Olanzapine Orally Disintegrating Tablets

Schizophrenia

Olanzapine Orally Disintegrating Tablets are indicated for the treatment of schizophrenia. Efficacy was established in three clinical trials in adult patients with schizophrenia: two 6-week trials and one maintenance trial. In adolescent patients with schizophrenia (ages 13 to 17), efficacy was established in one 6-week trial [see Clinical Studies (14.1)].

When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see Warnings and Precautions (5.5)].

Bipolar I Disorder (Manic or Mixed Episodes)

Monotherapy Olanzapine Orally Disintegrating Tablets are indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder. Efficacy was established in three clinical trials in adult patients with manic or mixed episodes of bipolar I disorder: two 3- to 4-week trials and one monotherapy maintenance trial. In adolescent patients with manic or mixed episodes associated with bipolar I disorder (ages 13 to 17), efficacy was established in one 3-week trial [see Clinical Studies (14.2)].

When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see Warnings and Precautions (5.5)].

Adjunctive Therapy to Lithium or Valproate Olanzapine Orally Disintegrating Tablets are indicated for the treatment of manic or mixed episodes associated with bipolar I disorder as an adjunct to lithium or valproate. Efficacy was established in two 6-week clinical trials in adults. The effectiveness of adjunctive therapy for longer-term use has not been systematically evaluated in controlled trials [see Clinical Studies (14.2)].

Special Considerations in Treating Pediatric Schizophrenia and Bipolar I Disorder

Pediatric schizophrenia and bipolar I disorder are serious mental disorders; however, diagnosis can be challenging. For pediatric schizophrenia, symptom profiles can be variable, and for bipolar I disorder, pediatric patients may have variable patterns of periodicity of manic or mixed symptoms. It is recommended that medication therapy for pediatric schizophrenia and bipolar I disorder be initiated only after a thorough diagnostic evaluation has been performed and careful consideration given to the risks associated with medication treatment. Medication treatment for both pediatric schizophrenia and bipolar I disorder should be part of a total treatment program that often includes psychological, educational and social interventions.

Olanzapine Orally Disintegrating Tablets and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder

Olanzapine Orally Disintegrating Tablets and fluoxetine in combination are indicated for the treatment of depressive episodes associated with bipolar I disorder, based on clinical studies. When using Olanzapine Orally Disintegrating Tablets and fluoxetine in combination, refer to the Clinical Studies section of the package insert for Symbyax.

Olanzapine Orally Disintegrating Tablets monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder.

When using olanzapine and fluoxetine in combination, also refer to the Use in Specific Populations section of the package insert for Symbyax.

Pregnancy

Teratogenic Effects, Pregnancy Category C  - In oral reproduction studies in rats at doses up to 18 mg/kg/day and in rabbits at doses up to 30 mg/kg/day (9 and 30 times the maximum recommended human daily oral dose on a mg/m2 basis, respectively) no evidence of teratogenicity was observed. In an oral rat teratology study, early resorptions and increased numbers of nonviable fetuses were observed at a dose of 18 mg/kg/day (9 times the maximum recommended human daily oral dose on a mg/m2 basis). Gestation was prolonged at 10 mg/kg/day (5 times the maximum recommended human daily oral dose on a mg/m2 basis). In an oral rabbit teratology study, fetal toxicity (manifested as increased resorptions and decreased fetal weight) occurred at a maternally toxic dose of 30 mg/kg/day (30 times the maximum recommended human daily oral dose on a mg/m2 basis). 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.

Placental transfer of olanzapine occurs in rat pups.

There are no adequate and well-controlled trials with olanzapine in pregnant females. Seven pregnancies were observed during clinical trials with olanzapine, including 2 resulting in normal births, 1 resulting in neonatal death due to a cardiovascular defect, 3 therapeutic abortions, and 1 spontaneous abortion.

Nonteratogenic Effects - Neonates exposed to antipsychotic drugs (including olanzapine), during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, 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 intensive care unit support and prolonged hospitalization.

Olanzapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

The effect of olanzapine on labor and delivery in humans is unknown. Parturition in rats was not affected by olanzapine.

Nursing Mothers

In a study in lactating, healthy women, olanzapine was excreted in breast milk. Mean infant dose at steady state was estimated to be 1.8% of the maternal olanzapine dose. It is recommended that women receiving olanzapine should not breast-feed.

