Pilanz

Olanzapine.

PILANZ ODT (5 MG TABLET): Each orodispersible tablet contains Olanzapine 5 mg.
PILANZ ODT (10 MG TABLET): Each orodispersible tablet contains Olanzapine 10 mg.

Pharmacology: Pharmacodynamics: Olanzapine is a thienobenzodiazepine which is second generation antipsychotics or atypical antipsychotics. Olanzapine has high affinity binding to serotonin receptors (5-HT_2A, 5-HT_2C and 5-HT₃), muscarinic receptors (M₁-M₅), histamine receptors (H₁), adrenergic receptors (α₁) and dopamine receptors (D₁-D₄). Although the precise mechanism of action in schizophrenia and bipolar disorder is not known, the efficiency of Olanzapine is thought to be mediated through combined antagonism of dopamine and serotonin type 2 receptor sites.
Pharmacokinetics: Absorption: Olanzapine is well absorbed following oral administration. The peak plasma Olanzapine concentrations occur in approximately 6 hours after oral doses (average : 5-8 hours). Food does not appear to affect the rate or the extent of GI absorption of the drug. The relative oral bioavailability of Olanzapine has been shown to be equivalent following administration of the conventional and orally disintegrating tablets of the drug.
Distribution: Distribution of Olanzapine, a highly lipophilic drug, into human tissue is extensive. The volume of distribution of Olanzapine has been reported to be approximately 1000 L. Olanzapine binds with protein in plasma(albumin and α₁-acid glycoprotein) for about 93%.
Metabolism: Olanzapine has extensive hepatic metabolism, partially via glucuronidation and cytochrome P450 (CYP1A2 and CYP2D6). The principal metabolites of Olanzapine are 10-N-glucuronide and 4'-N-desmethyl olanzapine. Both of these metabolites lack pharmacologic activity.
Elimination: About 57% of a dose is excreted in the urine, mainly as metabolites, and about 30% appears in the feces, respectively. Half-life elimination of Olanzapine is around 30 to 38 hours related to age, gender, and smoking. In adult, the apparent plasma clearance of Olanzapine ranges from 12 to 47 L/hour (mean : 25 L/hour). The clearance of Olanzapine in smoker is approximately 40% higher than in nonsmokers. The clearance of Olanzapine in females may be reduced by approximately 30% compared with males. In children and adolescents 10-18 years, the apparent plasma clearance at steady-state averaged 9.6 L/hour. The elimination half-life of orally administered Olanzapine is 1.5 times longer in healthy geriatric individuals 65years of age or older than in healthy younger adults. The pharmacokinetics of Olanzapine were similar in patients with severe renal impairment and healthy individuals, suggesting that dosage adjustment based upon the degree of renal impairment is not necessary. Although the presence of hepatic impairment would be expected to reduce the clearance of Olanzapine, a pharmacokinetic study evaluating the effect of impaired hepatic function in individuals with clinically important cirrhosis revealed little effect on the pharmacokinetics of Olanzapine.

Olanzapine is indicated for the acute and maintenance treatment of schizophrenia and other psychoses where positive symptoms (e.g., delusions, hallucinations, disordered thinking, hostility, and suspiciousness) and/or negative symptoms (e.g. flattened affect, emotional and social withdrawal, poverty of speech) are prominent. Olanzapine also alleviates the secondary affective symptoms commonly associated with schizophrenia and related disorders.
Olanzapine is effective in maintaining the clinical improvement during continuing therapy in patients who have shown an initial treatment response.
Olanzapine is indicated for the treatment of moderate 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.

