Zyprexa

Zyprexa is a prescription medicine used to treat schizophrenia and bipolar disorder. When Zyprexa is combined with Prozac (fluoxetine) it is also used to treat:

• depression that happens with bipolar I (one) disorder
• depression that did not get better after 2 other medications

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Zyprexa 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). Zyprexa 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 Zyprexa and during treatment. In people who do not have diabetes, sometimes high blood sugar goes away when Zyprexa is stopped. People with diabetes and some people who did not have diabetes before taking Zyprexa need to take medicine for high blood sugar even after they stop taking Zyprexa.

If you have diabetes, follow your doctor's instructions about how often to check your blood sugar while taking Zyprexa.

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

• 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 Zyprexa, 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 Zyprexa and during treatment.

4. Weight gain. Weight gain is very common in people who take Zyprexa. 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 Zyprexa, 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.

• Zyprexa 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 Zyprexa affects you.
• Avoid drinking alcohol while taking Zyprexa. Drinking alcohol while you take Zyprexa may make you sleepier than if you take Zyprexa alone.

Zyprexa Intramuscular Injection

• It is recommended patients requiring subsequent intramuscular (IM) injections be assessed for orthostatic hypotension prior to the administration of any subsequent doses of intramuscular Zyprexa for injection.

Before starting Zyprexa, 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

Tell your doctor if you are pregnant or breastfeeding

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 nonprescription medicines, vitamins, and herbal supplements. Zyprexa 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 Zyprexa with your other medicines. Do not start or stop any medicine while taking Zyprexa without talking to your doctor first.

Tell your doctor if you are breastfeeding or plan to breastfeed. Zyprexa may be excreted in human breast milk. It may harm your nursing baby.

If you take too much Zyprexa, call your local Poison Control Center or seek emergency medical attention right away.

Absorption

Bioavailability

Well absorbed after oral administration, with peak plasma concentrations attained in approximately 6 hours (range: 5–8 hours).1 290 About 40% of oral dose is metabolized before reaching systemic circulation.1

Steady-state concentrations achieved after approximately 7 days of continuous oral dosing and are approximately twice those observed following single-dose administration.1 116 290

Exhibits linear and dose-proportional pharmacokinetics when given orally within the clinical dosage range.1 116 143 290

Conventional and orally disintegrating olanzapine tablets are bioequivalent.1 115

Fixed-combination olanzapine/fluoxetine capsules: Pharmacokinetics expected to resemble those of the individual components.312 Olanzapine pharmacokinetics slightly altered, but effects not clinically important.312 (See Specific Drugs under Interactions.)

Short-acting IM olanzapine (Zyprexa IntraMuscular): Rapidly absorbed following IM administration, with peak plasma concentrations occurring within 15–45 minutes.1 382 Peak olanzapine concentrations after 5-mg IM dose average about 5 times higher than those following a 5-mg oral dose.1 AUCs are similar following oral and IM administration.1 Exhibits linear pharmacokinetics when given IM within the clinical dosage range.1 Onset of antipsychotic action evident within 24 hours after IM administration, but may occur within 2 hours.207

Extended-release IM olanzapine (Zyprexa Relprevv): Following deep IM gluteal administration, slow dissolution of the pamoate ester (which is practically insoluble) results in prolonged plasma olanzapine concentrations over a period of weeks to months.382 IM injection every 2 or 4 weeks provides plasma olanzapine concentrations similar to those achieved with daily oral dosing.382 Steady-state olanzapine concentrations achieved with IM dosages of 150–405 mg every 2 or 4 weeks are within the range achieved with oral olanzapine dosages of 5–20 mg daily.382 Plasma concentrations generally reach a peak within the first week following each injection.382

Food

Food does not affect rate or extent of oral absorption.1 290

Distribution

Extent

Extensively distributed throughout the body.1 146 290

Olanzapine and its glucuronide metabolite cross the placenta.114 381 Distributed into milk in humans;1 110 111 112 113 319 mean infant dose at steady state estimated to be about 1.8% of maternal dose.1

Plasma Protein Binding

93% (mainly to albumin and α1-acid glycoprotein).1 139 290

Elimination

Metabolism

Metabolized to inactive metabolites, principally via direct glucuronidation and oxidation via CYP isoenzymes (mainly CYP1A2) and the flavin-containing monooxygenase system, with minor contribution of CYP2D6.1 116

