Olanzapine Information
Olanzapine () Indications And Usage
Oral Olanzapine () is 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 .
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 hyperlipidemia. 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 .
Information describing the use of Olanzapine () tablets and Olanzapine () orally disintegrating tablets in pediatric patients with schizophrenia is approved for Eli Lilly and Company’s Olanzapine () drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
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 hyperlipidemia. 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 .
Information describing the use of Olanzapine () tablets and Olanzapine () orally disintegrating tablets in pediatric patients with bipolar 1 disorder is approved for Eli Lilly and Company’s Olanzapine () drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
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Information on treating pediatric patients with schizophrenia and bipolar 1 disorder is approved for Eli Lilly and Company’s Olanzapine () drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Olanzapine () Dosage And Administration
Adults
Dose Selection
Efficacy in schizophrenia was demonstrated in a dose range of 10 to 15 mg/day in clinical trials. However, doses above 10 mg/day were not demonstrated to be more efficacious than the 10 mg/day dose. An increase to a dose greater than the target dose of 10 mg/day (i.e., to a dose of 15 mg/day or greater) is recommended only after clinical assessment. Olanzapine () is not indicated for use in doses above 20 mg/day.
Adolescents
Pediatric dosing information in pediatric patients with schizophrenia is approved for Eli Lilly and Company’s Olanzapine () drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Adults
Dose Selection for Monotherapy
Short-term (3 to 4 weeks) antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials. The safety of doses above 20 mg/day has not been evaluated in clinical trials .
Dose Selection for Adjunctive Treatment
Antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials . The safety of doses above 20 mg/day has not been evaluated in clinical trials.
Adolescents
Pediatric dosing information in pediatric patients with bipolar 1 disorder is approved for Eli Lilly and Company’s Olanzapine () drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
When using Olanzapine () and fluoxetine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.
Oral Olanzapine () should be administered in combination with fluoxetine once daily in the evening, without regard to meals, generally beginning with 5 mg of oral Olanzapine () and 20 mg of fluoxetine. Dosage adjustments, if indicated, can be made according to efficacy and tolerability within dose ranges of oral Olanzapine () 5 to 12.5 mg and fluoxetine 20 to 50 mg. Antidepressant efficacy was demonstrated with Olanzapine () and fluoxetine in combination in adult patients with a dose range of Olanzapine () 6 to 12 mg and fluoxetine 25 to 50 mg.
Safety and efficacy of Olanzapine () and fluoxetine in combination was determined in clinical trials supporting approval of Symbyax (fixed dose combination of Olanzapine () and fluoxetine). Symbyax is dosed between 3 mg/25 mg (Olanzapine () /fluoxetine) per day and 12 mg/50 mg (Olanzapine () /fluoxetine) per day. The following table demonstrates the appropriate individual component doses of Olanzapine () and fluoxetine versus Symbyax. Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability.
While there is no body of evidence to answer the question of how long a patient treated with Olanzapine () and fluoxetine in combination should remain on it, it is generally accepted that bipolar I disorder, including the depressive episodes associated with bipolar I disorder, is a chronic illness requiring chronic treatment. The physician should periodically reexamine the need for continued pharmacotherapy.
Safety of co-administration of doses above 18 mg Olanzapine () with 75 mg fluoxetine has not been evaluated in clinical studies.
Olanzapine () monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder.
Olanzapine () Dosage Forms And Strengths
Olanzapine () orally disintegrating tablets are yellow, round, and debossed with “P” and the Par tablet number as described below. Tablets are not scored. The tablets are available as follows:
Olanzapine () orally disintegrating tablets 5 mg are yellow, round, flat faced, beveled edge tablets debossed “P” on one side of the tablet and “320” on the other.
Olanzapine () orally disintegrating tablets 10 mg are yellow, round, flat faced, beveled edge tablets debossed “P” on one side of the tablet and “321” on the other.
Olanzapine () orally disintegrating tablets 15 mg are yellow, round, flat faced, beveled edge tablets debossed “P” on one side of the tablet and “322” on the other.
