Fesoterodine Fumarate

5 WARNINGS AND PRECAUTIONS Angioedema : Promptly discontinue fesoterodine fumarate extended-release tablets and provide appropriate therapy. (5.1) Urinary Retention : Fesoterodine fumarate extended-release tablets are not recommended in patients with clinically significant bladder outlet obstruction because of the risk of urinary retention. (5.2) Decreased Gastrointestinal Motility : Fesoterodine fumarate extended-release tablets are not recommended for use in patients with decreased gastrointestinal motility, such as those with severe constipation. (5.3) Worsening of Narrow -Angle Glaucoma : Use fesoterodine fumarate extended-release tablets with caution in patients being treated for narrow-angle glaucoma. (5.4) Central Nervous System Effects : Somnolence has been reported with fesoterodine fumarate extended-release tablets. Advise patients not to drive or operate heavy machinery until they know how fesoterodine fumarate extended-release tablets affects them. (5.5) Worsening of Myasthenia Gravis Symptoms : Use fesoterodine fumarate extended-release tablets with caution in patients with myasthenia gravis. (5.6) 5.1 Angioedema Angioedema of the face, lips, tongue, and/or larynx has been reported with fesoterodine. In some cases, angioedema occurred after the first dose; however, cases have been reported to occur hours after the first dose or after multiple doses. Angioedema associated with upper airway swelling may be life-threatening. Fesoterodine fumarate extended-release tablets are contraindicated in patients with a known or suspected hypersensitivity to fesoterodine fumarate extended-release tablets or any of its ingredients [see Contraindications ( 4 )]. If involvement of the tongue, hypopharynx, or larynx occurs, fesoterodine should be promptly discontinued and appropriate therapy and/or measures to ensure a patent airway should be promptly provided. 5.2 Urinary Retention in Adult Patients With Bladder Outlet Obstruction The use of fesoterodine fumarate extended-release tablets, like other antimuscarinic drugs, in patients with clinically significant bladder outlet obstruction, including patients with urinary retention, may result in further urinary retention and kidney injury. The use of fesoterodine fumarate extended-release tablets are not recommended in patients with clinically significant bladder outlet obstruction, and is contraindicated in patients with urinary retention [see Contraindications ( 4 ) and Adverse Reactions ( 6.1 )] . 5.3 Decreased Gastrointestinal Motility Fesoterodine fumarate extended-release tablets are associated with decreased gastric motility. Fesoterodine fumarate extended-release tablets are contraindicated in patients with gastric retention [see Contraindications ( 4 )]. The use of fesoterodine fumarate extended-release tablets are not recommended in patients with decreased gastrointestinal motility, such as those with severe constipation. 5.4 Worsening of Narrow-Angle Glaucoma Fesoterodine fumarate extended-release tablets can worsen controlled narrow-angle glaucoma. Fesoterodine fumarate extended-release tablets are contraindicated in patients with uncontrolled narrow-angle glaucoma [see Contraindications ( 4 )]. Fesoterodine fumarate extended-release tablets should be used with caution in patients being treated for narrow-angle glaucoma. 5.5 Central Nervous System Effects Fesoterodine fumarate extended-release tablets are associated with anticholinergic central nervous system (CNS) adverse reactions [see Adverse Reactions ( 6.1 )]. A variety of CNS anticholinergic effects have been reported, including headache, dizziness, and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how fesoterodine fumarate extended-release tablets affects them. If a patient experiences anticholinergic CNS effects, fesoterodine fumarate extended-release tablets dose reduction or discontinuation should be considered. 5.6 Worsening of Myasthenia Gravis Symptoms Fesoterodine fumarate extended-release tablets should be used with caution in patients with myasthenia gravis due to the risk of worsening of symptoms of the disease.