability: Activated charcoal reduced the oral bioavailability of olanzapine by 50–60% and should be administered at least 2 hours before or 2 hours after olanzapine.
Fluoxetine (CYP2D6 inhibitor), single doses of antacids (aluminum, magnesium), or cimetidine did not significantly affect the pharmacokinetics of olanzapine.
Olanzapine may affect the effects of other drugs. Olanzapine may antagonize the effects of direct and indirect dopamine agonists.
Olanzapine did not inhibit most CYP450 isoenzymes (e.g. 1A2, 2D6, 2C9, 2C19, 3A4) in vitro. Therefore, no specific interactions are expected, as confirmed by in vivo studies, where no inhibition of olanzapine metabolism was observed with the following active substances: tricyclic antidepressants (primarily CYP2D6 isoenzymes), warfarin (CYP2C9), theophylline (CYP 1A2) or diazepam (CYP 3A4 and 2C19).
No interactions were noted when olanzapine was administered with lithium or biperiden.
Therapeutic monitoring of valproate plasma levels did not reveal the need for valproate dose adjustment when co-administered with olanzapine.
General central nervous system activity: Caution should be exercised in patients who consume alcohol or are taking medications that may cause central nervous system depression.
Concomitant use of olanzapine with antiparkinsonian drugs is not recommended in patients with Parkinson's disease and dementia.
QTc interval: Caution should be exercised when olanzapine is administered with other drugs that may prolong the QTc interval.
Application features
During treatment with antipsychotics, clinical improvement may take from a few days to a few weeks. During this period, patients should be closely monitored.
Psychosis associated with dementia and/or behavioural disturbances. Olanzapine is not indicated for the treatment of psychosis associated with dementia and/or behavioural disturbances and is not recommended for use in such patients due to an increased risk of mortality and cerebrovascular accidents. In placebo-controlled clinical trials (6–12 weeks duration) in elderly patients (mean age 78 years) with psychosis associated with dementia and/or behavioural disturbances, the rate of deaths was 2-fold higher in patients treated with olanzapine compared to placebo (3.5% vs. 1.5%, respectively). The higher mortality was not related to the dose of olanzapine used (mean daily dose was 4.4 mg) or to the duration of treatment. Risk factors for increased mortality include age 65 years or older, dysphagia, sedation, malnutrition and dehydration, the presence of pulmonary pathology (e.g., pneumonia with or without aspiration), and concomitant use of benzodiazepines. However, mortality was higher with olanzapine than with placebo, regardless of risk factors.
Parkinson's disease. Olanzapine is not recommended for the treatment of psychosis associated with dopamine agonists. Concomitant use of olanzapine and antiparkinsonian medicinal products is not recommended in patients with Parkinson's disease and dementia. In clinical trials, worsening of Parkinson's disease symptoms and hallucinations were very common, more frequently than with placebo; olanzapine was not more effective than placebo for psychotic symptoms. From the outset of these studies, patients were required to continue on the lowest effective dose of antiparkinsonian medicinal products (dopamine agonists) and to continue on the same antiparkinsonian medicinal products and doses throughout the study. Olanzapine was initiated at a dose of 2.5 mg/day and titrated to a maximum of 15 mg/day.
Neuroleptic malignant syndrome. Neuroleptic malignant syndrome (NMS) is a potentially fatal symptom complex associated with antipsychotic drugs. Rare cases of NMS have been reported with olanzapine. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, loss of consciousness, and symptoms of cardiac instability (irregular pulse or blood pressure changes, tachycardia, increased sweating, and cardiac arrhythmia). Additional features may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Clinical manifestations of NMS or the presence of hyperthermia without clinical manifestations of NMS require immediate discontinuation of all antipsychotic drugs, including olanzapine.
Hyperglycemia and diabetes mellitus: Hyperglycemia and/or development of diabetes mellitus or worsening of pre-existing diabetes mellitus associated with ketoacidosis or diabetic coma, as well as fatal cases, have been reported uncommonly. Pre-existing weight gain has occasionally been reported, which may be a risk factor.
