Fluoxetine hydrochloride; olanzapine

What is Fluoxetine hydrochloride; olanzapine?

• Fluoxetine hydrochloride; olanzapine (Symbyax) combines olanzapine, an atypical antipsychotic and fluoxetine, a selective serotonin reuptake inhibitor, used to treat the depressive episodes of bipolar I disorder as well as treatment-resistant depression.

Olanzapine

Fluoxetine

What are the uses of this medicine?

Fluoxetine hydrochloride; olanzapine (SYMBYAX) is a prescription medicine used for:

• short-term treatment of episodes of depression that happen with Bipolar I Disorder in people age 10 or older.
• treatment of episodes of depression that do not respond to 2 other medicines, also called treatment resistant depression, in adults.

• SYMBYAX contains two medicines, olanzapine and fluoxetine hydrochloride.

Bipolar I Disorder:

• 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. With treatment, some of your symptoms of Bipolar I Disorder may improve.

Depression:

• 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. With treatment, some of your symptoms of treatment resistant depression may improve.

How does this medicine work?

• The mechanism of action of olanzapine and fluoxetine in the listed indications, is unclear.
• However, the combined effect of olanzapine and fluoxetine at the monoaminergic neural systems (serotonin, norepinephrine, and dopamine) could be responsible for the pharmacological effect.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• take a Monoamine Oxidase Inhibitor (MAOI).
• Do not take an MAOI within 5 weeks of stopping SYMBYAX unless directed to do so by your physician.
• Do not start SYMBYAX if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.

• take Mellaril® (thioridazine).
• Do not take Mellaril® within 5 weeks of stopping SYMBYAX.
• Mellaril can cause serious heart rhythm problems and you could die suddenly.

• take the antipsychotic medicine pimozide (Orap®).
• Do not take pimozide (Orap®) within 5 weeks of stopping SYMBYAX.

What drug interactions can this medicine cause?

• SYMBYAX and some medicines may interact with each other and may not work as well, or cause possible serious side effects.

If you take SYMBYAX, you should not take any other medicines that contain:

• olanzapine (the active ingredient in Zyprexa® and Zyprexa® Zydis®) or
• fluoxetine hydrochloride (the active ingredient in Prozac®, and Sarafem®).

Caution is advised if the concomitant administration of SYMBYAX and other CNS-active drugs is required.

• Do not take an MAOI within 5 weeks of stopping SYMBYAX unless directed to do so by your physician.
• Do not start SYMBYAX if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.
• Do not take Mellaril® within 5 weeks of stopping SYMBYAX.
• Do not take pimozide (Orap®) within 5 weeks of stopping SYMBYAX.
• Patients receiving warfarin therapy should be carefully monitored when SYMBYAX is initiated or discontinued.
• Co-administration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine.
• Higher daily doses of carbamazepine may cause an even greater increase in olanzapine clearance.
• Lower doses of the olanzapine component of SYMBYAX should be considered in patients receiving concomitant treatment with fluvoxamine.
• The coadministration of ethanol with SYMBYAX may potentiate sedation and orthostatic hypotension.
• Because of the potential for olanzapine to induce hypotension, SYMBYAX may enhance the effects of certain antihypertensive agents.
• The dose of Tricyclic Antidepressants (TCA) may need to be reduced and plasma TCA concentrations may need to be monitored temporarily when SYMBYAX is coadministered or has been recently discontinued.
• The olanzapine component of SYMBYAX may antagonize the effects of levodopa and dopamine agonists.
• Coadministration of alprazolam and fluoxetine has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels.
• Elevation of blood levels of clozapine has been observed in patients receiving concomitant fluoxetine.
• Elevation of blood levels of haloperidol has been observed in patients receiving concomitant fluoxetine.

Is this medicine FDA approved?

• Olanzapine/fluoxetine was approved by the U.S. Food and Drug Administration (FDA) to treat the depressive episodes of bipolar I disorder in 2003.
• In 2009, it was granted approval for the treatment of treatment-resistant depression.

How should this medicine be used?

