Olanzapine: Package Insert and Label Information (Page 7 of 8)

14.2 Bipolar I Disorder (Manic or Mixed Episodes)

Adults

Monotherapy

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

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

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

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

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

Adjunct to Lithium or Valproate

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

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

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Olanzapine Tablets USP, 7.5 mg are available as off-white, round, unscored, film-coated tablets, debossed with “TEVA” on one side and “5769” on the other side, containing 7.5 mg olanzapine, and packaged in bottles of 30, 100 and 1000 tablets.

16.2 Storage and Handling

Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

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 FROM LIGHT AND MOISTURE

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

17 PATIENT COUNSELING INFORMATION

See the FDA-approved Medication Guide for the oral formulations.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking olanzapine. 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 olanzapine and fluoxetine in combination.

17.1 Information on Medication Guide

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

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

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

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

17.3 Neuroleptic Malignant Syndrome (NMS)

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

17.4 Hyperglycemia

Patients should be advised of the potential risk of hyperglycemia-related adverse reactions. Patients should be monitored regularly for worsening of glucose control. Patients who have diabetes should follow their doctor’s instructions about how often to check their blood sugar while taking olanzapine [see Warnings and Precautions (5.4) ].

17.5 Hyperlipidemia

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

17.6 Weight Gain

Patients should be counseled that weight gain has occurred during treatment with olanzapine. Patients should have their weight monitored regularly [see Warnings and Precautions (5.6) ].

17.7 Orthostatic Hypotension

Patients should be advised of the risk of orthostatic hypotension, especially during the period of initial dose titration and in association with the use of concomitant drugs that may potentiate the orthostatic effect of olanzapine, e.g., diazepam or alcohol [see Warnings and Precautions (5.8) and Drug Interactions (7)]. Patients should be advised to change positions carefully to help prevent orthostatic hypotension, and to lie down if they feel dizzy or faint, until they feel better. Patients should be advised to call their doctor if they experience any of the following signs and symptoms associated with orthostatic hypotension: dizziness, fast or slow heart beat, or fainting.

17.8 Potential for Cognitive and Motor Impairment

Because olanzapine has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that olanzapine therapy does not affect them adversely [see Warnings and Precautions (5.12) ].

17.9 Body Temperature Regulation

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

17.10 Concomitant Medication

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

17.11 Alcohol

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

17.13 Use in Specific Populations

Pregnancy

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

Nursing Mothers

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

Pediatric Use

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 transaminase levels. Safety and effectiveness of olanzapine in patients under 13 years of age have not been established. Safety and effectiveness of olanzapine and fluoxetine in combination in patients < 18 years of age have not been established [see Warnings and Precautions (5.5, 5.6) and Use in Specific Populations (8.4)].

Pediatric use information in pediatric patients with schizophrenia and bipolar I 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.

17.14 Need for Comprehensive Treatment Program in Pediatric Patients

Pediatric use information in pediatric patients with schizophrenia and bipolar I 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.

Manufactured By:

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Rev. C 10/2011

Repackaged by:

REBEL DISTRIBUTORS CORP.

Thousand Oaks, CA 91320

Medication guide

Olanzapine Tablets USP

Read the Medication Guide that comes with olanzapine 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.

What is the most important information I should know about olanzapine?

Olanzapine may cause serious side effects, including:

1. Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis).

2. High blood sugar (hyperglycemia).

3. High fat levels in your blood (increased cholesterol and triglycerides), especially in teenagers age 13 to 17.

4. Weight gain, especially in teenagers age 13 to 17.

These serious side effects are described below.

1. Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis). Olanzapine is not approved for treating psychosis in elderly people with dementia.

2. High blood sugar (hyperglycemia). High blood sugar can happen if you have diabetes already or if you have never had diabetes. High blood sugar could lead to:

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

Your doctor should do tests to check your blood sugar before you start taking olanzapine 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.

Call your doctor if you have any of these symptoms of high blood sugar (hyperglycemia) while taking olanzapine:

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

3. High fat levels in your blood (cholesterol and triglycerides). High fat levels may happen in people treated with olanzapine, especially in teenagers (13 to 17 years old). You may not have any symptoms, so your doctor should do blood tests to check your cholesterol and triglyceride levels before you start taking olanzapine and during treatment.

