Warnings and Precautions (5.5) 7/2014

BRINTELLIX is indicated for the treatment of major depressive disorder (MDD) (1, 14).

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The recommended starting dose is 10 mg administered orally once daily without regard to meals (2.1).

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The dose should then be increased to 20 mg/day, as tolerated (2.1).

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Consider 5 mg/day for patients who do not tolerate higher doses (2.1).

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BRINTELLIX can be discontinued abruptly. However, it is recommended that doses of 15 mg/day or 20 mg/day be reduced to 10 mg/day for one week prior to full discontinuation if possible (2.3).

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The maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers (2.6).

BRINTELLIX is available as 5 mg, 10 mg, 15 mg, and 20 mg immediate release tablets (3).

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Hypersensitivity to vortioxetine or any components of the BRINTELLIX formulation (4).

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Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with BRINTELLIX or within 21 days of stopping treatment with BRINTELLIX. Do not use BRINTELLIX within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start BRINTELLIX in a patient who is being treated with linezolid or intravenous methylene blue (4).

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Serotonin Syndrome has been reported with serotonergic antidepressants (SSRIs, SNRIs, and others), including with BRINTELLIX, both when taken alone, but especially when co-administered with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort). If such symptoms occur, discontinue BRINTELLIX and initiate supportive treatment. If concomitant use of BRINTELLIX 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 (5.2).

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Treatment with serotonergic antidepressants (SSRIs, SNRIs, and others) may increase the risk of abnormal bleeding. Patients should be cautioned about the increased risk of bleeding when BRINTELLIX is coadministered with nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or other drugs that affect coagulation (5.3).

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Activation of Mania/Hypomania can occur with antidepressant treatment. Screen patients for bipolar disorder (5.4).

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Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants (5.5).

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Hyponatremia can occur in association with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) (5.6).

Most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were: nausea, constipation and vomiting (6).

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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Strong inhibitors of CYP2D6: Reduce BRINTELLIX dose by half when a strong CYP2D6 inhibitor (e.g., bupropion, fluoxetine, paroxetine, or quinidine) is coadministered (2.6 and 7.3).

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Strong CYP Inducers: Consider increasing BRINTELLIX dose when a strong CYP inducer (e.g., rifampin, carbamazepine, or phenytoin) is coadministered for more than 14 days. The maximum recommended dose should not exceed 3 times the original dose (2.7 and 7.3).

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Pregnancy: Based on animal data, BRINTELLIX may cause fetal harm (8.1).

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Nursing Mothers: Discontinue BRINTELLIX or nursing (8.3).