Recommended dosage: Depressive Episodes Associated with Bipolar I Disorder:

• Adult Starting Dose: 6 mg olanzapine with 25 mg fluoxetine (6 mg/25 mg, once daily in the evening.
• Adult Maximum Dose: 12 mg/50 mg once daily.
• Pediatric Bipolar Depression Starting Dose: 3 mg/25 mg once daily (for ages 10 to 17 years).
• Pediatric Bipolar Depression Maximum Dose: 12 mg/50 mg.

• Starting dose in patients predisposed to hypotensive reactions, hepatic impairment, or with potential for slowed metabolism: 3 mg/25 mg to 6 mg/25 mg. Escalate dose cautiously

Treatment Resistant Depression:

• Administer SYMBYAX once daily in the evening, generally beginning with the 6 mg/25 mg capsule.
• Antidepressant efficacy was demonstrated with SYMBYAX in a dose range of olanzapine 6 mg to 18 mg and fluoxetine 25 mg to 50 mg.
• The safety of doses above 18 mg/75 mg has not been evaluated in clinical studies.

Administration:

• Take SYMBYAX exactly as prescribed. Your doctor may need to change (adjust) the dose of SYMBYAX until it is right for you.
• If you miss a dose of SYMBYAX, take the missed dose as soon as you remember.
• If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of SYMBYAX at the same time.
• To prevent serious side effects, do not stop taking SYMBYAX suddenly. If you need to stop taking SYMBYAX, your doctor can tell you how to safely stop taking it.
• If you take too much SYMBYAX, call your doctor or poison control center right away, or get emergency treatment.
• SYMBYAX can be taken with or without food.
• SYMBYAX is usually taken one time each day, in the evening.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 3 mg/25 mg, 6 mg/25 mg (mg olanzapine/mg equivalent fluoxetine)

This medicine is available in fallowing brand namesː

• SYMBYAX

What side effects can this medication cause?

The most common side effects of this medicine include:

• dry mouth, tiredness, sleeping for long period of time, increased appetite, swelling of your hands and feet, drowsiness, tremors (shakes), or blurred vision

SYMBYAX may cause serious side effects, including:

• Suicidal thoughts or actions
• dementia-related psychosis
• hyperglycemia
• increased cholesterol and triglycerides
• Weight gain, especially in children and adolescents age 10 to 17
• transient ischemic attacks
• Severe allergic reactions
• Neuroleptic malignant syndrome (NMS)
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
• Tardive Dyskinesia
• Serotonin Syndrome
• Visual problems
• Abnormal bleeding
• hyponatremia
• QT prolongation and ventricular arrhythmia including Torsade de Pointes
• Decreased blood pressure
• Difficulty swallowing
• Seizures
• Problems with control of body temperature
• Sexual dysfunction

What special precautions should I follow?

