1 INDICATIONS AND USAGE Darifenacin extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency.

( 1 ) Darifenacin extended-release tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency.

6 ADVERSE REACTIONS The most frequently reported adverse reactions (greater than 3%) for darifenacin extended-release tablets are: constipation, dry mouth, headache, dyspepsia, nausea, urinary tract infection, accidental injury, and flu symptoms ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cipla Limited, India at 1-866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 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.

The safety of darifenacin extended-release tablet was evaluated in controlled clinical trials in a total of 8,830 patients, 6,001 of whom were treated with darifenacin extended-release tablet.

Of this total, 1,069 patients participated in three, 12-week, randomized, placebo-controlled, fixed-dose efficacy and safety studies (Studies 1, 2 and 3).

Of this total, 337 and 334 patients received darifenacin extended-release tablets 7.5 mg daily and 15 mg daily, respectively.

In all long-term trials combined, 1,216 and 672 patients received treatment with darifenacin extended-release tablets for at least 24 and 52 weeks, respectively.

In Studies 1, 2 and 3 combined, the serious adverse reactions to darifenacin extended-release tablets were urinary retention and constipation.

In Studies 1, 2 and 3 combined, dry mouth leading to study discontinuation occurred in 0%, 0.9%, and 0% of patients treated with darifenacin extended-release tablets 7.5 mg daily, darifenacin extended-release tablets 15 mg daily and placebo, respectively.

Constipation leading to study discontinuation occurred in 0.6%, 1.2%, and 0.3% of patients treated with darifenacin extended-release tablets 7.5 mg daily, darifenacin extended-release tablets 15 mg daily and placebo, respectively.

Table 1 lists the rates of identified adverse reactions, derived from all reported adverse events in 2% or more of patients treated with 7.5 mg or 15 mg darifenacin extended-release tablets, and greater than placebo in Studies 1, 2 and 3.

In these studies, the most frequently reported adverse reactions were dry mouth and constipation.

The majority of the adverse reactions were mild or moderate in severity and most occurred during the first two weeks of treatment.

Table 1: Incidence of Identified Adverse Reactions, Derived from All Adverse Events Reported in greater than or equal to 2% of Patients Treated with Darifenacin Extended-Release Tablets and More Frequent with Darifenacin Extended-Release Tablets than with Placebo in Studies 1, 2, and 3 Body System Adverse Reaction % of Subjects Darifenacin extended-release tablet 7.5 mg N = 337 Darifenacin extended- release tablet 15 mg N = 334 Placebo N = 338 Digestive Dry Mouth 20.2 35.3 8.2 Constipation 14.8 21.3 6.2 Dyspepsia 2.7 8.4 2.6 Abdominal Pain 2.4 3.9 0.5 Nausea 2.7 1.5 1.5 Diarrhea 2.1 0.9 1.8 Urogenital Urinary Tract Infection 4.7 4.5 2.6 Nervous Dizziness 0.9 2.1 1.3 Body as a Whole Asthenia 1.5 2.7 1.3 Eye Dry Eyes 1.5 2.1 0.5 Other adverse reactions reported by 1% to 2% of darifenacin extended-release tablets -treated patients include: abnormal vision, accidental injury, back pain, dry skin, flu syndrome, hypertension, vomiting, peripheral edema, weight gain, arthralgia, bronchitis, pharyngitis, rhinitis, sinusitis, rash, pruritus, urinary tract disorder and vaginitis.

Study 4 was a randomized, 12-week, placebo-controlled, dose-titration regimen study in which darifenacin extended-release tablet was administered in accordance with dosing recommendations [see Dosage and Administration ( 2 )] .

All patients initially received placebo or darifenacin extended-release tablets 7.5 mg daily, and after two weeks, patients and physicians were allowed to adjust upward to darifenacin extended-release tablet 15 mg if needed.

In this study, the most commonly reported adverse reactions were also constipation and dry mouth.

Table 2 lists the identified adverse reactions, derived from all adverse events reported in greater than 3% of patients treated with darifenacin extended-release tablets and greater than placebo.

Table 2: Number (%) of Adverse Reactions, Derived from All Adverse Events Reported in greater than 3% of Patients Treated with Darifenacin Extended-Release Tablets, and More Frequent with Darifenacin Extended-Release Tablets than Placebo, in Study 4 Adverse Reaction Darifenacin extended-release tablet 7.5 mg/15 mg N = 268 Placebo N = 127 Constipation 56 (20.9%) 10 (7.9%) Dry Mouth 50 (18.7%) 11 (8.7%) Headache 18 (6.7%) 7 (5.5%) Dyspepsia 12 (4.5%) 2 (1.6%) Nausea 11 (4.1%) 2 (1.6%) Urinary Tract Infection 10 (3.7%) 4 (3.1%) Accidental Injury 8 (3.0%) 3 (2.4%) Flu Syndrome 8 (3.0%) 3 (2.4%) 6.2 Post Marketing Experience The following adverse reactions have been reported during post-approval use of darifenacin extended-release tablets (darifenacin).

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate frequency or establish a causal relationship to drug exposure.

Dermatologic: erythema multiforme, interstitial granuloma annulare General: hypersensitivity reactions, including angioedema with airway obstruction and anaphylactic reaction Central Nervous: confusion, hallucinations and somnolence Cardiovascular: palpitations and syncope