Olanzapine

Brand names: ZYPREXA, Zyprexa, Olanzapine, ZYPREXA Zydis, olanzapine, OLANZAPINE, ZYPREXA Intramuscular, Olanzapine Intramuscular

Boxed warning

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Olanzapine is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.1) , Use in Specific Populations (8.5) , and Patient Counseling Information (17) ] . When using olanzapine and fluoxetine in combination, also refer to the Boxed Warning section of the package insert for Symbyax. WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Olanzapine is not approved for the treatment of patients with dementia-related psychosis. ( 5.1 , 8.5 , 17 ) When using olanzapine and fluoxetine in combination, also refer to the Boxed Warning section of the package insert for Symbyax.

Warnings

BOXED WARNING: "Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death," with most deaths related to cardiovascular events or infection; olanzapine is "not approved for the treatment of patients with dementia-related psychosis." Major warnings include Neuroleptic Malignant Syndrome, "hyperglycemia, in some cases extreme and associated with ketoacidosis or...death," tardive dyskinesia, significant weight gain and dyslipidemia, leukopenia/neutropenia/agranulocytosis, orthostatic hypotension with syncope, and increased cerebrovascular events (including stroke) in elderly dementia patients.

Contraindications

4 CONTRAINDICATIONS None with olanzapine orally disintegrating tablets monotherapy. When using olanzapine orally disintegrating tablets and fluoxetine in combination, also refer to the Contraindications section of the package insert for Symbyax. For specific information about the contraindications of lithium or valproate, refer to the Contraindications section of the package inserts for these other products. None with olanzapine orally disintegrating tablets monotherapy. ( 4 ) When using olanzapine orally disintegrating tablets and fluoxetine in combination, also refer to the Contraindications section of the package insert for Symbyax ® . (4) When using olanzapine orally disintegrating tablets in combination with lithium or valproate, refer to the Contraindications section of the package inserts for those products. (4)

Overdose

10 OVERDOSAGE 10.1 Human Experience 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. 10.2 Management of Overdose There is no specific antidote to an overdose of olanzapine. The possibility of multiple drug involvement should be considered. Establish and maintain an airway and ensure adequate oxygenation and ventilation. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. Contact a Certified Poison Control Center for the most up to date information on the management of overdosage (1-800-222-1222). For specific information about overdosage with lithium or valproate, refer to the Overdosage section of the prescribing information for those products. For specific information about overdosage with olanzapine and fluoxetine in combination, refer to the Overdosage section of the Symbyax prescribing information.

