Venlafaxine Hcl 150 mg (SR) · Hard-gelatin capsules

The mechanism of action of venlafaxine in the treatment of MDD, GAD, SAD, and PD is unclear, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake.

Venlafaxine and ODV steady-state concentrations are reached within 3 days. Venlafaxine and ODV exhibited linear kinetics over the dosage range of 75 to 450 mg per day (0.33 to 2 times the maximum recommended dosage). Time of administration (AM versus PM) did not affect the pharmacokinetics of venlafaxine and ODV from the 75 mg venlafaxine hydrochloride extended-release capsules.

Absorption — Venlafaxine is well absorbed. On the basis of mass balance studies, at least 92% of a single oral dose of venlafaxine is absorbed. The absolute bioavailability of venlafaxine is approximately 45%.

Administration of venlafaxine hydrochloride extended-release capsules (150 mg once daily) generally resulted in lower Cmax and later Tmax values than for venlafaxine hydrochloride tablets administered twice daily (Table 17). When equal daily doses of venlafaxine were administered as either an immediate-release tablet or the extended-release capsule, the exposure to both venlafaxine and ODV was similar for the two treatments, and the fluctuation in plasma concentrations was slightly lower with the venlafaxine hydrochloride extended-release capsules. Therefore, venlafaxine hydrochloride extended-release capsules provide a slower rate of absorption, but the same extent of absorption compared with the immediate-release tablet.

Distribution — Venlafaxine is 27% and ODV is 30% bound to plasma proteins. The apparent volume of distribution at steady-state is 7.5±3.7 L/kg for venlafaxine and 5.7±1.8 L/kg for ODV.

Elimination — Mean ± SD plasma apparent clearance at steady-state is 1.3±0.6 L/h/kg for venlafaxine and 0.4±0.2 L/h/kg for ODV. The apparent elimination half-life is 5±2 hours for venlafaxine and 11±2 hours for ODV.

Specific Populations — The effect of intrinsic patient factors on the pharmacokinetics of venlafaxine and its active metabolite ODV is presented in Figure 1.

ODV=O-desmethylvenlafaxine; AUC=area under the curve; Cmax=peak plasma concentrations.

*Similar effect is expected with strong CYP2D6 inhibitors.