Olanzapine () orally disintegrating tablets 20 mg are yellow, round, flat faced, beveled edge tablets debossed “P” on one side of the tablet and “323” on the other.
Olanzapine () Warnings And Precautions
When using Olanzapine () and fluoxetine in combination, also refer to the Warnings and Precautions section of the package insert for Symbyax.
In placebo-controlled clinical trials of elderly patients with dementia-related psychosis, the incidence of death in Olanzapine () -treated patients was significantly greater than placebo-treated patients (3.5% vs 1.5%, respectively).
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including Olanzapine () . Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.
The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported .
Physicians should consider the risks and benefits when prescribing Olanzapine () to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level (fasting 100 to 126 mg/dL, nonfasting 140 to 200 mg/dL). Patients taking Olanzapine () should be monitored regularly for worsening of glucose control. Patients starting treatment with Olanzapine () should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug ( .
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including Olanzapine () . Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and Olanzapine () appears to have a greater association than some other atypical antipsychotics.
Mean increases in blood glucose have been observed in patients treated (median exposure of 9.2 months) with Olanzapine () in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). The mean increase of serum glucose (fasting and nonfasting samples) from baseline to the average of the 2 highest serum concentrations was 15.0 mg/dL.
In a study of healthy volunteers, subjects who received Olanzapine () (N=22) for 3 weeks had a mean increase compared to baseline in fasting blood glucose of 2.3 mg/dL. Placebo-treated subjects (N=19) had a mean increase in fasting blood glucose compared to baseline of 0.34 mg/dL.
Olanzapine () Monotherapy in Adults
In an analysis of 8 placebo-controlled studies (median treatment exposure 4 to 5 weeks), 6.1% of Olanzapine () -treated subjects (N=855) had treatment-emergent glycosuria compared to 2.8% of placebo-treated subjects (N=599). Table 2 shows short-term and long-term changes in fasting glucose levels from adult Olanzapine () monotherapy studies.
The mean change in fasting glucose for patients exposed at least 48 weeks was 4.2 mg/dL (N=487). In analyses of patients who completed 9 to 12 months of Olanzapine () therapy, mean change in fasting and nonfasting glucose levels continued to increase over time.
Olanzapine () Monotherapy in Adolescents
Undesirable alterations in lipids have been observed with Olanzapine () use. Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using Olanzapine () , is recommended
Clinically significant, and sometimes very high (>500 mg/dL), elevations in triglyceride levels have been observed with Olanzapine () use. Modest mean increases in total cholesterol have also been seen with Olanzapine () use.
Olanzapine () Monotherapy in Adults
In long-term studies (at least 48 weeks), patients had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.6 mg/dL, 2.5 mg/dL, and 18.7 mg/dL, respectively, and a mean decrease in fasting HDL cholesterol of 0.16 mg/dL. In an analysis of patients who completed 12 months of therapy, the mean nonfasting total cholesterol did not increase further after approximately 4 to 6 months.
The proportion of patients who had changes (at least once) in total cholesterol, LDL cholesterol or triglycerides from normal or borderline to high, or changes in HDL cholesterol from normal or borderline to low, was greater in long-term studies (at least 48 weeks) as compared with short-term studies. Table 4 shows categorical changes in fasting lipids values.
In phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), over a median exposure of 9.2 months, the mean increase in triglycerides in patients taking Olanzapine () was 40.5 mg/dL. In phase 1 of CATIE, the mean increase in total cholesterol was 9.4 mg/dL.
Olanzapine () Monotherapy in Adolescents
In long-term studies (at least 24 weeks), adolescents had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.5 mg/dL, 5.4 mg/dL, and 20.5 mg/dL, respectively, and a mean decrease in fasting HDL cholesterol of 4.5 mg/dL. Table 5 shows categorical changes in fasting lipids values in adolescents.
Potential consequences of weight gain should be considered prior to starting Olanzapine () . Patients receiving Olanzapine () should receive regular monitoring of weight
Olanzapine () Monotherapy in Adults
In long-term studies (at least 48 weeks), the mean weight gain was 5.6 kg (12.3 lb) (median exposure of 573 days, N=2021). The percentages of patients who gained at least 7%, 15%, or 25% of their baseline body weight with long-term exposure were 64%, 32%, and 12%, respectively. Discontinuation due to weight gain occurred in 0.4% of Olanzapine () -treated patients following at least 48 weeks of exposure.