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Angioedema [see Warnings and Precautions (5.1)] Urinary Retention [see Warnings and Precautions (5.2)] Decreased Gastrointestinal Motility [see Warnings and Precautions (5.3)] Most frequently reported adverse events with fesoterodine fumarate extended-release tablets in adult patients with OAB (≥4%) were: dry mouth (placebo, 7%; fesoterodine fumarate extended-release tablet 4 mg, 19%; fesoterodine fumarate extended-release tablet 8 mg, 35%) and constipation (placebo, 2%; fesoterodine fumarate extended-release tablet 4 mg, 4%; fesoterodine fumarate extended-release tablet 8 mg, 6%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Pediatric use information is approved for Pfizer Inc.'s TOVIAZ® (fesoterodine fumarate) Extended-Release Tablets. However, due to Pfizer Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult Overactive Bladder (OAB) The safety of fesoterodine fumarate extended-release tablets was evaluated in Phase 2 and 3 controlled trials in a total of 2,859 patients with overactive bladder, of which 2,288 were treated with fesoterodine fumarate extended-release tablets. Of this total, 782 received fesoterodine fumarate extended-release tablets 4 mg/day, and 785 received fesoterodine fumarate extended-release tablets 8 mg/day with treatment periods of 8-or 12-weeks. Approximately 80% of these patients had greater than 10-weeks of exposure to fesoterodine fumarate extended-release tablets in these trials. A total of 1,964 patients participated in two 12-week, Phase 3 efficacy and safety studies and subsequent open- label extension studies. In these two studies combined, 554 patients received fesoterodine fumarate extended-release tablets 4 mg/day and 566 patients received fesoterodine fumarate extended-release tablets 8 mg/day. In Phase 2 and 3 placebo-controlled trials combined, the incidences of serious adverse events in patients receiving placebo, fesoterodine fumarate extended-release tablets 4 mg, and fesoterodine fumarate extended-release tablets 8 mg were 1.9%, 3.5%, and 2.9%, respectively. All serious adverse events were judged to be not related or unlikely to be related to study medication by the investigator, except for four patients receiving fesoterodine fumarate extended-release tablets who reported one serious adverse reaction each: angina, chest pain, gastroenteritis, and QT prolongation on ECG. The most commonly reported adverse event in patients treated with fesoterodine fumarate extended-release tablets was dry mouth. The incidence of dry mouth was higher in those taking 8 mg/day (35%) and in those taking 4 mg/day (19%), as compared to placebo (7%). Dry mouth led to discontinuation in 0.4%, 0.4%, and 0.8% of patients receiving placebo, fesoterodine fumarate extended-release tablets 4 mg, and fesoterodine fumarate extended-release tablets 8 mg, respectively. For those patients who reported dry mouth, most had their first occurrence of the event within the first month of treatment. The second most commonly reported adverse event was constipation. The incidence of constipation was 2% in those taking placebo, 4% in those taking 4 mg/day, and 6% in those taking 8 mg/day. Table 4 lists adverse events, regardless of causality, that were reported in the combined Phase 3, randomized, placebo-controlled trials at an incidence greater than placebo and in 1% or more of patients treated with fesoterodine fumarate extended-release tablets 4 mg or 8 mg once daily for up to 12-weeks. T able 4: Adverse Events With an Incidence Exceeding the Placebo Rate and Reported by ≥1% of Patients From Double-Blind, Placebo-Controlled Phase 3 Trials of 12-Weeks Treatment Duration System organ class/Preferred term Placebo N=554 % Fesoterodine fumarate extended-release tablet 4 mg/day N=554 % Fesoterodine fumarate extended-release tablet 8 mg/day N=566 % ALT = alanine aminotransferase; GGT = gamma glutamyltransferase Gastrointestinal disorders Dry mouth 7.0 18.8 34.6 Constipation 2.0 4.2 6.0 Dyspepsia 0.5 1.6 2.3 Nausea 1.3 0.7 1.9 Abdominal pain upper 0.5 1.1 0.5 Infections Urinary tract infection 