Drug interactions

7 DRUG INTERACTIONS The risks of using olanzapine in combination with other drugs have not been extensively evaluated in systematic studies. Diazepam: May potentiate orthostatic hypotension. (7.1 , 7.2) Alcohol: May potentiate orthostatic hypotension. (7.1) Carbamazepine: Increased clearance of olanzapine. (7.1) Fluvoxamine: May increase olanzapine levels. (7.1) Olanzapine and Fluoxetine in Combination: Also refer to the Drug Interactions section of the package insert for Symbyax. (7.1) CNS Acting Drugs: Caution should be used when taken in combination with other centrally acting drugs and alcohol. (7.2) Antihypertensive Agents: Enhanced antihypertensive effect. (7.2) Levodopa and Dopamine Agonists: May antagonize levodopa/dopamine agonists. (7.2) Other Concomitant Drug Therapy: When using olanzapine in combination with lithium or valproate, refer to the Drug Interactions sections of the package insert for those products. (7.2) 7.1 Potential for Other Drugs to Affect Olanzapine Diazepam — The co-administration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine [see Drug Interactions (7.2) ] . Cimetidine and Antacids — Single doses of cimetidine (800 mg) or aluminum- and magnesium-containing antacids did not affect the oral bioavailability of olanzapine. Inducers of CYP1A2 — Carbamazepine therapy (200 mg bid) causes an approximately 50% increase in the clearance of olanzapine. This increase is likely due to the fact that carbamazepine is a potent inducer of CYP1A2 activity. Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance. Alcohol — Ethanol (45 mg/70 kg single dose) did not have an effect on olanzapine pharmacokinetics. The co-administration of alcohol (i.e., ethanol) with olanzapine potentiated the orthostatic hypotension observed with olanzapine [see Drug Interactions (7.2) ] . Inhibitors of CYP1A2 Fluvoxamine: Fluvoxamine, a CYP1A2 inhibitor, decreases the clearance of olanzapine. This results in a mean increase in olanzapine C max following fluvoxamine of 54% in female nonsmokers and 77% in male smokers. The mean increase in olanzapine AUC is 52% and 108%, respectively. Lower doses of olanzapine should be considered in patients receiving concomitant treatment with fluvoxamine. Inhibitors of CYP2D6 Fluoxetine: Fluoxetine (60 mg single dose or 60 mg daily dose for 8 days) causes a small (mean 16%) increase in the maximum concentration of olanzapine and a small (mean 16%) decrease in olanzapine clearance. The magnitude of the impact of this factor is small in comparison to the overall variability between individuals, and therefore dose modification is not routinely recommended. When using olanzapine and fluoxetine in combination, also refer to the Drug Interactions section of the package insert for Symbyax. Warfarin — Warfarin (20 mg single dose) did not affect olanzapine pharmacokinetics [see Drug Interactions (7.2) ] . Inducers of CYP1A2 or Glucuronyl Transferase — Omeprazole and rifampin may cause an increase in olanzapine clearance. Charcoal — The administration of activated charcoal (1 g) reduced the C max 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. Anticholinergic Drugs — Concomitant treatment with olanzapine and other drugs with anticholinergic activity can increase the risk for severe gastrointestinal adverse reactions related to hypomotility. Olanzapine should be used with caution in patients receiving medications having anticholinergic (antimuscarinic) effects [see Warnings and Precautions (5.14) ] . 7.2 Potential for Olanzapine to Affect Other Drugs CNS Acting Drugs — Given the primary CNS effects of olanzapine, caution should be used when olanzapine is taken in combination with other centrally acting drugs and alcohol. Antihypertensive Agents — Olanzapine, because of its potential for inducing hypotension, may enhance the effects of certain antihypertensive agents. Levodopa and Dopamine Agonists — Olanzapine may antagonize the effects of levodopa and dopamine agonists. Lithium — Multiple doses of olanzapine (10 mg for 8 days) did not influence the kinetics of lithium. Therefore, concomitant olanzapine administration does not require dosage adjustment of lithium [see Warnings and Precautions (5.16) ] . Valproate — Olanzapine (10 mg daily for 2 weeks) did not affect the steady state plasma concentrations of valproate. Therefore, concomitant olanzapine administration does not require dosage adjustment of valproate [see Warnings and Precautions (5.16) ] . Effect of Olanzapine on Drug Metabolizing Enzymes — In vitro studies utilizing human liver microsomes suggest that olanzapine has little potential to inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A. Thus, olanzapine is unlikely to cause clinically important drug interactions mediated by these enzymes. Imipramine — Single doses of olanzapine did not affect the pharmacokinetics of imipramine or its active metabolite desipramine. Warfarin — Single doses of olanzapine did not affect the pharmacokinetics of warfarin [see Drug Interactions (7.1) ] . Diazepam — Olanzapine did not influence the pharmacokinetics of diazepam or its active metabolite N-desmethyldiazepam. However, diazepam co-administered with olanzapine increased the orthostatic hypotension observed with either drug given alone [see Drug Interactions (7.1) ] . Alcohol — Multiple doses of olanzapine did not influence the kinetics of ethanol [see Drug Interactions (7.1) ] . Biperiden — Multiple doses of olanzapine did not influence the kinetics of biperiden. Theophylline — Multiple doses of olanzapine did not affect the pharmacokinetics of theophylline or its metabolites.