Table 6 includes data on adult weight gain with Olanzapine () pooled from 86 clinical trials. The data in each column represent data for those patients who completed treatment periods of the durations specified.
Olanzapine () Monotherapy in Adolescents
In long-term studies (at least 24 weeks), the mean weight gain was 11.2 kg (24.6 lb); (median exposure of 201 days, N=179). The percentages of adolescents who gained at least 7%, 15%, or 25% of their baseline body weight with long-term exposure were 89%, 55%, and 29%, respectively. Among adolescent patients, mean weight gain by baseline BMI category was 11.5 kg (25.3 lb), 12.1 kg (26.6 lb), and 12.7 kg (27.9 lb), respectively, for normal (N=106), overweight (N=26) and obese (N=17). Discontinuation due to weight gain occurred in 2.2% of Olanzapine () -treated patients following at least 24 weeks of exposure.
Table 8 shows data on adolescent weight gain with Olanzapine () pooled from 6 clinical trials. The data in each column represent data for those patients who completed treatment periods of the durations specified. Little clinical trial data is available on weight gain in adolescents with Olanzapine () beyond 6 months of treatment.
A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.
The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, Olanzapine () should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients (1) who suffer from a chronic illness that is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on Olanzapine () , drug discontinuation should be considered. However, some patients may require treatment with Olanzapine () despite the presence of the syndrome.
For specific information about the warnings of lithium or valproate, refer to the Warnings section of the package inserts for these other products.
Olanzapine () may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia and, in some patients, syncope, especially during the initial dose-titration period, probably reflecting its α -adrenergic antagonistic properties .
For oral Olanzapine () therapy, the risk of orthostatic hypotension and syncope may be minimized by initiating therapy with 5 mg QD . A more gradual titration to the target dose should be considered if hypotension occurs.
Syncope was reported in 0.6% (15/2500) of Olanzapine () -treated patients in phase 2-3 oral Olanzapine () studies. The risk for this sequence of hypotension, bradycardia, and sinus pause may be greater in nonpsychiatric patients compared to psychiatric patients who are possibly more adapted to certain effects of psychotropic drugs.
Olanzapine () should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications) where the occurrence of syncope, or hypotension and/or bradycardia might put the patient at increased medical risk.
Caution is necessary in patients who receive treatment with other drugs having effects that can induce hypotension, bradycardia, respiratory or central nervous system depression )].
Class Effect
Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of Olanzapine () should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count
Somnolence was a commonly reported adverse reaction associated with Olanzapine () treatment, occurring at an incidence of 26% in Olanzapine () patients compared to 15% in placebo patients. This adverse reaction was also dose related. Somnolence led to discontinuation in 0.4% (9/2500) of patients in the premarketing database.
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 .
Clinical experience with Olanzapine () in patients with certain concomitant systemic illnesses is limited .
Olanzapine () exhibits muscarinic receptor affinity. In premarketing clinical trials with Olanzapine () , Olanzapine () was associated with constipation, dry mouth, and tachycardia, all adverse reactions possibly related to cholinergic antagonism. Such adverse reactions were not often the basis for discontinuations from Olanzapine () , but Olanzapine () should be used with caution in patients with clinically significant prostatic hypertrophy, narrow angle glaucoma, or a history of paralytic ileus or related conditions.
In 5 placebo-controlled studies of Olanzapine () in elderly patients with dementia-related psychosis (n=1184), the following treatment-emergent adverse reactions were reported in Olanzapine () -treated patients at an incidence of at least 2% and significantly greater than placebo-treated patients: falls, somnolence, peripheral edema, abnormal gait, urinary incontinence, lethargy, increased weight, asthenia, pyrexia, pneumonia, dry mouth and visual hallucinations. The rate of discontinuation due to adverse reactions was greater with Olanzapine () than placebo (13% vs 7%). Elderly patients with dementia-related psychosis treated with Olanzapine () are at an increased risk of death compared to placebo. Olanzapine () is not approved for the treatment of patients with dementia-related psychosis .
