BRINTELLIX- vortioxetine hydrobromide tablet, film coated
Takeda Pharmaceuticals America, Inc.
WARNING: 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 trend toward reduced risk with antidepressant use in patients aged 65 and older [see Warnings and Precautions (5.1)].
In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber [see Warnings and Precautions (5.1)].
BRINTELLIX has not been evaluated for use in pediatric patients [see Use in Specific Populations (8.4)].
1 INDICATIONS AND USAGE
1.1 Major Depressive Disorder
BRINTELLIX is indicated for the treatment of major depressive disorder (MDD). The efficacy of BRINTELLIX was established in six 6 to 8 week studies (including one study in the elderly) and one maintenance study in adults [see Clinical Studies (14)].
2 DOSAGE AND ADMINISTRATION
2.1 General Instruction for Use
The recommended starting dose is 10 mg administered orally once daily without regard to meals. Dosage should then be increased to 20 mg/day, as tolerated, because higher doses demonstrated better treatment effects in trials conducted in the United States. The efficacy and safety of doses above 20 mg/day have not been evaluated in controlled clinical trials. A dose decrease down to 5 mg/day may be considered for patients who do not tolerate higher doses [see Clinical Studies (14)].
2.2 Maintenance/Continuation/Extended Treatment
It is generally agreed that acute episodes of major depression should be followed by several months or longer of sustained pharmacologic therapy. A maintenance study of BRINTELLIX demonstrated that BRINTELLIX decreased the risk of recurrence of depressive episodes compared to placebo.
2.3 Discontinuing Treatment
Although BRINTELLIX can be abruptly discontinued, in placebo-controlled trials patients experienced transient adverse reactions such as headache and muscle tension following abrupt discontinuation of BRINTELLIX 15 mg/day or 20 mg/day. To avoid these adverse reactions, it is recommended that the dose be decreased to 10 mg/day for one week before full discontinuation of BRINTELLIX 15 mg/day or 20 mg/day [see Adverse Reactions (6)].
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 a MAOI intended to treat psychiatric disorders and initiation of therapy with BRINTELLIX to avoid the risk of Serotonin Syndrome [see Warnings and Precautions (5.2)]. Conversely, at least 21 days should be allowed after stopping BRINTELLIX before starting an MAOI intended to treat psychiatric disorders [see Contraindications (4)].
2.5 Use of BRINTELLIX with Other MAOIs such as Linezolid or Methylene Blue
Do not start BRINTELLIX 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)].
In some cases, a patient already receiving BRINTELLIX 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 treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, BRINTELLIX should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 21 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with BRINTELLIX may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue [see Warnings and Precautions (5.2)].
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 BRINTELLIX is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use [see Warnings and Precautions (5.2)].
2.6 Use of BRINTELLIX in Known CYP2D6 Poor Metabolizers or in Patients Taking Strong CYP2D6 Inhibitors
The maximum recommended dose of BRINTELLIX is 10 mg/day in known CYP2D6 poor metabolizers. Reduce the dose of BRINTELLIX by one-half when patients are receiving a CYP2D6 strong inhibitor (e.g., bupropion, fluoxetine, paroxetine, or quinidine) concomitantly. The dose should be increased to the original level when the CYP2D6 inhibitor is discontinued [see Drug Interactions (7.3)].
2.7 Use of BRINTELLIX in Patients Taking Strong CYP Inducers
Consider increasing the dose of BRINTELLIX when a strong CYP inducer (e.g., rifampin, carbamazepine, or phenytoin) is coadministered for greater than 14 days. The maximum recommended dose should not exceed three times the original dose. The dose of BRINTELLIX should be reduced to the original level within 14 days, when the inducer is discontinued [see Drug Interactions (7.3)].
3 DOSAGE FORMS AND STRENGTHS
BRINTELLIX is available as immediate-release, film-coated tablets in the following strengths:
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5 mg: pink, almond shaped biconvex film coated tablet, debossed with "5" on one side and "TL" on the other side
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10 mg: yellow, almond shaped biconvex film coated tablet, debossed with "10" on one side and "TL" on the other side
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15 mg: orange, almond shaped biconvex film coated tablet, debossed with "15" on one side and "TL" on the other side
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20 mg: red, almond shaped biconvex film coated tablet, debossed with "20" on one side and "TL" on the other side