Vortioxetine: uses, appearance and warnings

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

TRINTELLIX is available as: 5 mg: pink, almond shaped biconvex film coated tablet, debossed with "5" on one side and "TL" on the other side 10 mg: yellow, almond shaped biconvex film coated tablet, debossed with "10" on one side and "TL" on the other side 20 mg: red, almond shaped biconvex film coated tablet, debossed with "20" on one side and "TL" on the other side Tablets: 5 mg, 10 mg, and 20 mg ( 3 ).

TRINTELLIX tablets are available as follows: Features Strengths 5 mg 10 mg 20 mg Color pink yellow red Debossment "5" on one side of tablet "10" on one side of tablet "20" on one side of tablet "TL" on other side of tablet "TL" on other side of tablet "TL" on other side of tablet Presentations and NDC Codes Bottles of 30 64764-720-30 64764-730-30 64764-750-30 Bottles of 90 64764-720-90 64764-730-90 64764-750-90 Bottles of 500 64764-720-77 64764-730-77 64764-750-77 Store at 77°F (25°C); excursions permitted to 59°F to 86°F (15°C to 30°C) [see USP Controlled Room Temperature].

Hypersensitivity to vortioxetine or any component of the formulation. Hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported in patients treated with TRINTELLIX [see Adverse Reactions (6.2) ] . The use of MAOIs intended to treat psychiatric disorders with TRINTELLIX or within 21 days of stopping treatment with TRINTELLIX is contraindicated because of an increased risk of serotonin syndrome. The use of TRINTELLIX within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.4) , Warnings and Precautions (5.2) ] . Starting TRINTELLIX in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.2) ] . Hypersensitivity to vortioxetine or any components of the TRINTELLIX formulation ( 4 ). 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 ( 4 ).

Serotonin Syndrome : Increased risk when coadministered with other serotonergic agents, but also when taken alone. If it occurs, discontinue TRINTELLIX and serotonergic agents and initiate supportive measures ( 5.2 ). Increased Risk of Bleeding : Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, or other drugs that affect coagulation may increase risk ( 5.3 ). Activation of Mania/Hypomania : Screen patients for bipolar disorder ( 5.4 ). Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants ( 5.6 ). Hyponatremia : Can occur in association with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) ( 5.7 ). Sexual Dysfunction: TRINTELLIX may cause symptoms of sexual dysfunction ( 5.8 ). 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1 . Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric TRINTELLIX is not approved for use in pediatric patients. and Adult Patients Age Range Drug-Placebo Difference in Number of Patients with Suicidal Thoughts and Behaviors per 1000 Patients Treated Increases Compared to Placebo <18 years old 14 additional patients 18 to 24 years old 5 additional patients Decreases Compared to Placebo 25 to 64 years old 1 fewer patient ≥65 years old 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in adolescents and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that the use of antidepressants can delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients for all approved populations 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 emergent suicidal thoughts and behaviors. 5.2 Serotonin Syndrome Serotonergic antidepressants, including TRINTELLIX, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, buspirone, amphetamines, and St. John's Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications (4) , Drug Interactions (7.1) ] . Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome signs and 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 gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of TRINTELLIX with MAOIs is contraindicated. In addition, do not initiate TRINTELLIX in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking TRINTELLIX, discontinue TRINTELLIX before initiating treatment with the MAOI [see Contraindications (4) , Drug Interactions (7.1) ] . Monitor all patients taking TRINTELLIX for the emergence of serotonin syndrome. Discontinue treatment with TRINTELLIX and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of TRINTELLIX with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 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. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. …

The following adverse reactions are discussed in greater detail in other sections of the label. Hypersensitivity [see Contraindications (4) ] Clinical Worsening and Suicide Risk [see Warnings and Precautions (5.1) ] Serotonin Syndrome [see Warnings and Precautions (5.2) ] Increased Risk of Bleeding [see Warnings and Precautions (5.3) ] Activation of Mania/Hypomania [see Warnings and Precautions (5.4) ] Discontinuation Syndrome [see Warnings and Precautions (5.5) ] Angle Closure Glaucoma [see Warnings and Precautions (5.6) ] Hyponatremia [see Warnings and Precautions (5.7) ] 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 America, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

Strong inhibitors of CYP2D6: Reduce TRINTELLIX dose by half when coadministered ( 2.5 , 7.1 ). Strong CYP Inducers: Consider dose increase of TRINTELLIX dose when coadministered for more than 14 days. The maximum recommended dose should not exceed 3 times the original dose ( 2.6 , 7.1 ). 7.1 Drugs Having Clinically Important Interactions with TRINTELLIX Table 4: Clinically Important Drug Interactions with TRINTELLIX Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs and SNRIs including TRINTELLIX with MAOIs increases the risk of serotonin syndrome. Intervention Concomitant use of TRINTELLIX is contraindicated: With an MAOI intended to treat psychiatric disorders or within 21 days of stopping treatment with TRINTELLIX. Within 14 days of stopping an MAOI intended to treat psychiatric disorders. …