Pediatric Use

The safety and effectiveness of oral olanzapine in the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder were established in short-term studies in adolescents (ages 13 to 17 years). Use of olanzapine in adolescents is supported by evidence from adequate and well-controlled studies of olanzapine in which 268 adolescents received olanzapine in a range of 2.5 to 20 mg/day [see Clinical Studies (14.1, 14.2)]. Recommended starting dose for adolescents is lower than that for adults [see Dosage and Administration (2.1, 2.2)].  Compared to patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin and hepatic aminotransferase levels [see Warnings and Precautions (5.5, 5.15,  5.17) and Adverse Reactions (6.3)]. When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential (in adolescents as compared with adults) for weight gain and dyslipidemia. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents [see Indications and Usage (1.1, 1.2)].

Safety and effectiveness of olanzapine in children <13 years of age have not been established [see Patient Counseling Information (17.14)].

Safety and efficacy of olanzapine and fluoxetine in combination in children and adolescents (10 to 17 years of age) have been established for the acute treatment of depressive episodes associated with bipolar I disorder.

Safety and effectiveness of olanzapine and fluoxetine in combination in children <10 years of age have not been established. 

Geriatric Use

Of the 2500 patients in premarketing clinical studies with oral olanzapine, 11% (263) were 65 years of age or over. In patients with schizophrenia, there was no indication of any different tolerability of olanzapine in the elderly compared to younger patients. Studies in elderly patients with dementia-related psychosis have suggested that there may be a different tolerability profile in this population compared to younger patients with schizophrenia. Elderly patients with dementia-related psychosis treated with olanzapine are at an increased risk of death compared to placebo. In placebo-controlled studies of olanzapine in elderly patients with dementia-related psychosis, there was a higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) in patients treated with olanzapine compared to patients treated with placebo. Olanzapine is not approved for the treatment of patients with dementia-related psychosis. Also, the presence of factors that might decrease pharmacokinetic clearance or increase the pharmacodynamic response to olanzapine should lead to consideration of a lower starting dose for any geriatric patient [see Boxed Warning, Dosage and Administration (2.1), and Warnings and Precautions (5.1)].

Clinical studies of olanzapine and fluoxetine in combination did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger patients.

Dependence

In studies prospectively designed to assess abuse and dependence potential, olanzapine was shown to have acute depressive CNS effects but little or no potential of abuse or physical dependence in rats administered oral doses up to 15 times the maximum recommended human daily oral dose (20 mg) and rhesus monkeys administered oral doses up to 8 times the maximum recommended human daily oral dose on a mg/m2 basis.

Olanzapine has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic, and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, patients should be evaluated carefully for a history of drug abuse, and such patients should be observed closely for signs of misuse or abuse of olanzapine (e.g., development of tolerance, increases in dose, drug-seeking behavior).

When using olanzapine and fluoxetine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.

Schizophrenia

Adults

The efficacy of oral olanzapine in the treatment of schizophrenia was established in 2 short-term (6-week) controlled trials of adult inpatients who met DSM III-R criteria for schizophrenia. A single haloperidol arm was included as a comparative treatment in 1 of the 2 trials, but this trial did not compare these 2 drugs on the full range of clinically relevant doses for both.

Several instruments were used for assessing psychiatric signs and symptoms in these studies, among them the Brief Psychiatric Rating Scale (BPRS), a multi-item inventory of general psychopathology traditionally used to evaluate the effects of drug treatment in schizophrenia. The BPRS psychosis cluster (conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) is considered a particularly useful subset for assessing actively psychotic schizophrenic patients. A second traditional assessment, the Clinical Global Impression (CGI), reflects the impression of a skilled observer, fully familiar with the manifestations of schizophrenia, about the overall clinical state of the patient. In addition, 2 more recently developed scales were employed; these included the 30-item Positive and Negative Symptoms Scale (PANSS), in which are embedded the 18 items of the BPRS, and the Scale for Assessing Negative Symptoms (SANS). The trial summaries below focus on the following outcomes: PANSS total and/or BPRS total; BPRS psychosis cluster; PANSS negative subscale or SANS; and CGI Severity. The results of the trials follow:

(1) In a 6-week, placebo-controlled trial (n=149) involving 2 fixed olanzapine doses of 1 and 10 mg/day (once daily schedule), olanzapine, at 10 mg/day (but not at 1 mg/day), was superior to placebo on the PANSS total score (also on the extracted BPRS total), on the BPRS psychosis cluster, on the PANSS Negative subscale, and on CGI Severity.