Olanzapine () has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were excluded from premarketing clinical studies. Because of the risk of orthostatic hypotension with Olanzapine () , caution should be observed in cardiac patients .
As with other drugs that antagonize dopamine D receptors, Olanzapine () elevates prolactin levels, and the elevation persists during chronic administration. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects.
Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent , a factor of potential importance if the prescription of these drugs is contemplated in a patient with previously detected breast cancer. As is common with compounds which increase prolactin release, an increase in mammary gland neoplasia was observed in the Olanzapine () carcinogenicity studies conducted in mice and rats . Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of this class of drugs and tumorigenesis in humans; the available evidence is considered too limited to be conclusive at this time.
In placebo-controlled Olanzapine () clinical studies (up to 12 weeks), changes from normal to high in prolactin concentrations were observed in 30% of adults treated with Olanzapine () as compared to 10.5% of adults treated with placebo. In a pooled analysis from clinical studies including 8136 adults treated with Olanzapine () , potentially associated clinical manifestations included menstrual-related events (2% [49/3240] of females), sexual function-related events (2% [150/8136] of females and males), and breast-related events (0.7% [23/3240] of females, 0.2% [9/4896] of males).
In placebo-controlled Olanzapine () monotherapy studies in adolescent patients (up to 6 weeks) with schizophrenia or bipolar I disorder (manic or mixed episodes), changes from normal to high in prolactin concentrations were observed in 47% of Olanzapine () -treated patients compared to 7% of placebo-treated patients. In a pooled analysis from clinical trials including 454 adolescents treated with Olanzapine () , potentially associated clinical manifestations included menstrual-related events (1% [2/168] of females), sexual function-related events (0.7% [3/454] of females and males), and breast-related events (2% [3/168] of females, 2% [7/286] of males) .
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Olanzapine () Adverse Reactions
When using Olanzapine () and fluoxetine in combination, also refer to the Adverse Reactions section of the package insert for Symbyax.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice.
Clinical Trials in Adults
The information below for Olanzapine () is derived from a clinical trial database for Olanzapine () consisting of 8661 adult patients with approximately 4165 patient-years of exposure to oral Olanzapine () and 722 patients with exposure to intramuscular Olanzapine () for injection. This database includes: (1) 2500 patients who participated in multiple-dose oral Olanzapine () premarketing trials in schizophrenia and Alzheimer's disease representing approximately 1122 patient-years of exposure as of February 14, 1995; (2) 182 patients who participated in oral Olanzapine () premarketing bipolar I disorder (manic or mixed episodes) trials representing approximately 66 patient-years of exposure; (3) 191 patients who participated in an oral Olanzapine () trial of patients having various psychiatric symptoms in association with Alzheimer's disease representing approximately 29 patient-years of exposure; (4) 5788 patients from 88 additional oral Olanzapine () clinical trials as of December 31, 2001; and (5) 722 patients who participated in intramuscular Olanzapine () for injection premarketing trials in agitated patients with schizophrenia, bipolar I disorder (manic or mixed episodes), or dementia. In addition, information from the premarketing 6-week clinical study database for Olanzapine () in combination with lithium or valproate, consisting of 224 patients who participated in bipolar I disorder (manic or mixed episodes) trials with approximately 22 patient-years of exposure, is included below.
The conditions and duration of treatment with Olanzapine () varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and dose-titration studies, and short-term or longer-term exposure. Adverse reactions were assessed by collecting adverse reactions, results of physical examinations, vital signs, weights, laboratory analytes, ECGs, chest x-rays, and results of ophthalmologic examinations.
Certain portions of the discussion below relating to objective or numeric safety parameters, namely, dose-dependent adverse reactions, vital sign changes, weight gain, laboratory changes, and ECG changes are derived from studies in patients with schizophrenia and have not been duplicated for bipolar I disorder (manic or mixed episodes) or agitation. However, this information is also generally applicable to bipolar I disorder (manic or mixed episodes) and agitation.
