OLANDUS 10 Olanzapine 10mg Film-Coated Tablet 1's

Used in the management of schizophrenia and for the treatment of moderate to severe mania associated with bipolar disorder.
Olandus ODT 15: It is indicated for the short-term treatment of acute manic episodes associated with Bipolar Disorder. It is also indicated for the treatment of schizophrenia. In patients whose manic episodes has responded to olanzapine treatment, olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder.

Olandus 5/Olandus 10: Schizophrenia, combination therapy for mania, preventing recurrence in bipolar disorder: ADULT over 18 years: 10 mg daily adjusted to usual range of 5-20 mg daily; doses greater than 10 mg daily adjusted to usual range of 5-20 mg daily; doses greater than 10 mg daily only after reassessment; max. 30 mg daily. Monotherapy for mania: ADULT over 18 years: 15mg daily adjusted to usual range of 5-20 mg daily doses greater than 15 mg only after reassessment max. 20 mg daily.
Olandus ODT 5/Olandus ODT 10: Schizophrenia: Adults: Dose Selection: Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 to 10 mg initially, with a target dose of 10 mg/day within several days. Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for olanzapine would not be achieved for approximately 1 week in the typical patient.
When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended.
Efficacy in schizophrenia was demonstrated in a dose range of 10 to 15 mg/day in clinical trials. However, doses above 10 mg/day were not demonstrated to be more efficacious than the 10 mg/day dose. An increase to a dose greater than the target dose of 10 mg/day (i.e., to a dose of 15 mg/day or greater) is recommended only after clinical assessment. Olanzapine is not indicated for use in doses above 20 mg/day.
Dosing in Special Populations: The recommended starting dose is 5 mg in patients who are debilitated, who have a predisposition to hypotensive reactions, who otherwise exhibit a combination of factors that may result in slower metabolism of olanzapine (e.g., nonsmoking female patients ≥65 years of age), or who may be more pharmacodynamically sensitive to olanzapine. When indicated, dose escalation should be performed with caution in these patients.
Maintenance Treatment: The effectiveness of oral olanzapine, 10 mg/day to 20 mg/day, in maintaining treatment response in schizophrenic patients who had been stable on olanzapine for approximately 8 weeks and were then followed for relapse has been demonstrated in a placebo-controlled trial. The physician who elects to use olanzapine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Adolescents: Dose Selection: Oral olanzapine should be administered on a once-a-day schedule without regard to meals with a recommended starting dose of 2.5 or 5 mg, with a target dose of 10 mg/day. Efficacy in adolescents with schizophrenia was demonstrated based on a flexible dose range of 2.5 to 20 mg/day in clinical trials, with a mean modal dose of 12.5 mg/day (mean dose of 11.1 mg/day). When dosage adjustments are necessary, dose increments/decrements of 2.5 or 5 mg are recommended.
The safety and effectiveness of doses above 20 mg/day have not been evaluated in clinical trials.
Maintenance Treatment: The efficacy of olanzapine for the maintenance treatment of schizophrenia in the adolescent population has not been systematically evaluated; however, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients. Thus, it is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.
Bipolar I Disorder (Manic or Mixed Episodes): Adults: Dose Selection for Monotherapy: Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 10 or 15 mg. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours, reflecting the procedures in the placebo-controlled trials. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended. Short-term (3-4 weeks) antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials. The safety of doses above 20 mg/day has not been evaluated in clinical trials.
Maintenance Monotherapy: The benefit of maintaining bipolar I patients on monotherapy with oral olanzapine at a dose of 5 to 20 mg/day, after achieving a responder status for an average duration of 2 weeks, was demonstrated in a controlled trial. The physician who elects to use olanzapine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Dose Selection for Adjunctive Treatment: When administered as adjunctive treatment to lithium or valproate, oral olanzapine dosing should generally begin with 10 mg once-a-day without regard to meals.
Antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials.
The safety of doses above 20 mg/day has not been evaluated in clinical trials.
Adolescents: Dose Selection: Oral olanzapine should be administered on a once-a-day schedule without regard to meals with a recommended starting dose of 2.5 or 5 mg, with a target dose of 10 mg/day. Efficacy in adolescents with bipolar I disorder (manic or mixed episodes) was demonstrated based on a flexible dose range of 2.5 to 20 mg/day in clinical trials, with a mean modal dose of 10.7 mg/day (mean dose of 8.9 mg/day). When dosage adjustments are necessary, dose increments/decrements of 2.5 or 5 mg are recommended.
