Olavex 5/Olavex 10

Olavex 5/Olavex 10

olanzapine

Manufacturer:

Vexxa Lifesciences

Distributor:

VE Pharma
Full Prescribing Info
Contents
Olanzapine.
Description
OLAVEX 5 (Olanzapine Tablet USP 5 MG): Each uncoated tablets contains: Olanzapine USP 5 mg.
OLAVEX 10 (Olanzapine Tablet USP 10 MG): Each uncoated tablets contains: Olanzapine USP 10 mg.
Olanzapine is a yellow crystalline solid. It is soluble in n-propanol, sparingly soluble in acetonitrile. Slightly soluble inmethanol. Practically insoluble in water. Its molecular Formula is C17H20N4S and molecular weight is 312.43.
Action
Pharmacological Classification: Antipsychotic.
Pharmacology: Pharmacodynamics: OLANZAPINE (OLAVEX 5/10) an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, olanzapine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors.
Mechanism of Action: The mechanism of action of olanzapine, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug's efficacy in schizophrenia is mediated through a combination of dopamine and serotonin type 2 (5HT2) antagonism. The mechanism of action of olanzapine in the treatment of acute manic or mixed episodes associated with bipolar I disorder is unknown.
Pharmacokinetics: Absorption: Readily absorbed orally and IM. C max is approximately 6 h (oral) and 15 to 45 min (short-acting injection). Steady state is approximately 1 wk (oral). Food does not affect the rate or extent of oral olanzapine absorption.
Distribution: Extensively distributed throughout the body. Vd is approximately 1,000 L; 93% is protein bound.
Metabolism: In liver by glucuronidation and CYP-450-mediated oxidation; major circulating metabolites are inactive.
Elimination: Elimination is 57% in urine (7% unchanged); 30% eliminated in feces. The half-life is 21 to 54 h (oral, short-acting injection) and 30 days (ER injection). Plasma Cl is 12 to 47 L/h.
Indications/Uses
Olanzapine is indicated for the treatment of schizophrenia. It is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response. Olanzapine is indicate for the treatment of moderate to severe manic episode. In patients whose manic episode has responded to Olanzapine treatment, Olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder.
Dosage/Direction for Use
Adults: Schizophrenia: The recommended starting dose for Olanzapine is 10 mg/day.
Manic episode: The starting dose is 15 mg as a single daily dose in monotherapy or 10 mg daily in combination therapy.
Preventing recurrence in bipolar disorder: The recommended starting dose is 10 mg/day. For patients who have been receiving Olanzapine for treatment of manic episode, continue therapy for preventing recurrence at the same dose. If a new manic, mixed, or depressive episode occurs, Olanzapine treatment should be continued (with dose optimization as needed), with supplementary therapy to treat mood symptoms, as clinically indicated.
During treatment for schizophrenia, manic episode, and recurrence prevention in bipolar disorder, daily dosage may subsequently be adjusted on the basis of individual clinical status within the range 5-20 mg/day. An increase to a dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.
Olanzapine can be given without regard for meals, as absorption is not affected by food. Gradual tapering of the dose should be considered when discontinuing Olanzapine.
Special populations: Paediatric population: Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy. A greater magnitude of weight gain, lipid and prolactin alterations has been reported in short-term studies of adolescent patients than in studies of adult patients.
Elderly patients: A lower starting dose (5 mg/day) is not routinely indicated but should be considered for those 65 and over when clinical factors warrant.
Patients with renal and/or hepatic impairment: A lower starting dose (5 mg) should be considered for such patients. In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh class A or B), the starting dose should be 5 mg and only increased with caution.
Gender: The starting dose and dose range need not be routinely altered for female patients relative to male patients.
Smokers: The starting dose and dose range need not be routinely altered for non-smokers relative to smokers. The metabolism of Olanzapine may be induced by smoking. Clinical monitoring is recommended and an increase of Olanzapine dose may be considered if necessary.
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.
Overdosage
Signs and Symptoms: Very common symptoms in overdose (> 10% incidence) include tachycardia, agitation/aggressiveness, dysarthria, various extra pyramidal symptoms, and reduced level of consciousness ranging from sedation to coma.
Other medically significant sequelae of overdose include delirium, convulsion, coma, possible neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, cardiac arrhythmias (<2% of overdose cases), and cardiopulmonary arrest. Fatal outcomes have been reported for acute overdoses as low as 450 mg, but survival has also been reported following acute overdose of approximately 2 g of oral Olanzapine.
