Olanzapine

RECENT MAJOR CHANGES SECTION Warnings and Precautions, Tardive Dyskinesia ( 5.6 ) 10/2019 Warnings and Precautions, Use in Patients with Concomitant Illness ( 5.14 ) Removed 4/2020 Warnings and Precautions, Anticholinergic (antimuscarinic) Effects ( 5.14 ) 4/2020

1 INDICATIONS AND USAGE Olanzapine tablets are an atypical antipsychotic indicated: As oral formulation for the: • Treatment of schizophrenia. ( 1.1 ) o Adults: Efficacy was established in three clinical trials in patients with schizophrenia: two 6-week trials and one maintenance trial. ( 14.1 ) o Adolescents (ages 13 to 17): Efficacy was established in one 6-‐ week trial in patients with schizophrenia ( 14.1 ). The increased potential (in adolescents compared with adults) for weight gain and dyslipidemia may lead clinicians to consider prescribing other drugs first in adolescents. ( 1.1 ) • Acute treatment of manic or mixed episodes associated with bipolar I disorder and maintenance treatment of bipolar I disorder. ( 1.2 ) o Adults: Efficacy was established in three clinical trials in patients with manic or mixed episodes of bipolar I disorder: two 3- to 4-week trials and one maintenance trial. ( 14.2 ) o Adolescents (ages 13 to 17): Efficacy was established in one 3‐- week trial in patients with manic or mixed episodes associated with bipolar I disorder ( 14.2 ). The increased potential (in adolescents compared with adults) for weight gain and dyslipidemia may lead clinicians to consider prescribing other drugs first in adolescents. ( 1.2 ) • Medication therapy for pediatric patients with schizophrenia or bipolar I disorder should be undertaken only after a thorough diagnostic evaluation and with careful consideration of the potential risks. ( 1.3 ) • Adjunct to valproate or lithium in the treatment of manic or mixed episodes associated with bipolar I disorder. ( 1.2 ) o Efficacy was established in two 6-week clinical trials in adults ( 14.2 ). Maintenance efficacy has not been systematically evaluated. As Olanzapine tablets and Fluoxetine in Combination for the: • Treatment of depressive episodes associated with bipolar I disorder. ( 1.5 ) o Efficacy was established with Symbyax (olanzapine and fluoxetine in combination); refer to the product label for Symbyax. • Treatment of treatment resistant depression. ( 1.6 ) • Efficacy was established with Symbyax (olanzapine and fluoxetine in combination) in adults; refer to the product label for Symbyax. 1.1 Schizophrenia Oral olanzapine 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 )]. 1.2 Bipolar I Disorder (Manic or Mixed Episodes) Monotherapy — Oral olanzapine 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 )]. …

2 DOSAGE & ADMINISTRATION Schizophrenia in adults ( 2.1 ) Oral: Start at 5‐10 mg once daily; Target: 10 mg/day within several days Schizophrenia in adolescents ( 2.1 ) Oral: Start at 2.5‐5 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 2.5-5 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 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 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 for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient. Adolescents …

3 DOSAGE FORMS & STRENGTHS Olanzapine Tablets USP, 2.5 mg are white to off white coloured, round shaped, biconvex, film coated tablets debossed 'CL' on one side and '39' on other side. Olanzapine Tablets USP, 5 mg are white to off white coloured, round shaped, biconvex, film coated tablets debossed 'CL 40' on one side, and plain on other side. Olanzapine Tablets USP, 7.5 mg are white to off white coloured, round shaped, biconvex, film coated tablets debossed 'CL 41' on one side and plain on other side. Olanzapine Tablets USP, 10 mg are white to off white coloured, round shaped, biconvex, film coated tablets debossed 'CL 42' on one side and plain on other side. Olanzapine Tablets USP, 15 mg are blue coloured, oval shaped biconvex film coated tablets having 'CL 43' debossed on one side and plain on other side. Olanzapine Tablets USP, 20 mg are pink coloured, oval shaped biconvex film coated tablets having 'CL 44' debossed on one side and plain on other side. The tablets are available as follows: Tablets are not scored. TABLET STRENGTH 2.5 mg 5 mg 7.5 mg 10 mg 15 mg 20 mg Identification CL CL CL CL CL CL 39 40 41 42 43 44 Tablets (not scored): 2.5, 5, 7.5, 10, 15, 20 mg. ( 3 )