Adverse reactions during exposure were obtained by spontaneous report and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of reactions into a smaller number of standardized reaction categories. In the tables and tabulations that follow, MedDRA and COSTART Dictionary terminology has been used to classify reported adverse reactions.
The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. The reported reactions do not include those reaction terms that were so general as to be uninformative. Reactions listed elsewhere in labeling may not be repeated below. It is important to emphasize that, although the reactions occurred during treatment with Olanzapine () , they were not necessarily caused by it. The entire label should be read to gain a complete understanding of the safety profile of Olanzapine () .
The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse reactions incidence in the population studied.
Incidence of Adverse Reactions in Short-Term, Placebo-Controlled and Combination Trials
The following findings are based on premarketing trials of (1) oral Olanzapine () for schizophrenia, bipolar I disorder (manic or mixed episodes), a subsequent trial of patients having various psychiatric symptoms in association with Alzheimer's disease, and premarketing combination trials.
Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled Trials
Schizophrenia
Bipolar I Disorder (Manic or Mixed Episodes) Monotherapy
Adverse Reactions Associated with Discontinuation of Treatment in Short-Term Combination Trials
Bipolar I Disorder (Manic or Mixed Episodes), Olanzapine () as Adjunct to Lithium or Valproate
Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials
The most commonly observed adverse reactions associated with the use of oral Olanzapine () (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (Olanzapine () incidence at least twice that for placebo) were:
Adverse Reactions Occurring at an Incidence of 2% or More among Oral Olanzapine () -Treated Patients in Short-Term, Placebo-Controlled Trials
Table 11 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred in 2% or more of patients treated with oral Olanzapine () (doses ≥2.5 mg/day) and with incidence greater than placebo who participated in the acute phase of placebo-controlled trials.
Commonly Observed Adverse Reactions in Short-Term Trials of Oral Olanzapine () as Adjunct to Lithium or Valproate
In the bipolar I disorder (manic or mixed episodes) adjunct placebo-controlled trials, the most commonly observed adverse reactions associated with the combination of Olanzapine () and lithium or valproate (incidence of ≥5% and at least twice placebo) were:
Adverse Reactions Occurring at an Incidence of 2% or More among Oral Olanzapine () -Treated Patients in Short-Term Trials of Olanzapine () as Adjunct to Lithium or Valproate
Table 13 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred in 2% or more of patients treated with the combination of Olanzapine () (doses ≥5 mg/day) and lithium or valproate and with incidence greater than lithium or valproate alone who participated in the acute phase of placebo-controlled combination trials.
For specific information about the adverse reactions observed with lithium or valproate, refer to the Adverse Reactions section of the package inserts for these other products.
Additional Findings Observed in Clinical Trials
Dose Dependency of Adverse Reactions in Short-Term, Placebo-Controlled Trials
Extrapyramidal Symptoms:
The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by spontaneously reported adverse reactions during acute therapy in the same controlled clinical trial comparing Olanzapine () at 3 fixed doses with placebo in the treatment of schizophrenia in a 6-week trial.
The following table enumerates the percentage of adolescent patients with treatment-emergent extrapyramidal symptoms as assessed by spontaneously reported adverse reactions during acute therapy (dose range: 2.5 to 20 mg/day).
Dystonia, Class Effect:
Other Adverse Reactions:
Differences among Fixed-Dose Groups Observed in Other Olanzapine () Clinical Trials
In a single 8-week randomized, double-blind, fixed-dose study comparing 10 (N=199), 20 (N=200) and 40 (N=200) mg/day of oral Olanzapine () in patients with schizophrenia or schizoaffective disorder, differences among 3 dose groups were observed for the following safety outcomes: weight gain, prolactin elevation, fatigue and dizziness. Mean baseline to endpoint increase in weight (10 mg/day: 1.9 kg; 20 mg/day: 2.3 kg; 40 mg/day: 3 kg) was observed with significant differences between 10 vs 40 mg/day. Incidence of treatment-emergent prolactin elevation >24.2 ng/mL (female) or >18.77 ng/mL (male) at any time during the trial (10 mg/day: 31.2%; 20 mg/day: 42.7%; 40 mg/day: 61.1%) with significant differences between 10 vs 40 mg/day and 20 vs 40 mg/day; fatigue (10 mg/day: 1.5%; 20 mg/day: 2.1%; 40 mg/day: 6.6%) with significant differences between 10 vs 40 and 20 vs 40 mg/day; and dizziness (10 mg/day: 2.6%; 20 mg/day: 1.6%; 40 mg/day: 6.6%) with significant differences between 20 vs 40 mg, was observed.