Management: There is no specific antidote for Olanzapine. Induction of emesis is not recommended. Standard procedures for management of overdose may be indicated (i.e., gastric lavage, administration of activated charcoal). The concomitant administration of activated charcoal was shown to reduce the oral bioavailability of Olanzapine by 50 to 60%.
Symptomatic treatment and monitoring of vital organ function should be instituted according to clinical presentation, including treatment of hypotension and circulatory collapse and support of respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-agonist activity, since beta stimulation may worsen hypotension. Cardiovascular monitoring is necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue until the patient recovers.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Patients with known risk of narrow-angle glaucoma.
Special Precautions
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.
Dementia-related psychosis and/or behavioural disturbances: Olanzapine is not recommended for use in patients with dementia-related psychosis and/or behavioural disturbances because of an increase in mortality and the risk of cerebrovascular accident.
Parkinson's disease: The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended.
Neuroleptic Malignant Syndrome (NMS): NMS is a potentially life-threatening condition associated with antipsychotic medicinal products.
Rare cases reported as NMS have also been received in association with 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 creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.
Hyperglycaemia and diabetes: Hyperglycaemia and/or development or exacerbation of diabetes, occasionally associated with ketoacidosis or coma, has been reported uncommonly, including some fatal cases. In some cases, a prior increase in body weight has been reported, which may be a predisposing factor. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g., measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually thereafter. Patients treated with any antipsychotic medicines, including Olanzapine, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly, e.g., at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter.
Lipid alterations: Undesirable alterations in lipids have been observed in olanzapine-treated patients. Lipid alterations should be managed as clinically appropriate, particularly in dyslipidaemia patients and in patients with risk factors for the development of lipids disorders. Patients treated with any antipsychotic medicines, including Olanzapine, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g., at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter.
Anticholinergic activity: While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events. However, as clinical experience with olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, or paralytic ileus and related conditions.
Hepatic function: Transient, asymptomatic elevations of hepatic aminotransferases, ALT, AST have been seen commonly, especially in early treatment. Caution should be exercised and follow-up organised 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 medicines. In cases where hepatitis (including hepatocellular, cholestasis or mixed liver injury) has been diagnosed, olanzapine treatment should be discontinued.
Neutropenia: Caution should be exercised in patients with low leukocyte and/or neutrophil counts for any reason, in patients receiving medicines known to cause neutropenia, 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 hyper eosinophilic conditions or with myeloproliferative disease. Neutropenia has been reported commonly when olanzapine and valproate are used concomitantly.
Discontinuation of treatment: Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported rarely (≥ 0.01 % and < 0.1 %) when olanzapine is stopped abruptly.
QT interval: Caution should be exercised when olanzapine is prescribed with medicines known to increase QTc interval, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia.
Thromboembolism: Temporal association of olanzapine treatment and venous thromboembolism has been reported uncommonly (≥ 0.1% and < 1%). A causal relationship between the occurrences of venous thromboembolism and treatment with olanzapine has not been established. However, since patients with schizophrenia often present with acquired risk factors for venous thromboembolism, all possible risk factors of VTE e.g., immobilisation of patients, should be identified and preventive measures undertaken.
General CNS activity: Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism, olanzapine may antagonise the effects of direct and indirect dopamine agonists.
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 uncommonly in patients when treated with olanzapine.
Tardive dyskinesia: Olanzapine was associated with a statistically significant lower incidence of treatment-emergent dyskinesia. However, the risk of tardive dyskinesia increases with long-term exposure, and therefore if signs or symptoms of tardive dyskinesia appear in a patient on olanzapine, a dose reduction or discontinuation should be considered. These symptoms can temporally deteriorate or even arise after discontinuation of treatment.