The safety and effectiveness of doses above 20 mg/day have not been evaluated in clinical trials.
Maintenance Treatment: The efficacy of olanzapine for the maintenance treatment of bipolar I disorder in the adolescent population has not been evaluated; however, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients. Thus, it is generally recommended that responding patients be continued beyond the acute response, but at the lowest dose needed to maintain remission. Patients should be periodically reassessed to determine the need for maintenance treatment.
Olandus ODT 15: Olanzapine orally disintegrating tablets should be placed in the mouth and allowed to completely dissolve before swallowing the saliva. A glass of water may be taken following administration to assist with swallowing the saliva. Alternatively, the Olanzapine ODT may be dispersed in a full glass of water immediately before administration.
Schizophrenia and Related Disorders: The recommended starting dose for Olanzapine orally disintegrating tablets is 5-10 mg/day, administered as a single daily dose without regard to meals. Daily dosage may subsequently be adjusted on the basis of individual clinical status within the range of 5-20 mg daily. An increase to a dose greater than the routine therapeutic dose of 10 mg/day is recommended only after appropriate clinical reassessment.
Acute Mania Associated with Bipolar Disorder: The recommended starting dose for Olanzapine orally disintegrating tablets is 10 or 15 mg administered once a day as monotherapy or 10 mg administered once daily in combination therapy with lithium or valproate. It may be given without regard to meals. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours. When dosage adjustments are necessary, dose increments/decrements of 5 mg daily are recommended. Antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials. The safety of doses above 20 mg/day has not been evaluated in clinical trials.
Preventing Recurrence in Bipolar Disorder: Patients who have been receiving Olanzapine for the treatment of acute mania should initially continue therapy for preventing recurrence in bipolar disorder at the same dose. For patients already in remission, the suggested starting dose for Olanzapine orally disintegrating tablets is 10 mg once a day. Subsequent daily dosage should be adjusted on the basis of clinical status within a range of 5 mg to 20 mg per day. Olanzapine ODT may be given without regard to meals, as its absorption is not affected by food.
Children: The safety and efficacy of Olanzapine have not been established in patients under 18 years of age.
Elderly patients: A low starting dose of 5 mg/day should be considered for those patients 65 and over when clinical factors warrant.
Patients with hepatic and/or renal impairment: Small single-dose clinical pharmacology studies did not reveal any major alterations in Olanzapine pharmacokinetics in subjects with renal or hepatic impairment. However, as clinical experience is limited in these patients, a lower starting dose (5 mg/day) should be considered. Further dose adjustments, when indicated, should be conservative in these patients.
Female compared with male patients: The starting dose and dose range need not be routinely altered for female patients relative to male patients.
Non-smoking patients compared with smoking patients: The starting dose and dose range need not be routinely altered for non-smoking patients relative to smoking patients.
When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the starting dose. Dose escalation, when indicated, should be conservative in such patients.

May be taken with or without food: ODT 5/ODT 10 Tab: Place in the mouth & allow to dissolve completely; it can then be swallowed w/ or w/o liqd. ODT 15 Tab: Place in the mouth & allow to dissolve completely then, swallow w/ saliva & follow w/ a glass of water. Alternatively, disperse in a full glass of water immediately prior administration.

Olanzapine is contraindicated in those patients with a known hypersensitivity to any ingredient of the product.

Olandus 5/Olandus 10: A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
A syndrome of potentially irreversible, involuntary, dyskinetic movements known as tardive dyskinesia may develop in patients treated with antipsychotic drugs. Olanzapine tablets should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
Olanzapine may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period, probably reflecting its 1-adrenergic antagonistic properties. This risk of orthostatic hypotension and syncope may be minimized by initiating therapy with 5 mg once daily. A more gradual titration to the target dose should be considered if hypotension occurs. Olanzapine tablets should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications).
Olanzapine should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold, e.g. Alzheimer's dementia.
Caution should be exercised in patients with signs and symptoms of hepatic impairment, in patients with preexisting conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic drugs. Periodic assessment of transaminases is recommended in patients with significant hepatic disease.
Since Olanzapine has the potential to impair judgment thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Olanzapine therapy does not affect them adversely.
Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing Olanzapine tablets for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration. Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Olanzapine tablets and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.
The possibility of a suicide attempt is inherent in schizophrenia, and close supervision of high-risk patients should accompany drug therapy. Prescriptions for Olanzapine tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Olanzapine tablets should be used with caution in patients with clinically significant prostatic hypertrophy, narrow angle glaucoma, or a history of paralytic ileus.
Use in Pregnancy & Lactation: There are no adequate and well-controlled trials with Olanzapine in pregnant females. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known if Olanzapine is excreted in human milk. It is recommended that women receiving Olanzapine tablets should not breast feed. Safety and effectiveness of the drug in pediatric patients have not been established.
Olandus ODT 5/Olandus ODT 10: Increased Mortality in Elderly Patients with Dementia: Elderly patients with dementia related psychosis treated with antipsychotic drugs are at an increased risk of death. Olanzapine is not approved for the treatment of patients with dementia-related psychosis. Older adults with dementia may also have a greater chance of having a stroke or mini-stroke during treatment.
Cerebrovascular Adverse Events (CVAE), Including Stroke: Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported inpatients in trials of olanzapine in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with olanzapine compared to patients treated with placebo.
Olanzapine is not approved for the treatment of patients with dementia-related psychosis.
Suicide: The possibility of a suicide attempt is inherent in Schizophrenia and in Bipolar I Disorder, and close supervision of high-risk patients should accompany drug therapy. Prescriptions for olanzapine should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.
The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
Hyperglycemia: Physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level (fasting 100-126 mg/dL, non-fasting 140-200 mg/dL). Patients taking olanzapine should be monitored regularly for worsening of glucose control. Patients starting treatment with olanzapine should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including olanzapine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics.
Hyperlipidemia: Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using olanzapine, is recommended. Clinically significant, and sometimes very high (>500 mg/dL), elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use.
Weight Gain: Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.
Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.
The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, olanzapine should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia.
Chronic antipsychotic treatment should generally be reserved for patients (1) who suffer from a chronic illness that is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on olanzapine, drug discontinuation should be considered. However, some patients may require treatment with olanzapine despite the presence of the syndrome.
Orthostatic Hypotension: Olanzapine may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia and, in some patients, syncope, especially during the initial dose-titration period, probably reflecting its α1-adrenergic antagonistic properties. Olanzapine should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications) where the occurrence of syncope, or hypotension and/or bradycardia might put the patient at increased medical risk.
Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in patients with advanced Alzheimer's disease. Olanzapine is not approved for the treatment of patients with Alzheimer's disease.
Seizures: Olanzapine should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold, e.g., Alzheimer's dementia. Olanzapine is not approved for the treatment of patients with Alzheimer's disease. Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.
Potential for Cognitive and Motor Impairment: Somnolence was a commonly reported adverse reaction associated with olanzapine treatment, occurring at an incidence of 26% in olanzapine patients compared to 15% in placebo patients.
Since olanzapine has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that olanzapine therapy does not affect them adversely.
Body Temperature Regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents.
Appropriate care is advised when prescribing olanzapine for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.
Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, olanzapine elevates prolactin levels, and a modest elevation persists during chronic administration. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion.
This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea. gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects.
Laboratory Tests: Fasting blood glucose testing and lipid profile at the beginning of, and periodically during, treatment is recommended.
Use in Pregnancy: Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with olanzapine.
Use in Lactation: Patients should be advised not to breast-feed an infant if they are taking olanzapine.
Use in Children: Olanzapine is indicated for treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adolescents 13 to 17 years of age. Patients should be counseled about the potential long-term risks associated with olanzapine and advised that these risks may lead them to consider other drugs first. Safety and effectiveness of olanzapine in patients under 13 years of age have not been established.
Olandus ODT 15: During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored during this period.
Concomitant illnesses: While Olanzapine demonstrated anticholinergic activity in vitro, experience during clinical trials revealed a low incidence of related events. As clinical experience with Olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, narrow-angle glaucoma or paralytic ileus and related conditions.
Hyperglycaemia and Diabetes Mellitus: Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including Olanzapine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycaemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycaemia-related adverse events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycaemia related adverse events in patients treated with atypical antipsychotics are not available.
Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycaemia including polydipsia, polyuria, polyphagia and weakness. Patients who develop symptoms of hyperglycaemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycaemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug.
