Important Safety Information for SYMBYAX®
(olanzapine and fluoxetine HCI)

Information for Patients About SYMBYAX

Please read this information carefully before you start taking SYMBYAX (SIM-bee-ax) and each time your prescription is refilled in case anything has changed or new information has become available. This information is not meant to take the place of discussions with your doctor. Talk with your doctor, pharmacist, or other healthcare provider if there is something you do not understand or if you want to learn more about SYMBYAX. Do not change or stop treatment without first talking with your doctor. Always follow your healthcare provider's instructions for taking SYMBYAX.

What is SYMBYAX?

SYMBYAX is a prescription medicine that is proven effective for treating the symptoms of bipolar depression. SYMBYAX contains two medicines, olanzapine and fluoxetine hydrochloride. Olanzapine is also the active ingredient in Zyprexa® and Zyprexa® Zydis®. Fluoxetine hydrochloride is also the active ingredient in Prozac®, Prozac Weekly™, and Sarafem®.

What is bipolar disorder?

Bipolar disorder, once called manic-depressive illness, is a brain disorder that causes unusual changes in a person's mood, energy level, and ability to function. Bipolar disorder is a long-term illness that can be treated with medicines, but it usually requires lifelong treatment. Bipolar depression can be associated with periods when symptoms can worsen or thoughts of suicide can emerge. Patients and their families should watch for these as well as for anxiety, agitation, panic, difficulty sleeping, irritability, hostility, aggressiveness, impulsivity, restlessness, or overexcitement and hyperactivity. Call your doctor if any of these symptoms are severe or occur suddenly.

Who should not take SYMBYAX?

You should not take SYMBYAX if you are:

Taking a medicine known as a monoamine oxidase inhibitor (MAOI) or have stopped taking an MAOI within the last 2 weeks. An MAOI is a medicine sometimes used for depression and other mental problems. Examples of MAOI medicines are Nardil® (phenelzine sulfate) and Parnate® (tranylcypromine sulfate). Taking SYMBYAX with an MAOI may cause serious side effects that can be life - threatening. Do not take an MAOI for at least 5 weeks after you stop taking SYMBYAX.
Taking Mellaril® (thioridazine) for mental problems. Mellaril® (thioridazine) can cause a heart problem that can cause death. Taking SYMBYAX with Mellaril® (thioridazine) can increase your chances of having this serious and life-threatening heart problem. Do not take Mellaril® (thioridazine) for at least 5 weeks after you stop taking SYMBYAX.
Taking a type of antipsychotic medicine known as Orap® (pimozide).
Allergic to SYMBYAX or any of its ingredients. The active ingredients are olanzapine and fluoxetine hydrochloride.

Suicidality and Antidepressant drugs—In clinical studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults with depression and other psychiatric disorders. Anyone considering the use of SYMBYAX or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely. Families and caregivers should discuss with the doctor any observation of worsening depression symptoms, suicidal thinking and behavior, or unusual changes in behavior. SYMBYAX is not approved for use in pediatric patients.

Increased Risk of Death in Elderly Patients with Dementia-Related Psychosis—Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks) in these patients revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-controlled 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 (eg, heart failure or sudden death) or infectious (eg, pneumonia) in nature. SYMBYAX is not approved for the treatment of elderly patients with dementia-related psychosis.

What should I tell my doctor and/or pharmacist before taking SYMBYAX?

Tell your doctor if you are older than age 65 and have a mental problem called dementia.
Tell your doctor if you are taking fluoxetine, Prozac, Prozac Weekly, Sarafem, olanzapine, Zyprexa, or Zyprexa Zydis. These medicines each contain an active ingredient that is also found in SYMBYAX.
Tell your doctor about all the nonprescription and prescription medicines you are taking, including those for migraine to avoid a potentially life-threatening condition. Also, tell your doctor about any vitamins or herbal supplements you take. Your doctor will decide if you can take SYMBYAX with your other medicines, or if your dose should be adjusted. Keep a list of your medicines with you and show it to your doctor and pharmacist every time you are prescribed a new medicine or start a new nonprescription medicine, vitamin, or herbal supplement.
Tell your doctor if you are taking SYMBYAX and are taking or plan to take nonsteroidal anti-inflammatory drugs(NSAIDs), aspirin or blood thinners, since combined use of these drug products has been associated with an increased risk of bleeding. Before taking SYMBYAX, tell your doctor if you have or have had the following medical conditions:

Are pregnant or plan to become pregnant. It is not known if SYMBYAX can harm your unborn baby. You and your doctor should decide if SYMBYAX is right for you during pregnancy.
Are breast-feeding or plan to breast-feed. SYMBYAX may pass into your milk and may harm your baby. You should choose either to breast-feed or take SYMBYAX, but not both.
High blood sugar, diabetes, or family history of diabetes
Liver problems. You may need a lower dose of SYMBYAX.
Seizures (convulsions or fits)
Low blood pressure. SYMBYAX may cause dizziness or fainting in people with low blood pressure.
Heart problems including heart attacks
Strokes, or mini-strokes called transient ischemic attacks (TIA)
High blood pressure
An enlarged prostate (men)
An eye problem called narrow angle glaucoma
A stomach problem called a paralytic ileus

Also, tell your doctor if you

Currently smoke
Drink alcohol, especially if you drink a lot
Exercise a lot or are often in hot places

How should I take SYMBYAX?

Take SYMBYAX exactly as instructed by your doctor. Your doctor will usually start you on a low dose of SYMBYAX. Your dose may be adjusted depending on your body's response to SYMBYAX. Your dose will also depend on certain medical problems you have. Do not stop taking SYMBYAX or change your dose even if you feel better, without talking with your doctor.
SYMBYAX is usually taken once a day in the evening. Take SYMBYAX at the same time each day. SYMBYAX may be taken with or without food.
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only your regularly scheduled dose. Do not take more than your doctor has prescribed for you.
Tell your doctor if your depression does not get better while taking SYMBYAX. Your doctor may adjust your dose or give you a different medicine.
If you take too much SYMBYAX or overdose, call your doctor or poison control center right away, or go to the nearest emergency room.

What should I avoid while taking SYMBYAX?

Do not drive or operate other dangerous machinery until you know how SYMBYAX affects you. SYMBYAX can impair your judgment, thinking, and motor skills.
Do not take medicines, including prescription and nonprescription medicines, vitamins, and herbal supplements unless you have talked to your doctor about them.
Do not get pregnant.
Do not breast-feed.
Do not drink alcohol.
Do not get overheated or dehydrated (loss of body fluids) during hot weather or exercise, or when using a hot tub.
Do not take an MAOI medicine or Mellaril (thioridazine) for at least 5 weeks after you stop taking SYMBYAX.
Do not take with Orap® (pimozide)

What are the possible side effects of SYMBYAX?

Like all medicines, SYMBYAX can cause side effects. Tell your doctor about any side effect that bothers you or won't go away. Common side effects of SYMBYAX are:

Weight gain
Sleepiness
Diarrhea
Dry mouth
Increased appetite
Feeling weak
Swelling of your hands and feet
Tremors (shakes)
Sore throat
Trouble concentrating
SYMBYAX can cause problems in keeping your body temperature regulated

Serious side effects reported by patients treated with SYMBYAX included:

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. SYMBYAX is not approved for the treatment of patients with dementia-related psychosis.
Strokes and "mini-strokes" called transient ischemic attacks (TIAs). These are more common in elderly patients with dementia. As with other mental health drugs, SYMBYAX should be used with caution in elderly patients with dementia. SYMBYAX is not approved for the treatment of elderly patients with dementia.
Severe allergic reactions that cause hives, swelling of your face, eyes, mouth, or tongue, trouble breathing, or a rash with fever and joint pain. Tell your doctor right away if you get these symptoms. Your doctor may stop SYMBYAX and prescribe medicines to treat your allergic reaction.
High blood sugar. People taking SYMBYAX should be monitored regularly for signs of high blood sugar. People who are at risk for getting diabetes should have a fasting blood sugar test at the beginning of treatment with SYMBYAX and regularly during treatment. You may be at risk for diabetes if you are overweight, have a family history of diabetes, or get little exercise. A fasting blood sugar test is done after you have not had anything to eat or drink for 6 hours.