Appropriate clinical monitoring is recommended in patients with diabetes mellitus and those at risk for diabetes mellitus, including measurement of blood glucose at baseline, 12 weeks, and annually thereafter. Patients treated with antipsychotics, including olanzapine, should be observed for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness). Patients with diabetes mellitus and those at risk for diabetes should have their glucose levels monitored regularly. Weight should be monitored regularly, e.g. at baseline, 4 weeks, 8 weeks, and 12 weeks, and quarterly thereafter.
Anticholinergic Activity: While olanzapine has demonstrated anticholinergic activity in vitro, clinical experience has shown a low incidence of anticholinergic events. However, due to limited clinical experience with olanzapine in patients with comorbid conditions, caution should be exercised when prescribing olanzapine to patients with prostatic hypertrophy, paralytic ileus, or conditions associated with these conditions.
Liver function: Transient, asymptomatic elevations of hepatic aminotransferases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), have been commonly observed with olanzapine, especially early in treatment. Olanzapine should be used with caution in patients with elevated ALT and/or AST, symptoms of liver dysfunction, conditions associated with hepatic insufficiency, and patients receiving potentially hepatotoxic drugs. If hepatitis (including hepatocellular, cholestatic, or mixed liver injury) is diagnosed, olanzapine should be discontinued.
Neutropenia: Olanzapine should be used with caution in patients with low white blood cell and/or neutrophil counts from any cause, in patients receiving medications that may cause neutropenia, in patients with a history of drug-induced bone marrow suppression/toxicity, in patients with bone marrow suppression due to underlying disease, radiation or chemotherapy, in patients with hypereosinophilia or myeloproliferative disease. Neutropenia has been commonly reported with the concomitant use of olanzapine and valproate.
Discontinuation of therapy. In the case of abrupt discontinuation of therapy, rare (≥ 0.01% and
QT interval: In studies involving patients treated with olanzapine, clinically significant prolongation of the QTc interval (Frederic's correction of QT [QTcF] ≥ 500 ms at any time after the isoline in patients with a QTcF isoline of 1000 ms) was uncommon (0.1–1%), but no significant difference in associated cardiac responses was observed compared to placebo. However, as with other antipsychotics, caution should be exercised when olanzapine is co-administered with drugs that prolong the QTc interval, especially in the elderly, patients with congenital long QT syndrome, congestive heart failure, cardiac hypertrophy, hypokalemia, or hypomagnesemia.
General effects on the central nervous system (CNS). Given the primary CNS effects of olanzapine, caution should be exercised when it is taken in combination with other centrally acting drugs and alcohol. Olanzapine exhibits dopamine antagonism in vitro and may antagonize the effects of direct and indirect dopamine agonists.
Seizures: Olanzapine should be used with caution in patients with a history of seizures or in patients with factors that lower the seizure threshold. Seizures have been reported uncommonly with olanzapine. In most of these cases, patients had a history of seizures or were at increased risk of seizures.
Tardive dyskinesia: In clinical trials of 1 year or less duration, olanzapine was associated with a statistically significant reduction in the incidence of treatment-emergent dyskinesia. Because of the increased risk of tardive dyskinesia with long-term use of antipsychotics, appropriate dose reduction or discontinuation of the drug is recommended if a patient develops symptoms of tardive dyskinesia. These symptoms may worsen over time or even reappear after treatment is discontinued.
Orthostatic hypotension: Orthostatic hypotension has been reported uncommonly in elderly patients in clinical trials. Periodic blood pressure monitoring is recommended in patients aged 65 years and older.
Sudden cardiac death. Cases of sudden cardiac arrest have been reported in postmarketing studies with olanzapine. In a retrospective observational cohort study, the risk of sudden cardiac arrest in patients treated with olanzapine was approximately twice that in patients not taking antipsychotics. In this study, the risk with olanzapine was comparable to the risk with atypical antipsychotics included in the pooled analysis.
Dopaminergic antagonism: Olanzapine exhibits dopamine antagonism in vitro and theoretically may antagonize the effects of levodopa and dopamine agonists, as do other antipsychotics.
