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boxed warning
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior 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 [see Warnings and Precautions (5.1) ] . TRINTELLIX is not approved for use in pediatric patients [see Use in Specific Populations (8.4) ] . WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. • Increased risk of suicidal thinking and behavior in pediatric and young adult patients taking antidepressants. • Closely monitor for worsening and emergence of suicidal thoughts and behaviors ( 5.1 ). • TRINTELLIX is not approved for use in pediatric patients ( 8.4 ).
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warnings and cautions
5 WARNINGS AND PRECAUTIONS • 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
warnings and cautions table
Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in PediatricTRINTELLIX is not approved for use in pediatric patients. and Adult PatientsAge RangeDrug-Placebo Difference in Number of Patients with Suicidal Thoughts and Behaviors per 1000 Patients TreatedIncreases Compared to Placebo<18 years old14 additional patients18 to 24 years old5 additional patientsDecreases Compared to Placebo25 to 64 years old1 fewer patient≥65 years old6 fewer patients
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adverse reactions
6 ADVERSE REACTIONS 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. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Patient Exposure TRINTELLIX was evaluated for safety in 5,852 patients (18 years to 88 years of age) diagnosed with MDD who participated in pre- and postmarketing clinical studies; 2,616 of those patients were exposed to TRINTELLIX in 6 to 8 week, placebo-controlled studies at doses ranging from 5 mg to 20 mg once daily; 204 patients were exposed to TRINTELLIX in a 24 to 64 week placebo-controlled maintenance study at doses of 5 mg to 10 mg once daily; and 429 patients were exposed to TRINTELLIX in a 32 week placebo-controlled maintenance study in the U.S. at doses of 5 mg, 10 mg, and 20 mg, once daily. Patients from the 6 to 8 week studies continued into 12-month open-label studies. A total of 2,586 patients were exposed to at least one dose of TRINTELLIX in open-label studies, 1,727 were exposed to TRINTELLIX for 6 months and 885 were exposed for at least 1 year. Adverse Reactions Reported as Reasons for Discontinuation of Treatment In pooled 6 to 8 week placebo-controlled studies the incidence of patients who received TRINTELLIX 5 mg/day, 10 mg/day, 15 mg/day, and 20 mg/day and discontinued treatment because of an adverse reaction was 5%, 6%, 8%, and 8%...
adverse reactions table
Table 2: Adverse Reactions Occurring in ≥2% of Patients Treated with Any TRINTELLIX Dose and at Least 2% Greater Than the Incidence in Placebo-Treated PatientsSystem Organ Class Preferred TermTRINTELLIX 5 mg/dayTRINTELLIX 10 mg/dayTRINTELLIX 15 mg/dayTRINTELLIX 20 mg/dayPlaceboN=1013 %N=699 %N=449 %N=455 %N=1621 %Gastrointestinal disorders Nausea212632329 Diarrhea771076 Dry mouth77686 Constipation35663 Vomiting35661 Flatulence13211Nervous system disorders Dizziness66896Psychiatric disordersAbnormal dreams<1<1231Skin and subcutaneous tissue disorders Pruritusincludes pruritus generalized12331