Symbyax

SYMBYAX- olanzapine and fluoxetine hydrochloride capsule
Eli Lilly and Company

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS and INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

Suicidal Thoughts and Behaviors — 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 healthcare provider. SYMBYAX is not approved for use in children less than 10 years of age [see Warnings and Precautions (5.1), Use in Specific Populations (8.4)].

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. SYMBYAX (olanzapine and fluoxetine) is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.2)] .

1 INDICATIONS AND USAGE

SYMBYAX® is indicated for the treatment of:

  • Acute depressive episodes in Bipolar I Disorder [see Clinical Studies (14.1)].
  • Treatment resistant depression (Major Depressive Disorder in patient who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode) [see Clinical Studies (14.2)].

2 DOSAGE AND ADMINISTRATION

2.1 Depressive Episodes Associated with Bipolar I Disorder

Adults — Administer SYMBYAX once daily in the evening, generally beginning with the 6 mg/25 mg (mg olanzapine/mg equivalent fluoxetine) capsule. While food has no appreciable effect on the absorption of olanzapine and fluoxetine given individually, the effect of food on the absorption of SYMBYAX has not been studied. Make dosage adjustments, if indicated, according to efficacy and tolerability. Antidepressant efficacy was demonstrated with SYMBYAX in a dose range of olanzapine 6 mg to 12 mg and fluoxetine 25 mg to 50 mg [see Clinical Studies (14.1)]. The safety of doses above 18 mg of olanzapine and 75 mg of fluoxetine has not been evaluated in adult clinical studies. Periodically reexamine the need for continued pharmacotherapy.

Children and Adolescents (10 to 17 years of age) Administer SYMBYAX once daily in the evening, generally beginning with the 3 mg/25 mg capsule, without regard to meals, with a recommended target dose within the approved dosing range (6/25; 6/50; 12/50 mg) [see Clinical Studies (14.1)]. The safety of doses above 12 mg of olanzapine and 50 mg of fluoxetine has not been evaluated in pediatric clinical studies. Periodically reexamine the need for continued pharmacotherapy.

2.2 Treatment Resistant Depression

Administer SYMBYAX once daily in the evening, generally beginning with the 6 mg/25 mg capsule. While food has no appreciable effect on the absorption of olanzapine and fluoxetine given individually, the effect of food on the absorption of SYMBYAX has not been studied. Adjust dosage, if indicated, according to efficacy and tolerability. Antidepressant efficacy was demonstrated with SYMBYAX in a dose range of olanzapine 6 mg to 18 mg and fluoxetine 25 mg to 50 mg [see Clinical Studies (14.2)]. The safety of doses above 18 mg/75 mg has not been evaluated in clinical studies. Periodically reexamine the need for continued pharmacotherapy.

2.3 Specific Populations

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. SYMBYAX has not been systematically studied in patients >65 years of age or in patients <10 years of age [see Use in Specific Populations (8.5) and Clinical Pharmacology (12.3, 12.4)].

2.4 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with SYMBYAX. Conversely, at least 5 weeks should be allowed after stopping SYMBYAX before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4.1)].

2.5 Use of SYMBYAX with Other MAOIs such as Linezolid or Methylene Blue

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. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered [see Contraindications (4.1)].

In some cases, a patient already receiving SYMBYAX therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue are judged to outweigh the risks of serotonin syndrome in a particular patient, SYMBYAX should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with SYMBYAX may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.6)].

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with SYMBYAX is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.6)].

2.6 Discontinuation of Treatment with SYMBYAX

Symptoms associated with discontinuation of fluoxetine, a component of SYMBYAX, SNRIs, and SSRIs, have been reported [see Warnings and Precautions (5.25)].

3 DOSAGE FORMS AND STRENGTHS

Capsules (mg olanzapine/mg equivalent fluoxetine):

  • 3 mg/25 mg
  • 6 mg/25 mg
  • 6 mg/50 mg
  • 12 mg/50 mg

4 CONTRAINDICATIONS

4.1 Monoamine Oxidase Inhibitors (MAOIs)

The use of MAOIs intended to treat psychiatric disorders with SYMBYAX or within 5 weeks of stopping treatment with SYMBYAX is contraindicated because of an increased risk of serotonin syndrome. The use of SYMBYAX within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.4) and Warnings and Precautions (5.6)].

Starting SYMBYAX in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration (2.5) and Warnings and Precautions (5.6)].

4.2 Other Contraindications

  • Pimozide [see Warnings and Precautions (5.20) and Drug Interactions (7.7, 7.8)]
  • Thioridazine [see Warnings and Precautions (5.20) and Drug Interactions (7.7, 7.8)]

Pimozide and thioridazine prolong the QT interval. SYMBYAX can increase the levels of pimozide and thioridazine through inhibition of CYP2D6. SYMBYAX can also prolong the QT interval.

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