(2) In a 6-week, placebo-controlled trial (n=253) involving 3 fixed dose ranges of olanzapine (5 ± 2.5 mg/day, 10 ± 2.5 mg/day, and 15 ± 2.5 mg/day) on a once daily schedule, the 2 highest olanzapine dose groups (actual mean doses of 12 and 16 mg/day, respectively) were superior to placebo on BPRS total score, BPRS psychosis cluster, and CGI severity score; the highest olanzapine dose group was superior to placebo on the SANS. There was no clear advantage for the high-dose group over the medium-dose group.

(3) In a longer-term trial, adult outpatients (n=326) who predominantly met DSM-IV criteria for schizophrenia and who remained stable on olanzapine during open-label treatment for at least 8 weeks were randomized to continuation on their current olanzapine doses (ranging from 10 to  20 mg/day) or to placebo. The follow-up period to observe patients for relapse, defined in terms of increases in BPRS positive symptoms or hospitalization, was planned for 12 months, however, criteria were met for stopping the trial early due to an excess of placebo relapses compared to olanzapine relapses, and olanzapine was superior to placebo on time to relapse, the primary outcome for this study. Thus, olanzapine was more effective than placebo at maintaining efficacy in patients stabilized for approximately 8 weeks and followed for an observation period of up to 8 months.

Examination of population subsets (race and gender) did not reveal any differential responsiveness on the basis of these subgroupings.

Adolescents

The efficacy of oral olanzapine in the acute treatment of schizophrenia in adolescents (ages 13 to 17 years) was established in a 6-week double-blind, placebo-controlled, randomized trial of inpatients and outpatients with schizophrenia (n=107) who met diagnostic criteria according to DSM-IV-TR and confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL).

The primary rating instrument used for assessing psychiatric signs and symptoms in this trial was the Anchored Version of the Brief Psychiatric Rating Scale for Children (BPRS-C) total score.

In this flexible-dose trial, olanzapine 2.5 to 20 mg/day (mean modal dose 12.5 mg/day, mean dose of 11.1 mg/day) was more effective than placebo in the treatment of adolescents diagnosed with schizophrenia, as supported by the statistically significantly greater mean reduction in BPRS-C total score for patients in the olanzapine treatment group than in the placebo group.

While there is no body of evidence available to answer the question of how long the adolescent patient treated with olanzapine should be maintained, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients. 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

Monotherapy The efficacy of oral olanzapine in the treatment of manic or mixed episodes was established in 2 short-term (one 3-week and one 4-week) placebo-controlled trials in adult patients who met the DSM-IV criteria for bipolar I disorder with manic or mixed episodes. These trials included patients with or without psychotic features and with or without a rapid-cycling course.

The primary rating instrument used for assessing manic symptoms in these trials was the Young Mania Rating Scale (Y-MRS), an 11-item clinician-rated scale traditionally used to assess the degree of manic symptomatology (irritability, disruptive/aggressive behavior, sleep, elevated mood, speech, increased activity, sexual interest, language/thought disorder, thought content, appearance, and insight) in a range from 0 (no manic features) to 60 (maximum score). The primary outcome in these trials was change from baseline in the Y-MRS total score. The results of the trials follow: 

(1) In one 3-week placebo-controlled trial (n=67) which involved a dose range of olanzapine (5 to 20 mg/day, once daily, starting at 10 mg/day), olanzapine was superior to placebo in the reduction of Y-MRS total score. In an identically designed trial conducted simultaneously with the first trial, olanzapine demonstrated a similar treatment difference, but possibly due to sample size and site variability, was not shown to be superior to placebo on this outcome.

(2) In a 4-week placebo-controlled trial (n=115) which involved a dose range of olanzapine (5 to 20 mg/day, once daily, starting at 15 mg/day), olanzapine was superior to placebo in the reduction of Y-MRS total score.

(3) In another trial, 361 patients meeting DSM-IV criteria for a manic or mixed episode of bipolar I disorder who had responded during an initial open-label treatment phase for about 2 weeks, on average, to olanzapine 5 to 20 mg/day were randomized to either continuation of olanzapine at their same dose (n=225) or to placebo (n=136), for observation of relapse. Approximately 50% of the patients had discontinued from the olanzapine group by day 59 and 50% of the placebo group had discontinued by day 23 of double-blind treatment. Response during the open-label phase was defined by having a decrease of the Y-MRS total score to ≤12 and HAM-D 21 to ≤8. Relapse during the double-blind phase was defined as an increase of the Y-MRS or HAM-D 21 total score to ≥15, or being hospitalized for either mania or depression. In the randomized phase, patients receiving continued olanzapine experienced a significantly longer time to relapse.