4 CONTRAINDICATIONS • None with olanzapine tablets monotherapy. • When using olanzapine 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 tablets monotherapy. • When using olanzapine tablets and fluoxetine in combination, also refer to the Contraindications section of the package insert for Symbyax ® . ( 4 ) • When using olanzapine tablets in combination with lithium or valproate, refer to the Contraindications section of the package inserts for those products. ( 4 )

6 ADVERSE REACTIONS When using olanzapine tablets and fluoxetine in combination, also refer to the Adverse Reactions section of the package insert for Symbyax ® . Most common adverse reactions (≥5% and at least twice that for placebo) associated with: Oral Olanzapine Monotherapy: • Schizophrenia (Adults) – postural hypotension, constipation, weight gain, dizziness, personality disorder, akathisia ( 6.1 ) • Schizophrenia (Adolescents) – sedation, weight increased, headache, increased appetite, dizziness, abdominal pain, pain in extremity, fatigue, dry mouth ( 6.1 ) • Manic or Mixed Episodes, Bipolar I Disorder (Adults) – asthenia, dry mouth, constipation, increased appetite, somnolence, dizziness, tremor ( 6.1 ) • Manic or Mixed Episodes, Bipolar I Disorder (Adolescents) – sedation, weight increased, increased appetite, headache, fatigue, dizziness, dry mouth, abdominal pain, pain in extremity ( 6.1 ) Combination of Olanzapine Tablets and Lithium or Valproate: • Manic or Mixed Episodes, Bipolar I Disorder (Adults) – dry mouth, weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, paresthesia ( 6.1 ) Olanzapine tablets and Fluoxetine in Combination: Also refer to the Adverse Reactions section of the package insert for Symbyax ® . ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-667-4708 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience 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 ha …

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 tablets 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 tablets 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 tablets 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. Antihype …

8 USE IN SPECIFIC POPULATIONS When using olanazapine and fluoxetine in combination, also refer to the Use in Specific Populations section of the package insert for Symbyax. • Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 ) · Pediatric Use: Safety and effectiveness of olanzapine in children <13 years of age have not been established. Safety and effectiveness of olanzapine and fluoxetine in combination in children <10 years of age have not been established. ( 8.4 ). 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including olanzapine, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-researchprograms/ pregnancyregistry/. Risk Summary Neonates exposed to antipsychotic drugs, including olanzapine, during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery (see Clinical Considerations). Overall available data from published epidemiologic studies of pregnant women exposed to olanzapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data ). There are risks to the mother associated with untreated schizophrenia or bipolar I disorder and with exposure to antipsychotics, including olanzapine, during pregnancy (see Clinical Considerations). Olanzapine was not teratogenic when administered orally to pregnant rats and rabbits at doses that are 9- and 30-times the daily oral maximum recommended human dose (MRHD), based on mg/m2 body surface area; some fetal toxicities were observed at these doses (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk There is a risk to the mother from untreated schizophrenia or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide. Schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is a direct result of the illness or other comorbid factors. Fetal/Neonatal adverse reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs, including olanzapine, during the third trimester of pregnancy. These symptoms have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Data Human Data Placental passage has been reported in published study reports; however, the placental passage ratio was highly variable ranging between 7% to 167% at birth following exposure during pregnancy. The clinical relevance of this finding is unknown. Published data from observational studies, birth registries, and case reports that have evaluated the use of atypical antipsychotics during pregnancy do not establish an increased risk of major birth defects. A retrospective cohort study from a Medicaid database of 9258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. Animal Data In oral reproduction studies in rats at doses up to 18 mg/kg/day and in r …

12.1 Mechanism of Action The mechanism of action of olanzapine, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that this drug's efficacy in schizophrenia is mediated through a combination of dopamine and serotonin type 2 (5HT 2 ) antagonism. The mechanism of action of olanzapine in the treatment of acute manic or mixed episodes associated with bipolar I disorder is unknown.