Uses

Olanzapine is indicated for: - "Acute and maintenance treatment of Schizophrenia" in adults and certain adolescents - "Acute treatment of manic or mixed episodes associated with Bipolar I Disorder," as monotherapy or combined with lithium or valproate, and maintenance monotherapy - "Treatment of depressive episodes associated with Bipolar I disorder" and "treatment resistant depression," both in combination with fluoxetine - Treatment of acute agitation associated with schizophrenia or bipolar mania (injectable formulation)

Dosage forms & strengths

Tablet Tablet, Film Coated Tablet, Orally Disintegrating TABLET, FILM COATED TABLET, ORALLY DISINTEGRATING POWDER TABLET INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION INJECTION, POWDER, FOR SOLUTION

OLANZAPINE 10 mg OLANZAPINE 15 mg OLANZAPINE 2.5 mg OLANZAPINE 20 mg OLANZAPINE 5 mg OLANZAPINE 7.5 mg Olanzapine 10 mg Olanzapine 15 mg Olanzapine 2.5 mg Olanzapine 20 mg Olanzapine 5 mg Olanzapine 7.5 mg Olanzapine\ 10 mg Olanzapine\ 15 mg Olanzapine\ 2.5 mg Olanzapine\ 20 mg Olanzapine\ 5 mg Olanzapine\ 7.5 mg olanzapine 10 mg olanzapine 15 mg olanzapine 2.5 mg olanzapine 20 mg olanzapine 5 mg olanzapine 7.5 mg OLANZAPINE 10 mg/1 OLANZAPINE 5 mg/1 OLANZAPINE 20 mg/1 OLANZAPINE 2.5 mg/1 OLANZAPINE 1 kg/kg OLANZAPINE 15 mg/1 OLANZAPINE 7.5 mg/1 OLANZAPINE 10 mg/2mL OLANZAPINE 100 kg/100kg OLANZAPINE 50 kg/50kg OLANZAPINE 25 kg/25kg

