Vortioxetine

Brand Names: Trintellix

Drug Class: General Prescription

Overview

11 DESCRIPTION TRINTELLIX is an immediate-release tablet for oral administration that contains the beta (β) polymorph of vortioxetine hydrobromide (HBr), an antidepressant. Vortioxetine HBr is known chemically as 1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]-piperazine, hydrobromide. The empirical formula is C 18 H 22 N 2 S, HBr with a molecular weight of 379.36 g/mol.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of the antidepressant effect of vortioxetine is not fully understood, but is thought to be related to its enhancement of serotonergic activity in the CNS through inhibition of the reuptake of serotonin (5-HT). It also has several other activities including 5-HT3 receptor antagonism and 5-HT1A receptor agonism. The contribution of these activities to vortioxetine's antidepressant effect has not been established. 12.2 Pharmacodynamics Vortioxetine binds with high affinity to the human serotonin transporter (Ki=1.6 nM), but not to the norepinephrine (Ki=113 nM) or dopamine (Ki>1000 nM) transporters. Vortioxetine potently and selectively inhibits reuptake of serotonin (IC50=5.4 nM). Vortioxetine binds to 5-HT3 (Ki=3.

Indications

  • 1 INDICATIONS AND USAGE 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 ).

Common Doses

  • 10 mg
  • 20 mg
  • 5 mg
  • 15 mg

Dosage

2 DOSAGE AND ADMINISTRATION The recommended starting dose is 10 mg administered orally once daily without regard to meals ( 2.1 ). The dose should then be increased to 20 mg/day, as tolerated ( 2.1 ). Consider 5 mg/day for patients who do not tolerate higher doses ( 2.1 ). TRINTELLIX can be discontinued abruptly. However, 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 possible ( 2.3 ). The maximum recommended dose is 10 mg/day in known CYP2D6 poor metabolizers ( 2.5 ). 2.

Black Box 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.

Contraindications

  • 4 CONTRAINDICATIONS 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.

Side Effects

  • 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.

Interactions

  • 7 DRUG INTERACTIONS 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...