Lipid Alterations: Undesirable alterations in lipids have been observed in Olanzapine-treated patients in placebo-controlled trials. Olanzapine-treated patients had a greater mean increase in fasting total cholesterol, LDL cholesterol, and triglycerides compared to placebo-treated patients. Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline. Appropriate clinical monitoring is recommended.
Weight Gain: Potential consequences of weight gain should be considered prior to starting Olanzapine. As with all antipsychotics, patients receiving Olanzapine should receive regular monitoring of weight. In clinical trials significant weight gain was observed across all baseline Body Mass Index (BMI) categories in olanzapine-treated patients.
Hepatic: Transient, asymptomatic elevations of hepatic transaminases, alanine transferase (ALT), aspartate transferase (AST) have been seen occasionally, especially in early treatment. Rare postmarketing reports of hepatitis have been noted. Very rare cases of jaundice, cholestatic or mixed liver injury have also been reported in the postmarketing period. Caution should be exercised in patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve and in patients who are being treated with potentially hepatotoxic drugs.
Blood: As with other neuroleptic drugs, caution should be exercised in patients with low leukocyte and/or neutrophil counts for any reason, in patients with a history of drug-induced bone marrow depression/toxicity, in patients with bone marrow depression caused by concomitant illness, radiation therapy or chemotherapy and in patients with hypereosinophilic conditions or with myeloproliferative disease. Thirty-two patients with clozapine-related neutropenia or agranulocytosis histories received olanzapine without decreases in baseline neutrophil counts.
Neuroleptic Malignant Syndromes (NMS): NMS, a potentially fatal syndrome complex, is associated with antipsychotic drugs, including Olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure. In such an event or with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic drugs, including olanzapine should be discontinued.
Seizures: Olanzapine should be used cautiously in patients who have a history of seizures or are subject to factors which may lower the seizure threshold. Seizures have been reported to occur rarely in such patients when treated with Olanzapine.
Cardiac: Postural hypotension was infrequently observed in elderly subjects in clinical trials. As with other antipsychotics, it is recommended that blood pressure is measured periodically in patients over 65 years.
Sudden cardiac death: In a retrospective observational study, patients treated with atypical antipsychotics (including Olanzapine) or typical antipsychotics had a similar dose-related increase of presumed sudden cardiac death compared to non-users of antipsychotics, with almost twice the risk than that for non-users. In post-marketing reports with Olanzapine, the event of sudden cardiac death has been reported very rarely.
Body Temperature Regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing Olanzapine for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g. exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.
Dysphagia: Oesophageal dysmotility and aspiration have been associated with antipsychotic drug use. Olanzapine orally disintegrating tablets and other antipsychotic agents should be used cautiously in patients at risk for aspiration pneumonia.
Suicide: The possibility of a suicide attempt is inherent in schizophrenia and in bipolar disorder, and close supervision of high-risk patients should accompany therapy. Prescriptions for Olanzapine should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Dementia-related psychosis and/or behavioural disturbances: Olanzapine is not approved for the treatment of dementia-related psychosis and/or behavioural disturbances and is not recommended for use in this particular group of patients because of an increased risk in mortality and the risk of cerebrovascular accident.
Parkinson's diseases: The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended.
Use in Pregnancy: Category C. There are no adequate and well-controlled studies in pregnant women. Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during treatment with Olanzapine. Neonates exposed to antipsychotic drugs (including Olanzapine) during the third trimester of pregnancy are at risk of experiencing extrapyramidal neurological disturbances and/or withdrawal symptoms following delivery. There have been post-market reports of agitation, hypertonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required additional medical treatment or monitoring. Olanzapine ODT should be used during pregnancy only if the anticipated benefit outweighs the risk, and the administered dose and duration of treatment should be as low and as short as possible.
Use in Lactation: In a study in lactating, healthy women Olanzapine was excreted in breast milk. Mean infant exposure (mg/kg) at steady state was estimated to be 1.8% of the maternal Olanzapine dose (mg/kg). Patients should be advised not to breast feed if they are taking Olanzapine.
Use in the Elderly: Caution should be used when Olanzapine is administered to the elderly, especially if there are other factors that may influence drug metabolism and/or pharmacodynamic parameters.

