Medications: Effexor^® – venlafaxine

Effexor XR is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of:

• Major Depressive Disorder (MDD)
• Generalized Anxiety Disorder (GAD)
• Social Anxiety Disorder (SAD)
• Panic Disorder (PD)

DOSAGE AND ADMINISTRATION

• Take once daily with food (2). Capsules should be taken whole; do not divide, crush, chew, or dissolve (2).
• When discontinuing treatment, reduce the dose gradually (2.8, 5.7).
• Renal impairment: reduce the total daily dose by 25% to 50% in patients with renal impairment. Reduce the total daily dose by 50% or more in patients undergoing dialysis or with severe renal impairment (2.6).
• Hepatic impairment: reduce the daily dose by 50% in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment or hepatic cirrhosis, it may be necessary to reduce the dose by more than 50% (2.6).

Most common adverse reactions (incidence ≥ 5% and at least twice the rate of placebo): nausea, somnolence, dry mouth, sweating, abnormal ejaculation, anorexia, constipation, erectile dysfunction, and libido decreased (6.1).

• Hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate, or any excipients in the Effexor XR formulation (4.1).
• Do not use with an MAOI or within 14 days of stopping an MAOI. Allow 7 days after stopping Effexor XR before starting an MAOI, because of the risk of serotonin syndrome (4.2, 5.2, 7.3).

WARNINGS AND PRECAUTIONS:

• Clinical Worsening/Suicide Risk: Monitor for clinical worsening and suicide risk (5.1).
• Serotonin Syndrome: Risk increases with concomitant use of other serotonergic drugs. Discontinue Effexor XR and initiate supportive treatment if serotonin syndrome occurs (4.2, 5.2, 7.3).
• Elevations in Blood Pressure: Control hypertension before initiating treatment. Monitor blood pressure regularly during treatment (5.3).
• Abnormal Bleeding: Effexor XR may increase risk of bleeding events. Caution patients about the risk of bleeding associated with the concomitant use of Effexor XR and NSAIDs, aspirin, or other drugs that affect coagulation (5.4).
• Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants. (5.5).
• Activation of Mania/Hypomania: Use cautiously in patients with bipolar disorder. Caution patients about the risk of activation of mania/hypomania (5.6).

Serotonergic Drugs (e.g., MAOIs, triptans, SSRIs, other SNRIs, linezolid, lithium, tramadol, or St. John’s wort): Potential for serotonin syndrome. Careful patient observation is advised (4.2, 5.2, 7.3).

During the premarketing evaluations of Effexor XR (for MDD, GAD, SAD, and PD) and Effexor (for MDD), there were twenty reports of acute overdosage with Effexor (6 and 14 reports in Effexor XR and Effexor patients, respectively), either alone or in combination with other drugs and/or alcohol.

Somnolence was the most commonly reported symptom. Among the other reported symptoms were paresthesia of all four limbs, moderate dizziness, nausea, numb hands and feet, and hot-cold spells 5 days after the overdose. In most cases, no signs or symptoms were associated with overdose. The majority of the reports involved ingestion in which the total dose of venlafaxine taken was estimated to be no more than several-fold higher than the usual therapeutic dose. One patient who ingested 2.75 g of venlafaxine was observed to have two generalized convulsions and a prolongation of QTc to 500 msec, compared with 405 msec at baseline. Mild sinus tachycardia was reported in two of the other patients.

Actions taken to treat the overdose included no treatment, hospitalization and symptomatic treatment, and hospitalization plus treatment with activated charcoal. All patients recovered.

In postmarketing experience, overdose with venlafaxine has occurred predominantly in combination with alcohol and/or other drugs. The most commonly reported events in overdosage include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, seizures, and vomiting. Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death have been reported.

Published retrospective studies report that venlafaxine overdosage may be associated with an increased

risk of fatal outcomes compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Epidemiological studies have shown that venlafaxine-treated patients have a higher preexisting burden of suicide risk factors than SSRI-treated patients. The extent to which the finding of an increased risk of fatal outcomes can be attributed to the toxicity of venlafaxine in overdosage, as opposed to some characteristic(s) of venlafaxine-treated patients, is not clear. Prescriptions for Effexor XR should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose.

Management of Overdosage

Consult a Certified Poison Control Center for up-to-date guidance and advice (1-800-222-1222 or www.poison.org). In case of an overdose, provide supportive care, including close medical supervision and monitoring. Treatment should consist of those general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Provide supportive and symptomatic measures.