Elimination Route

Excreted in urine (57%) and feces (30%); 7% of dose is excreted in urine as unchanged drug.1

Half-life

Oral administration: 21–54 hours.1 116 139

IM administration of short-acting olanzapine injection: Half-life similar to that observed with oral administration.1

IM administration of extended-release olanzapine pamoate injection: Approximately 30 days.382 Exposure to olanzapine may persist for months after a single long-acting IM injection.382

Special Populations

In patients with severe renal impairment, pharmacokinetics were similar to healthy individuals.1

Not appreciably removed by hemodialysis, probably due to large volume of distribution and extensive protein binding.1 116 119 146

Although hepatic impairment may be expected to reduce clearance, a study in patients with clinically important cirrhosis (Child-Pugh class A and B) revealed little effect on the pharmacokinetics of olanzapine.1

In children and adolescents 10–18 years of age treated with oral olanzapine for schizophrenia, clearance at steady state was approximately half of that in adults but was similar to that reported in nonsmoking male and female schizophrenic patients.1 116 148 290 Elimination half-life averaged 37.2 hours in this study.148

In geriatric patients, the mean elimination half-life of orally administered olanzapine was about 1.5 times that of younger patients.1

In women, clearance of olanzapine is approximately 30% lower than in men; there were no apparent differences between men and women in efficacy or adverse effects.1

In smokers, olanzapine clearance is about 40% higher than in nonsmokers, although dosage adjustment is not recommended.1

Combined effects of age, smoking, and gender may contribute to substantial pharmacokinetic differences in populations.1

Storage

Oral

20–25°C (may be exposed to 15–30°C).1 Store orally disintegrating tablets in their original sealed blister.1 Protect from light and moisture.1

Tight containers at 25°C (may be exposed to 15–30°C).312 Protect from moisture.312

Parenteral

20–25°C (may be exposed to 15–30°C).1 Protect from light and avoid freezing.1

Reconstituted solution may be stored for up to 1 hour at 20–25°C, if necessary; after 1 hour, discard any unused portion.1

Store at room temperature (not to exceed 30°C).382

Reconstituted suspension may be stored for up to 24 hours at room temperature; once withdrawn into syringe for administration, use immediately.382

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Long-acting IM olanzapine pamoate (Zyprexa Relprevv) is available only through a restricted distribution program.382 (See Restricted Distribution under Dosage and Administration.)

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Olanzapine is used to treat nervous, emotional, and mental conditions (eg, schizophrenia). It may also be used alone or with other medicines (eg, lithium or valproate) to treat bipolar disorder (manic-depressive illness) or mania that is part of bipolar disorder. This medicine should not be used to treat behavioral problems in older adult patients who have dementia or Alzheimer's disease.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of olanzapine in children. However, safety and efficacy of olanzapine in children younger than 13 years of age have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of olanzapine in the elderly. However, elderly patients are more likely to have dementia or age-related liver, kidney, or heart problems, which may require caution or an adjustment in the dose for patients receiving olanzapine.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Bromopride
• Cisapride
• Dronedarone
• Levomethadyl
• Mesoridazine
• Metoclopramide
• Pimozide
• Piperaquine
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil
• Amiodarone
• Anagrelide
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Bromazepam
• Buprenorphine
• Buserelin
• Butorphanol
• Carbamazepine
• Clarithromycin
• Clomipramine
• Clozapine
• Codeine
• Crizotinib
• Dabrafenib
• Degarelix
• Delamanid
• Deslorelin
• Deutetrabenazine
• Dihydrocodeine
• Donepezil
• Doxylamine
• Efavirenz
• Escitalopram
• Fentanyl
• Flibanserin
• Fluconazole
• Fluoxetine
• Foscarnet
• Gonadorelin
• Goserelin
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroxychloroquine
• Hydroxyzine
• Ivabradine
• Ketoconazole
• Leuprolide
• Levofloxacin
• Levorphanol
• Lithium
• Meperidine
• Methadone
• Metronidazole
• Milnacipran
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nafarelin
• Nalbuphine
• Ondansetron
• Oxycodone
• Oxymorphone
• Panobinostat
• Pasireotide
• Pazopanib
• Pentazocine
• Periciazine
• Pimavanserin
• Pitolisant
• Pixantrone
• Posaconazole
• Quetiapine
• Remifentanil
• Ribociclib
• Sevoflurane
• Sotalol
• Sufentanil
• Sulpiride
• Tacrolimus
• Tapentadol
• Tetrabenazine
• Tiotropium
• Tramadol
• Triptorelin
• Vandetanib
• Vemurafenib
• Vinflunine
• Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amprenavir
• Betel Nut
• Ciprofloxacin
• Fluvoxamine
• Fosamprenavir
• Haloperidol
• Ritonavir
• Valproic Acid

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood vessel disease or circulation problems or
• Dehydration or
• Heart attack or stroke, history of or
• Heart disease or
• Heart failure or
• Heart rhythm problems or
• Hypotension (low blood pressure) or
• Hypovolemia (low blood volume)—May cause side effects to become worse.

