Pharmacokinetics

• Parent drug has 3–7 hour half-life

• Active metabolite has 9–13 hour half-life

Drug Interactions

• Tramadol increases the risk of seizures in patients taking an antidepressant

• Can cause a fatal “serotonin syndrome” when combined with MAO inhibitors, so do not use with MAO inhibitors or for at least 14 days after MAOIs are stopped

• Do not start an MAO inhibitor for at least 5 half-lives (5 to 7 days for most drugs) after discontinuing venlafaxine

• Possible increased risk of bleeding, especially when combined with anticoagulants (e.g., warfarin, NSAIDs)

• Concomitant use with cimetidine may reduce clearance of venlafaxine and raise venlafaxine levels

• Could theoretically interfere with the analgesic actions of codeine or possibly with other triptans

• Few known adverse drug interactions

Other Warnings/Precautions

• Use with caution in patients with history of seizures

• Use with caution in patients with heart disease

• Use with caution in patients with bipolar disorder unless treated with concomitant mood-stabilizing agent

• When treating children, carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Distribute the brochures provided by the FDA and the drug companies

• Warn patients and their caregivers about the possibility of activating side effects and advise them to report such symptoms immediately

• Monitor patients for activation of suicidal ideation, especially children and adolescents

Do Not Use

• If patient has uncontrolled angle-closure glaucoma

• If patient is taking an MAO inhibitor

• If there is a proven allergy to venlafaxine

VENLAFAXINE: SPECIAL POPULATIONS

Renal Impairment

• Lower dose by 25–50%

• Patients on dialysis should not receive subsequent dose until dialysis is completed

Hepatic Impairment

• Lower dose by 50%

Cardiac Impairment

• Drug should be used with caution

• Hypertension should be controlled prior to initiation of venlafaxine and should be monitored regularly during treatment

• Venlafaxine has a dose-dependent effect on increasing blood pressure

• Venlafaxine is contraindicated in patients with heart disease in the U.K.

• Venlafaxine can block cardiac ion channels in vitro

• Venlafaxine worsens (i.e., reduces) heart rate variability in depression, perhaps due to norepinephrine reuptake inhibition

Elderly

• Some patients may tolerate lower doses better

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

• Use with caution, observing for activation of known or unknown bipolar disorder and/or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• Not specifically approved, but preliminary data suggest that venlafaxine is effective in children and adolescents with depression, anxiety disorders, and ADHD