2 DOSAGE AND ADMINISTRATION Schizophrenia in adults ( 2.1 ) Oral: Start at 5 to 10 mg once daily; Target: 10 mg/day within several days Schizophrenia in adolescents ( 2.1 ) Oral: Start at 2.5 to 5 mg once daily; Target: 10 mg/day Bipolar I Disorder (manic or mixed episodes) in adults ( 2.2 ) Oral: Start at 10 or 15 mg once daily Bipolar I Disorder (manic or mixed episodes) in adolescents ( 2.2 ) Oral: Start at 2.5 to 5 mg once daily; Target: 10 mg/day Bipolar I Disorder (manic or mixed episodes) with lithium or valproate in adults ( 2.2 ) Oral: Start at 10 mg once daily Depressive Episodes associated with Bipolar I Disorder in adults ( 2.5 ) Oral in combination with fluoxetine: Start at 5 mg of oral olanzapine and 20 mg of fluoxetine once daily Depressive Episodes associated with Bipolar I Disorder in children and adolescents ( 2.5 ) Oral in combination with fluoxetine: Start at 2.5 mg of oral olanzapine and 20 mg of fluoxetine once daily Treatment Resistant Depression in adults ( 2.6 ) Oral in combination with fluoxetine: Start at 5 mg of oral olanzapine and 20 mg of fluoxetine once daily Lower starting dose recommended in debilitated or pharmacodynamically sensitive patients or patients with predisposition to hypotensive reactions, or with potential for slowed metabolism. (2.1) Olanzapine may be given without regard to meals. (2.1) Olanzapine Orally Disintegrating Tablets and Fluoxetine in Combination: Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability. ( 2.5 , 2.6 ) Olanzapine monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder or treatment resistant depression. ( 2.5 , 2.6 ) Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in adults. ( 2.5 , 2.6 ) Safety of co-administration of doses above 12 mg olanzapine with 50 mg fluoxetine has not been evaluated in children and adolescents ages 10 to 17. ( 2.5 ) 2.1 Schizophrenia Adults Dose Selection — Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 5 to 10 mg initially, with a target dose of 10 mg/day within several days. Further dosage adjustments, if indicated, should generally occur at intervals of not less than 1 week, since steady state for olanzapine would not be achieved for approximately 1 week in the typical patient. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended. 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. Dosing in Special Populations — The recommended starting dose is 5 mg in patients who are debilitated, who have a predisposition to hypotensive reactions, who otherwise exhibit a combination of factors that may result in slower metabolism of olanzapine (e.g., nonsmoking female patients ≥65 years of age), or who may be more pharmacodynamically sensitive to olanzapine [see Warnings and Precautions (5.14) , Drug Interactions (7) , and Clinical Pharmacology (12.3) ] . When indicated, dose escalation should be performed with caution in these patients. Maintenance Treatment — The effectiveness of oral olanzapine, 10 mg/day to 20 mg/day, in maintaining treatment response in schizophrenic patients who had been stable on olanzapine orally disintegrating tablets for approximately 8 weeks and were then followed for relapse has been demonstrated in a placebo-controlled trial [see Clinical Studies (14.1) ] . The healthcare provider who elects to use olanzapine orally disintegrating tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient. Adolescents Dose Selection — Oral olanzapine should be administered on a once-a-day schedule without regard to meals with a recommended starting dose of 2.5 or 5 mg, with a target dose of 10 mg/day. Efficacy in adolescents with schizophrenia was demonstrated based on a flexible dose range of 2.5 to 20 mg/day in clinical trials, with a mean modal dose of 12.5 mg/day (mean dose of 11.1 mg/day). When dosage adjustments are necessary, dose increments/decrements of 2.5 or 5 mg are recommended. The safety and effectiveness of doses above 20 mg/day have not been evaluated in clinical trials [see Clinical Studies (14.1) ]. Maintenance Treatment — The efficacy of olanzapine orally disintegrating tablets for the maintenance treatment of schizophrenia in the adolescent population has not been systematically evaluated; however, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients. Thus, 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. 2.2 Bipolar I Disorder (Manic or Mixed Episodes) Adults Dose Selection for Monotherapy — Oral olanzapine should be administered on a once-a-day schedule without regard to meals, generally beginning with 10 or 15 mg. Dosage adjustments, if indicated, should generally occur at intervals of not less than 24 hours, reflecting the procedures in the placebo-controlled trials. When dosage adjustments are necessary, dose increments/decrements of 5 mg QD are recommended. 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 [see Clinical Studies (14.2) ] . Maintenance Monotherapy — The benefit of maintaining bipolar I patients on monotherapy with olanzapine orally disintegrating tablets at a dose of 5 to 20 mg/day, after achieving a responder status for an average duration of 2 weeks, was demonstrated in a controlled trial [see Clinical Studies (14.2) ] . The healthcare provider who elects to use olanzapine orally disintegrating tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient. Dose Selection for Adjunctive Treatment — When administered as adjunctive treatment to lithium or valproate, oral olanzapine dosing should generally begin with 10 mg once-a-day without regard to meals. Antimanic efficacy was demonstrated in a dose range of 5 mg to 20 mg/day in clinical trials [see Clinical Studies (14.2) ] . The safety of doses above 20 mg/day has not been evaluated in clinical trials. Adolescents Dose Selection — Oral olanzapine should be administered on a once-a-day schedule without regard to meals with a recommended starting dose of 2.5 or 5 mg, with a target dose of 10 mg/day. Efficacy in adolescents with bipolar I disorder (manic or mixed episodes) was demonstrated based on a flexible dose range of 2.5 to 20 mg/day in clinical trials, with a mean modal dose of 10.7 mg/day (mean dose of 8.9 mg/day). When dosage adjustments are necessary, dose increments/decrements of 2.5 or 5 mg are recommended. The safety and effectiveness of doses above 20 mg/day have not been evaluated in clinical trials [see Clinical Studies (14.2) ] . Maintenance Treatment — The efficacy of olanzapine orally disintegrating tablets for the maintenance treatment of bipolar I disorder in the adolescent population has not been evaluated; however, maintenance efficacy can be extrapolated from adult data along with comparisons of olanzapine pharmacokinetic parameters in adult and adolescent patients. Thus, 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. 