• Breast cancer, prolactin-dependent or
• Glaucoma, narrow-angle or
• Hyperlipidemia (high cholesterol or fat in the blood) or
• Hyperprolactinemia (high prolactin in the blood) or
• Liver disease or
• Paralytic ileus (severe intestinal problem), history of or
• Prostatic hypertrophy (enlarged prostate) or
• Seizures, history of—Use with caution. This medicine may make these conditions worse.

• Diabetes or
• Hyperglycemia (high blood sugar)—Use with caution. This medicine may raise blood sugar levels.

• Phenylketonuria (PKU, a genetic disease of metabolism)—The orally disintegrating tablet (Zyprexa® Zydis®) contains phenylalanine, which can make this condition worse.

• Tell all of your health care providers that you take Zyprexa. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• High blood sugar or diabetes, high cholesterol, and weight gain have happened with drugs like this one. These changes may raise the chance of heart and brain blood vessel disease. Talk with the doctor.
• Tell your doctor if you have signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Avoid drinking alcohol while taking Zyprexa.
• Talk with your doctor before you use other drugs and natural products that slow your actions.
• Dizziness, sleepiness, and feeling less stable may happen with this medicine. These may lead to falling. Broken bones or other health problems can happen from falling. Talk with the doctor.
• A very bad and sometimes deadly reaction has happened with Zyprexa. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
• Some people who take this medicine may get a very bad muscle problem called tardive dyskinesia. This muscle problem may not go away even if Zyprexa is stopped. Sometimes, signs may lessen or go away over time after this medicine is stopped. The risk of tardive dyskinesia may be greater in people with diabetes and in older adults, especially older women. The risk is also greater the longer you take Zyprexa or with higher doses. Muscle problems may also occur after short-term use with low doses. Call your doctor right away if you have trouble controlling body movements or if you have muscle problems with your tongue, face, mouth, or jaw like tongue sticking out, puffing cheeks, mouth puckering, or chewing.
• Older adults with dementia taking drugs like this one have had a higher number of strokes. Sometimes these strokes have been deadly. This drug is not approved to treat mental problems caused by dementia. Talk with your doctor.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Use with care in children. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Zyprexa (olanzapine tablets) while you are pregnant.
• Taking this medicine in the third trimester of pregnancy may lead to muscle movements that cannot be controlled and withdrawal in the newborn. Talk with the doctor.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

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 Zyprexa for approximately 8 weeks and were then followed for relapse has been demonstrated in a placebo-controlled trial [see Clinical Studies (14.1)]. The physician who elects to use Zyprexa 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 Zyprexa 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.

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 (3-4 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 oral Zyprexa 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 physician who elects to use Zyprexa 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 Zyprexa 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.

Administration of Zyprexa ZYDIS (olanzapine orally disintegrating tablets)

After opening sachet, peel back foil on blister. Do not push tablet through foil. Immediately upon opening the blister, using dry hands, remove tablet and place entire Zyprexa ZYDIS in the mouth. Tablet disintegration occurs rapidly in saliva so it can be easily swallowed with or without liquid.

Zyprexa IntraMuscular: Agitation Associated with Schizophrenia and Bipolar I Mania