Olandus 5/Olandus 10: The most frequently reported adverse effects with Olanzapine are somnolence and weight gain. Olanzapine has been associated with a low incidence of extrapyramidal symptoms including tardive dyskinesia. Hyperprolactinaemia may occur but is usually asymptomatic. Other adverse effects include increased appetite, peripheral oedema, and rarely elevated creatine kinase concentrations.
Olandus ODT 5/Olandus ODT 10: Olanzapine may cause side effects: drowsiness, dizziness, restlessness, unusual behavior, depression, difficulty falling asleep or staying asleep, weakness, difficulty walking, constipation, weight gain, dry mouth, pain in arms, legs, back, or joints, breast enlargement or discharge, late or missed menstrual periods, decreased sexual ability.
Olandus ODT 15: Adverse events identified from clinical trials of olanzapine: Body as a whole: Very common (≥10%): weight gain: weight gain ≥7% baseline body weight. Common (≥1% and <10%): asthenia, fatigue, weight gain ≥15% baseline body weight. Uncommon (≥0.1% and <1%): photosensitivity reaction.
Cardiovascular system: Common (≥1% and <10%): orthostatic hypotension. Uncommon (≥0.1% and <1%): bradycardia.
Digestive system: Common (≥1% and <10%): constipation; dry mouth; increased appetite.
Metabolic: Common (≥1% and <10%): peripheral oedema. Rare (<0.l% and ≥0.01%): elevated creatinine phosphokinase levels.
Nervous system: Very common (≥10%): somnolence. Common (≥1% and <10%): dizziness; akathisia.
Clinical chemistry: Very common (≥10%): prolactin-increased, cholesterol-total (fasting borderline to high), triglycerides (fasting borderline to high), glucose (fasting borderline to high). Common (≥1% and <10%): alanine transferase (ALT)-increased; aspartate transferase (AST)-increased, cholesterol-total (fasting normal to high), triglycerides (fasting normal to high), glucose (fasting normal to high), glycosuria.
Hepatic Transaminases: Transient, asymptomatic elevations of hepatic transaminases, ALT and AST, have been seen occasionally.
Haematology: Common (≥1% and <10%): eosinophilia.
Eosinophilia: Asymptomatic eosinophilia was occasionally seen.
Undesirable Effects for Special Populations: Elderly Patients: Undesirable effects associated with the use of Olanzapine in clinical trials with elderly patients with dementia-related psychosis: Body as a whole: Very common (≥10%): falls.
Nervous system: Very common (≥10%): abnormal gait.
Urogenital system: Common (≥1% and <10%): urinary incontinence.
Respiratory system: Common (≥1% and <10%): pneumonia.
Adolescents (Ages 13-17 years): Body as a whole: Very common (≥10%): weight gain ≥7% of baseline body weight 40.6%.
Common (≥1% and <10%): weight gain ≥15% of baseline body weight 7.1%.
Digestive system: Very common (≥10%): increased appetite 24.0%.
Common (≥1% and <10%): dry mouth 6.1%.
Nervous system: Very common (≥10%): sedation (including hypersomnia, lethargy, sedation, somnolence) 44.1%.
Clinical chemistry: Very common (≥10%): ALT >3 x ULN (all randomised patients with ALT baseline ≤3 x ULN) 12.1%, AST-increased 27.6%, total bilirubin-decreased 22.1%, GGT-increased 10.1%, prolactin-increased 47.4%, cholesterol-total (fasting borderline to high) 38.9%, triglycerides (fasting normal to high) 26.9%, triglycerides (fasting borderline to high) 59.5%, glucose (fasting borderline to high) 14.3%.
Common (≥1% and <10%): cholesterol-total (fasting normal to high) 6.9%.
Very rare (<0.01%): glucose (fasting normal to high).
Adverse events based on post marketing spontaneous reports with oral olanzapine: Body as a whole: Very rare (<0.01%): allergic reaction (e.g. anaphylactoid reaction, angioedema, pruritis or urticaria); discontinuation reaction (acute symptoms such as sweating, insomnia, tremor, anxiety, nausea or vomiting have been reported very rarely when olanzapine is stopped suddenly).
Digestive system: Very rare (<0.01%): pancreatitis.
Hepatobiliary disorders: Rare (<0.1% and ≥0.01%): hepatitis.
Very rare (<0.01%): jaundice.
Metabolic: Rare (<0.1% and ≥0.01%): hyperglycaemia.