Glucose: In clinical trials (up to 52 weeks), olanzapine produced greater changes in glucose levels compared to placebo. The difference in changes between olanzapine and placebo was greater in patients with a history of glucose dysregulation (including patients with diabetes or patients with hyperglycemia). These patients had significantly greater increases in HbA1c compared to placebo.
The percentage of patients whose glucose levels changed from normal or borderline to high has been steadily increasing.
In analyses of patients who underwent 9–12 months of olanzapine therapy, elevated blood glucose levels were reduced after 6 months.
Lipid changes. Undesirable changes in lipid levels may occur in patients treated with olanzapine. Lipid changes should be managed appropriately in patients with dyslipidemia and in patients with risk factors for lipid disorders. Patients treated with antipsychotics, including olanzapine, should have their blood lipid levels monitored regularly, for example: at baseline, after 12 weeks, and every 5 years thereafter.
In clinical trials lasting more than 12 weeks, patients taking olanzapine had increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides compared to the placebo group.
Significant increases in lipid levels (total cholesterol, low-density lipoprotein, triglycerides) were observed more frequently in patients without a history of lipid disorders.
There were no statistically significant differences in increases in high-density lipoprotein cholesterol between patients taking olanzapine and patients taking placebo.
The proportion of patients who changed their total cholesterol, low-density lipoprotein, or triglyceride levels from normal or borderline to high or their high-density lipoprotein levels from normal or borderline to low was greater in the long-term studies (at least 48 weeks) compared with the short-term studies. In patients who received 12 months of therapy, total cholesterol levels did not increase after 4 to 6 months.
Suicide: Suicidality is common in both schizophrenia and bipolar I disorder, and patients at high risk of suicide receiving olanzapine should be carefully monitored. To reduce the risk of overdose, olanzapine should be prescribed in small doses sufficient to achieve the desired therapeutic effect.
Olanzapine monotherapy in adults. In 13 placebo-controlled clinical trials, olanzapine-treated patients experienced a mean weight gain of 2.6 kg compared with a mean weight loss of 0.3 kg in the placebo group over a median of 6 weeks; 22.2% of olanzapine-treated patients experienced a weight gain of at least 7% of their baseline weight compared with 3% of placebo patients over a median of 8 weeks; 4.2% of olanzapine-treated patients experienced a weight gain of at least 15% of their baseline weight compared with 0.3% of placebo patients over a median of 12 weeks. Clinically significant weight gain was observed in all patient groups by BMI (body mass index). Discontinuation of therapy due to weight gain occurred in 0.2% of olanzapine-treated patients compared with 0% of placebo patients.
In long-term clinical trials (at least 48 weeks), the mean weight gain in patients was 5.6 kg (median duration of 573 days; N = 2021). The proportion of patients who gained at least 7%, 15%, or 25% of their baseline weight during long-term olanzapine treatment was 64%, 32%, and 12%, respectively. Discontinuation of therapy due to weight gain occurred in 0.4% of patients treated with olanzapine for at least 48 weeks.
Dysphagia. Esophageal motility disorders and dyspnea have been associated with antipsychotic use. Aspiration pneumonia has been a common cause of morbidity and mortality in patients with Alzheimer's disease. Olanzapine is not approved for the treatment of patients with Alzheimer's disease.
Body temperature regulation: Impairment of the body's ability to cool itself has been observed with antipsychotics. This should be considered when prescribing olanzapine to patients who may experience an increase in body temperature, such as during strenuous exercise, exposure to extreme temperatures, concomitant use of anticholinergic agents, or dehydration.