Dose Selection for Agitated Adult Patients with Schizophrenia and Bipolar I Mania  The efficacy of intramuscular olanzapine for injection in controlling agitation in these disorders was demonstrated in a dose range of 2.5 mg to 10 mg. The recommended dose in these patients is 10 mg. A lower dose of 5 or 7.5 mg may be considered when clinical factors warrant [see Clinical Studies (14.3)]. If agitation warranting additional intramuscular doses persists following the initial dose, subsequent doses up to 10 mg may be given. However, the efficacy of repeated doses of intramuscular olanzapine for injection in agitated patients has not been systematically evaluated in controlled clinical trials. Also, the safety of total daily doses greater than 30 mg, or 10 mg injections given more frequently than 2 hours after the initial dose, and 4 hours after the second dose have not been evaluated in clinical trials. Maximal dosing of intramuscular olanzapine (e.g., 3 doses of 10 mg administered 2-4 hours apart) may be associated with a substantial occurrence of significant orthostatic hypotension [see Warnings and Precautions (5.7)]. Thus, it is recommended that patients requiring subsequent intramuscular injections be assessed for orthostatic hypotension prior to the administration of any subsequent doses of intramuscular olanzapine for injection. The administration of an additional dose to a patient with a clinically significant postural change in systolic blood pressure is not recommended.

If ongoing olanzapine therapy is clinically indicated, oral olanzapine may be initiated in a range of 5-20 mg/day as soon as clinically appropriate [see Dosage and Administration (2.1, 2.2)].

Intramuscular Dosing in Special Populations A dose of 5 mg/injection should be considered for geriatric patients or when other clinical factors warrant. A lower dose of 2.5 mg/injection should be considered for patients who otherwise might be debilitated, be predisposed to hypotensive reactions, or be more pharmacodynamically sensitive to olanzapine [see Warnings and Precautions (5.14), Drug Interactions (7), and Clinical Pharmacology (12.3)].

Administration of Zyprexa IntraMuscular Zyprexa IntraMuscular is intended for intramuscular use only. Do not administer intravenously or subcutaneously. Inject slowly, deep into the muscle mass.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Directions for Preparation of Zyprexa IntraMuscular with Sterile Water for Injection Dissolve the contents of the vial using 2.1 mL of Sterile Water for Injection to provide a solution containing approximately 5 mg/mL of olanzapine. The resulting solution should appear clear and yellow. Zyprexa IntraMuscular reconstituted with Sterile Water for Injection should be used immediately (within 1 hour) after reconstitution. Discard any unused portion.

The following table provides injection volumes for delivering various doses of intramuscular olanzapine for injection reconstituted with Sterile Water for Injection.

Physical Incompatibility Information Zyprexa IntraMuscular should be reconstituted only with Sterile Water for Injection. Zyprexa IntraMuscular should not be combined in a syringe with diazepam injection because precipitation occurs when these products are mixed. Lorazepam injection should not be used to reconstitute Zyprexa IntraMuscular as this combination results in a delayed reconstitution time. Zyprexa IntraMuscular should not be combined in a syringe with haloperidol injection because the resulting low pH has been shown to degrade olanzapine over time.

Zyprexa and Fluoxetine in Combination: Depressive Episodes Associated with Bipolar I Disorder

When using Zyprexa 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 Zyprexa 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 (10-17 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 Zyprexa and fluoxetine in combination was determined in clinical trials supporting approval of Symbyax (fixed dose combination of Zyprexa 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 Zyprexa 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 Zyprexa 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.

Zyprexa monotherapy is not indicated for the treatment of depressive episodes associated with bipolar I disorder.

Zyprexa and Fluoxetine in Combination: Treatment Resistant Depression

When using Zyprexa 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 Zyprexa 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 Zyprexa 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 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.

Zyprexa 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).

Zyprexa and Fluoxetine in Combination: Dosing in Special Populations

The starting dose of oral olanzapine 2.5-5 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. Zyprexa 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)].

See FDA-approved Medication Guide for the oral formulations.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Zyprexa 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 Zyprexa, call your doctor. When using Zyprexa and fluoxetine in combination, also refer to the Patient Counseling Information section of the package insert for Symbyax.

Information on Medication Guide

Prescribers or other health professionals should inform patients, their families, and their caregivers about the potential benefits and potential risks associated with treatment with Zyprexa, and should counsel them in its appropriate use. A patient Medication Guide is available for Zyprexa. 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 Zyprexa and fluoxetine in combination, also refer to the Medication Guide for Symbyax.

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

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

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

Neuroleptic Malignant Syndrome (NMS)

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

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

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

Hyperglycemia and Diabetes Mellitus

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

Dyslipidemia

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

Weight Gain

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

Orthostatic Hypotension

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

Potential for Cognitive and Motor Impairment

Because Zyprexa 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 Zyprexa therapy does not affect them adversely [see Warnings and Precautions (5.12)].