11 DESCRIPTION Olanzapine is an atypical antipsychotic that belongs to the thienobenzodiazepine class. The chemical designation is 2-methyl-4-(4-methyl-1-piperazinyl)-10 H -thieno[2,3- b ] [1,5]benzodiazepine. The molecular formula is C 17 H 20 N 4 S, which corresponds to a molecular weight of 312.43. The chemical structure is: Olanzapine is a yellow powder. Olanzapine tablets, USP are intended for oral administration only. Each tablet contains olanzapine equivalent to 2.5 mg (8 mcmol), 5 mg (16 mcmol), 7.5 mg (24 mcmol), 10 mg (32 mcmol), 15 mg (48 mcmol), or 20 mg (64 mcmol). Inactive ingredients are lactose, magnesium stearate, microcrystalline cellulose, starch. The color coating contains FD&C blue No.2 aluminum lake (15 mg), ferric oxide red (20 mg), ferric oxide yellow (20 mg), hydroxypropyl cellulose, hypromellose, polyethylene glycol and titanium dioxide (all strengths). FDA approved UV identification test differs from USP infrared identification test. structure

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. Reports have been received 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 For current information on the management of olanzapine overdose, contact a certified poison control center (1-800-222-1222 or www.poison.org). 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 Cmax 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.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Olanzapine tablets, USP 2.5 mg are white, round, biconvex film-coated tablets, engraved “APO” on one side, “OLA” over “2.5” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3110-3) Bottles of 1,000s (NDC 60505-3110-8) Blisters of 100 Unit Dose (NDC 60505-3110-0) Olanzapine tablets, USP 5 mg are white, round, biconvex film-coated tablets, engraved “APO” on one side, “OLA” over “5” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3111-3) Bottles of 1,000s (NDC 60505-3111-8) Blisters of 100 Unit Dose (NDC 60505-3111-0) Olanzapine tablets, USP 7.5 mg are white, round, biconvex film-coated tablets, engraved “APO” on one side, “OLA” over “7.5” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3112-3) Bottles of 1,000s (NDC 60505-3112-8) Blisters of 100 Unit Dose (NDC 60505-3112-0) Olanzapine tablets, USP 10 mg are white, round, biconvex film-coated tablets, engraved “APO” on one side, “OLA” over “10” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3113-3) Bottles of 1,000s (NDC 60505-3113-8) Blisters of 100 Unit Dose (NDC 60505-3113-0) Olanzapine tablets, USP 15 mg are light blue, elliptical, biconvex film-coated tablets, engraved “APO” on one side, “OLA 15” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3114-3) Bottles of 1,000s (NDC 60505-3114-8) Blisters of 100 Unit Dose (NDC 60505-3114-0) Olanzapine tablets, USP 20 mg are light pink, elliptical, biconvex film-coated tablets, engraved “APO” on one side, “OLA 20” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3140-3) Bottles of 1,000s (NDC 60505-3140-8) Blisters of 100 Unit Dose (NDC 60505-3140-0) 16.2 Storage and Handling Store olanzapine tablets at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect olanzapine tablets from light and moisture.

16.1 How Supplied Olanzapine tablets, USP 2.5 mg are white, round, biconvex film-coated tablets, engraved “APO” on one side, “OLA” over “2.5” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3110-3) Bottles of 1,000s (NDC 60505-3110-8) Blisters of 100 Unit Dose (NDC 60505-3110-0) Olanzapine tablets, USP 5 mg are white, round, biconvex film-coated tablets, engraved “APO” on one side, “OLA” over “5” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3111-3) Bottles of 1,000s (NDC 60505-3111-8) Blisters of 100 Unit Dose (NDC 60505-3111-0) Olanzapine tablets, USP 7.5 mg are white, round, biconvex film-coated tablets, engraved “APO” on one side, “OLA” over “7.5” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3112-3) Bottles of 1,000s (NDC 60505-3112-8) Blisters of 100 Unit Dose (NDC 60505-3112-0) Olanzapine tablets, USP 10 mg are white, round, biconvex film-coated tablets, engraved “APO” on one side, “OLA” over “10” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3113-3) Bottles of 1,000s (NDC 60505-3113-8) Blisters of 100 Unit Dose (NDC 60505-3113-0) Olanzapine tablets, USP 15 mg are light blue, elliptical, biconvex film-coated tablets, engraved “APO” on one side, “OLA 15” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3114-3) Bottles of 1,000s (NDC 60505-3114-8) Blisters of 100 Unit Dose (NDC 60505-3114-0) Olanzapine tablets, USP 20 mg are light pink, elliptical, biconvex film-coated tablets, engraved “APO” on one side, “OLA 20” on the other side. They are supplied as follows: Bottles of 30s (NDC 60505-3140-3) Bottles of 1,000s (NDC 60505-3140-8) Blisters of 100 Unit Dose (NDC 60505-3140-0)