What ZYPREXA is used for ? zyprexa dosage in elderly

 

What ZYPREXA is used for

Zyprexa IM olanzapine

 

Consumer Medicine Information

 

What is in this pamphlet

This pamphlet is designed to give you answers to some of the most common questions about this medicine. It does not contain all available information and does not replace speaking with your doctor.

 

The information in this pamphlet was last updated on the date shown on the last page. The latest information about this drug may be available. Be sure to speak with your pharmacist or doctor for the latest information on this medication. You can also download the most recent newsletter from www.lilly.com.au. The revised pamphlet may contain important information about ZYPREXA and its use that you should be aware of.

All medicines have risks and benefits. Your doctor knows more about this medication than is contained in this pamphlet. Also, your doctor has the benefit of taking a complete and detailed history for you and is in the best position to make a professional judgment to meet your individual needs.

 

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

 

Keep this tract with this medicine.

You may need to read it again.

 

What ZYPREXA is used for

ZYPREXA belongs to a group of drugs called antipsychotics. It helps to correct chemical imbalances in the brain, which can lead to mental illness.

 

The ZYPREXA IM injection is used to quickly control agitation and impaired behavior in patients with schizophrenia and related psychoses as well as patients with severe mania associated with Bipolar I Disorder.

 

Schizophrenia is a mental disorder that is characterized by mental, emotional, and behavioral disorders. Bipolar Disorder is a mental illness with symptoms such as “high” feeling, excessive energy, requiring less sleep than usual, rapid talk of impulsive thoughts and sometimes extreme irritability.

 

ZYPREXA IM injection is given when ZYPREXA pill treatment is not appropriate. Your doctor will change your treatment to ZYPREXA pills or ZYPREXA Zydis waffles as soon as possible.

 

Your doctor may prescribe ZYPREXA for another reason.

 

Ask your doctor if you have any questions about why ZYPREXA is prescribed for you.

 

This medicine is only available through a prescription.

 

ZYPREXA is not recommended for use in children under 18 years of age as there is insufficient information on its effects on this age group.

 

Before you are given ZYPREXA

Tell your doctor if you have any of the following conditions or if you have ever had any of these conditions.

 

Where it should not be given

You do not have:

 

if you have ever had an allergy to any form of ZYPREXA or to any of the ingredients listed at the end of this pamphlet (see 'Product Description').

 

Symptoms of allergies may include skin rashes, itching, shortness of breath or swelling of the face, lips or tongue.

 

if the package is torn or shows signs of disruption.

 

when the expiration date in the pocket is over.

 

If you take this medicine after the expiration date you may not work with it.

 

If you are not sure if you should have ZYPREXA, talk to your doctor or pharmacist.

 

Before you have it

Tell your doctor if you have ever had an allergy to any medication you have taken before to treat your current condition.

 

Tell your doctor if you have any medical conditions, especially the following:

 

Tumor pituitary gland

 

anemia with a reduced number of white or red blood cells

 

vascular disease of the brain, including stroke

 

prostate problems

 

kidney or liver disease

 

high blood sugar, diabetes or a family history of diabetes

 

breast cancer or family history with breast cancer

 

deformed leus, a condition in which the small intestine does not function properly

 

epilepsy (epilepsy or paralysis)

 

glaucoma, a condition in which excess fluid builds up in the eye

 

heart disease, which includes abnormal heart rhythm

 

neuroleptic malignant syndrome, drug reactions with sudden rise in body temperature, high blood pressure, and severe convulsions.

 

tardive dyskinesia, a reaction to certain medications by uncontrolled movement or movement of the arms and legs.

 

Tell your doctor if you are pregnant or intend to get pregnant.

 

Like most antipsychotic drugs, ZYPREXA is not recommended for use during pregnancy. If you need to consider ZYPREXA during pregnancy, your doctor will discuss with you the benefits and risks of using it.

 

Tell your doctor if you are breastfeeding or planning to breastfeed.

 

It is recommended that you do not breastfeed while taking ZYPREXA.

 

Tell your doctor if you will be in a hot spot or exercise vigorously.

 

ZYPREXA may make you sweat a little, causing your body to become very hot.

 

Tell your doctor if you smoke.

 

Smoking may affect ZYPREXA or may affect the way it works.

 

Taking other medications

Tell your doctor if you are taking any other medicines, including any other than a prescription at a pharmacy, supermarket or health food store.

 

Some medicines may be affected by ZYPREXA or may affect the way it works. These include:

 

medications used to treat rapid or irregular heartbeat (arrhythmia)

 

Medications for anxiety or sleep apnea

 

oral medication for depression

 

carbamazepine, a drug used to stabilize emotions and treat epilepsy

 

other intermediate drugs (eg tranquillisers)

 

ciprofloxacin, a drug used to treat bacterial infections

 

medications that lower blood pressure

 

drugs used for Parkinson's disease

 

medications that can change the electrical activity of the heart or make it more likely to change.

 

Your doctor or pharmacist has more information about medicines that you should be aware of or avoid while you have ZYPREXA.

