What is the half-life of vortioxetine (Brintellix) in an adult patient with depression or anxiety disorder and impaired renal function?

Half-Life of Vortioxetine

The mean terminal half-life of vortioxetine is approximately 66 hours, and this elimination half-life is not altered by renal impairment, including end-stage renal disease (ESRD). 1, 2

Pharmacokinetic Profile

• Vortioxetine exhibits linear and dose-proportional pharmacokinetics when administered once daily across the therapeutic dose range of 2.5 mg to 60 mg 1
• Steady-state plasma concentrations are typically achieved within two weeks of dosing due to the long elimination half-life 1, 2
• The mean absolute oral bioavailability is 75%, with maximal plasma concentration (Cmax) reached within 7 to 11 hours post-dose 1

Impact of Renal Impairment

• Renal impairment (mild, moderate, severe, or ESRD) does not affect the apparent clearance of vortioxetine, meaning no dose adjustment is necessary based on kidney function alone 1
• The presence of renal impairment does not alter the plasma protein binding of vortioxetine, which remains at 98% regardless of renal function status 1

Metabolism and Elimination

• Vortioxetine is extensively metabolized primarily through oxidation via multiple cytochrome P450 isozymes (CYP2D6, CYP3A4/5, CYP2C19, CYP2C9, CYP2A6, CYP2C8, and CYP2B6) followed by glucuronic acid conjugation 1
• CYP2D6 is the primary enzyme catalyzing metabolism to the major pharmacologically inactive carboxylic acid metabolite 1, 2
• Following a single oral dose, approximately 59% of radioactivity is recovered in urine and 26% in feces as metabolites, with negligible amounts of unchanged vortioxetine excreted in urine 1

Clinical Implications of the Long Half-Life

• The 66-hour half-life means that vortioxetine can be administered once daily without concern for missed doses causing rapid plasma level fluctuations 2
• Due to the extended half-life, steady-state conditions require approximately 2 weeks of consistent dosing, and any dose adjustments will take a similar timeframe to reach new steady-state levels 1, 2
• The only population requiring dose adjustment is CYP2D6 poor metabolizers, who have approximately twice the vortioxetine plasma concentration of extensive metabolizers due to impaired metabolism rather than altered elimination 1