Adjunct to Lithium or Valproate The efficacy of oral olanzapine with concomitant lithium or valproate in the treatment of manic or mixed episodes was established in 2 controlled trials in patients who met the DSM-IV criteria for bipolar I disorder with manic or mixed episodes. These trials included patients with or without psychotic features and with or without a rapid-cycling course. The results of the trials follow:

(1) In one 6-week placebo-controlled combination trial, 175 outpatients on lithium or valproate therapy with inadequately controlled manic or mixed symptoms (Y-MRS ≥16) were randomized to receive either olanzapine or placebo, in combination with their original therapy. Olanzapine (in a dose range of 5 to 20 mg/day, once daily, starting at 10 mg/day) combined with lithium or valproate (in a therapeutic range of 0.6 mEq/L to 1.2 mEq/L or 50 mcg/mL to 125 mcg/mL, respectively) was superior to lithium or valproate alone in the reduction of Y-MRS total score.

(2) In a second 6-week placebo-controlled combination trial, 169 outpatients on lithium or valproate therapy with inadequately controlled manic or mixed symptoms (Y-MRS ≥16) were randomized to receive either olanzapine or placebo, in combination with their original therapy. Olanzapine (in a dose range of 5 to 20 mg/day, once daily, starting at 10 mg/day) combined with lithium or valproate (in a therapeutic range of 0.6 mEq/L to 1.2 mEq/L or 50 mcg/mL to  125 mcg/mL, respectively) was superior to lithium or valproate alone in the reduction of Y-MRS total score.

Adolescents

Acute Monotherapy The efficacy of oral olanzapine in the treatment of acute manic or mixed episodes in adolescents (ages 13 to 17 years) was established in a 3-week, double-blind, placebo-controlled, randomized trial of adolescent inpatients and outpatients who met the diagnostic criteria for manic or mixed episodes associated with bipolar I disorder (with or without psychotic features) according to the DSM-IV-TR (n=161). Diagnosis was confirmed by the K-SADS-PL.

The primary rating instrument used for assessing manic symptoms in this trial was the Adolescent Structured Young-Mania Rating Scale (Y-MRS) total score.

In this flexible-dose trial, olanzapine 2.5 to 20 mg/day (mean modal dose 10.7 mg/day, mean dose of 8.9 mg/day) was more effective than placebo in the treatment of adolescents with manic or mixed episodes associated with bipolar I disorder, as supported by the statistically significantly greater mean reduction in Y-MRS total score for patients in the olanzapine treatment group than in the placebo group.

While there is no body of evidence available to answer the question of how long the adolescent patient treated with olanzapine should be maintained, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients. 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.

How Supplied

Olanzapine Orally Disintegrating Tablets USP, 5 mg are yellow colored, circular, flat faced beveled edge tablets debossed with ‘C’ on one side and ‘51’ on the other side.

            Cartons of 30 (3 x 10) Unit-dose Tablets                   NDC 66993-686-38

Olanzapine Orally Disintegrating Tablets USP, 10 mg are yellow colored, circular, flat faced beveled edge tablets debossed with ‘C’ on one side and ‘52’ on the other side.

            Cartons of 30 (3 x 10) Unit-dose Tablets                   NDC 66993-687-38

Olanzapine Orally Disintegrating Tablets USP, 15 mg are yellow colored, circular, flat faced beveled edge tablets debossed with ‘C’ on one side and ‘53’ on the other side.

            Cartons of 30 (3 x 10) Unit-dose Tablets                   NDC 66993-688-38

Olanzapine Orally Disintegrating Tablets USP, 20 mg are yellow colored, circular, flat faced beveled edge tablets debossed with ‘C’ on one side and ‘54’ on the other side.

            Cartons of 30 (3 x 10) Unit-dose Tablets                   NDC 66993-689-38

Storage and Handling

Store Olanzapine Orally Disintegrating Tablets at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. The USP defines controlled room temperature as a temperature maintained thermostatically that encompasses the usual and customary working environment of 20° to 25°C (68° to 77°F); that results in a mean kinetic temperature calculated to be not more than 25°C; and that allows for excursions between 15° and 30°C (59° and 86°F) that are experienced in pharmacies, hospitals, and warehouses.

Protect Olanzapine Orally Disintegrating Tablets from light and moisture.

See FDA-approved Medication Guide for the oral formulations.
 
