VESIcare® (solifenacin succinate) is a muscarinic receptor antagonist. Chemically, solifenacin succinate is butanedioic acid, compounded with (1S)-(3R)-1-azabicyclo[2.2.2]oct-3-yl 3,4-dihydro-1-phenyl-2(1H)-iso- quinolinecarboxylate (1:1) having an empirical formula of C₂₃H₂₆N₂O₂ C₄H₆O₄, 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 formulated for oral administration. In addition to the active ingredient solifenacin succinate, each VESIcare tablet also contains the following inert 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).

Last updated on RxList: 1/8/2009

VESIcare is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

The recommended 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 liquids and swallowed whole. VESIcare can be administered with or without food.

Dose Adjustment in Renal Impairment

For patients with severe renal impairment (CL_cr < 30 mL/min), a daily dose of VESIcare greater than 5 mg is not recommended.

Dose Adjustment in Hepatic Impairment

For patients with moderate hepatic impairment (Child-Pugh B), a daily dose of VESIcare greater than 5 mg is not recommended. Use of VESIcare in patients with severe hepatic impairment (Child-Pugh C) is not recommended.

Dose Adjustment CYP3A4 Inhibitors

When administered with therapeutic doses of ketoconazole or other potent CYP3A4 inhibitors, a daily dose of VESIcare greater than 5 mg is not recommended.

VESIcare is supplied as round, film-coated tablets, available in bottles and unit dose blister packages as follows:

strength color debossed	5 mg light yellow logo, 150	10 mg light pink logo, 151
Bottle of 30	NDC 51248-150-01	NDC 51248-151-01
Bottle of 90	NDC 51248-150-03	NDC 51248-151-03
Unit Dose Pack of 100	NDC 51248-150-52	NDC 51248-151-52

Store at 25°C (77°F) with excursions permitted from 15°C to 30°C (59°F -86°F) [see USP Controlled Room Temperature]

Manufactured by: Astellas Pharma Technologies Inc., Norman, Oklahoma 73072. Marketed by: Astellas Pharma US, Inc., Deerfield, Illinois 60015-2548. Marketed and Distributed by: GlaxoSmithKline, Research Triangle Park, North Carolina 27709. Revised: November 2008. FDA revision date: 11/18/2008

Last updated on RxList: 1/8/2009

VESIcare has been evaluated for safety in 1811 patients in randomized, placebo-controlled trials. Expected side effects of antimuscarinic agents are dry mouth, constipation, blurred vision (accommodation abnormalities), urinary retention, and dry eyes. The most common adverse events reported in patients treated with VESIcare were dry mouth and constipation and the incidence of these side effects was higher in the 10 mg compared to the 5 mg dose group. In the four 12-week double-blind clinical trials there were three intestinal serious adverse events in patients, all treated with VESIcare 10 mg (one fecal impaction, one colonic obstruction, and one intestinal obstruction). The overall rate of serious adverse events in the double-blind trials was 2%. Angioneurotic edema has been reported in one patient taking VESIcare 5 mg. Compared to twelve weeks of treatment with VESIcare, the incidence and severity of adverse events were similar in patients who remained on drug for up to 12 months. The most frequent reason for discontinuation due to an adverse event was dry mouth, 1.5%. Table 6 lists adverse events, regardless of causality, that were reported in 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 6. Percentages of Patients with Treatment-emergent Adverse Events Exceeding Placebo Rate and Reported by 1% or More Patients for Combined Pivotal Studies

SYSTEM ORGAN CLASS MedDRA Preferred Term	Placebo (%)	VESIcare 5 mg (%)	VESIcare 10 mg (%)
Number of Patients	1216	578	1233
Number of Patients with Treatment-emergent AE	634	265	773
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

Post-Marketing Surveillance

The following events have been reported in association with solifenacin use in worldwide postmarketing experience: General: peripheral edema, hypersensitivity reactions, including angioedema, rash, pruritus, and urticaria; Central Nervous: headache, confusion and hallucinations; Cardiovascular: QT prolongation; Torsade de Pointes. Because these spontaneously reported events are from the worldwide postmarketing experience, the frequency of events and the role of solifenacin in their causation cannot be reliably determined.