Body Temperature Regulation

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

Concomitant Medication

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

Alcohol

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

Phenylketonurics

Zyprexa ZYDIS (olanzapine orally disintegrating tablets) contains phenylalanine (0.34, 0.45, 0.67, or 0.90 mg per 5, 10, 15, or 20 mg tablet, respectively) [see Description (11)].

Use in Specific Populations

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

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

Pediatric Use Zyprexa is indicated for treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adolescents 13 to 17 years of age. Compared to patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin, and hepatic aminotransferase levels. Patients should be counseled about the potential long-term risks associated with Zyprexa and advised that these risks may lead them to consider other drugs first [see Indications and Usage (1.1, 1.2)]. Safety and effectiveness of Zyprexa in patients under 13 years of age have not been established. Safety and efficacy of Zyprexa and fluoxetine in combination in patients 10 to 17 years of age have been established for the acute treatment of depressive episodes associated with bipolar I disorder. Safety and effectiveness of Zyprexa and fluoxetine in combination in patients <10 years of age have not been established [see Warnings and Precautions (5.5) and Use in Specific Populations (8.4)].

Need for Comprehensive Treatment Program in Pediatric Patients

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

Literature revised January 23, 2017

Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

Copyright © 1997, 2017, Eli Lilly and Company. All rights reserved.

ZYP-0005-USPI-20170123

Medication Guide

Zyprexa® (zy-PREX-a)

(olanzapine)

Tablet

Zyprexa® ZYDIS® (zy-PREX-a ZY-dis)

(olanzapine)

Tablet, Orally Disintegrating

Read the Medication Guide that comes with Zyprexa 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 Zyprexa.

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

Zyprexa may cause serious side effects, including:

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

These serious side effects are described below.

1. Increased risk of death in elderly people who are confused, have memory loss and have lost touch with reality (dementia-related psychosis). Zyprexa 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 Zyprexa and during treatment. In people who do not have diabetes, sometimes high blood sugar goes away when Zyprexa is stopped. People with diabetes and some people who did not have diabetes before taking Zyprexa need to take medicine for high blood sugar even after they stop taking Zyprexa.
   
   If you have diabetes, follow your doctor's instructions about how often to check your blood sugar while taking Zyprexa.
   
   Call your doctor if you have any of these symptoms of high blood sugar (hyperglycemia) while taking Zyprexa:
   • 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 Zyprexa, especially in teenagers (13 to 17 years old), or when used in combination with fluoxetine in children (10 to 17 years old). You may not have any symptoms, so your doctor should do blood tests to check your cholesterol and triglyceride levels before you start taking Zyprexa and during treatment.
4. Weight gain. Weight gain is very common in people who take Zyprexa. Teenagers (13 to 17 years old) are more likely to gain weight and to gain more weight than adults. Children (10 to 17 years old) are also more likely to gain weight and to gain more weight than adults when Zyprexa is used in combination with fluoxetine. Some people may gain a lot of weight while taking Zyprexa, 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 Zyprexa?

Zyprexa is a prescription medicine used to treat:

• schizophrenia in people age 13 or older.
• bipolar disorder, including:
  • manic or mixed episodes that happen with bipolar I disorder in people age 13 or older.
  • manic or mixed episodes that happen with bipolar I disorder, when used with the medicine lithium or valproate, in adults.
  • long-term treatment of bipolar I disorder in adults.
• episodes of depression that happen with bipolar I disorder, when used with the medicine fluoxetine (Prozac®) in people age 10 or older.
• episodes of depression that do not get better after 2 other medicines, also called treatment resistant depression, when used with the medicine fluoxetine (Prozac), in adults.

Zyprexa has not been approved for use in children under 13 years of age. Zyprexa in combination with fluoxetine has not been approved for use in children under 10 years of age.

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

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

The symptoms of treatment resistant depression include decreased mood, decreased interest, increased guilty feelings, decreased energy, decreased concentration, changes in appetite, and suicidal thoughts or behavior.

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

What should I tell my doctor before taking Zyprexa?

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

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

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 nonprescription medicines, vitamins, and herbal supplements. Zyprexa 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 Zyprexa with your other medicines. Do not start or stop any medicine while taking Zyprexa without talking to your doctor first.

How should I take Zyprexa?

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

What should I avoid while taking Zyprexa?

• Zyprexa 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 Zyprexa affects you.
• Avoid drinking alcohol while taking Zyprexa. Drinking alcohol while you take Zyprexa may make you sleepier than if you take Zyprexa alone.

