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Important Safety Information for EFFEXOR XR

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 EFFEXOR XR®(venlafaxine HCl) or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. EFFEXOR XR is not approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk, PRECAUTIONS: Information for Patients, and PRECAUTIONS: Pediatric Use.)
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EFFEXOR XR® Efficacy

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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.1

The first was 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 the second was 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.1

In one longer-term study, adult outpatients meeting DSM-IV criteria for major depressive disorder who had responded* during an 8-week open trial on Effexor XR (75, 150, or 225 mg, qAM) were randomized to continuation of their same Effexor XR dose or to placebo, for up to 26 weeks of observation for relapse.† Patients receiving continued Effexor XR treatment experienced significantly lower relapse rates over the subsequent 26 weeks compared with those receiving placebo.1

*Response during the open phase was defined as a CGI Severity of Illness item score of ≤3 and a HAM-D-21 total score of ≤10 at the day 56 evaluation.1

†Relapse during the double-blind phase was defined as follows: (1) a reappearance of major depressive disorder as defined by DSM-IV criteria and a CGI Severity of Illness item score of ≥4 (moderately ill), (2) 2 consecutive CGI Severity of Illness item scores of ≥4, or (3) a final CGI Severity of Illness item score of ≥4 for any patient who withdrew from the study for any reason.1

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Panic Disorder

EFFEXOR XR Provides Long-term Relief of Symptoms

The efficacy of Effexor XR capsules as a treatment for panic disorder was established in two double-blind, 12-week, multicenter, placebo-controlled studies in adult outpatients meeting DSM-IV criteria for panic disorder, with or without agoraphobia. Patients received fixed doses of 75 or 150 mg/day in one study and 75 or 225 mg/day in the other study.1

Efficacy was assessed on the basis of outcomes in three variables: (1) percentage of patients free of full-symptom panic attacks on the Panic and Anticipatory Anxiety Scale (PAAS); (2) mean change from baseline to endpoint on the Panic Disorder Severity Scale (PDSS) total score; and (3) percentage of patients rated as responders (much improved or very much improved) on the Clinical Global Impressions (CGI) Improvement scale.1

In these two trials, Effexor XR was significantly more effective than placebo in all three variables.1

In a longer-term study, adult outpatients meeting DSM-IV criteria for panic disorder who had responded* during a 12-week open phase with Effexor XR (75 to 225 mg/day) were randomly assigned to continue the same Effexor XR dose (75, 150, or 225 mg) or switch to placebo for observation for relapse† under double-blind conditions. Randomized patients were in response status for a mean time of 34 days prior to being randomized. In the randomized phase following the 12-week open-label period, patients receiving continued Effexor XR experienced a significantly longer time to relapse.1

*Response during the open phase was defined as ≤ 1 full-symptom panic attack per week during the last 2 weeks of the open phase and a CGI Improvement score of 1 (very much improved) or 2 (much improved).1

†Relapse during the double-blind phase was defined as having 2 or more full-symptom panic attacks per week for 2 consecutive weeks or having discontinued due to loss of effectiveness as determined by the investigators during the study.1

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Generalized Anxiety Disorder

Significantly Better Than Placebo Based on Primary Efficacy Measures

The efficacy of EFFEXOR XR capsules as a treatment for Generalized Anxiety Disorder (GAD) was established in two 8-week, placebo-controlled, fixed-dose studies, one 6-month placebo-controlled, fixed-dose study, and one 6-month, placebo-controlled, flexible-dose study in adult outpatients meeting DSM-!V criteria for GAD.1

One 8-week study evaluating EFFEXOR XR doses of 75, 150, and 225 mg/day, and placebo showed that the
225 mg/day dose was more effective than placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score, both the HAM-A anxiety and tension items, and the Clinical Global Impressions (CGI) scale. While there was also evidence for superiority over placebo for the 75 and 150 mg/day dose, these doses were not as consistently effective as the highest dose. A second 8-week study evaluating EFFEXOR XR doses of 75 and 150 mg/day and placebo showed that both doses were more effective than placebo on some of these same outcomes; however, the 75 mg/day dose was more consistently effective than the 150 mg/day dose. A dose-response relationship for effectiveness in GAD was not clearly established in the 75 to 225 mg/day dose range utilized in these two studies.1

Two 6-month studies, one evaluating EFFEXOR XR doses of 37.5, 75, and 150 mg/day and the other evaluating EFFEXOR XR doses of 75 to 225 mg/day, showed that daily doses of 75 mg or higher were more effective than placebo on the HAM-A total, both the HAM-A anxiety and tension items, and the CGI scale during 6 months of treatment. While there was also evidence for superiority over placebo for the 37.5 mg/day dose, this dose was not as consistently effective as the higher doses.1

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Social Anxiety Disorder

Proven Efficacy in Treatment of Social Anxiety Disorder

The efficacy of EFFEXOR XR capsules as a treatment for Social Anxiety Disorder (also known as Social Phobia) was established in four double-blind, parallel-group, 12-week, multicenter, placebo-controlled, flexible-dose studies and one double-blind, parallel-group, 6-month, placebo-controlled, fixed/flexible-dose study in adult outpatients meeting DSM-IV criteria for Social Anxiety Disorder. Patients received doses in a range of 75 to 225 mg/day. Efficacy was assessed with the Liebowitz Social Anxiety Scale (LSAS). In these five trials, EFFEXOR XR was significantly more effective than placebo on change from baseline to endpoint on the LSAS total score. There was no evidence for any greater effectiveness of the 150 to 225 mg/day group compared to the 75 mg/day group in the 6-month study.1

Review the EFFEXOR XR tolerability and dosing information »
 
Review the EFFEXOR XR tolerability and dosing information »

Indications

EFFEXOR XR (venlafaxine HCl) Extended-Release Capsules are indicated for the treatment, in adults, of Depression, Generalized Anxiety Disorder (GAD), Social Anxiety Disorder (SAD), and Panic Disorder (PD) with or without agoraphobia.

Important Safety Information for EFFEXOR XR

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 EFFEXOR XR®(venlafaxine HCl) or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. EFFEXOR XR is not approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk, PRECAUTIONS: Information for Patients, and PRECAUTIONS: Pediatric Use.)

  • Effexor XR is contraindicated in patients with a known hypersensitivity to venlafaxine hydrochloride or to any excipients in the formulation.
  • EFFEXOR XR is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs). EFFEXOR XR should not be used in combination with an MAOI or within at least 14 days of discontinuing treatment with an MAOI because of potential for serious adverse reactions. Based on the half-life of EFFEXOR XR, at least 7 days should be allowed after stopping EFFEXOR XR before starting an MAOI.
  • Adult and pediatric patients with MDD can experience worsening of their depression and/or the emergence of suicidal ideation and behavior, whether or not they are taking antidepressants. All patients treated with antidepressants should be monitored appropriately and observed closely for clinical worsening and suicidality, especially at the beginning of drug therapy, or at the time of increases or decreases in dose. Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania have been reported and may represent precursors to emerging suicidality. Stopping or modifying therapy should be considered especially when symptoms are severe, abrupt in onset, or not part of presenting symptoms.
  • Development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including EFFEXOR XR treatment, but particularly with concomitant use of serotonergic drugs (including triptans), with drugs that impair the metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. If concomitant use with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Concomitant use of EFFEXOR XR with serotonin precursors is not recommended.
  • Treatment with venlafaxine is associated with sustained increases in blood pressure (BP) in some patients. Three percent of EFFEXOR XR patients in MDD studies (doses of 75 to 375 mg/day), 0.5% in generalized anxiety disorder (GAD) studies (doses of 37.5 to 225 mg/day), 0.6% in social anxiety disorder (SAD) studies (doses of 75 to 225 mg/day), and 0.9% in panic disorder (PD) studies (doses of 75 to 225 mg/day) had sustained BP elevations. Experience with immediate-release venlafaxine in MDD studies showed that sustained hypertension was dose related, increasing from 3% to 7% at doses of 100 to 300 mg/day, to 13% at doses above 300 mg/day. Postmarketing cases of elevated BP requiring immediate treatment have been reported. Pre-existing hypertension should be controlled. Regular BP monitoring is recommended. For patients who experience a sustained increase in BP, either dose reduction or discontinuation should be considered.
  • SSRIs and SNRIs, including EFFEXOR XR, may increase the risk of bleeding events. Concomitant use of aspirin, NSAIDs, warfarin, and other anticoagulants may add to this risk.
  • Mydriasis has been reported in association with venlafaxine; therefore, patients with raised intraocular pressure or those at risk of acute narrow-angle glaucoma (angle-closure glaucoma) should be monitored.
  • Effexor XR is not approved for use in bipolar depression. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder.
  • As with all antidepressants, EFFEXOR XR should be used cautiously in patients with a history or family history of mania or hypomania, or with a history of seizure disorder.
  • Clinically relevant increases in serum cholesterol were observed in clinical studies in 5.3% of venlafaxine patients
  • Abrupt discontinuation or dose reduction has been associated with discontinuation symptoms. Patients should be counseled on possible discontinuation symptoms and monitored while discontinuing the drug; the dose should be tapered gradually. See the PRECAUTIONS section of the Prescribing Information.
  • For patients with renal or hepatic impairment, dosage adjustment may be required.
  • Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine therapy have been rarely reported.
  • Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including EFFEXOR XR. Discontinuation of EFFEXOR XR should be considered in patients with symptomatic hyponatremia
  • The most commonly observed adverse reactions in patients taking EFFEXOR XR vs placebo in short-term placebo-controlled studies (incidence ≥10% and at least twice the rate of placebo) of MDD were nausea (31% vs 12%), dizziness (20% vs 9%), somnolence (17% vs 8%), abnormal ejaculation (16% vs <1%), sweating (14% vs 3%), dry mouth (12% vs 6%), and nervousness (10% vs 5%); of GAD were nausea (35% vs 12%), dry mouth (16% vs 6%), abnormal ejaculation (11% vs <1%), sweating (10% vs 3%), and constipation (10% vs 4%); of SAD were nausea (31% vs 9%), dizziness (16% vs 8%), somnolence (20% vs 8%), abnormal ejaculation (19% vs <1%), sweating (13% vs 4%), dry mouth (17% vs 4%), nervousness (10% vs 5%), insomnia (24% vs 8%), asthenia (19% vs 9%), and anorexia (17% vs 2%); of panic disorder were somnolence (12% vs 6%), sweating (10% vs 2%), and dry mouth (12% vs 6%). [ Note: If speaking to only one indication, then list only AEs assoctiated with that indication ]
  • As with any psychotropic drug, EFFEXOR XR may impair judgment, thinking, or motor skills; patients should be advised to exercise caution until they have adapted to therapy.