• A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs, including olanzapine. Manage with immediate discontinuation and close monitoring.
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported with olanzapine exposure. Discontinue if DRESS is suspected.
• Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain. In some cases extreme and associated with ketoacidosis or hyperosmolar coma or death. Monitor for symptoms of hyperglycemia. Perform fasting blood glucose testing before beginning, and periodically during treatment.
• Undesirable alterations in lipids have been observed with SYMBYAX use. Appropriate clinical monitoring is recommended, including fasting blood lipid testing before beginning, and periodically during, treatment
• Potential consequences of weight gain should be considered prior to starting SYMBYAX. Consider potential consequences of weight gain. Monitor weight regularly
• Serotonin syndrome has been reported with SSRIs and SNRIs, including SYMBYAX, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort). If such symptoms occur, discontinue SYMBYAX and initiate supportive treatment. If concomitant use of SYMBYAX with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
• Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants.
• Allergic Reactions and Rash may occur. Discontinue upon appearance of rash or allergic phenomena.
• A major depressive episode may be the initial presentation of Bipolar Disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a manic episode in patients at risk for Bipolar Disorder. Screen for Bipolar Disorder and monitor for activation of mania/hypomania.
• A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Discontinue if clinically appropriate.
• SYMBYAX may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia, and in some patients, syncope. Risk is increased during initial dose titration. Use caution in patients with cardiovascular disease or cerebrovascular disease, and those conditions that could affect hemodynamic responses.
• Leukopenia, Neutropenia, and Agranulocytosis has been reported with antipsychotics, including SYMBYAX. Patients with a history of a clinically significant low white blood cell count (WBC) or drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy. Consider discontinuing SYMBYAX at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
• Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.
• SSRIs increase the risk of bleeding. Use with NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding.
• Hyponatremia Can occur in association with syndrome of inappropriate antidiuretic hormone (SIADH). Consider discontinuing SYMBYAX if symptomatic hyponatremia occurs (SIADH).
• SYMBYAX has the potential to impair judgment, thinking, or motor skills. Caution patients about operating machinery.
• QT prolongation and ventricular arrhythmia including Torsade de Pointes have been reported with fluoxetine. Use with caution in conditions that predispose to arrhythmias or increased fluoxetine exposure. Use cautiously in patients with risk factors for QT prolongation.
• Use with caution with other anticholinergic drugs and in patients with urinary retention, prostatic hypertrophy, constipation, history of paralytic ileus or related conditions.
• As with other drugs that antagonize dopamine D2 receptors, SYMBYAX elevates prolactin levels, and the elevation persists during administration.
• Because of the long elimination half-lives of fluoxetine and its major active metabolite, changes in dose will not be fully reflected in plasma for several weeks.
• SYMBYAX use may cause symptoms of sexual dysfunction. It is important for prescribers to inquire about sexual function prior to initiation of SYMBYAX and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• somnolence (sedation)
• impaired consciousness (coma)
• impaired neurologic function (ataxia, confusion, convulsions, dysarthria)
• arrhythmias, lethargy
• essential tremor
• agitation
• acute psychosis
• hypotension
• hypertension
• aggression

Management of overdosage:

• Consider contacting a Certified Poison Control Center (1-800-222-1222).
• Establish and maintain an airway and ensure adequate ventilation.
• Commence cardiovascular monitoring immediately and include continuous electrocardiographic monitoring to detect possible arrhythmias.
• Due to the large volume of distribution of olanzapine and fluoxetine, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit.
• No specific antidote for either fluoxetine or olanzapine overdose is known.

Can this medicine be used in pregnancy?

• It is not known if SYMBYAX will harm your unborn baby. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy.
• If you become pregnant while taking SYMBYAX, talk to your healthcare provider about registering with the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388.

Can this medicine be used in children?

• It is not known if SYMBYAX is safe and effective in children under the age of 10.

What are the active and inactive ingredients in this medicine?

• Active ingredients: olanzapine and fluoxetine hydrochloride
• Inactive ingredients: pregelatinized starch, gelatin, dimethicone, titanium dioxide, sodium lauryl sulfate, edible black ink, red iron oxide, yellow iron oxide, and/or black iron oxide.

Who manufactures and distributes this medicine?

• Marketed by: Lilly USA, LLC

Indianapolis, IN, USA

What should I know about storage and disposal of this medication?

• Store SYMBYAX at room temperature, between 59°F to 86°F (15°C to 30°C).
• Keep SYMBYAX away from light.
• Keep SYMBYAX dry and away from moisture. Keep the bottle closed tightly.
• Keep SYMBYAX and all medicines out of the reach of children.

• Dailymed label info on Fluoxetine hydrochloride; olanzapine
• FDA Fluoxetine hydrochloride; olanzapine

Fluoxetine hydrochloride; olanzapine Resources
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The following are antidepressant subclasses and drugs

MAO Inhibitors Isocarboxazid, Phenelzine, Tranylcypromine

SNRIs Duloxetine, Levomilnacipran, Venlafaxine

SSRIs Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Vilazodone, Vortioxetine

Tricyclics Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Nortriptyline, Protriptyline, Trimipramine

Miscellaneous Bupropion, Flibanserin, Mirtazapine, Nefazodone, Trazodone