What are the possible side effects of Zyprexa?

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

• See “What is the most important information I should know about Zyprexa?”, 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). Zyprexa 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 Zyprexa. NMS can cause death and must be treated in a hospital. Call your doctor right away if you become severely ill and have any of these symptoms:
  • high fever
  • excessive sweating
  • rigid muscles
  • confusion
  • changes in your breathing, heartbeat, and blood pressure.
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): DRESS can occur with Zyprexa. Features of DRESS may include rash, fever, swollen glands and other internal organ involvement such as liver, kidney, lung and heart. DRESS is sometimes fatal; therefore, tell your doctor immediately if you experience any of these signs.
• Tardive Dyskinesia: This condition causes body movements that keep happening and that you can not control. These movements usually affect the face and tongue. Tardive dyskinesia may not go away, even if you stop taking Zyprexa. It may also start after you stop taking Zyprexa. Tell your doctor if you get any body movements that you can not control.
• Decreased blood pressure when you change positions, with symptoms of dizziness, fast or slow heartbeat, or fainting.
• Difficulty swallowing, that can cause food or liquid to get into your lungs.
• Seizures: Tell your doctor if you have a seizure during treatment with Zyprexa.
• Problems with control of body temperature: You could become very hot, for instance when you exercise a lot or stay in an area that is very hot. It is important for you to drink water to avoid dehydration. Call your doctor right away if you become severely ill and have any of these symptoms of dehydration:
  • sweating too much or not at all
  • dry mouth
  • feeling very hot
  • feeling thirsty
  • not able to produce urine.

Common side effects of Zyprexa 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 (13-17 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 Zyprexa. 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 Zyprexa?

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

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

General information about Zyprexa

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

This Medication Guide summarizes the most important information about Zyprexa. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Zyprexa that was written for healthcare professionals. For more information about Zyprexa call 1-800-Lilly-Rx (1-800-545-5979).

What are the ingredients in Zyprexa?

Active ingredient: olanzapine

Inactive ingredients:

Tablets carnauba wax, crospovidone, hydroxypropyl cellulose, hypromellose, lactose, magnesium stearate, microcrystalline cellulose, and other inactive ingredients. The color coating contains: Titanium Dioxide, FD&C Blue No. 2 Aluminum Lake, or Synthetic Red Iron Oxide.

ZYDIS gelatin, mannitol, aspartame, sodium methyl paraben, and sodium propyl paraben.

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

Medication Guide revised October 6, 2016

Marketed by: Lilly USA, LLC
Indianapolis, IN 46285, USA

Copyright © 2009, 2016, Eli Lilly and Company. All rights reserved.

ZYP-0001-MG-20161006

PACKAGE LABEL - Zyprexa 2.5 mg tablet, bottle of 30

NDC 0002-4112-30

30 Tablets

No. 4112

Zyprexa

Olanzapine Tablets

2.5 mg

Rx only

Medication Guide is to be dispensed to patients.

Lilly

PACKAGE LABEL - Zyprexa 5 mg tablet, bottle of 30

NDC 0002-4115-30

30 Tablets

No. 4115

Zyprexa

Olanzapine Tablets

5 mg

Rx only

Medication Guide is to be dispensed to patients.

Lilly

PACKAGE LABEL - Zyprexa 7.5 mg tablet, bottle of 30

NDC 0002-4116-30

30 Tablets

No. 4116

Zyprexa

Olanzapine Tablets

7.5 mg

Rx only

Medication Guide is to be dispensed to patients.

Lilly

PACKAGE LABEL - Zyprexa 10 mg tablet, bottle of 30

NDC 0002-4117-30

30 Tablets

No. 4117

Zyprexa

Olanzapine Tablets

10 mg

Rx only

Medication Guide is to be dispensed to patients.

Lilly

PACKAGE LABEL - Zyprexa 15 mg tablet, bottle of 30

NDC 0002-4415-30

30 Tablets

No. 4415

Zyprexa

Olanzapine Tablets

15 mg

Rx only

Medication Guide is to be dispensed to patients.

Lilly

PACKAGE LABEL - Zyprexa 20 mg tablet, bottle of 30

NDC 0002-4420-30

30 Tablets

No. 4420

Zyprexa

Olanzapine Tablets

20 mg

Rx only

Medication Guide is to be dispensed to patients.