Very rare (<0.01%): diabetic coma; diabetic ketoacidosis; exacerbation of pre-existing diabetes; hypertriglyceridemia (random triglyceride levels of ≥11.29 mmol/L); hypercholesterolaemia (random cholesterol levels of ≥6.21 mmol/L).
Nervous system: Rare (<0.1% and ≥0.01%): seizures.
Very rare (<0.01%): neuroleptic malignant syndrome.
Skin and appendages: Rare (<0.1% and ≥0.01%): rash.
Very rare (<0.01%): alopecia.
Urogenital system: Very rare (<0.01%): priapism; urinary hesitation, urinary incontinence.
Haematology: Rare (<0.1% and ≥0.01%): leucopenia, including neutropenia.
Very rare (<0.01%): thrombocytopenia.
Cardiovascular: Very rare (<0.01%): venous thromboembolism, including pulmonary embolism and deep vein thrombosis. Cases of QT prolongation, ventricular arrhythmia, sudden unexplained death, cardiac arrest and torsades de pointes have been reported very rarely with the use of neuroleptics and may be considered a class effect.
Musculoskeletal System: Very rare (<0.01%): rhabdomyolysis.
Clinical chemistry: Very rare (<0.01%): alkaline phosphatase increased; total bilirubin increased, creatine phosphokinase increased.

Olandus 5/Olandus 10: Given the primary CNS effects of Olanzapine, caution should be used when Olanzapine tablets are taken in combination with other centrally acting drugs and alcohol. Because of its potential for inducing hypotension, Olanzapine tablets may enhance the effects of certain antihypertensive agents. Olanzapine may antagonize the effects of levodopa and dopamine agonists. The metabolism of Olanzapine is mediated to some extent by the cytochrome P450 isozyme CYP1A2. Concomitant administration of drugs which inhibit or act as a substrate to this isozyme may affect plasma concentrations of Olanzapine. The clearance of Olanzapine is increased by tobacco smoking.
Olandus ODT 5/Olandus ODT 10: The risks of using olanzapine in combination with other drugs have not been extensively evaluated in systematic studies. Potential for Other.
Drugs to Affect Olanzapine: Diazepam: The co-administration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine.
Cimetidine and Antacids: Single doses of cimetidine (800 mg) or aluminum- and magnesium-containing antacids did not affect the oral bioavailability of olanzapine.
Inducers of CYP1A2: Carbamazepine therapy (200 mg bid) causes an approximately 50% increase in the clearance of olanzapine. This increase is likely due to the fact that carbamazepine is a potent inducer of CYP1A2 activity. Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance.
Alcohol: Ethanol (45 mg/70 kg single dose) did not have an effect on olanzapine pharmacokinetics. The coadministration of alcohol (i.e., ethanol) with olanzapine potentiated the orthostatic hypotension observed with olanzapine.
Inhibitors of 1A2: Fluvoxamine: Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of olanzapine. This results in a mean increase in olanzapine C_max following fluvoxamine of 54% in female nonsmokers and 77% in male smokers.
The mean increase in olanzapine AUC is 52% and 108%, respectively. Lower doses of olanzapine should be considered in patients receiving concomitant treatment with fluvoxamine.
Fluoxetine: Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance. The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and therefore dose modification is not routinely recommended. When using olanzapine and fluoxetine in combination.
Warfarin: Warfarin (20 mg single dose) did not affect olanzapine pharmacokinetics.
Inducers of CYP1A2 or Glucuronyl Transferase: Omeprazole and rifampin, may cause an increase in olanzapine clearance.
Charcoal: The administration of activated charcoal (1 g) reduced the C_max and AUC of oral olanzapine by about 60%. As peak olanzapine levels are not typically obtained until about 6 hours after dosing, charcoal may be a useful treatment for olanzapine overdose.
Potential for Olanzapine to Affect Other Drugs: CNS Acting Drugs: Given the primary CNS effects of olanzapine, caution should be used when olanzapine is taken in combination with other centrally acting drugs and alcohol.
Antihypertensive Agents: Olanzapine, because of its potential for inducing hypotension, may enhance the effects of certain antihypertensive agents.
Levodopa and Dopamine Agonists: Olanzapine may antagonize the effects of levodopa and dopamine agonists.
Lorazepam (IM): Administration of intramuscular lorazepam (2 mg) 1 hour after intramuscular olanzapine for injection (5 mg) did not significantly affect the pharmacokinetics of olanzapine, unconjugated lorazepam, or total lorazepam. However, this coadministration of intramuscular lorazepam and intramuscular olanzapine for injection added to the somnolence observed with either drug alone.
