Indicated for the acute treatment of:

Acute Depressive Episodes Associated with Bipolar I Disorder: (adults, children, and adolescents 10 to 17 years of age)

The safety of doses above 18 mg of olanzapine and 75 mg of fluoxetine has not been evaluated in adult clinical studies.The safety of doses above 12 mg of olanzapine and 50 mg of fluoxetine has not been evaluated in pediatric clinical studies.

Treatment Resistant Depression: (adults)

• 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. The safety of doses above 18 mg/75 mg has not been evaluated in clinical studies.

SYMBYAX is not approved for use in children less than 10 years of age.

SYMBYAX has not been systematically studied in patients >65 years of age.

Start SYMBYAX at 3 mg/25 mg or 6 mg/25 mg in 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 SYMBYAX (female gender, geriatric age, nonsmoking status) or those patients who may be pharmacodynamically sensitive to olanzapine. Titrate slowly and adjust dosage as needed in patients who exhibit a combination of factors that may slow metabolism.

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. SYMBYAX is not approved for the treatment of patients with dementia-related psychosis.

Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in trials of olanzapine in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with olanzapine compared to patients treated with placebo.

SYMBYAX is not approved for the treatment of patients with Alzheimer’s disease.

Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain. Metabolic changes may be associated with increased cardiovascular/cerebrovascular risk.

Physicians should consider the risks and benefits when prescribing SYMBYAX to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level (fasting 100-126 mg/dL, non-fasting 140-200 mg/dL). Patients taking SYMBYAX should be monitored regularly for worsening of glucose control. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness.

SYMBYAX may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

SYMBYAX 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 SYMBYAX therapy does not affect them adversely.

A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs, including olanzapine.

Symptoms associated with discontinuation of fluoxetine, a component of SYMBYAX, SNRIs, and SSRIs, have been reported.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported with olanzapine exposure.

The pupillary dilation that occurs following use of many antidepressant drugs including SYMBYAX may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs.

In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including SYMBYAX.

SYMBYAX should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold, e.g., Alzheimer’s dementia. 

SNRIs and SSRIs, including fluoxetine, may increase the risk of bleeding reactions. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to this risk.

Post-marketing cases of QT interval prolongation and ventricular arrhythmia including Torsade de Pointes have been reported in patients treated with fluoxetine. SYMBYAX should be used with caution in patients with congenital long QT syndrome; a previous history of QT prolongation; a family history of long QT syndrome or sudden cardiac death; and other conditions that predispose to QT prolongation and ventricular arrhythmia.

Olanzapine exhibits in vitro muscarinic receptor affinity. In premarketing clinical studies, SYMBYAX was associated with constipation, dry mouth, and tachycardia, all adverse reactions possibly related to cholinergic antagonism. Such adverse reactions were not often the basis for study discontinuations; SYMBYAX should be used with caution in patients with a current diagnosis or prior history of urinary retention,clinically significant prostatic hypertrophy, constipation, a history of paralytic ileus, or related conditions.

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) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

Because of the risk of serotonin syndrome, do not use MAOIs intended to treat psychiatric disorders with SYMBYAX or within 5 weeks of stopping treatment with SYMBYAX. Do not use SYMBYAX within 14 days of stopping an MAOI intended to treat psychiatric disorders.

Thioridazine should not be given with SYMBYAX or within at least five weeks after stopping SYMBYAX.

Concomitant use of SYMBYAX in patients taking Pimozide is contraindicated.

Do not start SYMBYAX in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome.

Caution is advised if the concomitant administration of SYMBYAX and other CNS active drugs is required. In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status.

There are no clinical studies establishing the benefit of the combined use of ECT and fluoxetine.

Co-administration of diazepam with olanzapine potentiated the orthostatic hypotension observed with olanzapine.

Carbamazepine therapy (200 mg BID) causes an approximate 50% increase in the clearance of olanzapine.

The olanzapine component of SYMBYAX may antagonize the effects of levodopa and dopamine agonists.

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.

Patients on stable doses of phenytoin have developed elevated plasma levels of phenytoin with clinical phenytoin toxicity following initiation of concomitant fluoxetine.

There have been reports of both increased and decreased lithium levels when lithium was used concomitantly with fluoxetine.

Because fluoxetine is tightly bound to plasma protein, the administration of fluoxetine to a patient taking another drug that is tightly bound to protein (e.g., Coumadin, digitoxin) may cause a shift in plasma concentrations potentially resulting in an adverse effect.

Neonates exposed to fluoxetine, a component of SYMBYAX, and other SSRIs and SNRIs late in the third trimester have developed complications arising immediately upon delivery (respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying) requiring prolonged hospitalization, respiratory support, and tube feeding. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. In some cases, the clinical picture is consistent with serotonin syndrome.

Infants exposed to SSRIs in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN).

It is recommended that women not breastfeed when receiving SYMBYAX.

GoToSource

• Use in patients under 10 years of age for treatment of bipolar I depression. GoToSource

• Use in patients under 18 years of age for treatment resistant depression. GoToSource

• Use in patients over 65 years of age. GoToSource   

• Use in patients with alzheimer’s disease. GoToSource

• Sleep aid. GoToSource

• Generalized anxiety disorder. GoToSource

• Panic disorder. GoToSource

• Post-traumatic stress disorder. GoToSource

• Eating disorders. GoToSource

• Tourette syndrome. GoToSource

• Premature ejaculation, migraine headaches and diabetic neuropathy pain. GoToSource

⚠️  Patients with CYP2D6 variation are at higher risk for adverse effects.

Birth defects. GoToSource

Increased risk of death in elderly patients with dementia-related psychosis. GoToSource

Serotonin syndrome (life-threatening drug reaction). GoToSource

QT interval prolongation and ventricular arrhythmia. GoToSource

Type 2 diabetes. GoToSource

Suicidal thinking and behavior. GoToSource

Drug reaction with eosinophilia and systemic symptoms (potentially life-threatening, drug-induced hypersensitivity reaction). GoToSource

Osteoporosis, amenorrhea (absence of menstruation), gynecomastia (male breast enlargement) and galactorrhea (milky nipple discharge). GoToSource

Weight gain. GoToSource

Increased cholesterol levels. GoToSource

Hyperprolactinemia (high levels of prolactin in the blood a hormone secreted by the pituitary gland). GoToSource

Tardive dyskinesia (involuntary movements). GoToSource

Angle-closure glaucoma. GoToSource

Discontinuation syndrome. GoToSource

Seizures. GoToSource

Neuroleptic malignant syndrome (life-threatening drug reaction). GoToSource

Orthostatic hypotension (fall in blood pressure when an upright position is assumed). GoToSource

Leukopenia, neutropenia and agranulocytosis (low white blood cell count). GoToSource

Hyponatremia (low blood sodium level). GoToSource 

Lawsuits filed for birth defects, suicide, neuroleptic malignant syndrome, tardive dyskinesia, diabetes, strokes and mania.