Postural hypotension: Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials. It is recommended that blood pressure is measured periodically in patients over 65 years.
Sudden cardiac death: In postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in patients with olanzapine. In a retrospective observational cohort study, the risk of presumed sudden cardiac death in patients treated with olanzapine was approximately twice the risk in patients not using antipsychotics. In the study, the risk of olanzapine was comparable to the risk of atypical antipsychotics included in a pooled analysis.
Lactose: Olanzapine (Olavex) tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use in Children: Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic parameters and increases in prolactin levels.
Adverse Reactions
Blood and the lymphatic system disorders: Eosinophilia, Leukopenia, Neutropenia, Thrombocytopenia.
Immune system disorders: Hypersensitivity.
Metabolism and nutrition disorders: Weight gain, Elevated cholesterol levels, Elevated glucose levels, Elevated triglyceride levels, Glucosuria, Increased appetite, Development or exacerbation of diabetes occasionally associated with ketoacidosis or coma, including some fatal cases, Hypothermia.
Nervous system disorders: Somnolence, Dizziness, Akathisia, Parkinsonism, Dyskinesia, Seizures where in most cases a history of seizures or risk factors for seizures were reported, Dystonia (including oculogyration), Tardive dyskinesia, Amnesia, Dysarthria, Neuroleptic malignant syndrome, Discontinuation symptoms (Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting).
Cardiac disorders: Bradycardia, QTc prolongation, Ventricular tachycardia/ fibrillation, sudden death.
Vascular disorders: Orthostatic hypotension, Thromboembolism (including pulmonary embolism and deep vein thrombosis).
Respiratory, thoracic and mediastinal disorders: Epistaxis Gastrointestinal disorders: Mild, transient anticholinergic effects including constipation and dry mouth, Abdominal distension, Pancreatitis.
Hepatobiliary disorders: Transient, asymptomatic elevations of hepatic aminotransferases (ALT, AST), especially in early treatment, Hepatitis (including hepatocellular, cholestasis or mixed liver injury).
Skin and subcutaneous tissue disorders: Rash, Photosensitivity reaction, Alopecia.
Musculoskeletal and connective tissue disorders: Arthralgia, Rhabdomyolysis.
Renal and urinary disorders: Urinary incontinence, urinary retention, Urinary hesitation.
Reproductive system and breast disorders: Erectile dysfunction in males, Decreased libido in males and females, Amenorrhea, Breast enlargement, Galactorrhea in females, Gynaecomastia/ breast enlargement in males, Priapism.
General disorders and administration site conditions: Asthenia, Fatigue, Oedema, Pyrexia.
Investigations: Elevated plasma prolactin levels, increased alkaline phosphatase, High creatine phosphokinase, High Gamma Glutamyltransferase, High mic acid.
Drug Interactions
Pediatric population: Interaction studies have only been performed in adults.
Potential Interactions Affecting Olanzapine: Since Olanzapine is metabolized by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of Olanzapine.
Induction of CYP1A2: The metabolism of Olanzapine may be induced by smoking and carbamazepine, which may lead to reduced Olanzapine concentrations.
Inhibition of CYP1A2: Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of Olanzapine. The mean increase in Olanzapine Cmax following fluvoxamine was 54% in female non-smokers and 77% in male smokers. The mean increase in Olanzapine AUC was 52% and 108%, respectively.
Decreased bioavailability: Activated charcoal reduces the bioavailability of oral Olanzapine by 50 to 60% and should be taken at least 2 hours before or after Olanzapine.
Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminum, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of Olanzapine.
Potential for Olanzapine to Affect Other Medicinal Products: Olanzapine may antagonize the effects of direct and indirect dopamine agonists.
Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g., 1A2, 2D6, 2C9, 2C19, 3A4).
General CNS activity: Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression.
Qtc interval: Caution should be used if Olanzapine is being administered concomitantly with medicinal products known to increase QTc interval.
Storage
Store at temperatures not exceeding 30ºC. Protect from light.
Shelf Life: 3 years from the date of Manufacturing.
MIMS Class
ATC Classification
N05AH03 - olanzapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics
Presentation/Packing
Olavex 5: Tab 5 mg (yellow colored round biconvex, plain on both side and uncoated) x 30's.
Olavex 10: Tab 10 mg (yellow colored round biconvex, plain on both side and uncoated) x 30's.
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