Drug-Drug Interactions

Do not exceed a 5 mg daily dose of VESIcare when administered with therapeutic doses of ketoconazole or other potent CYP3A4 inhibitors. (See CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION)

Patients with Congenital or Acquired QT Prolongation

In a study of the effect of solifenacin on the QT interval in 76 healthy women (See CLINICAL PHARMACOLOGY, Cardiac Electrophysiology), the QT prolonging effect appeared less with solifenacin 10 mg than with 30 mg (three times the maximum recommended dose), and the effect of solifenacin 30 mg did not appear as large as that of the positive control moxifloxacin at its therapeutic dose. This observation should be considered in clinical decisions to prescribe VESIcare for patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.

Last updated on RxList: 1/8/2009

No information provided.

Bladder Outflow Obstruction

VESIcare, like other anticholinergic drugs, should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention.

Gastrointestinal Obstructive Disorders and Decreased GI Motility

VESIcare, like other anticholinergics, should be used with caution in patients with decreased gastrointestinal motility.

Controlled Narrow-Angle Glaucoma

VESIcare should be used with caution in patients being treated for narrow-angle glaucoma. (See CONTRAINDICATIONS)

Reduced Renal Function

VESIcare should be used with caution in patients with reduced renal function. Doses of VESIcare greater than 5 mg are not recommended in patients with severe renal impairment (CL_cr < 30 mL/min). (See CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION)

Reduced Hepatic Function

VESIcare should be used with caution in patients with reduced hepatic function. Doses of VESIcare greater than 5 mg are not recommended in patients with moderate hepatic impairment (Child-Pugh B). VESIcare is not recommended for patients with severe hepatic impairment (Child-Pugh C). (See CLINICAL PHARMACOLOGY, DOSAGE AND ADMINISTRATION)

Carcinogenesis, Mutagenesis, Impairment of Fertility

Solifenacin succinate was not mutagenic in the in vitro Salmonella typhimurium or Escherichia colimicrobial mutagenicity test or chromosomal aberration test in human peripheral blood lymphocytes with or without metabolic activation, or in the in vivo micronucleus test in rats.

No increase in tumors was found following the administration of solifenacin succinate to male and female mice for 104 weeks at doses up to 200 mg/kg/day (5 and 9 times human exposure at the maximum recommended human dose [MRHD], respectively), and male and female rats for 104 weeks at doses up to 20 and 15 mg/kg/day, respectively ( < 1 times exposure at the MRHD).

Solifenacin succinate had no effect on reproductive function, fertility or early embryonic development of the fetus in male and female mice treated with 250 mg/kg/day (13 times exposure at the MRHD) of solifenacin succinate, and in male rats treated with 50 mg/kg/day ( < 1 times exposure at the MRHD) and female rats treated with 100 mg/kg/day (1.7 times exposure at the MRHD) of solifenacin succinate.

Pregnancy, Teratogenic Effects, Pregnancy Category

Pregnancy Category C

Reproduction studies have been performed in mice, rats and rabbits. After oral administration of ¹⁴C-solifenacin succinate to pregnant mice, drug-related material was shown to cross the placental barrier. No embryotoxicity or teratogenicity was observed in mice treated with 30 mg/kg/day (1.2 times exposure at the maximum recommended human dose [MRHD]). Administration of solifenacin succinate to pregnant mice at doses of 100 mg/kg and greater (3.6 times exposure at the MRHD), during the major period of organ development resulted in reduced fetal body weights. Administration of 250 mg/kg (7.9 times exposure at the MRHD) to pregnant mice resulted in an increased incidence of cleft palate. In utero and lactational exposures to maternal doses of solifenacin succinate of 100 mg/kg/day and greater (3.6 times exposure at the MRHD) resulted in reduced peripartum and postnatal survival, reductions in body weight gain, and delayed physical development (eye opening and vaginal patency). An increase in the percentage of male offspring was also observed in litters from offspring exposed to maternal doses of 250 mg/kg/day. No embryotoxic effects were observed in rats at up to 50 mg/kg/day ( < 1 times exposure at the MRHD) or in rabbits at up to 50 mg/kg/day (1.8 times exposure at the MRHD). There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, VESIcare should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