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 regards for meals as absorption is not affected by food. Gradual tapering of the dose should be considered when discontinuing Olanzapine.
PILANZ ODT should be placed in the mouth, where it will rapidly disperse in saliva, so it can be easily swallow. Removal of the intact orodispersible tablet from the mouth is difficult. Since the orodispersible tablet is fragile, it should be taken immediately on opening the blister. Alternatively, it may be dispersed in a full glass of water or other suitable beverage (orange juice, apple juice, milk or coffee) immediately before administration.
Olanzapine orodispersible tablet is bioequivalent to Olanzapine coated tablets; with a similar rate and extent of absorption. It has the same dosage and frequency of administration as Olanzapine coated tablets. Olanzapine orodispersible tablets may be used as an alternative to Olanzapine coated tablets.
There is no experience in children.
Elderly patients: A lower starting dose (5 mg/day) is not routinely indicated but should be considered for the 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. 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.
In cases where dose increments of 2.5 mg are considered necessary, Olanzapine coated tablets should be use.

The most common of Olanzapine overdosage symptoms (>10% incidence) include agitation and/or aggressiveness, dysarthria, tachycardia, miosis, various extrapyramidal symptoms, hypersalivation and reduce level of consciousness ranging in severity from sedation to coma.
Less commonly reported of Olanzapine overdosage symptoms but potentially medically serious events included aspiration, cardiopulmonary arrest, cardiac arrhythmias, delirium, possible neuroleptic malignant syndrome, respiratory depression and/or arrest, convulsions, hypertension or hypotension and coma.
There is no specific antidote for Olanzapine. Standard treatment of overdose may be indicated (i.e. gastric lavage, administration of activated charcoal). 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. Continuous cardiovascular and respiratory monitoring are necessary.

Do not use PILANZ ODT in patient who has hypersensitivity to Olanzapine or to any component of the formulation.
Do not use PILANZ ODT in patient with known risk of narrow-angle glaucoma.

Hyperglycemia and diabetes mellitus: Hyperglycemia, diabetes, exacerbation of preexisting diabetes, ketoacidosis and diabetic coma have been reported. Appropriate clinical monitoring is recommended in all patients, particularly in diabetic patients and in patients with risk factors for the development of diabetes.
Discontinuation of treatment: Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported very rarely (<0.01%) when Olanzapine is stopped abruptly. Gradual dose reduction should be considered when discontinuing Olanzapine.
Anticholinergic effect: Olanzapine demonstrated anticholinergic activity in vitro. Use with caution in patients with decreased GI motility, urinary retention, benign prostatic hyperplasia, xerostomia, or narrow angle glaucoma.
Parkinson's disease: Olanzapine should be started at 2.5 mg/day and titrated to a maximum of 15 mg/day based on investigator judgement. The used of Olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinsonism is not recommended.
In elderly patient with dementia-related psychosis: Olanzapine is not recommended for elderly patient with dementia-related psychosis because it rises mortality rate and the risk of cerebrovascular accident.
Cerebrovascular adverse event including stroke in elderly patient with dementia: In trials of Olanzapine in elderly patient with dementia-related psychosis, cerebrovascular adverse events (CVAE e.g., transient ischemic stroke, stroke) including fatalities were reported.
Hepatic function indices: Caution should be exercised in patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, in patient with pre-existing conditions associated with limited hepatic functional reverse, and in patients who are being treated with potentially hepatotoxic medicines. In cases where hepatitis (including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, Olanzapine treatment was not established, 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. Frequently monitor complete blood count (CBC) in the first period of the Olanzapine use. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil counts <1000/mm³.
Neuroleptic malignant syndrome (NMS): NMS is a potentially life-threatening condition associated with antipsychotic medication. Rare cases report 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. If patient develop signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, Olanzapine must be discontinued.
Seizure: 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 patients when treated with Olanzapine.
Tardive dyskinesia: The risk of tardive dyskinesia increases with long term exposure, and therefore if signs and 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.
General CNS activity: Given the primary central nervous system 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 antagonize the effects of direct and indirect dopamine agonists.
Orthostatic hypotension: Orthostatic hypotension was infrequently observed in the elderly in Olanzapine trials. It is recommended that blood pressure is measured periodically in patients over 65 years.
Cardiac death: In post-marketing reports with Olanzapine, the event of sudden cardiac death has been reported very rarely(1/10000).
Lipid alteration: Using Olanzapine might alter serum lipid in adult and adolescent. Therefore, serum lipid should be monitored during Olanzapine use.
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 very rarely (0.01%) been reported. However, since patients with schizophrenia often present with acquired risk factors for venous thromboembolism all possible risk factors of VTE e.g. immobilization of patients should be identified and preventive measures undertaken.
Cardiovascular disease: Using Olanzapine in patients with cardiovascular disease should be closely monitored.

