Dosing & Administration | TRINTELLIX (vortioxetine)
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TRINTELLIX® (vortioxetine) is indicated for the treatment of Major Depressive Disorder (MDD) in adults.

Patient portrayal. 
Individual results may vary.

Dosing &
Administration

How does dosing fit into the story?

Once-daily dosing with or without food1

5mg pink TRINTELLIX (vortioxetine) tablet, debossed with "5" on one side

5 MG

10mg yellow TRINTELLIX (vortioxetine) tablet, debossed with "10" on one side

10 MG

20mg red TRINTELLIX (vortioxetine) tablet, debossed with "20" on one side

20 MG

Tablets shown not actual size.

  • The recommended starting dose of TRINTELLIX is 10 mg administered orally once daily, without regard to meals1
  • Dosage should then be increased ‌to 20 mg once daily, as tolerated1
    • The efficacy and safety of doses above 20 mg/day have not been evaluated in controlled clinical trials
    • 5 mg/day may be considered for patients who do not tolerate higher doses
  • Prior to initiating treatment with TRINTELLIX, screen patients for personal or family history of bipolar disorder, mania, or hypomania1
  • Although patients can abruptly discontinue therapy with TRINTELLIX, 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 possible1
    • In placebo-controlled trials, some patients experienced transient adverse reactions such as headache and muscle tension following abrupt discontinuation
  • The maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers1
  • Concomitant administration of TRINTELLIX and strong CYP2D6 inhibitors or strong CYP inducers may require a dose adjustment of TRINTELLIX1

For additional dosing information, please see the Full Prescribing Information.

Drug interactions

Clinically important drug interactions with TRINTELLIX1

Drug Class Clinical Impact & Recommendations

Monoamine Oxidase Inhibitors

selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue

CONCOMITANT USE WITH TRINTELLIX MAY INCREASE THE RISK OF SEROTONIN SYNDROME

MAOIs for psychiatric disorders are contraindicated with TRINTELLIX or within 21 days of stopping TRINTELLIX.

TRINTELLIX is contraindicated within 14 days of stopping MAOIs for psychiatric disorders.

Starting TRINTELLIX in patients on linezolid or IV methylene blue is also contraindicated.

Other Serotonergic Drugs

SNRIs, SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, amphetamines, tryptophan, St. John’s Wort

CONCOMITANT USE WITH TRINTELLIX MAY INCREASE THE RISK OF SEROTONIN SYNDROME

Monitor for serotonin syndrome when TRINTELLIX is coadministered with other serotonergic drugs.

If serotonin syndrome occurs, discontinue TRINTELLIX and other serotonergic drugs, and initiate supportive treatment.

Strong CYP2D6 Inhibitors

bupropion, fluoxetine, paroxetine, quinidine

CONCOMITANT USE WITH TRINTELLIX MAY INCREASE TRINTELLIX PLASMA LEVELS

Reduce the TRINTELLIX dose by half.

When discontinuing a strong CYP2D6 inhibitor, increase TRINTELLIX to its original dose.

Strong CYP Inducers

rifampin, carbamazepine, phenytoin

CONCOMITANT USE WITH TRINTELLIX DECREASES TRINTELLIX PLASMA LEVELS

Consider increasing the dose of TRINTELLIX when coadministered for more than 14 days.

The maximum TRINTELLIX dose should not be greater than three times the original TRINTELLIX dose.

When discontinuing a strong CYP inducer, reduce TRINTELLIX within 14 days to its original dose.

Antiplatelet Drugs and Anticoagulants

aspirin, NSAIDs, clopidogrel, heparin, warfarin

CONCOMITANT USE WITH TRINTELLIX MAY POTENTIATE BLEEDING RISK

Inform patients of increased bleeding risk.

For patients on warfarin, monitor INR carefully when initiating, titrating or discontinuing TRINTELLIX.

Drugs Highly Bound to Plasma Protein

warfarin

CONCOMITANT USE WITH TRINTELLIX MAY INCREASE FREE TRINTELLIX PLASMA LEVELS OR OTHER HIGHLY PROTEIN-BOUND DRUG LEVELS

Monitor for adverse reactions.

Reduce dosage of TRINTELLIX or other highly protein-bound drugs as needed.

Note: Class examples do not include all possible class members.

Abbreviations: INR, International Normalized Ratio; IV, Intravenous; MAOIs, Monoamine oxidase inhibitors; NSAIDs, Nonsteroidal anti-inflammatory drugs; SNRIs, Serotonin-norepinephrine reuptake inhibitors; SSRIs, Selective serotonin reuptake inhibitors.

For additional Drug Interactions information, please see the ​​​Full Prescribing Information.

Tools for your patients and practice

IMPORTANT SAFETY INFORMATION

WARNING: SUICIDAL THOUGHTS & BEHAVIORS

  • Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies.
  • Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors.
  • TRINTELLIX is not approved for use in pediatric patients.