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking olanzapine as monotherapy or in combination with fluoxetine. If you do not think you are getting better or have any concerns about your condition while taking olanzapine, call your doctor. When using olanzapine and fluoxetine in combination, also refer to the Patient Counseling Information section of the package insert for Symbyax.

Information on Medication Guide

Prescribers or other health professionals should inform patients, their families, and their caregivers about the potential benefits and potential risks associated with treatment with olanzapine, and should counsel them in its appropriate use. A patient Medication Guide is available for olanzapine. Prescribers or other health professionals should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. When using olanzapine and fluoxetine in combination, also refer to the Medication Guide for Symbyax.

Elderly Patients with Dementia-Related Psychosis: Increased Mortality and Cerebrovascular Adverse Events (CVAE), Including Stroke

Patients and caregivers should be advised that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Patients and caregivers should be advised that elderly patients with dementia-related psychosis treated with olanzapine had a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) compared with placebo.

Olanzapine is not approved for elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.1)].

Neuroleptic Malignant Syndrome (NMS)

Patients and caregivers should be counseled that a potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs, including olanzapine. Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see Warnings and Precautions (5.3)].

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Patients should be advised to report to their health care provider at the earliest onset of any signs and symptoms that may be associated with Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.4)].

Hyperglycemia and Diabetes Mellitus

Patients should be advised of the potential risk of hyperglycemia-related adverse reactions. Patients should be monitored regularly for worsening of glucose control. Patients who have diabetes should follow their doctor’s instructions about how often to check their blood sugar while taking olanzapine [see Warnings and Precautions (5.5)].

Dyslipidemia

Patients should be counseled that dyslipidemia has occurred during treatment with olanzapine. Patients should have their lipid profile monitored regularly [see Warnings and Precautions (5.5)].

Weight Gain

Patients should be counseled that weight gain has occurred during treatment with olanzapine. Patients should have their weight monitored regularly [see Warnings and Precautions (5.5)].

Orthostatic Hypotension

Patients should be advised of the risk of orthostatic hypotension, especially during the period of initial dose titration and in association with the use of concomitant drugs that may potentiate the orthostatic effect of olanzapine, e.g., diazepam or alcohol [see Warnings and Precautions (5.7) and Drug Interactions (7)]. Patients should be advised to change positions carefully to help prevent orthostatic hypotension, and to lie down if they feel dizzy or faint, until they feel better. Patients should be advised to call their doctor if they experience any of the following signs and symptoms associated with orthostatic hypotension: dizziness, fast or slow heartbeat, or fainting.

Potential for Cognitive and Motor Impairment

Because 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 [see Warnings and Precautions (5.12)].

Body Temperature Regulation

Patients should be advised regarding appropriate care in avoiding overheating and dehydration. Patients should be advised to call their doctor right away if they become severely ill and have some or all of these symptoms of dehydration: sweating too much or not at all, dry mouth, feeling very hot, feeling thirsty, not able to produce urine [see Warnings and Precautions (5.13)].

Concomitant Medication

Patients should be advised to inform their physicians if they are taking, or plan to take, Symbyax. Patients should also be advised to inform their physicians if they are taking, plan to take, or have stopped taking any prescription or over-the-counter drugs, including herbal supplements, since there is a potential for interactions [see Drug Interactions (7)].

Alcohol

Patients should be advised to avoid alcohol while taking olanzapine [see Drug Interactions (7)].

Phenylketonurics

Olanzapine Orally Disintegrating Tablets contain phenylalanine (0.28 mg, 0.56 mg, 0.84 mg, or 1.12 mg per 5 mg, 10 mg, 15 mg, or 20 mg tablet, respectively) [see Description (11)].

Use in Specific Populations

Pregnancy Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with olanzapine [see Use in Specific Populations (8.1)].

Nursing Mothers Patients should be advised not to breast-feed an infant if they are taking olanzapine [see Use in Specific Populations (8.3)].

Pediatric Use 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. Compared to patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin, and hepatic aminotransferase levels. 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 [see Indications and Usage (1.1,1.2)]. Safety and effectiveness of olanzapine in patients under 13 years of age have not been established. Safety and efficacy of olanzapine and fluoxetine in combination in patients 10 to 17 years of age have been established for the acute treatment of depressive episodes associated with bipolar I disorder. Safety and effectiveness of olanzapine and fluoxetine in combination in patients <10 years of age have not been established [see Warnings and Precautions (5.5) and Use in Specific Populations (8.4)].