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

What is olanzapine?

Olanzapine is a prescription medicine used to treat:

• schizophrenia.

• bipolar disorder, including:

• • manic or mixed episodes that happen with bipolar I disorder.
  • manic or mixed episodes that happen with bipolar I disorder, when used with the medicine lithium or valproate, in adults.
  • long-term treatment of bipolar I disorder in adults.
• episodes of depression that happen with bipolar I disorder, when used with the medicine fluoxetine, in adults.

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.

Pediatric use information is approved for Eli Lilly and Company’s olanzapine drug listing product labeling. However, due to Eli Lilly and Company’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

What should I tell my doctor before taking olanzapine?

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

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

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

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

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

How should I take olanzapine?

• Take olanzapine exactly as prescribed. Your doctor may need to change (adjust) the dose of olanzapine until it is right for you.

• If you miss a dose of olanzapine, take the missed dose as soon as you remember. If it is almost time for the next dose, just skip the missed dose and take your next dose at the regular time. Do not take two doses of olanzapine at the same time.
• To prevent serious side effects, do not stop taking olanzapine suddenly. If you need to stop taking olanzapine, your doctor can tell you how to safely stop taking it.
• If you take too much olanzapine, call your doctor or poison control center right away at 1-800-222-1222, or get emergency treatment.
• Olanzapine can be taken with or without food.
• Olanzapine is usually taken one time each day.
• Call your doctor if you do not think you are getting better or have any concerns about your condition while taking olanzapine.

What should I avoid while taking olanzapine?

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

What are the possible side effects of olanzapine?

Serious side effects may happen when you take olanzapine, including:

• See “What is the most important information I should know about olanzapine?”, which describes the increased risk of death in elderly people with dementia-related psychosis and the risks of high blood sugar, high cholesterol and triglyceride levels, and weight gain.

• Increased incidence of stroke or “mini-strokes” called transient ischemic attacks (TIAs) in elderly people with dementia-related psychosis (elderly people who have lost touch with reality due to confusion and memory loss). Olanzapine is not approved for these patients.

• Neuroleptic Malignant Syndrome (NMS): NMS is a rare but very serious condition that can happen in people who take antipsychotic medicines, including olanzapine. NMS can cause death and must be treated in a hospital. Call your doctor right away if you become severely ill and have any of these symptoms:
  • high fever
  • excessive sweating
  • rigid muscles
  • confusion
  • changes in your breathing, heartbeat, and blood pressure
• Tardive Dyskinesia: This condition causes body movements that keep happening and that you cannot control. These movements usually affect the face and tongue. Tardive dyskinesia may not go away, even if you stop taking olanzapine. It may also start after you stop taking olanzapine. Tell your doctor if you get any body movements that you cannot control.

• Decreased blood pressure when you change positions, with symptoms of dizziness, fast or slow heart beat, or fainting.

• Difficulty swallowing, that can cause food or liquid to get into your lungs.
• Seizures: Tell your doctor if you have a seizure during treatment with olanzapine.
• Problems with control of body temperature: You could become very hot, for instance when you exercise a lot or stay in an area that is very hot. It is important for you to drink water to avoid dehydration. Call your doctor right away if you become severely ill and have some or all of these symptoms of dehydration:
  • sweating too much or not at all
  • dry mouth
  • feeling very hot
  • feeling thirsty
  • not able to produce urine

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

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

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

These are not all the possible side effects with olanzapine. For more information, ask your doctor or pharmacist.

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

How should I store olanzapine?

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

Keep olanzapine and all medicines out of the reach of children.

General information about olanzapine

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. 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 call Teva Pharmaceuticals Medical Affairs at 1-888-838-2872.

What are the ingredients in olanzapine tablets USP?

Active ingredient: olanzapine USP

Inactive ingredients: anhydrous lactose, carrageenan, crospovidone, magnesium stearate, microcrystalline cellulose, and polyethylene glycol. In addition, the 2.5 mg, 5 mg, 7.5 mg and 10 mg tablets contain titanium dioxide, and the 15 mg tablets contain FD&C blue #2 aluminum lake.

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

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Rev. A 9/2011

Repackaged by:

REBEL DISTRIBUTORS CORP.

Thousand Oaks, CA 91320