 

Tell your doctor about these things before you have ZYPREXA.

 

How to Get ZYPREXA

 

 

What is Zyprexa and how is it used?

Zyprexa is a prescription medicine used to treat the symptoms of schizophrenia and bipolar disorder (manic depression). Zyprexa may be used alone or with other medications.

 

Zyprexa belongs to a class of drugs called Antipsychotics, 2nd Generation, Antimanic Agents.

 

It is not known if Zyprexa is safe and effective in children younger than 13 years of age.

 

What are the possible side effects of Zyprexa?

Zyprexa may cause serious side effects including:

 

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

Ø trouble speaking or swallowing,

Ø swelling in the hands or feet,

Ø confusion,

Ø unusual thoughts or behavior,

Ø hallucinations,

Ø thoughts about hurting yourself,

Ø sudden weakness or ill feeling,

Ø fever,

Ø chills,

Ø sore throat,

Ø swollen gums,

Ø painful mouth sores,

Ø pain when swallowing,

Ø skin sores,

Ø cold or flu symptoms,

Ø cough,

Ø feeling very thirsty or hot,

Ø inability to urinate,

Ø heavy sweating,

Ø hot or dry skin,

Ø upper stomach pain,

Ø itching,

Ø loss of appetite,

Ø dark urine,

Ø clay-colored stools,

Ø yellowing of the skin or eyes (jaundice),

Ø increased thirst,

Ø increased urination,

Ø hunger,

Ø dry mouth,

Ø fruity breath odor,

Ø drowsiness,

Ø blurred vision,

Ø weight loss,

Ø very stiff muscles,

Ø high fever,

Ø confusion,

Ø fast or uneven heartbeats,

Ø tremors, and

Ø lightheadedness

Get medical help right away, if you have any of the symptoms listed above.

 

The most common side effects of Zyprexa include:

 

weight gain (more common in teenagers),

increased appetite,

headaches,

dizziness,

drowsiness,

feeling tired or restless,

problems with speech or memory,

tremors or shaking,

numbness or tingly feeling,

personality changes,

dry mouth,

increased salivation,

stomach pain,

constipation, and

pain in your arms or legs

Tell the doctor if you have any side effect that bothers you or that does not go away.

 

These are not all the possible side effects of 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.

 

WARNING

 

INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

 

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. ZYPREXA (olanzapine) is not approved for the treatment of patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS and PATIENT INFORMATION].

 

When using ZYPREXA and fluoxetine in combination, also refer to the Boxed Warning section of the package insert for Symbyax.

 

DESCRIPTION

ZYPREXA (olanzapine) is an atypical antipsychotic that belongs to the thienobenzodiazepine class. The chemical designation is 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b] [1,5]benzodiazepine. The molecular formula is C17H20N4S, which corresponds to a molecular weight of 312.44. The chemical structure is:

 

ZYPREXA (olanzapine) Structural Formula Illustration

Olanzapine is a yellow crystalline solid, which is practically insoluble in water.

 

ZYPREXA tablets are intended for oral administration only.

 

Each tablet contains olanzapine equivalent to 2.5 mg (8 μmol), 5 mg (16 μmol), 7.5 mg (24 μmol), 10 mg (32 μmol), 15 mg (48 μmol), or 20 mg (64 μmol). Inactive ingredients are carnauba wax, crospovidone, hydroxypropyl cellulose, hypromellose, lactose, magnesium stearate, microcrystalline cellulose, and other inactive ingredients. The color coating contains Titanium Dioxide (all strengths), FD&C Blue No. 2 Aluminum Lake (15 mg), or Synthetic Red Iron Oxide (20 mg). The 2.5, 5, 7.5, and 10 mg tablets are imprinted with edible ink which contains FD&C Blue No. 2 Aluminum Lake.

 

ZYPREXA ZYDIS (olanzapine orally disintegrating tablets) is intended for oral administration only.

 

Each orally disintegrating tablet contains olanzapine equivalent to 5 mg (16 μmol), 10 mg (32 μmol), 15 mg (48 μmol) or 20 mg (64 μmol). It begins disintegrating in the mouth within seconds, allowing its contents to be subsequently swallowed with or without liquid. ZYPREXA ZYDIS (olanzapine orally disintegrating tablets) also contains the following inactive ingredients: gelatin, mannitol, aspartame, sodium methyl paraben, and sodium propyl paraben.

 

ZYPREXA IntraMuscular (olanzapine for injection) is intended for intramuscular use only.

 

Each vial provides for the administration of 10 mg (32 μmol) olanzapine with inactive ingredients 50 mg lactose monohydrate and 3.5 mg tartaric acid. Hydrochloric acid and/or sodium hydroxide may have been added during manufacturing to adjust pH.

 

 

Indications

INDICATIONS

Schizophrenia

Oral ZYPREXA is indicated for the treatment of schizophrenia. Efficacy was established in three clinical trials in adult patients with schizophrenia: two 6-week trials and one maintenance trial. In adolescent patients with schizophrenia (ages 13-17), efficacy was established in one 6-week trial [see Clinical Studies].

