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 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.