VESIcare (solifenacin succinate) is a muscarinic receptor antagonist. Chemically, solifenacin succinate is a butanedioic acid compound with (1 S )-(3 R )-1-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-1-phenyl-2(1 H )-iso-quinolinecarboxylate (1:1) having an empirical formula of C 23 H 26 N 2 O 2 •C 4 H 6 O 4 , and a molecular weight of 480.55. The structural formula of solifenacin succinate is: Solifenacin succinate is a white to pale-yellowish-white crystal or crystalline powder. It is freely soluble at room temperature in water, glacial acetic acid, dimethyl sulfoxide, and methanol. Each VESIcare tablet contains 5 or 10 mg of solifenacin succinate and is for oral administration. In addition to the active ingredient solifenacin succinate, each VESIcare tablet also contains the following inactive ingredients: lactose monohydrate, corn starch, hypromellose 2910, magnesium stearate, talc, polyethylene glycol 8000 and titanium dioxide with yellow ferric oxide (5 mg VESIcare tablet) or red ferric oxide (10 mg VESIcare tablet). structure of Solifenacin succinate

VESIcare ® is indicated for the treatment of adults with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. VESIcare is a muscarinic antagonist indicated for the treatment of adults with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

Tablets: • 5 mg: round, light yellow, debossed with 150 • 10 mg: round, light pink, debossed with 151 Tablets: 5 mg and 10 mg.

• 5 mg tablet taken orally once daily, and if well tolerated may be increased to 10 mg once daily. • Do not exceed the 5 mg dose of VESIcare in patients with: o Severe renal impairment creatinine clearance < 30 mL/min/1.73 m 2 . o Moderate hepatic impairment (Child-Pugh B). VESIcare is not recommended in patients with severe hepatic impairment (Child-Pugh C). o Concomitant use of strong CYP3A4 inhibitors

Dosing Information The recommended oral dose of VESIcare is 5 mg once daily. If the 5 mg dose is well tolerated, the dose may be increased to 10 mg once daily. VESIcare should be taken with water and swallowed whole. VESIcare can be administered with or without food

Dosing Recommendations in Patients with Renal Impairment Do not exceed 5 mg once daily in patients with severe renal impairment (CL cr < 30 mL/min/1.73 m 2 )

Dosing Recommendations in Patients with Hepatic Impairment Do not exceed 5 mg once daily in patients with moderate hepatic impairment (Child-Pugh B). Do not use VESIcare in patients with severe hepatic impairment (Child-Pugh C)

Dosing Recommendations in Patients Taking CYP3A4 Inhibitors Do not exceed 5 mg once daily when VESIcare is administered with strong CYP3A4 inhibitors such as ketoconazole .

• Angioedema and Anaphylactic Reactions : Promptly discontinue VESIcare and provide appropriate therapy. • Urinary Retention : VESIcare is not recommended for use in patients with clinically significant bladder outlet obstruction. • Gastrointestinal Disorders : VESIcare is not recommended for use in patients with decreased gastrointestinal motility. • Central Nervous System Effects : Somnolence has been reported with VESIcare. Advise patients not to drive or operate heavy machinery until they know how VESIcare affects them. • Controlled Narrow-Angle Glaucoma : Use VESIcare with caution in patients being treated for narrow-angle glaucoma. • QT Prolongation in Patients at High Risk of QT Prolongation : VESIcare is not recommended for use in patients at high risk of QT prolongation, including patients with a known history of QT prolongation and patients taking medications known to prolong the QT interval. 5.1 Angioedema and Anaphylactic Reactions Angioedema of the face, lips, tongue, and/or larynx have been reported with solifenacin succinate. 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. Anaphylactic reactions have also been reported in patients treated with solifenacin succinate. Angioedema associated with upper airway swelling and anaphylactic reactions may be life-threatening. VESIcare is contraindicated in patients with a known or suspected hypersensitivity to solifenacin succinate . If involvement of the tongue, hypopharynx, or larynx occurs, promptly discontinue VESIcare and provide appropriate therapy and/or measures necessary to ensure a patent airway

Urinary Retention The use of VESIcare, 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 VESIcare is not recommended in patients with clinically significant bladder outlet obstruction and is contraindicated in patients with urinary retention

Gastrointestinal Disorders The use of VESIcare, like other antimuscarinic drugs, in patients with conditions associated with decreased gastrointestinal motility may result in further decreased gastrointestinal motility. VESIcare is contraindicated in patients with gastric retention . The use of VESIcare is not recommended in patients with conditions associated with decreased gastrointestinal motility

Central Nervous System Effects VESIcare is associated with antimuscarinic central nervous system (CNS) adverse reactions . A variety of CNS antimuscarinic adverse reactions have been reported, including headache, confusion, hallucinations, and somnolence. Monitor patients for signs of antimuscarinic CNS adverse reactions, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how VESIcare affects them. If a patient experiences antimuscarinic CNS adverse reactions, consider dose reduction or drug discontinuation

Controlled Narrow-Angle Glaucoma VESIcare should be used with caution in patients being treated for narrow-angle glaucoma

QT Prolongation in Patients at High Risk of QT Prolongation In a study of the effect of solifenacin succinate on the QT interval conducted in 76 healthy women , solifenacin succinate 30 mg (three times the largest maximum recommended dose in adult patients) was associated with a mean increase in the Fridericia-corrected QT interval of 8 msec (90% CI, 4, 13). The QT prolonging effect appeared less with solifenacin succinate 10 mg than with solifenacin succinate 30 mg, and the effect of solifenacin succinate 30 mg did not appear as large as that of the positive control moxifloxacin at its therapeutic dose. The use of VESIcare is not recommended in patients at high risk of QT prolongation, including patients with a known history of QT prolongation and patients who are taking medications known to prolong the QT interval.

CYP3A4 Inhibitors : Do not exceed the 5 mg dose of VESIcare with concomitant use of strong CYP3A4 inhibitors

Strong CYP3A4 Inhibitors Solifenacin is a substrate of CYP3A4. Concomitant use of ketoconazole, a strong CYP3A4 inhibitor, significantly increased the exposure of solifenacin . The dosage of VESIcare greater than 5 mg once daily is not recommended when concomitantly used with strong CYP3A4 inhibitors .