TRINTELLIX®  (vortioxetine) tablets

•Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.
•Monitor for worsening and emergence of suicidal thoughts and behaviors.
•TRINTELLIX has not been evaluated for use in pediatric patients .

TRINTELLIX is an immediate-release tablet for oral administration that contains the beta (ß) polymorph of vortioxetine hydrobromide (HBr), an antidepressant. Vortioxetine HBr is known chemically as 1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]-piperazine, hydrobromide. The empirical formula is C18 H22 N2 S, HBr with a molecular weight of 379.36 g/mol.

Vortioxetine HBr is a white to very slightly beige powder that is slightly soluble in water.

Each TRINTELLIX tablet contains 6.355 mg, 12.71 mg, 19.065 mg, or 25.42 mg of vortioxetine HBr equivalent to 5 mg, 10 mg, 15 mg, or 20 mg of vortioxetine, respectively. The inactive ingredients in TRINTELLIX tablets include mannitol, microcrystalline cellulose, hydroxypropyl cellulose, sodium starch glycolate, magnesium stearate and film coating which consists of hypromellose, titanium dioxide, polyethylene glycol 400, iron oxide red (5 mg, 15 mg, and 20 mg) and iron oxide yellow (10 mg and 15 mg).

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

WARNINGS AND PRECAUTIONS

1. Serotonin Syndrome has been reported with serotonergic antidepressants (SSRIs, SNRIs, and others), including with TRINTELLIX, 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 TRINTELLIX and initiate supportive treatment. If concomitant use of TRINTELLIX 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.
2. 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 TRINTELLIX is coadministered with nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or other drugs that affect coagulation.
3. Activation of Mania/Hypomania can occur with antidepressant treatment. Screen patients for bipolar disorder.
4. Hyponatremia can occur in association with the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

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

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.

DRUG INTERACTIONS
>Strong inhibitors of CYP2D6: Reduce TRINTELLIX dose by half when a strong CYP2D6 inhibitor (e.g., bupropion, fluoxetine, paroxetine, or quinidine) is coadministered.

>Strong CYP Inducers: Consider increasing TRINTELLIX 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.

USE IN SPECIFIC POPULATIONS
> Pregnancy: Based on animal data, TRINTELLIX may cause fetal harm.
>Nursing Mothers: Discontinue TRINTELLIX or nursing.

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

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

The dose should then be increased to 20 mg/day, as tolerated.
Consider 5 mg/day for patients who do not tolerate higher doses.

TRINTELLIX 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.

The maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers

TRINTELLIX is available as 5 mg, 10 mg, 15 mg, and 20 mg immediate release tablets

Marketed by:
Lundbeck
Deerfield, IL 60015

TRINTELLIX is a trademark of H. Lundbeck A/S and is used under license by Takeda Pharmaceuticals America, Inc.

All other trademarks are the property of their respective owners.
©2013 Takeda Pharmaceuticals America, Inc.
LUN205M R1 September 2013