Everyone taking SYMBYAX should be aware of the signs of high blood sugar. These signs include:

Being very thirsty
Needing to urinate more than you usually do
Feeling very hungry
Feeling weak or tired

High lipid levels (fats in the blood). People taking SYMBYAX should have lipid level tests, including triglyceride and cholesterol levels, at the beginning of treatment and have follow-up tests during treatment.
Weight gain. People taking SYMBYAX may gain weight and should have their weight checked regularly while taking SYMBYAX.
Neuroleptic malignant syndrome (NMS). This is a rare, but life-threatening reaction to certain medicines for mental problems, including SYMBYAX. Stop taking SYMBYAX and call your doctor right away if you get any of the following symptoms of NMS, such as a high fever, sweating, muscle stiffness, trouble thinking clearly, a change in mental functioning, sleepiness, or changes in your breathing, heartbeat, and blood pressure. NMS can cause death and must be treated in a hospital.
Tardive dyskinesia. This is a condition caused by certain medicines for mental problems, including SYMBYAX. It causes body movements, mostly in your face or tongue, that keep happening and that you cannot control. It may start after you stop taking SYMBYAX. Tardive dyskinesia may not go away, even if you stop taking SYMBYAX. Tell your doctor if you get body movements that you can't control.
Low blood pressure. SYMBYAX may cause low blood pressure in some patients. Low blood pressure is more likely in patients who have heart problems, who have brain problems such as strokes, who take certain medicines, or who drink alcohol. Signs of low blood pressure include dizziness, fast heartbeat, and fainting. To lower your chances of fainting while taking SYMBYAX, stand up slowly if you have been sitting or lying down.
Seizures. SYMBYAX should be used cautiously in people who have had seizures in the past or who have conditions that increase their risk for seizures.
Impaired judgment, thinking, and motor skills
Trouble swallowing
Abnormal bleeding. When SYMBYAX is used alone, and especially with certain other medicines that can increase bleeding risk (for example; ibuprofen, aspirin or blood thinners), your risk of bleeding can increase. If you notice increased or unusual bruising or other bleeding, contact your doctor.
Low salt levels in the blood. SYMBYAX can cause a low salt level in the blood. Weakness, confusion, or trouble thinking can be caused by low salt levels in the blood. If you develop any of these symptoms, contact your doctor.
Body temperature problems. SYMBYAX can cause problems in keeping your body temperature regular. Do not become overheated or dehydrated during hot weather or exercise, or when using a hot tub.

This is not a complete list of possible side effects. If you have questions or develop any side effects that concern you, talk to your doctor and/or pharmacist.

What happens when I stop taking SYMBYAX?

SYMBYAX should not be stopped suddenly, since that may result in symptoms like dizziness, nausea, or headache. Talk with your doctor before stopping SYMBYAX as he or she may wish to decrease the dose slowly to help you avoid these kinds of symptoms.

Other important safety information about SYMBYAX

The symptoms of bipolar disorder may include thoughts of harming yourself or others or committing suicide. Tell your doctor immediately or go to an emergency center if you have any of these thoughts.
Symptoms of bipolar disorder may include mania. If you experience manic symptoms (for example; racing thoughts, poor sleep, irritability, mood swings, extra energy), contact your doctor.
If your depression becomes worse, contact your doctor.
Rarely, people taking medicines of this type have started to leak milk from their breasts, and women have missed periods or had irregular periods. If these symptoms occur, contact your doctor.
Problems with sexual functioning have commonly occurred in patients taking SYMBYAX. If these symptoms occur, contact your doctor.

General advice about SYMBYAX

Store SYMBYAX at room temperature and out of the reach of children. Keep the container tightly closed and protect from moisture.
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not take SYMBYAX for a condition for which it was not prescribed. Do not give SYMBYAX to other people, even if they have the same symptoms that you have. It may harm them.
If you have any questions or concerns, want to report any problems with the use of SYMBYAX, or want more information, contact your doctor, pharmacist, or other healthcare provider. Additional information can be found at www.SYMBYAX.com, or call 1-800-LillyRx.

Eli Lilly and Company
Lilly Corporate Center
Indianapolis, IN USA

www.SYMBYAX.com

SYMBYAX is a registered trademark of Eli Lilly and Company. All other brand names are the property of their respective owners.

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Important Safety Information for SYMBYAX®(olanzapine and fluoxetine HCI)