Pharmacy & Therapeutics - September 2008 - (Page 495)

therefore, patients with raised intraocular pressure or those at risk of acute narrow-angle glaucoma (angle-closure glaucoma) should be monitored. Activation of Mania/Hypomania-During all MDD and VMS (vasomotor symptoms) phase 2 and phase 3 studies, mania was reported for approximately 0.1% of patients treated with Pristiq. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorder who were treated with other marketed antidepressants. As with all antidepressants, Pristiq should be used cautiously in patients with a history or family history of mania or hypomania. Cardiovascular/Cerebrovascular Disease-Caution is advised in administering Pristiq to patients with cardiovascular, cerebrovascular, or lipid metabolism disorders [see Adverse Reactions (6.1)]. Increases in blood pressure and heart rate were observed in clinical studies with Pristiq. Pristiq has not been evaluated systematically in patients with a recent history of myocardial infarction, unstable heart disease, uncontrolled hypertension, or cerebrovascular disease. Patients with these diagnoses, except for cerebrovascular disease, were excluded from clinical studies. Serum Cholesterol and Triglyceride Elevation-Dose-related elevations in fasting serum total cholesterol, LDL (low density lipoprotein) cholesterol, and triglycerides were observed in the controlled studies. Measurement of serum lipids should be considered during treatment with Pristiq [see Adverse Reactions (6.1)]. Discontinuation of Treatment with Pristiq-Discontinuation symptoms have been systematically and prospectively evaluated in patients treated with Pristiq during clinical studies in Major Depressive Disorder. Abrupt discontinuation or dose reduction has been associated with the appearance of new symptoms that include dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams, and hyperhidrosis. In general, discontinuation events occurred more frequently with longer duration of therapy. During marketing of SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors) and SSRIs (Selective Serotonin Reuptake Inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms. Patients should be monitored for these symptoms when discontinuing treatment with Pristiq. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate [see Dosage and Administration (2.4) and Adverse Reactions (6.1) in full prescribing information]. Renal Impairment-In patients with moderate or severe renal impairment or end-stage renal disease (ESRD) the clearance of Pristiq was decreased, thus prolonging the elimination half-life of the drug. As a result, there were potentially clinically significant increases in exposures to Pristiq [see Clinical Pharmacology (12.6) in full prescribing information]. Dosage adjustment (50 mg every other day) is necessary in patients with severe renal impairment or ESRD. The doses should not be escalated in patients with moderate or severe renal impairment or ESRD [see Dosage and Administration (2.2) in full prescribing information]. Seizure- Cases of seizure have been reported in premarketing clinical studies with Pristiq. Pristiq should be prescribed with caution in patients with a seizure disorder. Hyponatremia- Hyponatremia can occur as a result of treatment with SSRIs and SNRIs, including Pristiq. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Elderly patients can be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also, patients taking diuretics or who are otherwise volume depleted can be at greater risk [see Use in Specific Populations (8.5) and Clinical Pharmacology (12.6) in full prescribing information]. Discontinuation of Pristiq should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted. Coadministration of Drugs Containing Desvenlafaxine and Venlafaxine- Desvenlafaxine is the major active metabolite of venlafaxine. Products containing desvenlafaxine and products containing venlafaxine should not be used concomitantly with Pristiq. Interstitial Lung Disease and Eosinophilic Pneumonia- Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine (the parent drug of Pristiq) therapy have been rarely reported. The possibility of these adverse events should be considered in patients treated with Pristiq who present with progressive dyspnea, cough, or chest discomfort. Such patients should undergo a prompt medical evaluation, and discontinuation of Pristiq should be considered. ADVERSE REACTIONS: Clinical Studies Experience: The most commonly observed adverse reactions in Pristiq-treated MDD patients in short-term fixed-dose studies (incidence ≥5% and at least twice the rate of placebo in the 50- or 100-mg dose groups) were nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, and