Adults

Major Depressive Disorder: Initial dose 75 mg extended-release capsule once daily. May be increased to 150 mg/day after 2 weeks, and further up to 225 mg/day or 375 mg/day (for some conditions) if needed. Max 375 mg/day.

Elderly

Generally, no dose adjustment is required, but caution is advised due to potential age-related decrease in renal clearance. Start with a lower dose and monitor.

Renal_impairment

For moderate renal impairment (CrCl 30-70 mL/min), reduce total daily dose by 25%. For severe renal impairment (CrCl < 30 mL/min), reduce total daily dose by 50%. For hemodialysis patients, reduce total daily dose by 50% and administer after dialysis.

Onset

Therapeutic effects may be observed within 2-4 weeks, although some patients may respond earlier.

Excretion

Primarily excreted in the urine as ODV (approximately 30%), unconjugated venlafaxine (approximately 4%), and other minor metabolites.

Half life

Venlafaxine: approximately 5 hours; O-desmethylvenlafaxine (ODV): approximately 11 hours.

Absorption

Well absorbed from the gastrointestinal tract, approximately 92% bioavailable for immediate release formulations. Peak plasma concentrations of venlafaxine and ODV are reached within 2-4 hours and 4-6 hours, respectively, for extended-release.

Metabolism

Extensively metabolized in the liver, primarily by CYP2D6 to its major active metabolite, O-desmethylvenlafaxine (ODV), and by CYP3A4 to a minor, less active metabolite.

MAOIs

Serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes (including extreme agitation progressing to delirium and coma) have been reported. Do not use concomitantly.

Warfarin

Potentiation of anticoagulant effect, increased bleeding risk.

Cimetidine

May inhibit first-pass metabolism of venlafaxine, increasing plasma levels.

SSRIs/SNRIs/Triptans

Increased risk of serotonin syndrome.