Lilly

PACKAGE LABEL - Zyprexa ZYDIS 5 mg tablet, 30 sachets

5 mg orally disintegrating tablets

30 Sachets, No. 4453

NDC 0002-4453-85

Rx only

Medication Guide is to be dispensed to patients.

Zyprexa® ZYDIS®

Olanzapine Orally Disintegrating Tablets

5 mg

Phenylketonurics: Contains phenylalanine 0.34 mg per tablet.

DO NOT OPEN POUCH UNTIL IMMEDIATELY PRIOR TO USE.

Lilly

PACKAGE LABEL - Zyprexa ZYDIS 10 mg tablet, 30 sachets

10 mg orally disintegrating tablets

30 Sachets, No. 4454

NDC 0002-4454-85

Rx only

Medication Guide is to be dispensed to patients.

Zyprexa® ZYDIS®

Olanzapine Orally Disintegrating Tablets

10 mg

Phenylketonurics: Contains phenylalanine 0.45 mg per tablet.

DO NOT OPEN POUCH UNTIL IMMEDIATELY PRIOR TO USE.

Lilly

PACKAGE LABEL - Zyprexa ZYDIS 15 mg tablet, 30 sachets

15 mg orally disintegrating tablets

30 Sachets, No. 4455

NDC 0002-4455-85

Rx only

Medication Guide is to be dispensed to patients.

Zyprexa® ZYDIS®

Olanzapine Orally Disintegrating Tablets

15 mg

Phenylketonurics: Contains phenylalanine 0.67 mg per tablet.

DO NOT OPEN POUCH UNTIL IMMEDIATELY PRIOR TO USE.

Lilly

PACKAGE LABEL - Zyprexa ZYDIS 20 mg tablet, 30 sachets

20 mg orally disintegrating tablets

30 Sachets, No. 4456

NDC 0002-4456-85

Rx only

Medication Guide is to be dispensed to patients.

Zyprexa® ZYDIS®

Olanzapine Orally Disintegrating Tablets

20 mg

Phenylketonurics: Contains phenylalanine 0.90 mg per tablet.

DO NOT OPEN POUCH UNTIL IMMEDIATELY PRIOR TO USE.

Lilly

PACKAGE LABEL - Zyprexa INTRAMUSCULAR 10 mg/vial

NDC 0002-7597-01

1 Vial

No. VL7597

Zyprexa® IntraMuscular

Olanzapine for Injection

Sterile Single Use Vial

Rx only

For intramuscular use only.

10 mg/vial

Lilly

Get emergency medical help if you have any signs of an allergic reaction to Zyprexa: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

In rare cases, olanzapine may cause a severe skin reaction that can be fatal if it spreads to other parts of the body. Seek medical treatment if you have a new or worsening skin rash with fever, swollen glands, or swelling in your face.

Call your doctor at once if you have:

• uncontrolled muscle movements in your face (chewing, lip smacking, frowning, tongue movement, blinking or eye movement);

• trouble speaking or swallowing;

• swelling in your hands or feet;

• confusion, unusual thoughts or behavior, hallucinations, or thoughts about hurting yourself;

• sudden weakness or ill feeling, fever, chills, sore throat, swollen gums, painful mouth sores, pain when swallowing, skin sores, cold or flu symptoms, cough;

• signs of dehydration - feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin;

• liver problems - upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• high blood sugar - increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss; or

• severe nervous system reaction - very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, feeling like you might pass out.

Common Zyprexa side effects may include:

• weight gain (more likely in teenagers), increased appetite;

• headache, dizziness, drowsiness, feeling tired or restless;

• problems with speech or memory;

• tremors or shaking, numbness or tingly feeling;

• changes in personality;

• dry mouth, or increased salivation;

• stomach pain, constipation; or

• pain in your arms or legs.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• Report any symptoms of increased thirst, increased urination, increased appetite or weakness to your doctor.
• May be administered with or without food.
• Zyprex Zydis are orally-disintegrating tablets. Open by peeling back the foil on the blister with dry hands (do not push the tablet through foil). Remove and place the entire Zyprexa Zydis tablet on the tongue; disintegration should occur rapidly.
• May cause sedation or impair judgment skills and affect your ability to drive or operate machinery. Avoid alcohol.
• Avoid over-heating and dehydration.
• Seek urgent medical advice if you develop uncontrolled body movements, confusion, high fever, lightheadedness, fainting, seizures, have problems controlling your body temperature, or difficulty swallowing.