Other Adverse Reactions Observed During the Clinical Trial Evaluation of Oral Olanzapine ()
Following is a list of treatment-emergent adverse reactions reported by patients treated with oral Olanzapine () (at multiple doses ≥1 mg/day) in clinical trials. This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative, (4) which were not considered to have significant clinical implications, or (5) which occurred at a rate equal to or less than placebo. Reactions are classified by body system using the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients.
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Clinical Trials in Adolescent Patients (age 13 to 17 years)
Commonly Observed Adverse Reactions in Oral Olanzapine () Short-Term, Placebo-Controlled Trials
Adverse reactions in adolescent patients treated with oral Olanzapine () (doses ≥2.5 mg) reported with an incidence of 5% or more and reported at least twice as frequently as placebo-treated patients are listed in Table 21.
Adverse reactions in adolescent patients treated with oral Olanzapine () (doses ≥2.5 mg) reported with an incidence of 2% or more and greater than placebo are listed in Table 22.
Laboratory Changes
Olanzapine () Monotherapy in Adults:
In placebo-controlled Olanzapine () monotherapy studies in adults, clinically significant ALT elevations (change from
Rare postmarketing reports of hepatitis have been received. Very rare cases of cholestatic or mixed liver injury have also been reported in the postmarketing period.
Caution should be exercised 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.
Olanzapine () administration was also associated with increases in serum prolactin , with an asymptomatic elevation of the eosinophil count in 0.3% of patients, and with an increase in CPK.
Olanzapine () Monotherapy in Adolescents:
In placebo-controlled Olanzapine () monotherapy studies in adolescents, clinically significant ALT elevations (change from
The following adverse reactions have been identified during post-approval use of Olanzapine () . Because these reactions are reported voluntarily from a population of uncertain size, it is difficult to reliably estimate their frequency or evaluate a causal relationship to drug exposure.
Adverse reactions reported since market introduction that were temporally (but not necessarily causally) related to Olanzapine () therapy include the following: allergic reaction (e.g., anaphylactoid reaction, angioedema, pruritus or urticaria), diabetic coma, diabetic ketoacidosis, discontinuation reaction (diaphoresis, nausea or vomiting), jaundice, neutropenia, pancreatitis, priapism, rash, rhabdomyolysis, and venous thromboembolic events (including pulmonary embolism and deep venous thrombosis). Random cholesterol levels of ≥240 mg/dL and random triglyceride levels of ≥1000 mg/dL have been reported.
Olanzapine () Drug Interactions
The risks of using Olanzapine () in combination with other drugs have not been extensively evaluated in systematic studies.
Cimetidine and Antacids
Inducers of CYP1A2
Inhibitors of CYP1A2
Fluvoxamine:
max
Inhibitors of CYP2D6
Fluoxetine:
Inducers of CYP1A2 or Glucuronyl Transferase
Charcoal
max
CNS Acting Drugs
Antihypertensive Agents
Levodopa and Dopamine Agonists
Imipramine
Biperiden
Theophylline
Olanzapine () Use In Specific Populations
When using Olanzapine () and fluoxetine in combination, also refer to the Use in Specific Populations section of the package insert for Symbyax.
Teratogenic Effects, Pregnancy Category C
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
Olanzapine () should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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 . 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 hyperlipidemia.
Safety and effectiveness of Olanzapine () and fluoxetine in children
Safety and effectiveness of Olanzapine () and fluoxetine in combination in children and adolescents
Pediatric use information in pediatric patients with schizophrenia and bipolar 1 disorder is approved for Eli Lilly and Company’s Olanzapine () drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
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 ( .
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.