3.1 3.2 4.2 Upper respiratory tract infection 2.2 2.5 1.8 Eye disorders Dry eyes 0 1.4 3.7 Renal and urinary disorders Dysuria 0.7 1.3 1.6 Urinary retention 0.2 1.1 1.4 Respiratory disorders Cough 0.5 1.6 0.9 Dry throat 0.4 0.9 2.3 General disorders Edema peripheral 0.7 0.7 1.2 Musculoskeletal disorders Back pain 0.4 2.0 0.9 Psychiatric disorders Insomnia 0.5 1.3 0.4 Investigations ALT increased 0.9 0.5 1.2 GGT increased 0.4 0.4 1.2 Skin disorders Rash 0.5 0.7 1.1 Patients also received fesoterodine fumarate extended-release tablets for up to three years in open-label extension phases of one Phase 2 and two Phase 3 controlled trials. In all open-label trials combined, 857, 701, 529, and 105 patients received fesoterodine fumarate extended-release tablets for at least 6 months, 1 year, 2 years, and 3 years, respectively. The adverse events observed during long-term, open-label studies were similar to those observed in the 12-week, placebo-controlled studies, and included dry mouth, constipation, dry eyes, dyspepsia, and abdominal pain. Similar to the controlled studies, most adverse events of dry mouth and constipation were mild to moderate in intensity. Serious adverse events, judged to be at least possibly related to study medication by the investigator and reported more than once during the open-label treatment period of up to 3 years, included urinary retention (3 cases), diverticulitis (3 cases), constipation (2 cases), irritable bowel syndrome (2 cases), and electrocardiogram QT corrected interval prolongation (2 cases). Pediatric use information is approved for Pfizer Inc.'s TOVIAZ ® (fesoterodine fumarate) Extended-Release Tablets. However, due to Pfizer Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of fesoterodine fumarate extended-release tablet. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac disorders: Palpitations Central nervous system disorders: Dizziness, headache, somnolence Eye disorders: Blurred vision Gastrointestinal disorders: Hypoaesthesia oral General disorders and administrative site conditions: Hypersensitivity reactions, including angioedema with airway obstruction, face edema Psychiatric disorders: Confusional state Skin and subcutaneous tissue disorders: Urticaria, pruritus

<table cellspacing="0" cellpadding="0" border="0"><thead><tr><th styleCode="Lrule Rrule Toprule">System organ class/Preferred term</th><th styleCode="Lrule Rrule Toprule" align="center">Placebo N=554 %</th><th styleCode="Lrule Rrule Toprule" align="center">Fesoterodine fumarate extended-release tablet 4 mg/day N=554 %</th><th styleCode="Lrule Rrule Toprule" align="center">Fesoterodine fumarate extended-release tablet 8 mg/day N=566 %</th></tr></thead><tfoot><tr><td colspan="4"> ALT = alanine aminotransferase; GGT = gamma glutamyltransferase </td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" valign="middle"> Gastrointestinal disorders</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Dry mouth</td><td styleCode="Rrule" align="center" valign="middle"> 7.0</td><td styleCode="Rrule" align="left" valign="middle"> 18.8</td><td styleCode="Rrule" align="left" valign="middle"> 34.6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Constipation</td><td styleCode="Rrule" align="center" valign="middle"> 2.0</td><td styleCode="Rrule" align="left" valign="middle"> 4.2</td><td styleCode="Rrule" align="left" valign="middle"> 6.0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Dyspepsia</td><td styleCode="Rrule" align="center" valign="middle"> 0.5</td><td styleCode="Rrule" align="left" valign="middle"> 1.6</td><td styleCode="Rrule" align="left" valign="middle"> 2.3</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Nausea</td><td styleCode="Rrule" align="center" valign="middle"> 1.3</td><td styleCode="Rrule" align="left" valign="middle"> 0.7</td><td styleCode="Rrule" align="left" valign="middle"> 1.9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Abdominal pain upper</td><td styleCode="Rrule" align="center" valign="middle"> 0.5</td><td styleCode="Rrule" align="left" valign="middle"> 1.1</td><td styleCode="Rrule" align="left" valign="middle"> 