The effect of VESIcare on labor and delivery in humans has not been studied.

There were no effects on natural delivery in mice treated with 30 mg/kg/day (1.2 times exposure at the maximum recommended human dose [MRHD]). Administration of solifenacin succinate at 100 mg/kg/day (3.6 times exposure at the MRHD) or greater increased peripartum pup mortality.

Nursing Mothers

After oral administration of ¹⁴C-solifenacin succinate to lactating mice, radioactivity was detected in maternal milk. There were no adverse observations in mice treated with 30 mg/kg/day (1.2 times exposure at the maximum recommended human dose [MRHD]). Pups of female mice treated with 100 mg/kg/day (3.6 times exposure at the MRHD) or greater revealed reduced body weights, postpartum pup mortality or delays in the onset of reflex and physical development during the lactation period.

It is not known whether solifenacin is excreted in human milk. Because many drugs are excreted in human milk, VESIcare should not be administered during nursing. A decision should be made whether to discontinue nursing or to discontinue VESIcare in nursing mothers.

Pediatric Use

The safety and effectiveness of VESIcare in pediatric patients have not been established.

Geriatric Use

In placebo controlled clinical studies, similar safety and effectiveness were observed between older (623 patients ≥ 65 years and 189 patients ≥ 75 years) and younger patients (1188 patients < 65 years) treated with VESIcare (See CLINICAL PHARMACOLOGY, Pharmacokinetics in Special Populations).

Last updated on RxList: 1/8/2009

Acute

Overdosage with VESIcare can potentially result in severe anticholinergic effects and should be treated accordingly. The highest dose ingested in an accidental overdose of solifenacin succinate was 280 mg in a 5-hour period. This case was associated with mental status changes. Some cases reported a decrease in the level of consciousness.

Chronic

Intolerable anticholinergic side effects (fixed and dilated pupils, blurred vision, failure of heel-to-toe exam, tremors and dry skin) occurred on day 3 in normal volunteers taking 50 mg daily (5 times the maximum recommended therapeutic dose) and resolved within 7 days following discontinuation of drug.

Treatment of Overdosage

In the event of overdose with VESIcare, treat with gastric lavage and appropriate supportive measures. ECG monitoring is also recommended.

VESIcare is contraindicated in patients with urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and in patients who have demonstrated hypersensitivity to the drug substance or other components of the product.

Last updated on RxList: 1/8/2009

Solifenacin is a competitive muscarinic receptor antagonist. Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of urinary bladder smooth muscle and stimulation of salivary secretion.

Pharmacokinetics

Absorption

After oral administration of VESIcare to healthy volunteers, peak plasma levels (Cmax) of solifenacin are reached within 3 to 8 hours after administration, and at steady state ranged from 32.3 to 62.9 ng/mL for the 5 and 10 mg VESIcare tablets, respectively. The absolute bioavailability of solifenacin is approximately 90%, and plasma concentrations of solifenacin are proportional to the dose administered.

Effect of food

There is no significant effect of food on the pharmacokinetics of solifenacin.

Distribution

Solifenacin is approximately 98% (in vivo) bound to human plasma proteins, principally to α₁-acid glycoprotein. Solifenacin is highly distributed to non-CNS tissues, having a mean steady-state volume of distribution of 600L.