Use in patients with comorbid conditions. Clinical experience with olanzapine in patients with certain medical conditions is limited. Olanzapine increases muscarinic receptor affinity in vitro. In premarketing clinical studies, olanzapine was associated with constipation, dry mouth, tachycardia, and other adverse events possibly related to cholinergic antagonism. Such adverse reactions have infrequently led to discontinuation of olanzapine therapy, but olanzapine should be used with caution in patients with clinically significant prostatic hypertrophy, narrow-angle glaucoma, a history of paralytic ileus, or related conditions caused by cholinergic antagonism that may be exacerbated by olanzapine. In 5 placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis (n = 1184), the following treatment-related adverse reactions were observed with an incidence of at least 2% and a significantly higher incidence compared to placebo: fall, somnolence, peripheral edema, gait disturbance, urinary incontinence, lethargy, weight gain, asthenia, pyrexia, pneumonia, dry mouth, and visual hallucinations. The rate of discontinuation due to adverse events was higher in the olanzapine group compared to placebo (13% vs. 7%, respectively). Elderly patients with dementia-related psychosis treated with olanzapine had a higher rate of death compared to placebo. Olanzapine is not indicated for the treatment of elderly patients with dementia-related psychosis. Olanzapine has not been used in sufficient numbers in patients with recent myocardial infarction or unstable cardiac disease. Patients with the above diagnoses were excluded from premarketing clinical trials. Olanzapine should be used with caution in patients with cardiac disease due to the risk of orthostatic hypotension.
Laboratory tests: It is recommended to monitor fasting glucose and lipid profile at the beginning of treatment and periodically during treatment.
Additional Investigations/Laboratory Data: Given that neutropenia associated with other psychotropic agents and leukopenia associated with olanzapine have been observed in some animal studies (see Animal Toxicology Studies below), hematological parameters were evaluated with particular care in premarketing studies of olanzapine. There was no indication in the premarketing database of olanzapine of a risk of clinically significant neutropenia associated with olanzapine treatment.
Postmarketing reports: Postmarketing reports of adverse reactions involving neutropenia have been temporally associated with olanzapine use, but not necessarily causally.
Animal Toxicology Studies: In animal studies with olanzapine, the major hematological effects were reversible peripheral cytopenia in individual dogs at 10 mg/kg (17 times the maximum recommended daily human oral dose based on mg/m2 body surface area), dose-related decreases in lymphocytes and neutrophils in mice, and lymphopenia in rats. Several dogs treated with 10 mg/kg developed reversible neutropenia and/or reversible hemolytic anemia between months 1 and 10 of treatment. Dose-related decreases in lymphocytes and neutrophils were observed in mice treated with 10 mg/kg (equivalent to twice the maximum recommended daily human oral dose based on mg/m2 body surface area) during the 3-month study. Non-specific lymphopenia, consistent with decreased body weight gain, was observed in rats given 22.5 mg/kg (11 times the maximum recommended daily human oral dose based on mg/m2 body surface area) for 3 months or 16 mg/kg (8 times the maximum recommended daily human oral dose based on mg/m2 body surface area) for 6 or 12 months. There was no evidence of bone marrow cytotoxicity in any of the species studied. Bone marrow cells were normocellular or hypercellular, suggesting that the decrease in circulating blood cells was likely due to peripheral (non-bone marrow) factors.
This medicinal product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Use during pregnancy or breastfeeding
Pregnancy
There are no adequate and well-controlled studies of olanzapine in pregnant women. Patients receiving olanzapine should inform their physician if they are pregnant or intend to become pregnant. Because experience with olanzapine in pregnant women is limited, olanzapine should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus.
Neonates exposed to antipsychotics (including olanzapine) during the third trimester of pregnancy are at risk of adverse reactions, including extrapyramidal disorders and/or withdrawal syndrome, which may vary in severity and duration after birth. Agitation, hypertension, hypotension, tremor, somnolence, respiratory distress syndrome, or feeding disorders have been reported. Therefore, close monitoring of the neonate is necessary.
Breastfeeding
In a study of healthy lactating women, olanzapine was detected in breast milk. The mean infant exposure (mg/kg) at steady state was approximately 1.8% of the maternal olanzapine dose (mg/kg).
Patients should be advised not to breastfeed if they are taking olanzapine.
Fertility
The effect on fertility is unknown.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies have been conducted on the effects of olanzapine on the ability to drive or use machines. Since olanzapine may cause drowsiness and dizziness, patients should be warned about the dangers associated with operating machinery, including motor vehicles.
Method of administration and doses
Adults
Schizophrenia: The recommended starting dose of olanzapine is 10 mg once daily.
Manic episodes: The initial dose is 15 mg/day as a single dose in monotherapy or 10 mg/day in combination therapy.
Prevention of relapse in bipolar disorder. The recommended starting dose is 10 mg per day. In patients who are in