2.3 Administration of Olanzapine Orally Disintegrating Tablets Peel back foil on blister. Do not push tablet through foil. Immediately upon opening the blister, using dry hands, remove tablet and place entire olanzapine orally disintegrating tablet in the mouth. Tablet disintegration occurs rapidly in saliva so it can be easily swallowed with or without liquid. 2.5 Olanzapine Orally Disintegrating Tablets and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder When using olanzapine orally disintegrating tablets and fluoxetine in combination, also refer to the Clinical Studies section of the package insert for Symbyax. Adults 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 orally disintegrating tablets and fluoxetine in combination in adult patients with a dose range of olanzapine 6 to 12 mg and fluoxetine 25 to 50 mg. Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies. Children and Adolescents (10 to 17 years of age) Oral olanzapine should be administered in combination with fluoxetine once daily in the evening, without regard to meals, generally beginning with 2.5 mg of oral olanzapine and 20 mg of fluoxetine. Dosage adjustments, if indicated, can be made according to efficacy and tolerability. Safety of co-administration of doses above 12 mg olanzapine with 50 mg fluoxetine has not been evaluated in pediatric clinical studies. Safety and efficacy of olanzapine orally disintegrating tablets and fluoxetine in combination was determined in clinical trials supporting approval of Symbyax (fixed dose combination of olanzapine orally disintegrating tablets 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 orally disintegrating tablets and fluoxetine versus Symbyax. Dosage adjustments, if indicated, should be made with the individual components according to efficacy and tolerability. Table 1: Approximate Dose Correspondence Between Symbyax a and the Combination of Olanzapine Orally Disintegrating Tablets and Fluoxetine a Symbyax (olanzapine/fluoxetine hydrochloride) is a fixed-dose combination of olanzapine orally disintegrating tablets and fluoxetine. For Symbyax (mg/day) Use in Combination Olanzapine Orally Disintegrating Tablets (mg/day) Fluoxetine (mg/day) 3 mg olanzapine/25 mg fluoxetine 2.5 20 6 mg olanzapine/25 mg fluoxetine 5 20 12 mg olanzapine/25 mg fluoxetine 10+2.5 20 6 mg olanzapine/50 mg fluoxetine 5 40+10 12 mg olanzapine/50 mg fluoxetine 10+2.5 40+10 While there is no body of evidence to answer the question of how long a patient treated with olanzapine orally disintegrating tablets 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 healthcare provider should periodically reexamine the need for continued pharmacotherapy. Olanzapine orally disintegrating tablets monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder. 2.6 Olanzapine Orally Disintegrating Tablets and Fluoxetine in Combination: Treatment Resistant Depression When using olanzapine orally disintegrating tablets 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 20 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 18 mg and fluoxetine 25 to 50 mg. Safety and efficacy of olanzapine in combination with fluoxetine 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. Table 1 above demonstrates the appropriate individual component doses of olanzapine orally disintegrating tablets 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 orally disintegrating tablets and fluoxetine in combination should remain on it, it is generally accepted that treatment resistant depression (major depressive disorder in adult patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) is a chronic illness requiring chronic treatment. The healthcare provider 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 orally disintegrating tablets monotherapy is not indicated for treatment of treatment resistant depression (major depressive disorder in patients who do not respond to 2 antidepressants of adequate dose and duration in the current episode). 2.7 Olanzapine Orally Disintegrating Tablets and Fluoxetine in Combination: Dosing in Special Populations The starting dose of oral olanzapine 2.5 to 5 mg with fluoxetine 20 mg should be used for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine or fluoxetine in combination (female gender, geriatric age, nonsmoking status), or those patients who may be pharmacodynamically sensitive to olanzapine. Dosing modification may be necessary in patients who exhibit a combination of factors that may slow metabolism. When indicated, dose escalation should be performed with caution in these patients. Olanzapine orally disintegrating tablets and fluoxetine in combination have not been systematically studied in patients over 65 years of age or in patients under 10 years of age [see Warnings and Precautions (5.14) , Drug Interactions (7) , and Clinical Pharmacology (12.3) ] .

All identified pills

APO OLA

WHITE ROUND · Olanzapine

4 manufacturers

APO OLA

WHITE ROUND · Olanzapine

9 manufacturers

APO OLA

WHITE ROUND · Olanzapine

3 manufacturers

Olanzapine

Boxed warning

Warnings

Contraindications

Overdose

Drug interactions

Uses

Dosage forms & strengths

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Side effects

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