Metabolism

Solifenacin is extensively metabolized in the liver. The primary pathway for elimination is by way of CYP3A4; however, alternate metabolic pathways exist. The primary metabolic routes of solifenacin are through N-oxidation of the quinuclidin ring and 4R-hydroxylation of tetrahydroisoquinoline ring. One pharmacologically active metabolite (4R-hydroxy solifenacin), occurring at low concentrations and unlikely to contribute significantly to clinical activity, and three pharmacologically inactive metabolites (N-glucuronide and the N-oxide and 4R-hydroxy-N-oxide of solifenacin) have been found in human plasma after oral dosing.

Excretion

Following the administration of 10 mg of ¹⁴C-solifenacin succinate to healthy volunteers, 69.2% of the radioactivity was recovered in the urine and 22.5% in the feces over 26 days. Less than 15% (as mean value) of the dose was recovered in the urine as intact solifenacin. The major metabolites identified in urine were N-oxide of solifenacin, 4R-hydroxy solifenacin and 4R-hydroxy-N-oxide of solifenacin and in feces 4R-hydroxy solifenacin. The elimination half-life of solifenacin following chronic dosing is approximately 45-68 hours.

Pharmacokinetics in Special Populations

Age

Multiple dose studies of VESIcare in elderly volunteers (65 to 80 years) showed that Cmax, AUC and t1/2 values were 20-25% higher as compared to the younger volunteers (18 to 55 years). (See PRECAUTIONS, Geriatric Use).

Pediatric

The pharmacokinetics of solifenacin has not been established in pediatric patients.

Gender

The pharmacokinetics of solifenacin is not significantly influenced by gender.

Race

The number of subjects of different races studied is not adequate to make any conclusions on the effect of race on the pharmacokinetics of solifenacin.

Renal Impairment

VESIcare should be used with caution in patients with renal impairment. There is a 2.1-fold increase in AUC and 1.6-fold increase in t1/2 of solifenacin in patients with severe renal impairment. Doses of VESIcare greater than 5 mg are not recommended in patients with severe renal impairment (CL_cr < 30 mL/min) (see PRECAUTIONS, DOSAGE AND ADMINISTRATION).

Hepatic Impairment

VESIcare should be used with caution in patients with reduced hepatic function. There is a 2-fold increase in the t1/2 and 35% increase in AUC of solifenacin in patients with moderate hepatic impairment. Doses of VESIcare greater than 5 mg are not recommended in patients with moderate hepatic impairment (Child-Pugh B). VESIcare is not recommended for patients with severe hepatic impairment (Child-Pugh C) (see PRECAUTIONS, DOSAGE AND ADMINISTRATION).

Drug-Drug Interactions

Drugs Metabolized by Cytochrome P450

At therapeutic concentrations, solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes.

CYP3A4 Inhibitors

In vitro drug metabolism studies have shown that solifenacin is a substrate of CYP3A4. Inducers or inhibitors of CYP3A4 may alter solifenacin pharmacokinetics.

Ketoconazole Interaction Study

Following the administration of 10 mg of VESIcare in the presence of 400 mg of ketoconazole, a potent inhibitor of CYP3A4, the mean Cmax and AUC of solifenacin increased by 1.5 and 2.7-fold, respectively. Therefore, it is recommended not to exceed a 5 mg daily dose of VESIcare when administered with therapeutic doses of ketoconazole or other potent CYP3A4 inhibitors (see PRECAUTIONS, DOSAGE AND ADMINISTRATION).

Oral Contraceptives

In the presence of solifenacin there are no significant changes in the plasma concentrations of combined oral contraceptives (ethinyl estradiol/levogestrel).

Warfarin

Solifenacin has no significant effect on the pharmacokinetics of R-warfarin or S-warfarin.

Digoxin

Solifenacin had no significant effect on the pharmacokinetics of digoxin (0.125 mg/day) in healthy subjects.

