Effexor XR - Clinical Pharmacology

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Liver Disease:

In 9 patients with hepatic cirrhosis, the pharmacokinetic disposition of both venlafaxine and ODV was significantly altered after oral administration of venlafaxine. Venlafaxine elimination half-life was prolonged by about 30, and clearance decreased by about 50 in cirrhotic patients compared to normal subjects. ODV elimination half-life was prolonged by about 60 , and clearance decreased by about 30 in cirrhotic patients compared to normal subjects. A large degree of intersubject variability was noted. Three patients with more severe cirrhosis had a more substantial decrease in venlafaxine clearance (about 90 ) compared to normal subjects. Dosage adjustment is necessary in these patients (see DOSAGE AND ADMINISTRATION).

Renal Disease:

In a renal impairment study, venlafaxine elimination half-life after oral administration was prolonged by about 50 and clearance was reduced by about 24 in renally impaired patients (GFR 10 to 70 mL/ min), compared to normal subjects. In dialysis patients, venlafaxine elimination half-life was prolonged by about 180 and clearance was reduced by about 57 compared to normal subjects.

Similarly, ODV elimination half-life was prolonged by about 40 although clearance was unchanged in patients with renal impairment (GFR 10 to 70 mL/ min) compared to normal subjects. In dialysis patients, ODV elimination half-life was prolonged by about 142 and clearance was reduced by about 56 compared to normal subjects. A large degree of intersubject variability was noted. Dosage adjustment is necessary in these patients (see DOSAGE AND ADMINISTRATION).

Clinical Trials Major Depressive Disorder

The efficacy of Effexor XR (venlafaxine hydrochloride) extended-release capsules as a treatment for major depressive disorder was established in two placebo-controlled, short-term, flexible-dose studies in adult outpatients meeting DSM-III-R or DSM-IV criteria for major depressive disorder.

A 12-week study utilizing Effexor XR doses in a range 75 to 150 mg/ day (mean dose for completers was 136 mg/ day) and an 8-week study utilizing Effexor XR doses in a range 75 to 225 mg/ day (mean dose for completers was 177 mg/ day) both demonstrated superiority of Effexor XR over placebo on the HAM-D total score, HAM-D Depressed Mood Item, the MADRS total score, the Clinical Global Impressions (CGI) Severity of Illness item, and the CGI Global Improvement item. In both studies, Effexor XR was also significantly better than placebo for certain factors of the HAM-D, including the anxiety/ somatization factor, the cognitive disturbance factor, and the retardation factor, as well as for the psychic anxiety score.