Need for Comprehensive Treatment Program in Pediatric Patients

Olanzapine is indicated as an integral part of a total treatment program for pediatric patients with schizophrenia and bipolar disorder that may include other measures (psychological, educational, social) for patients with the disorder. Effectiveness and safety of olanzapine have not been established in pediatric patients less than 13 years of age. Atypical antipsychotics are not intended for use in the pediatric patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders. Appropriate educational placement is essential and psychosocial intervention is often helpful. The decision to prescribe atypical antipsychotic medication will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms [see Indications and Usage (1.3)].

Dispense with Medication Guide available at: www.prasco.com

Revised: 03/2017

Olanzapine Orally Disintegrating Tablets USP 
(oh lan' za peen)

Read the Medication Guide that comes with Olanzapine Orally Disintegrating Tablets before you start taking them and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or treatment. Talk with your doctor or pharmacist if there is something you do not understand or you want to learn more about Olanzapine Orally Disintegrating Tablets.


What is the most important information I should know about Olanzapine Orally Disintegrating Tablets?

Olanzapine Orally Disintegrating Tablets may cause serious side effects, including:

1.  Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis).
2.  High blood sugar (hyperglycemia).
3.  High fat levels in your blood (increased cholesterol and triglycerides), especially in teenagers age 13 to 17 or when used in combination with fluoxetine in children age 10 to 17.
4.  Weight gain, especially in teenagers age 13 to 17 or when used in combination with fluoxetine in children age 10 to 17.

These serious side effects are described below.

1.  Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis). Olanzapine Orally Disintegrating Tablets are not approved for treating psychosis in elderly people with dementia.
2.  High blood sugar (hyperglycemia). High blood sugar can happen if you have diabetes already or if you have never had diabetes. High blood sugar could lead to: 

• a build up of acid in your blood due to ketones (ketoacidosis)
• coma
• death

Your doctor should do tests to check your blood sugar before you start taking Olanzapine Orally Disintegrating Tablets and during treatment. In people who do not have diabetes, sometimes high blood sugar goes away when Olanzapine Orally Disintegrating Tablets are stopped. People with diabetes and some people who did not have diabetes before taking Olanzapine Orally Disintegrating Tablets need to take medicine for high blood sugar even after they stop taking Olanzapine Orally Disintegrating Tablets.

If you have diabetes, follow your doctor’s instructions about how often to check your blood sugar while taking Olanzapine Orally Disintegrating Tablets.

Call your doctor if you have any of these symptoms of high blood sugar (hyperglycemia) while taking Olanzapine Orally Disintegrating Tablets: 

• feel very thirsty
• need to urinate more than usual
• feel very hungry
• feel weak or tired
• feel sick to your stomach
• feel confused or your breath smells fruity

3. High fat levels in your blood (cholesterol and triglycerides). High fat levels may happen in people treated with Olanzapine Orally Disintegrating Tablets, especially in teenagers (13 to 17 years old), or when used in combination with fluoxetine in children (10 to 17 years old). You may not have any symptoms, so your doctor should do blood tests to check your cholesterol and triglyceride levels before you start taking Olanzapine Orally Disintegrating Tablets and during treatment.

4. Weight gain.  Weight gain is very common in people who take Olanzapine Orally Disintegrating Tablets. Teenagers (13 to 17 years old) are more likely to gain weight and to gain more weight than adults. Children (10 to 17 years old) are also more likely to gain weight and to gain more weight than adults when Olanzapine Orally Disintegrating Tablets are used in combination with fluoxetine. Some people may gain a lot of weight while taking Olanzapine Orally Disintegrating Tablets, so you and your doctor should check your weight regularly. Talk to your doctor about ways to control weight gain, such as eating a healthy, balanced diet, and exercising.

What are Olanzapine Orally Disintegrating Tablets?
 
Olanzapine Orally Disintegrating Tablets are a prescription medicine used to treat:

• schizophrenia in people age 13 or older.
• bipolar disorder, including:
  • manic or mixed episodes that happen with bipolar I disorder in people age 13 or older.
  • manic or mixed episodes that happen with bipolar I disorder, when used with the medicine lithium or valproate, in adults.
  • long-term treatment of bipolar I disorder in adults.
• episodes of depression that happen with bipolar I disorder, when used with the medicine fluoxetine (Prozac®) in people age 10 or older.

Olanzapine Orally Disintegrating Tablets have not been approved for use in children under 13 years of age. Olanzapine Orally Disintegrating Tablets in combination with fluoxetine has not been approved for use in children under 10 years of age.

The symptoms of schizophrenia include hearing voices, seeing things that are not there, having beliefs that are not true, and being suspicious or withdrawn.