Lithium: Multiple doses of olanzapine (10 mg for 8 days) did not influence the kinetics of lithium. Therefore, concomitant olanzapine administration does not require dosage adjustment of lithium.
Valproate: Olanzapine (10 mg daily for 2 weeks) did not affect the steady state plasma concentrations of valproate. Therefore, concomitant olanzapine administration does not require dosage adjustment of valproate.
Effect of Olanzapine on Drug Metabolizing Enzymes: In vitro studies utilizing human liver microsomes suggest that olanzapine has little potential to inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. Thus, olanzapine is unlikely to cause clinically important drug interactions mediated by these enzymes.
Imipramine: Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite desipramine.
Biperiden: Multiple doses of olanzapine did not influence the kinetics of biperiden.
Theophylline: Multiple doses of olanzapine did not affect the pharmacokinetics of theophylline or its metabolites.
Olandus ODT 15: Given the primary central nervous system effects of Olanzapine, caution should be used when it is taken in combination with other centrally acting drugs and alcohol. As it exhibits in vitro dopamine antagonism, Olanzapine may antagonise the effects of direct and indirect dopamine agonists.
Caution should be exercised when Olanzapine is used concomitantly with medicines known to cause electrolyte imbalance or to increase QT interval.
Potential for other medicines to affect Olanzapine: Single-doses of antacids (containing aluminium and magnesium) or cimetidine do not affect the oral bioavailability of Olanzapine. The concomitant administration of activated charcoal reduces the oral bioavailability of Olanzapine by 50 to 60%.
Fluoxetine (60 mg single dose or 60 mg daily for 8 days) caused a 16% increase in the maximum plasma concentration of Olanzapine and a 16% decrease in Olanzapine clearance. The magnitude of this is small in comparison to the overall variability between individuals and therefore dose modification is not routinely recommended.
The metabolism of Olanzapine may be induced by concomitant smoking (the clearance of olanzapine is 33% lower and the terminal elimination half-life is 21% longer in non-smokers compared to smokers) or carbamazepine therapy (clearance is increased 44% and the terminal elimination half-life is reduced by 20% when administered with carbamazepine). Smoking and carbamazepine therapy induce P450-1A2 activity. The pharmacokinetics of theophylline, which is metabolised by P450-1A2, is not altered by olanzapine.
Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of Olanzapine. This results in a mean increase in Olanzapine C_max following fluvoxamine of 54% in female non-smokers and 77% in male smokers. The mean increase in Olanzapine AUC is 52% and 108%, respectively. Lower doses of olanzapine should be considered in patients receiving concomitant treatment with fluvoxamine or any other P450-1A2 inhibitor, such as ciprofloxacin.
Potential for Olanzapine to affect other medicines: In clinical trials with single doses of olanzapine, no inhibition of the metabolism of imipramine/ desipramine (P450-2D6, P450- 3A or P450-1A2), warfarin (P450-2C19), theophylline (P450-1A2) or diazepam (P450-3A4 and P450-2C19) was evident. Olanzapine showed no interaction when coadministered with lithium or biperiden. The in vitro ability of Olanzapine to inhibit metabolism by five principle cytochromes has been examined. These studies found inhibitory constants for 3A4 (491 mcM), 2C9 (751 mcM), 1A2 (36 mcM), 2C19 (920 mcM), 2D6 (89 mcM) that compared to Olanzapine plasma concentrations of approximately 0.2 mcM, would mean maximum inhibition of these P450 systems by Olanzapine would be less than 0.7%. The clinical relevance of these findings is unknown.
Steady state concentrations of Olanzapine had no effect on the pharmacokinetics of ethanol (45 mg/70 kg). However, additive pharmacological effects such as increased sedation may occur when ethanol is ingested together with Olanzapine.
Studies in vitro using human liver microsomes showed that Olanzapine has little potential to inhibit the major metabolic pathway of valproate, which is glucuronidation. Further, valproate was found to have little effect on the oxidative metabolism of Olanzapine in vitro. Daily concomitant in vivo administration of 10 mg Olanzapine for 2 weeks did not affect steady state plasma concentrations of valproate. Therefore, concomitant Olanzapine administration does not require dosage adjustment of valproate.