TRINTELLIX SAFETY PROFILE

INDICATION: 

TRINTELLIX is indicated for the treatment of major depressive disorder (MDD) in adults.

Individual results may vary.

Adverse Reactions

Common adverse reactions occurring in ≥ 2% of patients treated with TRINTELLIX and at least 2% greater than the incidence in placebo-treated patients in 6- to 8-week trials*1

SYSTEM ORGAN CLASS 
PREFERRED TERM
PLACEBO, %
n=1621
5 MG/DAY, %
n=1013
10 MG/DAY, %
n=699
20 MG/DAY,%
n=455
GASTROINTESTINAL DISORDERS
Nausea 9 21 26 32
Diarrhea 6 7 7 7
Dry Mouth 6 7 7 8
Constipation 3 3 5 6
Vomiting 1 3 5 6
Flatulence 1 1 3 1
NERVOUS SYSTEM DISORDERS  
Dizziness 6 6 6 9
PSYCHIATRIC DISORDERS
Abnormal Dreams 1 <1 <1 3
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Pruritus 1 1 2 3

*Based on the rates for 5-, 10-, 15- and 20-mg doses.1

Includes pruritus generalized.1

Discontinuation rates

TRINTELLIX discontinuation rates due to adverse reactions in pooled 6- to 8-week clinical studies1

PLACEBO 5 MG 10 MG 20 MG
4% 5% 6% 8%
  • The most common adverse reaction reported as a reason for discontinuation was nausea

Additional Information About Nausea1

  • Frequency was dose-related
  • Usually considered mild or moderate in intensity
  • Most commonly occurred in the first week of treatment, with 15% to 20% of patients experiencing nausea after 1 to 2 days of treatment
  • Approximately 10% of patients taking TRINTELLIX 10 mg/day to 20 mg/day still had nausea at the end of the 6- to 8-week placebo-controlled studies
  • Median duration was 2 weeks

No Significant Effect on Body Weight in Short- and Long-term Studies

Effect on body weight in randomized, double-blind, placebo-controlled studies1,10

  SHORT-TERM STUDIES
(6 TO 8 WEEKS)
LONG-TERM STUDY
(6 MONTHS)
  PLACEBO
n=1536
TRINTELLIX
5 MG TO 20 MG/DAY

n=2477
PLACEBO
n=187
TRINTELLIX
5 MG OR 10 MG/DAY

n=198
Mean change in weight from baseline +0.1 kg 0.0 kg +0.1 kg +0.4 kg

Short-term: TRINTELLIX 5 mg/day to 20 mg/day had no significant effect on body weight as measured by the mean change from baseline in 6- to 8-week placebo-controlled studies1

Long-term: In the 6-month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to TRINTELLIX during the initial 12-week, open-label phase, there was no significant effect on body weight between TRINTELLIX and placebo-treated patients1

 

Some reports of weight gain have been received since product approval.1

Sexual dysfunction was voluntarily and prospectively assessed

Voluntary reports of sexual dysfunction with TRINTELLIX were low (≤5%)1

Voluntary reports of sexual dysfunction in 6- to 8-week placebo-controlled trials*1

  PLACEBO TRINTELLIX
5MG
TRINTELLIX
10MG
TRINTELLIX
20 MG
Females <1% <1% 1% 2%
Males 2% 3% 4% 5%

*Voluntarily reported adverse reactions related to sexual dysfunction were captured as individual event terms and aggregated to report overall incidence.1

Because voluntary reports of sexual dysfunction are known to be underreported, a separate, self-rated questionnaire was provided to patients prospectively in TRINTELLIX clinical studies.1

 

Prospectively assessed rates of sexual dysfunction with TRINTELLIX1

Incidence of treatment-emergent sexual dysfunction using ASEX in patients without sexual dysfunction at baseline in 7 placebo-controlled trials†1

Barchart Asex

Abbreviation: ASEX, Arizona Sexual Experiences Scale.

Incidence based on the number of subjects with sexual dysfunction during the study/number of subjects without sexual dysfunction at baseline (approximately 1/3 of the population across all study groups). Sexual dysfunction was defined as a subject scoring any of the following on the ASEX scale at 2 consecutive visits during the study: total score ≥19; any single item ≥5; or three or more items each with a score of ≥4.1

Important Safety Information for TRINTELLIX (vortioxetine)

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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.

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.

TRINTELLIX has not been evaluated for use in pediatric patients.

CONTRAINDICATIONS

Hypersensitivity: Hypersensitivity to vortioxetine or any components of the TRINTELLIX formulation. Angioedema has been reported in patients treated with TRINTELLIX.

Monoamine Oxidase Inhibitors (MAOIs): Due to an increased risk of serotonin syndrome, 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. Do not start TRINTELLIX in a patient who is being treated with linezolid or intravenous methylene blue.

WARNINGS AND PRECAUTIONS

Clinical Worsening and Suicide Risk: All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality (anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania), especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients daily.

Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with serotonergic antidepressants (SNRIs, SSRIs, and others), including TRINTELLIX, when used alone but more often when used concomitantly with other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, 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 (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If such symptoms occur, discontinue TRINTELLIX and any concomitant serotonergic agents, and initiate supportive symptomatic treatment. If concomitant use of TRINTELLIX is clinically warranted, patients should be made aware of and monitored for potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.

Abnormal Bleeding: 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 NSAIDs, aspirin, or other drugs that affect coagulation.

Activation of Mania/Hypomania: Activation of mania/hypomania can occur with antidepressant treatment. Prior to initiating treatment with an antidepressant, screen patients for bipolar disorder. As with all antidepressants, use TRINTELLIX cautiously in patients with a history or family history of bipolar disorder, mania, or hypomania.

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 serotonergic drugs 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. More severe or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. Discontinue TRINTELLIX in patients with symptomatic hyponatremia and initiate appropriate medical intervention.

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 by dose (5 mg, 10 mg, 15 mg, 20 mg) vs placebo: nausea (21%, 26%, 32%, 32% vs 9%), constipation (3%, 5%, 6%, 6% vs 3%), and vomiting (3%, 5%, 6%, 6% vs 1%).

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

Indication

TRINTELLIX is indicated for the treatment of major depressive disorder in adults.

Please see Full Prescribing Information and Medication Guide for TRINTELLIX.

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