The symptoms of bipolar I disorder include alternating periods of depression and high or irritable mood, increased activity and restlessness, racing thoughts, talking fast, impulsive behavior, and a decreased need for sleep.

Some of your symptoms may improve with treatment. If you do not think you are getting better, call your doctor. 

What should I tell my doctor before taking Olanzapine Orally Disintegrating Tablets? 

Olanzapine Orally Disintegrating Tablets may not be right for you. Before starting Olanzapine Orally Disintegrating Tablets, tell your doctor if you have or had:

• heart problems
• seizures
• diabetes or high blood sugar levels (hyperglycemia)
• high cholesterol or triglyceride levels in your blood
• liver problems
• low or high blood pressure
• strokes or “mini-strokes” also called transient ischemic attacks (TIAs)
• Alzheimer’s disease
• narrow-angle glaucoma
• enlarged prostate in men
• bowel obstruction
• phenylketonuria, because Olanzapine Orally Disintegrating Tablets contain phenylalanine
• breast cancer 
• thoughts of suicide or hurting yourself
• any other medical condition
• are pregnant or plan to become pregnant. It is not known if Olanzapine Orally Disintegrating Tablets will harm your unborn baby.
• are breast-feeding or plan to breast-feed. Olanzapine can pass into your breast milk and may harm your baby. You should not breast-feed while taking Olanzapine Orally Disintegrating Tablets. Talk to your doctor about the best way to feed your baby if you take Olanzapine Orally Disintegrating Tablets.

Tell your doctor if you exercise a lot or are in hot places often. 

The symptoms of bipolar I disorder or schizophrenia may include thoughts of suicide or of hurting yourself or others. If you have these thoughts at any time, tell your doctor or go to an emergency room right away.

Tell your doctor about all the medicines that you take,  including prescription and nonprescription medicines, vitamins, and herbal supplements. Olanzapine Orally Disintegrating Tablets and some medicines may interact with each other and may not work as well, or cause possible serious side effects. Your doctor can tell you if it is safe to take Olanzapine Orally Disintegrating Tablets with your other medicines. Do not start or stop any medicine while taking Olanzapine Orally Disintegrating Tablets without talking to your doctor first.

How should I take Olanzapine Orally Disintegrating Tablets?

• Take Olanzapine Orally Disintegrating Tablets exactly as prescribed. Your doctor may need to change (adjust) the dose of Olanzapine Orally Disintegrating Tablets until it is right for you.
• If you miss a dose of Olanzapine Orally Disintegrating Tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, just skip the missed dose and take your next dose at the regular time. Do not take two doses of Olanzapine Orally Disintegrating Tablets at the same time.
• To prevent serious side effects, do not stop taking Olanzapine Orally Disintegrating Tablets suddenly. If you need to stop taking Olanzapine Orally Disintegrating Tablets, your doctor can tell you how to safely stop taking them.
• If you take too much olanzapine, call your doctor or poison control center at 1-800-222-1222 right away, or get emergency treatment.
• Olanzapine Orally Disintegrating Tablets  can be taken with or without food.
• Olanzapine Orally Disintegrating Tablets  are usually taken one time each day.
• Take Olanzapine Orally Disintegrating Tablets as follows:
  • Be sure that your hands are dry.
  • Peel back the foil on the blister. Do not push the tablet through the foil.
  • As soon as you open the blister, remove the tablet and put it into your mouth.
  • The tablet will disintegrate quickly in your saliva so that you can easily swallow it with or without drinking liquid.
• Call your doctor if you do not think you are getting better or have any concerns about your condition while taking Olanzapine Orally Disintegrating Tablets.

What should I avoid while taking Olanzapine Orally Disintegrating Tablets?

• Olanzapine Orally Disintegrating Tablets  can cause sleepiness and may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how Olanzapine Orally Disintegrating Tablets affect you.
• Avoid drinking alcohol while taking Olanzapine Orally Disintegrating Tablets. Drinking alcohol while you take Olanzapine Orally Disintegrating Tablets may make you sleepier than if you take Olanzapine Orally Disintegrating Tablets alone.

What are the possible side effects of Olanzapine Orally Disintegrating Tablets?
 