Olanzapine () Overdosage
In premarketing trials involving more than 3100 patients and/or normal subjects, accidental or intentional acute overdosage of Olanzapine () was identified in 67 patients. In the patient taking the largest identified amount, 300 mg, the only symptoms reported were drowsiness and slurred speech. In the limited number of patients who were evaluated in hospitals, including the patient taking 300 mg, there were no observations indicating an adverse change in laboratory analytes or ECG. Vital signs were usually within normal limits following overdoses.
In postmarketing reports of overdose with Olanzapine () alone, symptoms have been reported in the majority of cases. In symptomatic patients, symptoms with ≥10% incidence included agitation/aggressiveness, dysarthria, tachycardia, various extrapyramidal symptoms, and reduced level of consciousness ranging from sedation to coma. Among less commonly reported symptoms were the following potentially medically serious reactions: aspiration, cardiopulmonary arrest, cardiac arrhythmias (such as supraventricular tachycardia and 1 patient experiencing sinus pause with spontaneous resumption of normal rhythm), delirium, possible neuroleptic malignant syndrome, respiratory depression/arrest, convulsion, hypertension, and hypotension. Eli Lilly and Company has received reports of fatality in association with overdose of Olanzapine () alone. In 1 case of death, the amount of acutely ingested Olanzapine () was reported to be possibly as low as 450 mg of oral Olanzapine () ; however, in another case, a patient was reported to survive an acute Olanzapine () ingestion of approximately 2 g of oral Olanzapine () .
The possibility of multiple drug involvement should be considered. In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation, which may include intubation. Gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. The administration of activated charcoal (1 g) reduced the C and AUC of oral Olanzapine () by about 60%. As peak Olanzapine () levels are not typically obtained until about 6 hours after dosing, charcoal may be a useful treatment for Olanzapine () overdose.
The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias.
There is no specific antidote to Olanzapine () . Therefore, appropriate supportive measures should be initiated. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. (Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity, since beta stimulation may worsen hypotension in the setting of Olanzapine () -induced alpha blockade.) Close medical supervision and monitoring should continue until the patient recovers.
For specific information about overdosage with lithium or valproate, refer to the Overdosage section of the package inserts for these products. For specific information about overdosage with Olanzapine () and fluoxetine in combination, refer to the Overdosage section of the Symbyax package insert.
Olanzapine () Description
Olanzapine () is an atypical antipsychotic that belongs to the thienobenzodiazepine class. The chemical designation is 2-methyl-4-(4-methyl-1-piperazinyl)-10 -thieno[2,3-] [1,5]benzodiazepine. The molecular formula is CHNS, which corresponds to a molecular weight of 312.44. The chemical structure is:
Olanzapine () is a yellow crystalline solid, which is practically insoluble in water.
Olanzapine () orally disintegrating tablets are intended for oral administration only.
Each orally disintegrating tablet contains Olanzapine () equivalent to 5 mg (16 μmol), 10 mg (32 μmol), 15 mg (48 μmol) or 20 mg (64 μmol). It begins disintegrating in the mouth within seconds, allowing its contents to be subsequently swallowed with or without liquid. Olanzapine () orally disintegrating tablets also contains the following inactive ingredients: aspartame, crospovidone, magnesium stearate, mannitol, silicone dioxide, sorbitol, talc, and artificial pineapple flavor.
Olanzapine () Clinical Pharmacology
Olanzapine () binds with high affinity to the following receptors: serotonin 5HT , 5HT (K=4, 11, and 5 nM, respectively), dopamine D (K=11-31 nM), histamine H (K=7 nM), and adrenergic α receptors (K=19 nM). Olanzapine () is an antagonist with moderate affinity binding for serotonin 5HT (K=57 nM) and muscarinic M(K=73, 96, 132, 32, and 48 nM, respectively). Olanzapine () binds weakly to GABA, BZD, and β-adrenergic receptors (K>10 μM).
Antagonism at receptors other than dopamine and 5HT may explain some of the other therapeutic and side effects of Olanzapine () . Olanzapine () ’s antagonism of muscarinic M receptors may explain its anticholinergic-like effects. Olanzapine () ’s antagonism of histamine H receptors may explain the somnolence observed with this drug. Olanzapine () ’s antagonism of adrenergic α receptors may explain the orthostatic hypotension observed with this drug.