CONTRAINDICATIONS

  • Hypersensitivity: Hypersensitivity to vortioxetine or any component of the TRINTELLIX formulation. Hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported in patients treated with TRINTELLIX.
  • Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with TRINTELLIX or within 21 days of stopping treatment with TRINTELLIX, due to an increased risk of serotonin syndrome. Do not use TRINTELLIX within 14 days of stopping an MAOI intended to treat psychiatric disorders.
  • Linezolid and Methylene Blue: Do not start TRINTELLIX in a patient being treated with MAOIs such as linezolid or intravenous methylene blue, due to an increased risk of serotonin syndrome.

WARNINGS AND PRECAUTIONS

  • Suicidal Thoughts and Behaviors in Adolescents and Young Adults: Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing TRINTELLIX, in patients whose depression is persistently worse, or who are experiencing emergence of suicidal thoughts and behaviors. In pooled analyses of placebo-controlled trials of antidepressants, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients ages 24 and younger was greater than in placebo-treated patients.
  • Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with serotonergic antidepressants, including TRINTELLIX, when used alone but more often when used concomitantly with other serotonergic drugs (including triptans, tricyclic antidepressants, opioids [e.g., fentanyl and tramadol], lithium, tryptophan, buspirone, 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). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Monitor patients for emergence of serotonin syndrome. If concomitant use of serotonergic antidepressants, including TRINTELLIX, is clinically warranted, make patients aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. If symptoms occur, immediately discontinue TRINTELLIX and any concomitant serotonergic agents, and initiate supportive symptomatic treatment.
  • Increased Risk of Bleeding: The use of drugs that interfere with serotonin reuptake inhibition, including TRINTELLIX, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk. Inform patients about the increased risk of bleeding when TRINTELLIX is coadministered with NSAIDs, aspirin, or other drugs that affect coagulation or bleeding.
  • Activation of Mania/Hypomania: In patients with bipolar disorder, treating a depressive episode with TRINTELLIX or another antidepressant may precipitate a mixed/manic episode. Prior to initiating treatment with TRINTELLIX, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.
  • Discontinuation Syndrome: Adverse reactions have been reported upon abrupt discontinuation of treatment with TRINTELLIX at doses of 15 mg/day and 20 mg/day. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.
  • Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs, including TRINTELLIX, may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
  • Hyponatremia: Hyponatremia has occurred as a result of treatment with serotonergic drugs, including TRINTELLIX, and in many cases appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Elderly patients and patients taking diuretics or who are otherwise volume-depleted can be at greater risk. Symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to falls. More severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. Discontinue TRINTELLIX in patients with symptomatic hyponatremia and institute appropriate medical intervention.
  • Sexual Dysfunction: Use of serotonergic antidepressants, including TRINTELLIX, may cause symptoms of sexual dysfunction. In male patients, serotonergic antidepressant use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, use may result in decreased libido and delayed or absent orgasm.

ADVERSE REACTIONS

The most commonly observed adverse reactions for TRINTELLIX in 6- to 8-week placebo-controlled studies (incidence ≥5% and at least twice the rate of placebo) were: nausea, constipation, and vomiting.

DRUG INTERACTIONS

Concomitant administration of TRINTELLIX and strong CYP2D6 inhibitors or strong CYP inducers may require a dose adjustment of TRINTELLIX.

PREGNANCY

Exposure to serotonergic antidepressants, including TRINTELLIX, in late pregnancy may increase the risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN). Monitor neonates who were exposed to TRINTELLIX in the third trimester for PPHN and drug discontinuation syndrome.

INDICATION

TRINTELLIX is indicated for the treatment of Major Depressive Disorder (MDD) in adults.

Please click for Full Prescribing Information.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at 

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  3. Henigsberg N, Mahableshwarkar AR, Jacobsen P, Chen Y, Thase ME. A randomized, double-blind, placebo-controlled 8-week trial of the efficacy and tolerability of multiple doses of Lu AA21004 in adults with Major Depressive Disorder. J Clin Psychiatry. 2012;73(7):953-959.
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  5. Mahableshwarkar AR, Jacobsen P, Chen Y, Serenko M, Trivedi MH. A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD. Psychopharmacology (Berl). 2015;232(12):2061-2070.
  6. Jacobsen P, Mahableshwarkar AR, Serenko M, Chan S, Trivedi MH. A randomized, double-blind, placebo-controlled study of the efficacy and safety of vortioxetine 10 mg and 20 mg in adults with Major Depressive Disorder. J Clin Psychiatry. 2015;76(5):575-582.
  7. Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with Major Depressive Disorder. Int Clin Psychopharmacol. 2012;27(4):215-223.
  8. McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014;17(10):1557-1567.
  9. Mahableshwarkar AR, Zajecka J, Jacobson W, Chen Y, Keefe RSE. A randomized, placebo-controlled, active-reference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in Major Depressive Disorder. Neuropsychopharmacology. 2015;40(8):2025-2037.
  10. Data on file. Takeda Pharmaceuticals.
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