TRINTELLIX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRINTELLIX (TRINTELLIX).
Trintellix (vortioxetine) is a serotonin modulator and reuptake inhibitor. Its exact mechanism is not fully understood, but it is thought to work by inhibiting the reuptake of serotonin (5-HT) and by modulating several serotonin receptors, including 5-HT1A agonism, 5-HT1B partial agonism, 5-HT3 and 5-HT7 antagonism.
| Metabolism | Primarily metabolized by CYP2D6; minor pathways via CYP3A4/5, CYP2C9, CYP2C19, CYP2A6, CYP2B6, and CYP2C8. Primary metabolite is an inactive carboxylic acid metabolite. |
| Excretion | Primarily hepatic metabolism via CYP3A4 and CYP2C19, with approximately 26% of the dose recovered in urine (mostly as metabolites) and 60% in feces (mostly as metabolites). Less than 1% excreted as unchanged drug in urine. |
| Half-life | Terminal elimination half-life is approximately 66 hours (range 58-78 hours) for vortioxetine. This supports once-daily dosing; steady-state is reached within 2-3 weeks. |
| Protein binding | Approximately 98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 2600 L (or ~37 L/kg for a 70 kg person), indicating extensive tissue distribution. |
| Bioavailability | Absolute bioavailability is approximately 75% for the oral tablet. Bioavailability is unaffected by food. |
| Onset of Action | Oral: Therapeutic effects may be observed within 2-4 weeks, consistent with other antidepressants. Some improvement in symptoms may occur earlier, but full response typically requires 4-8 weeks. |
| Duration of Action | Sustained throughout the dosing interval (24 hours) with once-daily administration. Due to long half-life, withdrawal symptoms are unlikely, but gradual dose reduction is recommended to avoid discontinuation syndrome. |
10 mg orally once daily initially, then increase to 20 mg orally once daily based on tolerability; maximum 20 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended in severe renal impairment (CrCl <15 mL/min). |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh A). For moderate impairment (Child-Pugh B): limit dose to 10 mg/day. Not recommended in severe impairment (Child-Pugh C). |
| Pediatric use | Not FDA-approved for pediatric patients; no established dosing guidelines. |
| Geriatric use | Initiate at 10 mg orally once daily; titrate cautiously. No specific dose adjustment other than careful monitoring. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRINTELLIX (TRINTELLIX).
| Breastfeeding | Excreted in breast milk in animals; not studied in humans. M/P ratio unknown. Caution recommended; benefit of breastfeeding should be weighed against potential risk of serotonin syndrome or other adverse effects in the infant. If used, monitor infant for drowsiness, fussiness, and poor feeding. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: there is no adequate and well-controlled studies in pregnant women; based on animal data, there is potential risk of neural tube defects and cardiovascular malformations at doses lower than maximum recommended therapeutic dose. Second and third trimesters: exposure may increase risk of persistent pulmonary hypertension of the newborn (PPHN) and serotonin syndrome in the neonate if used near term; consider the risk of neonatal adaptation syndrome including respiratory distress, feeding difficulties, and irritability. |
■ FDA Black Box Warning
WARNING: SUICIDAL THOUGHTS AND 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 emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Trintellix is not approved for use in pediatric patients.
| Serious Effects |
["Hypersensitivity to vortioxetine or any inactive ingredients","Concomitant use of MAOIs or within 14 days of discontinuing an MAOI"]
| Precautions | ["Clinical Worsening and Suicide Risk","Serotonin Syndrome","Increased Risk of Bleeding","Activation of Mania/Hypomania","Angle-Closure Glaucoma","Hyponatremia","Sexual Dysfunction"] |
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| Fetal Monitoring | Monitor maternal mood, suicidal ideation, and serotonin syndrome (including symptoms like shivering, hyperthermia, agitation, myoclonus, hyperreflexia). Fetal monitoring: ultrasound for growth and anatomy; consider fetal echocardiogram if first-trimester exposure. Neonatal monitoring for PPHN (pulse oximetry), serotonin syndrome (including jitteriness, hypertonia, tremors), and adaptation syndrome (respiratory distress, feeding difficulties). |
| Fertility Effects | No effect on fertility in animal studies; no human fertility data available. Potential for serotonin-related effects (e.g., altered libido, erectile dysfunction) that may impact reproductive function. |