Oral Administration, Monotherapy
Olanzapine () displays linear kinetics over the clinical dosing range. Its half-life ranges from 21 to 54 hours (5th to 95th percentile; mean of 30 hr), and apparent plasma clearance ranges from 12 to 47 L/hr (5th to 95th percentile; mean of 25 L/hr).
Administration of Olanzapine () once daily leads to steady-state concentrations in about 1 week that are approximately twice the concentrations after single doses. Plasma concentrations, half-life, and clearance of Olanzapine () may vary between individuals on the basis of smoking status, gender, and age.
Olanzapine () is extensively distributed throughout the body, with a volume of distribution of approximately 1000 L. It is 93% bound to plasma proteins over the concentration range of 7 to 1100 ng/mL, binding primarily to albumin and α -acid glycoprotein.
Metabolism and Elimination
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Direct glucuronidation and cytochrome P450 (CYP) mediated oxidation are the primary metabolic pathways for Olanzapine () . studies suggest that CYPs 1A2 and 2D6, and the flavin-containing monooxygenase system are involved in Olanzapine () oxidation. CYP2D6 mediated oxidation appears to be a minor metabolic pathway , because the clearance of Olanzapine () is not reduced in subjects who are deficient in this enzyme.
Specific Populations
Renal Impairment
Hepatic Impairment
Gender
Smoking Status
Adolescents (ages 13 to 17 years)
Pharmacokinetic information in pediatric patients is approved for Eli Lilly and Company’s Olanzapine () drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Olanzapine () Clinical Studies
When using Olanzapine () and fluoxetine in combination, also refer to the Clinical Studies section of the package insert for Symbyax.
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
Clinical trial information in pediatric patients with schizophrenia is approved for Eli Lilly and Company’s Olanzapine () drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Adults
Monotherapy
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
(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 μg/mL to 125 μg/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 μg/mL to 125 μg/mL, respectively) was superior to lithium or valproate alone in the reduction of Y-MRS total score.
Adolescents
Clinical trial information in pediatric patients with bipolar 1 disorder is approved for Eli Lilly and Company’s Olanzapine () drug product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.
Olanzapine () How Supplied
Store Olanzapine () orally disintegrating tablets at controlled room temperature, 20° to 25°C (68° to 77°F) [ USP].
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.
Olanzapine () Patient Counseling Information
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.
Olanzapine () Medication Guide
Read the Medication Guide that comes with Olanzapine () Orally Disintegrating Tablets before you start taking it 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 () .
Your doctor should do tests to check your blood sugar before you start taking Olanzapine () and during treatment. In people who do not have diabetes, sometimes high blood sugar goes away when Olanzapine () is stopped. People with diabetes and some people who did not have diabetes before taking Olanzapine () need to take medicine for high blood sugar even after they stop taking Olanzapine () .
If you have diabetes, follow your doctor’s instructions about how often to check your blood sugar while taking Olanzapine () .
Olanzapine () has not been approved for use in children under 13 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.
Olanzapine () may not be right for you. Before starting Olanzapine () , tell your doctor if you have or had:
Tell your doctor if you exercise a lot or are in hot places often.
The symptoms of bipolar I disorder or schizophrenia may include 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 any side effect that bothers you or that does not go away.
These are not all the possible side effects with Olanzapine () . 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.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Olanzapine () for a condition for which it was not prescribed. Do not give Olanzapine () to other people, even if they have the same condition. It 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 () that was written for healthcare professionals. For more information about Olanzapine () Orally Disintegrating Tablets call Par Pharmaceuticals, Inc. at 1-800-828-9393 or visit www.parpharm.com
Manufactured by:
Spring Valley, NY 10977, USA
SYMBYAX and PROZAC are the registered trademarks of Eli Lilly and Company.
Issued: 09/11
Olanzapine () Principal Display Panel - Mg
Olanzapine () Principal Display Panel - Mg
Olanzapine () Principal Display Panel - Mg
Olanzapine () Principal Display Panel - Mg