Pregnancy: Pregnancy category C.
There are no adequate and well-controlled studies to date using Olanzapine in pregnant women, and the drug should be used during pregnancy only when the potential benefit justify the potential risk to the fetus. Women should be advised to notify their clinician if they become pregnant or plan to become pregnant during therapy with the drug. There is the report in infants born to mothers who had used Olanzapine during the third trimester of pregnancy are at risk for abnormal muscle movements (extrapyramidal symptoms) and/or withdrawal symptoms. Symptoms in the infant may include agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress and feeding disorder.
Lactation: Olanzapine is distributed into milk. The mean dosage received by an infant at steady state is estimated to be about 1.8% of the maternal dosage. Women should avoid breast-feed during receiving Olanzapine.

Undesirable Effects may be founded during treatment with Olanzapine.
Cardiovascular system: orthostatic hypotension, peripheral edema, venous thromboembolic effects, including pulmonary embolism and deep vein thrombosis, QTc prolongation, tachycardia, bradycardia.
Central nervous system: anxiety, dizziness, somnolence, lethargy, abnormal gait, akathisia, dystonia, dyskinesia, tardive dyskinesia, neuroleptic malignant syndrome (NMS), parkinsonism, extrapyramidal syndrome, falling, fatigue, insomnia, tremor, seizure, amnesia, hallucination.
Endocrine and metabolic system: increased serum prolactin, breast changes (including discharge, enlargement, galactorrhea, gynecomastia, lactation disorder) , weight gain, increased appetite, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, diabetic ketoacidosis, diabetic coma, hypothermia, increased body temperature.
Gastrointestinal system: constipation, abdominal distension, nausea, vomiting, dry mouth, pancreatitis.
Genitourinary system: urinary incontinence, urinary retention, urinary hesitation.
Hepatic: Transient, asymptomatic elevations of hepatic aminotransferase, increased serum ALT/SGPT, increased serum AST/SGOT, hepatic injury (cholestatic or mixed), hepatitis, increased total bilirubin, jaundice.
Neuromuscular and skeletal system: arthralgia, rhabdomyolysis.
Skin and cutaneous tissue: alopecia, photosensitivity reaction, erythema.
Hematologic and immunologic system: leukopenia, neutropenia, thrombocytopenia, eosinophilia, anaphylactoid reaction, angioedema, pruritus, urticaria, rash.
Respiratory system: epistaxis, pneumonia.
Miscellaneous: fever, asthenia, priapism, increased creatine phosphokinase, cardiac death.

Olanzapine is a substrate for cytochrome P-450 (CYP) isoenzyme 1A2. Smoking and administration of drug that induce CYP1A2 such as carbamazepine may cause an increase in Olanzapine clearance. On the other hand, CYP1A2 inhibition of some drug such as fluvoxamine might reduce excretion of Olanzapine.
Caution should be exercised when Olanzapine is administered concomitantly with other centrally acting drug and alcohol. Use of Olanzapine and diazepam or other benzodiazepines that are associated with hypotension may potentiate the orthostatic hypotension associated with Olanzapine.
Concurrent administration of activated charcoal reduced the bioavailability of oral Olanzapine by 50-60% and should be taken at least 2 hours before or after Olanzapine.

Store below 30°C, protect from light.

Antipsychotics

N05AH03 - olanzapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics

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