specific male sexual function disorders. Adverse reactions reported as reasons for discontinuation of treatment- The most common adverse reactions leading to discontinuation in at least 2% of the Pristiq-treated patients in the short-term studies, up to 8 weeks, were nausea (4%); dizziness, headache and vomiting (2% each); in the long-term study, up to 9 months, the most common was vomiting (2%). Common adverse reactions in placebo-controlled MDD studies- Table 3 in full PI shows the incidence of common adverse reactions that occurred in ≥2% of Pristiq-treated MDD patients at any dose in the 8-week, placebo-controlled, fixed-dose, premarketing clinical studies. In general, the adverse reactions were most frequent in the first week of treatment. Cardiac disorders: Palpitations, Tachycardia, Blood pressure increased; Gastrointestinal disorders: Nausea, Dry mouth, Diarrhea, Constipation, Vomiting; General disorders and administration site conditions: Fatigue, Chills, Feeling jittery, Asthenia; Metabolism and nutrition disorders: Decreased appetite, weight decreased; Nervous system disorders: Dizziness, Somnolence, Headache, Tremor, Paraesthesia, Disturbance in attention; Psychiatric Disorders: Insomnia, Anxiety, Nervousness, Irritability, Abnormal dreams; Renal and urinary disorders: Urinary hesitation; Respiratory, thoracic, and mediastinal disorders: Yawning; Skin and subcutaneous tissue disorders: Hyperhidrosis, Rash; Special Senses: Vision blurred; Mydriasis, Tinnitus, Dysgeusia; Vascular Disorders: Hot flush. Sexual function adverse reactions-Table 4 shows the incidence of sexual function adverse reactions that occurred in ≥2% of Pristiq-treated MDD patients in any fixed-dose group (8-week, placebo-controlled, fixed and flexible-dose, premarketing clinical studies). Men Only: Anorgasmia, Libido decreased, Orgasm abnormal, Ejaculation delayed, Erectile dysfunction, Ejaculation disorder, Ejaculation failure, Sexual dysfunction; Women Only: Anorgasmia Other adverse reactions observed in premarketing clinical studies: Other infrequent adverse reactions occurring at an incidence of <2% in MDD patients treated with Pristiq were: Immune system disorders – Hypersensitivity. Investigations – Liver function test abnormal, blood prolactin increased. Nervous system disorders – Convulsion, syncope, extrapyramidal disorder. Psychiatric disorders – Depersonalization, hypomania. Respiratory, t horacic and mediastinal disorders – Epistaxis. Vascular disorders – Orthostatic hypotension. In clinical studies, there were uncommon reports of ischemic cardiac adverse events, including myocardial ischemia, myocardial infarction, and coronary occlusion requiring revascularization; these patients had multiple underlying cardiac risk factors. More patients experienced these events during Pristiq treatment as compared to placebo [see Warnings and Precautions (5.7)]. Discontinuation events-Adverse events reported in association with abrupt discontinuation, dose reduction or tapering of treatment in MDD clinical studies at a rate of ≥5% include dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, abnormal dreams, fatigue, and hyperhidrosis. In general, discontinuation events occurred more frequently with longer duration of therapy [see Dosage and Administration (2.4) and Warnings and Precautions (5.9) in full prescribing information]. Laboratory, ECG and vital sign changes observed in MDD clinical studies- The following changes were observed in placebocontrolled, short-term, premarketing MDD studies with Pristiq. Lipids-Elevations in fasting serum total cholesterol, LDL (low density lipoproteins) cholesterol, and triglycerides occurred in the controlled studies. Some of these abnormalities were considered potentially clinically significant [see Warnings and Precautions (5.8)]. Proteinuria-Proteinuria, greater than or equal to trace, was observed in the fixed-dose controlled studies (see Table 6 in full prescribing information). This proteinuria was not associated with increases in BUN or creatinine and was generally transient. ECG changes-Electrocardiograms were obtained from 1,492 Pristiq-treated patients with major depressive disorder and 984 placebo-treated patients in

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Pharmacy & Therapeutics - September 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Effect of Prescription Copays on Adherence and Treatment Failure with Oral Antidiabetic Medications Vaccine Declinations Present New Challenges for Public Health Universal Health Care in America Digestive Disease Week and American Diabetes Association Pharmaceutical Approval Update

Pharmacy & Therapeutics - September 2008

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