Half-Life of Venlafaxine
Venlafaxine has an elimination half-life of 5 ± 2 hours, while its active metabolite O-desmethylvenlafaxine (ODV) has a half-life of 11 ± 2 hours at steady state. 1
Pharmacokinetic Details
Parent Compound (Venlafaxine)
- The elimination half-life ranges from 3-4 hours in most studies, with FDA labeling specifying 5 ± 2 hours at steady state 1, 2, 3
- Steady-state plasma concentrations are achieved within 3 days of multiple-dose therapy 1
- Mean steady-state plasma clearance is 1.3 ± 0.6 L/h/kg 1
Active Metabolite (O-desmethylvenlafaxine/ODV)
- The half-life is approximately 10-11 hours, with FDA labeling specifying 11 ± 2 hours at steady state 1, 4, 5
- ODV is the only major active metabolite and accounts for much of venlafaxine's therapeutic effect 1
- Mean steady-state plasma clearance of ODV is 0.4 ± 0.2 L/h/kg 1
Clinical Implications of Short Half-Life
Dosing Frequency
- The short half-life of venlafaxine necessitates twice-daily or three-times-daily dosing with immediate-release formulations to maintain therapeutic levels 1
- Extended-release formulations were developed specifically to address the short half-life and allow once-daily dosing 1
Discontinuation Syndrome Risk
- The short half-life increases risk of withdrawal symptoms if doses are missed or the medication is abruptly stopped 6
- Tapering over 10-14 days is recommended when discontinuing to minimize withdrawal syndrome 6
Special Populations with Altered Half-Life
Renal Impairment
- In patients with renal impairment (GFR 10-70 mL/min), venlafaxine half-life is prolonged by approximately 50% 1, 7
- In dialysis patients, venlafaxine half-life increases by approximately 180% and ODV half-life by 142% 1, 7
- Dosage adjustment is mandatory in patients with creatinine clearance below 30 mL/min 1, 7
Hepatic Impairment
- In patients with hepatic cirrhosis, venlafaxine half-life is prolonged by approximately 30% 1
- ODV half-life is prolonged by approximately 60% in cirrhotic patients 1
- In Child-Pugh B patients, oral elimination half-life is approximately twice as long as normal subjects 1