Version July 2025
| Drug | Bioavailability (%) | Time to peak plasma concentration (hours) | Primary metabolism* | Active metabolite(s) | Effect(s) on drug metabolism* | Elimination half-life (hours) | Clearance |
| Desvenlafaxine | 80 Unaffected by food | 7.5 to 9 | UGT glucuronidation | No | None | 9 to 11 Prolonged in renal or hepatic impairment | Renal and hepatic; 45% excreted unchanged Dose adjustment needed in renal or hepatic impairment |
| Duloxetine | 50 Wide interindividual variation (30 to 80); minimally affected by food | 6 (unfed) 10 (fed) | CYP1A2, CYP2D6 | No | Inhibits CYP2D6 | 10 to 12 Prolonged in hepatic impairment | Hepatic and renal; avoid in hepatic insufficiency (any degree), liver disease, or substantial alcohol use Dose adjustment needed in renal impairment |
| Levomilnacipran ER | >90 Unaffected by food | 6 to 8 Avoid concurrent administration with alcohol which can accelerate release of levomilnacipran from the extended-release preparation | Primarily CYP3A4 | No | None | 12 Prolonged in moderate to severe renal impairment | Renal and hepatic; 50 to 60% excreted unchanged Dose adjustment needed renal impairment |
| Milnacipran | 85 to 90 Unaffected by food | 2 to 4 | Glucuronidation | No | None | 8 to 10 Prolonged in moderate to severe renal impairment and severe hepatic impairment | Renal and hepatic; 50 to 60% excreted unchanged Dose adjustment needed in renal impairment |
| Venlafaxine | |||||||
| Immediate release | 13¶ Unaffected by food | 1 to 2 | CYP2D6, CYP3A4 | Yes (desvenlafaxine also known as O-dexmethylvenlafaxine or ODV) | None | 5 (parent) 11 (active metabolite) Prolonged in renal or hepatic impairment | Renal and hepatic; ~34% excreted as active desvenlafaxine (ODV) or unchanged Dose adjustment needed in renal or hepatic impairment |
| Extended release | 45¶ Unaffected by food | 5.5 | |||||
CYP: cytochrome P450; UGT: uridine diphosphate glucuronosyltransferase.
* The classification of effects on drug metabolism are based upon US Food and Drug Administration (FDA) guidance.[1,2] Other sources may use a different classification system resulting in some agents being classified differently. Weak inhibitor effects are not listed. Clinically significant interactions can occasionally occur due to weak inhibitors, particularly if the target drug has a narrow therapeutic margin. Refer to the drug interactions program for a full review of potential interactions.
¶ Oral bioavailability is increased by two- to threefold in mild to moderate hepatic impairment.
Data from:
