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Activation of Mania/ Hypomania During premarketing major depressive disorder studies, mania or hypomania occurred in 0.3 of Effexor XR-treated patients and 0.0 placebo patients. In premarketing GAD studies, 0.0 of
Effexor XR-treated patients and 0.2 of placebo-treated patients experienced mania or hypomania. In premarketing Social Anxiety Disorder studies, no Effexor XR-treated patients and no placebo-treated patients experienced mania or hypomania. In all premarketing major depressive disorder trials with Effexor, mania or hypomania occurred in 0.5% of venlafaxine-treated patients compared with 0 of placebo patients. Mania/ hypomania has also been reported in a small proportion of patients with mood disorders who were treated with other marketed drugs to treat major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, Effexor XR should be used cautiously in patients with a history of mania. Hyponatremia Text Continues Below
Hyponatremia and/ or the syndrome of inappropriate antidiuretic hormone secretion (SIADH) may occur with venlafaxine. This should be taken into consideration in patients who are, for example, volume-depleted, elderly, or taking diuretics. Mydriasis Mydriasis has been reported in association with venlafaxine; therefore patients with raised intraocular pressure or those at risk of acute narrow-angle glaucoma should be monitored. Seizures During premarketing experience, no seizures occurred among 705 Effexor XR-treated patients in the major depressive disorder studies, among 1381 Effexor XR-treated patients in GAD studies, or among 277 Effexor XR-treated patients in Social Anxiety Disorder studies. In all premarketing major depressive disorder trials with Effexor, seizures were reported at various doses in 0.3 (8/ 3082) of venlafaxine-treated patients. Effexor XR, like many antidepressants, should be used cautiously in patients with a history of seizures and should be discontinued in any patient who develops seizures. Abnormal Bleeding There have been reports of abnormal bleeding (most commonly ecchymosis) associated with venlafaxine treatment. While a causal relationship to venlafaxine is unclear, impaired platelet aggregation may result from platelet serotonin depletion and contribute to such occurrences. Serum Cholesterol Elevation Clinically relevant increases in serum cholesterol were recorded in 5.3% of venlafaxine-treated patients and 0.0% of placebo-treated patients treated for at least 3 months in placebo-controlled trials (see ADVERSE REACTIONS-Laboratory Changes). Measurement of serum cholesterol levels should be considered during long-term treatment. Suicide The possibility of a suicide attempt is inherent in major depressive disorder and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy. 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. The same precautions observed when treating patients with major depressive disorder should be observed when treating patients with GAD or Social Anxiety Disorder. Use in Patients With Concomitant Illness Premarketing experience with venlafaxine in patients with concomitant systemic illness is limited. Caution is advised in administering Effexor XR to patients with diseases or conditions that could affect hemodynamic responses or metabolism. Venlafaxine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were systematically excluded from many clinical studies during venlafaxine's premarketing testing. The electrocardiograms were analyzed for 275 patients who received Effexor XR and 220 patients who received placebo in 8-to 12-week double-blind, placebo-controlled trials in major depressive disorder, for 610 patients who received Effexor XR and 298 patients who received placebo in 8-week double-blind, placebo-controlled trials in GAD, and for 195 patients who received Effexor XR and 228 patients who received placebo in 12-week double-blind, placebo-controlled trials in Social Anxiety Disorder. The mean change from baseline in corrected QT interval (QTc) for Effexor XR-treated patients in major depressive disorder studies was increased relative to that for placebo-treated patients (increase of 4.7 msec for Effexor XR and decrease of 1.9 msec for placebo). The mean change from baseline in corrected QT interval (QTc) for Effexor XR-treated patients in the GAD studies did not differ significantly from that with placebo. The mean change from baseline in QTc for Effexor XR-treated patients in the Social Anxiety Disorder studies was increased relative to that for placebo-treated patients (increase of 2.8 msec for Effexor XR and decrease of 2.0 msec for placebo). In these same trials, the mean change from baseline in heart rate for Effexor XR-treated patients in the major depressive disorder studies was significantly higher than that for placebo (a mean increase of 4 beats per minute for Effexor XR and 1 beat per minute for placebo). The mean change from baseline in heart rate for Effexor XR-treated patients in the GAD studies was significantly higher than that for placebo (a mean increase of 3 beats per minute for Effexor XR and no change for placebo). The mean change from baseline in heart rate for Effexor XR-treated patients in the Social Anxiety Disorder studies was significantly higher than that for placebo (a mean increase of 5 beats per minute for Effexor XR and no change for placebo). In a flexible-dose study, with Effexor doses in the range of 200 to 375 mg/ day and mean dose greater than 300 mg/ day, Effexor-treated patients had a mean increase in heart rate of 8.5 beats per minute compared with 1.7 beats per minute in the placebo group. As increases in heart rate were observed, caution should be exercised in patients whose underlying medical conditions might be compromised by increases in heart rate (eg, patients with hyperthyroidism, heart failure, or recent myocardial infarction), particularly when using doses of Effexor above 200 mg/ day. Evaluation of the electrocardiograms for 769 patients who received immediate release Effexor in 4-to 6-week double-blind, placebo-controlled trials showed that the incidence of trial-emergent conduction abnormalities did not differ from that with placebo. In patients with renal impairment (GFR = 10 to 70 mL/ min) or cirrhosis of the liver, the clearances of venlafaxine and its active metabolites were decreased, thus prolonging the elimination half-lives of these substances. A lower dose may be necessary (see DOSAGE AND ADMINISTRATION). Effexor XR, like all drugs effective in the treatment of major depressive disorder, should be used with caution in such patients.
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