0.5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" valign="middle"> Infections </td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Urinary tract infection</td><td styleCode="Rrule" align="center" valign="middle"> 3.1</td><td styleCode="Rrule" align="left" valign="middle"> 3.2</td><td styleCode="Rrule" align="left" valign="middle"> 4.2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Upper respiratory tract infection</td><td styleCode="Rrule" align="center" valign="middle"> 2.2</td><td styleCode="Rrule" align="left" valign="middle"> 2.5</td><td styleCode="Rrule" align="left" valign="middle"> 1.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" align="left" valign="middle"> Eye disorders</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Dry eyes</td><td styleCode="Rrule" align="center" valign="middle"> 0</td><td styleCode="Rrule" align="left" valign="middle"> 1.4</td><td styleCode="Rrule" align="left" valign="middle"> 3.7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" valign="middle"> Renal and urinary disorders</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Dysuria</td><td styleCode="Rrule" align="center" valign="middle"> 0.7</td><td styleCode="Rrule" align="left" valign="middle"> 1.3</td><td styleCode="Rrule" align="left" valign="middle"> 1.6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Urinary retention</td><td styleCode="Rrule" align="center" valign="middle"> 0.2</td><td styleCode="Rrule" align="left" valign="middle"> 1.1</td><td styleCode="Rrule" align="left" valign="middle"> 1.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" valign="middle"> Respiratory disorders</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Cough</td><td styleCode="Rrule" align="center" valign="middle"> 0.5</td><td styleCode="Rrule" align="left" valign="middle"> 1.6</td><td styleCode="Rrule" align="left" valign="middle"> 0.9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Dry throat</td><td styleCode="Rrule" align="center" valign="middle"> 0.4</td><td styleCode="Rrule" align="left" valign="middle"> 0.9</td><td styleCode="Rrule" align="left" valign="middle"> 2.3</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" valign="middle"> General disorders</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Edema peripheral</td><td styleCode="Rrule" align="center" valign="middle"> 0.7</td><td styleCode="Rrule" align="left" valign="middle"> 0.7</td><td styleCode="Rrule" align="left" valign="middle"> 1.2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" valign="middle"> Musculoskeletal disorders</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Back pain</td><td styleCode="Rrule" align="center" valign="middle"> 0.4</td><td styleCode="Rrule" align="left" valign="middle"> 2.0</td><td styleCode="Rrule" align="left" valign="middle"> 0.9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" valign="middle"> Psychiatric disorders</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> Insomnia</td><td styleCode="Rrule" align="center" valign="middle"> 0.5</td><td styleCode="Rrule" align="left" valign="middle"> 1.3</td><td styleCode="Rrule" align="left" valign="middle"> 0.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" valign="middle"> Investigations</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> ALT increased</td><td styleCode="Rrule" align="center" valign="middle"> 0.9</td><td styleCode="Rrule" align="left" valign="middle"> 0.5</td><td styleCode="Rrule" align="left" valign="middle"> 1.2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" valign="middle"> GGT increased</td><td styleCode="Rrule" align="center" valign="middle"> 0.4</td><td styleCode="Rrule" align="left" valign="middle"> 0.4</td><td styleCode="Rrule" align="left" valign="middle"> 1.2</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="4" valign="middle"> Skin disorders</td></tr><tr><td styleCode="Lrule Rrule" valign="middle"> Rash</td><td styleCode="Rrule" align="center" valign="middle"> 0.5</td><td styleCode="Rrule" align="left" valign="middle"> 0.7</td><td styleCode="Rrule" align="left" valign="middle"> 1.1</td></tr></tbody></table>