Safety Info & Adverse Events | 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.

Safety Data

How the safety profile fits in the story

Established safety profile: Safety of TRINTELLIX was evaluated in more than 5800 adult patients across multiple clinical studies1

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

Common Adverse Reactions (6- to 8-Week Studies) Table

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

Discontinuation rates

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

Discontinuation Rates (6- to 8-Week Studies) Table
  • Nausea was the most common adverse reaction reported as a reason for discontinuation1

Nausea1

  • The most common adverse reaction
  • Frequency was dose-related
  • Typically found to have been 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 6 short-term MDD studies and 1 long‑term MDD study1

Change in weight in randomized, double-blind, placebo-controlled studies10,11

Effect on body weight in randomized, double-blind, placebo-controlled studies table

No statistical analyses were conducted with regard to weight change in the US-based long-term study (Study 10); weight increase was a reported adverse reaction in the TRINTELLIX 20 mg group (≥5%).

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 the non-US long-term study (Study 9) 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 approval1

Switching from SSRIs to TRINTELLIX resulted in statistically superior improvement in TESD vs escitalopram in MDD patients1,13

Head-to-head study results showed TRINTELLIX lessened SSRI-induced sexual side effects for adult MDD patients more than escitalopram.1,13

Mean change from baseline in CSFQ-14 total score1,13

TRINTELLIX VS LEXAPRO® (ESCITALOPRAM) graphic

At Week 8, improvement in SSRI-induced sexual dysfunction in MDD patients switched to TRINTELLIX was superior to improvement in patients who switched to escitalopram.1

  • Clinically meaningful improvement considered to be 2- to 3-point increase in CSFQ-14 total score1
  • Assesses 3 phases of the sexual response cycle (desire, arousal, and orgasm)1,13
  • Results based on 8-week, head-to-head, randomized, double-blind study comparing TRINTELLIX (n=217) with escitalopram (n=207) in patients with well-treated MDD experiencing SSRI-induced sexual dysfunction as measured by CSFQ-141,13
  • Patients switched from citalopram, paroxetine, or sertraline to either TRINTELLIX or escitalopram (both groups started on 10 mg once daily, then increased to 20 mg at Week 1, followed by flexible dosing)1,13

Antidepressant efficacy was not lost when patients switched to TRINTELLIX or escitalopram1,13

Mean change from baseline in MADRS total score13

TRINTELLIX and escitalopram maintained antidepressant efficacy chart
  • Common adverse events (incidence ≥5% for TRINTELLIX) were nausea (25.0%, 5.4%), headache (9.4%, 7.7%), dizziness (8.0%, 5.0%), and pruritus, generalized (5.8%, 0%) for TRINTELLIX and escitalopram, respectively.13  Three patients experienced a total of 5 SAEs in the TRINTELLIX group and 1 patient in the escitalopram group reported 1 SAE. There was 1 case of suicidal behavior in the TRINTELLIX group but no attempted or completed suicides. Twenty patients (8.9%) in the TRINTELLIX group and 14 (6.3%) in the escitalopram group withdrew because of an AE
  • In clinical studies, TESD was both voluntarily and prospectively assessed in patients taking TRINTELLIX1
  • Warning and Precaution for 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 orgasm1

Abbrevations: CSFQ-14, Changes in Sexual Functioning Questionnaire; SAE, serious adverse event; SSRI, selective serotonin reuptake inhibitor; TESD, treatment-emergent sexual dysfunction.

Adverse sexual reactions were voluntarily and prospectively assessed1

  • Voluntary reports of adverse sexual reactions are known to be underreported1

Voluntary reports with TRINTELLIX were ≤5% in 6- to 8-week placebo-controlled studies*1

Voluntarily reported adverse sexual reactions table

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

Prospectively assessed rates of adverse sexual reactions1

  • Separate, self-rated questionnaire was provided to patients during clinical studies

Incidence of adverse sexual reactions using ASEX in patients without sexual dysfunction at baseline in 7 placebo-controlled studies†1

Prospectively assessed adverse sexual reactions bar graph

†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).1 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 3 or more items each with a score of ≥4.

Abbrevation: ASEX, Arizona Sexual Experiences Scale.

 

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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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