 

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].

 

Bipolar I Disorder (Manic or Mixed Episodes)

Monotherapy

Oral ZYPREXA is 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 13-17), efficacy was established in one 3-week trial [see Clinical Studies].

 

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].

 

Adjunctive Therapy To Lithium Or Valproate

Oral ZYPREXA is indicated for the treatment of manic or mixed episodes associated with bipolar I disorder as an adjunct to lithium or valproate. Efficacy was established in two 6-week clinical trials in adults. The effectiveness of adjunctive therapy for longer-term use has not been systematically evaluated in controlled trials [see Clinical Studies].

 

Special Considerations In Treating Pediatric Schizophrenia And Bipolar I Disorder

Pediatric schizophrenia and bipolar I disorder are serious mental disorders; however, diagnosis can be challenging. For pediatric schizophrenia, symptom profiles can be variable, and for bipolar I disorder, pediatric patients may have variable patterns of periodicity of manic or mixed symptoms. It is recommended that medication therapy for pediatric schizophrenia and bipolar I disorder be initiated only after a thorough diagnostic evaluation has been performed and careful consideration given to the risks associated with medication treatment. Medication treatment for both pediatric schizophrenia and bipolar I disorder should be part of a total treatment program that often includes psychological, educational and social interventions.

 

ZYPREXA Intra Muscular: Agitation Associated With Schizophrenia And Bipolar I Mania

ZYPREXA IntraMuscular is indicated for the treatment of acute agitation associated with schizophrenia and bipolar I mania.

 

Efficacy was demonstrated in 3 short-term (24 hours of IM treatment) placebo-controlled trials in agitated adult inpatients with: schizophrenia or bipolar I disorder (manic or mixed episodes) [see Clinical Studies].

 

“Psychomotor agitation” is defined in DSM-IV as “excessive motor activity associated with a feeling of inner tension.” Patients experiencing agitation often manifest behaviors that interfere with their diagnosis and care, e.g., threatening behaviors, escalating or urgently distressing behavior, or self-exhausting behavior, leading clinicians to the use of intramuscular antipsychotic medications to achieve immediate control of the agitation.

 

ZYPREXA And Fluoxetine In Combination: Depressive Episodes Associated With Bipolar I Disorder

Oral ZYPREXA and fluoxetine in combination is indicated for the treatment of depressive episodes associated with bipolar I disorder, based on clinical studies. When using ZYPREXA and fluoxetine in combination, refer to the Clinical Studies section of the package insert for Symbyax.

 

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

 

ZYPREXA And Fluoxetine In Combination: Treatment Resistant Depression

Oral ZYPREXA and fluoxetine in combination is indicated for the treatment of treatment resistant depression (major depressive disorder in patients who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode), based on clinical studies in adult patients. When using ZYPREXA and fluoxetine in combination, refer to the Clinical Studies section of the package insert for Symbyax.

 

ZYPREXA monotherapy is not indicated for the treatment of treatment resistant depression.

 

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, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY]. 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]. The healthcare provider 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].

 

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].

 

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]. The healthcare provider 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]. 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].

 

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 Intra Muscular: 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]. 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]. 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 Schizophrenia and Bipolar I Disorder (Manic or Mixed Episodes)].

 

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, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].

 

Administration Of ZYPREXA Intra Muscular

ZYPREXA Intra Muscular 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.

 

Dose, ma Olanzapine        Volume of Injection, mL

10       Withdraw total contents of vial

7.5      1.5

5          1

2.5      0.5

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.

 

Table 1: Approximate Dose Correspondence Between Symbyaxa and the Combination of ZYPREXA and Fluoxetine

For Symbyax (mg/day)     Use in Combination

ZYPREXA (mg/day)            Fluoxetine (mg/day)

3 mg olanzapine/25 mg fluoxetine       2.5      20

6 mg olanzapine/25 mg fluoxetine       5          20

12 mg olanzapine/25 mg fluoxetine     10+2.5          20

6 mg olanzapine/50 mg fluoxetine       5          40+10

12 mg olanzapine/50 mg fluoxetine     10+2.5          40+10

a Symbyax (olanzapine/fluoxetine HCl) is a fixed-dose combination of ZYPREXA and fluoxetine.

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 healthcare provider 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 healthcare provider should periodically reexamine the need for continued pharmacotherapy.

 

Safety of co-administration of doses above 18 mg olanzapine with 75 mg fluoxetine has not been evaluated in clinical studies.

 

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, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].

 

HOW SUPPLIED

Dosage Forms And Strengths

The ZYPREXA 2.5 mg, 5 mg, 7.5 mg, and 10 mg tablets are white, round, and imprinted in blue ink with LILLY and tablet number. The 15 mg tablets are elliptical, blue, and debossed with LILLY and tablet number. The 20 mg tablets are elliptical, pink, and debossed with LILLY and tablet number. Tablets are not scored. The tablets are available as follows: