Venlafaxine

INDICATIONS AND USAGE Venlafaxine tablets, USP is indicated for the treatment of major depressive disorder. The efficacy of venlafaxine tablets, USP in the treatment of major depressive disorder was established in 6 week controlled trials of adult outpatients whose diagnoses corresponded most closely to the DSM-III or DSM-III-R category of major depression and in a 4 week controlled trial of inpatients meeting diagnostic criteria for major depression with melancholia (see CLINICAL TRIALS ).

ADVERSE REACTIONS Associated With Discontinuation of Treatment Nineteen percent (537/2897) of venlafaxine patients in Phase 2 and Phase 3 depression studies discontinued treatment due to an adverse event. The more common events (≥1%) associated with discontinuation and considered to be drug-related (i.e., those events associated with dropout at a rate approximately twice or greater for venlafaxine compared to placebo) included: Venlafaxine Placebo CNS Somnolence 3% 1% Insomnia 3% 1% Dizziness 3% - Nervousness 2% - Dry mouth 2% - Anxiety 2% 1% Gastrointestinal Nausea 6% 1% Urogenital Abnormal ejaculation* 3% - Other Headache 3% 1% Asthenia 2% - Sweating 2% - * Percentages based on the number of males.

Pregnancy Teratogenic Effects Venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 11 times (rat) or 12 times (rabbit) the maximum recommended human daily dose on a mg/kg basis, or 2.5 times (rat) and 4 times (rabbit) the human daily dose on a mg/m 2 basis. However, in rats, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. The cause of these deaths is not known.

Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of venlafaxine tablets, USP or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. WARNINGS Clinical Worsening and Suicide Risk Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. CONTRAINDICATIONS Hypersensitivity to venlafaxine hydrochloride or to any excipients in the formulation. The use of MAOIs intended to treat psychiatric disorders with Venlafaxine tablets, USP or within 7 days of stopping treatment with venlafaxine tablets, USP is contraindicated because of an increased risk of serotonin syndrome.