Solifenacinside effects

The most common adverse reactions (> 4% in VESIcare-treated patients and > placebo-treated patients) were dry mouth and constipation at both 5 mg and 10 mg doses; and urinary tract infection and blurred vision at the 10 mg dose. To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 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. VESIcare has been evaluated for safety in 1811 adult patients in four randomized, placebo-controlled trials (Studies 1-4). Expected adverse reactions of antimuscarinic agents are dry mouth, constipation, blurred vision (accommodation abnormalities), urinary retention, and dry eyes. The incidence of dry mouth and constipation in patients treated with VESIcare was higher in the 10 mg dose group compared to the 5 mg dose group. In the four 12-week double-blind clinical trials, severe fecal impaction, colonic obstruction, and intestinal obstruction were reported in one patient each, all in the VESIcare 10 mg group. Angioneurotic edema was reported in one patient taking VESIcare 5 mg. Compared to 12 weeks of treatment with VESIcare, the incidence and severity of adverse reactions were similar in patients who remained on drug for up to 12 months in Study 5. The most frequent adverse reaction leading to study discontinuation was dry mouth (1.5%). Table 1 lists the rates of identified adverse reactions, in the four randomized, placebo-controlled trials at an incidence greater than placebo and in 1% or more of patients treated with VESIcare 5 or 10 mg once daily for up to 12 weeks.

Table 1: Adverse Reactions Reported by ≥ 1% of Patients and Exceeding Placebo in Studies 1, 2, 3 and 4 Placebo (%) VESIcare 5 mg (%) VESIcare 10 mg (%) Number of Patients 1216 578 1233 GASTROINTESTINAL DISORDERS Dry Mouth 4.2 10.9 27.6 Constipation 2.9 5.4 13.4 Nausea 2.0 1.7 3.3 Dyspepsia 1.0 1.4

3.9 Abdominal

Pain Upper 1.0 1.9 1.2 Vomiting NOS 0.9 0.2

1.1 INFECTIONS AND INFESTATIONS

Urinary Tract Infection NOS 2.8 2.8 4.8 Influenza 1.3 2.2 0.9 Pharyngitis NOS 1.0 0.3

1.1 NERVOUS SYSTEM DISORDERS

Dizziness 1.8 1.9

1.8 EYE DISORDERS

Vision Blurred 1.8 3.8 4.8 Dry Eyes NOS 0.6 0.3

1.6 RENAL AND URINARY DISORDERS

Urinary Retention 0.6 0

1.4 GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

Edema Lower Limb 0.7 0.3 1.1 Fatigue 1.1 1.0

2.1 PSYCHIATRIC DISORDERS

Depression NOS 0.8 1.2

0.8 RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

Cough 0.2 0.2

1.1 VASCULAR DISORDERS

Hypertension NOS 0.6 1.4 0.5

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of solifenacin succinate in the U.S. and/or outside of the U.S. 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. General disorders and administration site conditions: peripheral edema, hypersensitivity reactions (including angioedema with airway obstruction, rash, pruritus, urticaria, anaphylactic reaction);

Nervous system disorders: dizziness, headache, confusion, hallucinations, delirium, somnolence;

Cardiac disorders: QT prolongation, Torsade de Pointes, atrial fibrillation, tachycardia, palpitations;

Hepatobiliary disorders: liver disorders mostly characterized by abnormal liver function tests, AST (aspartate aminotransferase), ALT (alanine aminotransferase), GGT (gamma-glutamyl transferase);

Renal and urinary disorders: renal impairment, urinary retention;

Metabolism and nutrition disorders: decreased appetite, hyperkalemia; Skin and subcutaneous tissue disorders: exfoliative dermatitis, erythema multiforme, dry skin;

Eye disorders: glaucoma;

Gastrointestinal disorders: gastroesophageal reflux disease, ileus, vomiting, abdominal pain, dysgeusia, sialadenitis; Respiratory, thoracic and mediastinal disorders: dysphonia, nasal dryness; Musculoskeletal and connective tissue disorders: muscular weakness.