Serious side effects may happen when you take Olanzapine Orally Disintegrating Tablets, including:

• See “What is the most important information I should know about Olanzapine Orally Disintegrating Tablets?”, which describes the increased risk of death in elderly people with dementia-related psychosis and the risks of high blood sugar, high cholesterol and triglyceride levels, and weight gain.
• Increased incidence of stroke or “mini-strokes” called transient ischemic attacks (TIAs) in elderly people with dementia-related psychosis (elderly people who have lost touch with reality due to confusion and memory loss). Olanzapine Orally Disintegrating Tablets are not approved for these patients.
• Neuroleptic Malignant Syndrome (NMS): NMS is a rare but very serious condition that can happen in people who take antipsychotic medicines, including Olanzapine Orally Disintegrating Tablets. NMS can cause death and must be treated in a hospital. Call your doctor right away if you become severely ill and have any of these symptoms:
  • high fever
  • excessive sweating
  • rigid muscles
  • confusion
  • changes in your breathing, heartbeat, and blood pressure.
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): DRESS can occur with Olanzapine Orally Disintegrating Tablets. Features of DRESS may include rash, fever, swollen glands and other internal organ involvement such as liver, kidney, lung and heart. DRESS is sometimes fatal; therefore, tell your doctor immediately if you experience any of these signs.
• Tardive Dyskinesia: This condition causes body movements that keep happening and that you can not control. These movements usually affect the face and tongue. Tardive dyskinesia may not go away, even if you stop taking Olanzapine Orally Disintegrating Tablets. It may also start after you stop taking Olanzapine Orally Disintegrating Tablets. Tell your doctor if you get any body movements that you can not control.
• Decreased blood pressure when you change positions, with symptoms of dizziness, fast or slow heartbeat, or fainting.
• Difficulty swallowing, that can cause food or liquid to get into your lungs.
• Seizures: Tell your doctor if you have a seizure during treatment with Olanzapine Orally Disintegrating Tablets.
• Problems with control of body temperature: You could become very hot, for instance when you exercise a lot or stay in an area that is very hot. It is important for you to drink water to avoid dehydration. Call your doctor right away if you become severely ill and have any of these symptoms of dehydration:
  • sweating too much or not at all
  • dry mouth
  • feeling very hot
  • feeling thirsty
  • not able to produce urine.

Common side effects of Olanzapine Orally Disintegrating Tablets include: lack of energy, dry mouth, increased appetite, sleepiness, tremor (shakes), having hard or infrequent stools, dizziness, changes in behavior, or restlessness.

Other common side effects in teenagers (13 to 17 years old) include:  headache, stomach-area (abdominal) pain, pain in your arms or legs, or tiredness. Teenagers experienced greater increases in prolactin, liver enzymes, and sleepiness, as compared with adults.

Tell your doctor about any side effect that bothers you or that does not go away.

These are not all the possible side effects with Olanzapine Orally Disintegrating Tablets. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Olanzapine Orally Disintegrating Tablets?

• Store Olanzapine Orally Disintegrating Tablets at room temperature, between 20° to 25°C (68° to 77°F).
• Keep Olanzapine Orally Disintegrating Tablets away from light.
• Keep Olanzapine Orally Disintegrating Tablets dry and away from moisture.

Keep Olanzapine Orally Disintegrating Tablets and all medicines out of the reach of children. 

General information about Olanzapine Orally Disintegrating Tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Olanzapine Orally Disintegrating Tablets for a condition for which it was not prescribed. Do not give Olanzapine Orally Disintegrating Tablets to other people, even if they have the same condition. They may harm them.

This Medication Guide summarizes the most important information about Olanzapine Orally Disintegrating Tablets. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Olanzapine Orally Disintegrating Tablets that was written for healthcare professionals. For more information about Olanzapine Orally Disintegrating Tablets call Prasco Laboratories at 1-866-525-0688.

What are the ingredients in Olanzapine Orally Disintegrating Tablets?

Active ingredient:  olanzapine

Inactive ingredients:  art pineapple, aspartame, colloidal silicon dioxide, crospovidone, mannitol, microcrystalline cellulose, polacrilin potassium, and sodium stearyl fumarate. 

This Medication Guide has been approved by the U.S. Food and Drug Administration. 

Prozac®  is a registered trademark of Eli Lilly and Company.

Dispense with Medication Guide available at: www.prasco.com


Manufactured for:
Prasco Laboratories
Mason, OH 45040 USA

Manufactured by:
Aurobindo Pharma Limited
Unit-VII (SEZ)
Mahaboob Nagar (Dt)-509302
India

Revised: 11/2016

NDC 66993-688-38
PRASCO                Rx only 
Olanzapine Orally Disintegrating Tablets USP 
15 mg
PHARMACIST: Dispense the accompanying Medication Guide to each patient.
30 (3 x 10) Unit-dose Tablets