Cardiac Electrophysiology

The effect of 10 mg and 30 mg solifenacin succinate on the QT interval was evaluated at the time of peak plasma concentration of solifenacin in a multi-dose, randomized, double-blind, placebo and positive-controlled (moxifloxacin 400 mg) trial. Subjects were randomized to one of two treatment groups after receiving placebo and moxifloxacin sequentially. One group (n=51) went on to complete 3 additional sequential periods of dosing with solifenacin 10, 20, and 30 mg while the second group (n=25) in parallel completed a sequence of placebo and moxifloxacin. Study subjects were female volunteers aged 19 to 79 years. The 30 mg dose of solifenacin succinate (three times the highest recommended dose) was chosen for use in this study because this dose results in a solifenacin exposure that covers those observed upon co-administration of 10 mg VESIcare with potent CYP3A4 inhibitors (e.g. ketoconazole, 400 mg). Due to the sequential dose escalating nature of the study, baseline EKG measurements were separated from the final QT assessment (of the 30 mg dose level) by 33 days.

The median difference from baseline in heart rate associated with the 10 and 30 mg doses of solifenacin succinate compared to placebo was -2 and 0 beats/minute, respectively. Because a significant period effect on QTc was observed, the QTc effects were analyzed utilizing the parallel placebo control arm rather than the pre-specified intra-patient analysis. Representative results are shown in Table 1.

Table 1. QTc changes in msec (90%CI) from baseline at Tmax (relative to placebo)*

Drug/Dose	Fridericia method (using mean difference)
Solifenacin 10 mg	2 (-3,6)
Solifenacin 30 mg	8 (4,13)
*Results displayed are those derived from the parallel design portion of the study and represent the comparison of Group 1 to time-matched placebo effects in Group 2

Moxifloxacin was included as a positive control in this study and, given the length of the study, its effect on the QT interval was evaluated in 3 different sessions. The placebo subtracted mean changes (90% CI) in QTcF for moxifloxacin in the three sessions were 11 (7, 14), 12 (8, 17), and 16 (12, 21), respectively.

The QT interval prolonging effect appeared greater for the 30 mg compared to the 10 mg dose of solifenacin. Although the effect of the highest solifenacin dose (three times the maximum therapeutic dose) studied did not appear as large as that of the positive control moxifloxacin at its therapeutic dose, the confidence intervals overlapped. This study was not designed to draw direct statistical conclusions between the drugs or the dose levels.

Clinical Studies

VESIcare was evaluated in four twelve-week, double-blind, randomized, placebo-controlled, parallel group, multicenter clinical trials for the treatment of overactive bladder in patients having symptoms of urinary frequency, urgency, and/or urge or mixed incontinence (with a predominance of urge). Entry criteria required that patients have symptoms of overactive bladder for ≥ 3 months duration. These studies involved 3027 patients (1811 on VESIcare and 1216 on placebo), and approximately 90% of these patients completed the 12-week studies. Two of the four studies evaluated the 5 and 10 mg VESIcare doses and the other two evaluated only the 10 mg dose. All patients completing the 12-week studies were eligible to enter an open label, long term extension study and 81% of patients enrolling completed the additional 40-week treatment period. The majority of patients were Caucasian (93%) and female (80%) with a mean age of 58 years.

The primary endpoint in all four trials was the mean change from baseline to 12 weeks in number of micturitions/24 hours. Secondary endpoints included mean change from baseline to 12 weeks in number of incontinence episodes/24 hours, and mean volume voided per micturition. The efficacy of VESIcare was similar across patient age and gender. The mean reduction in the number of micturitions per 24 hours was significantly greater with VESIcare 5 mg (2.3; p < 0.001) and VESIcare 10 mg (2.7; p < 0.001) compared to placebo, (1.4).

The mean reduction in the number of incontinence episodes per 24 hours was significantly greater with VESIcare 5 mg (1.5; p < 0.001) and VESIcare 10 mg (1.8; p < 0.001) treatment groups compared to placebo (1.1). The mean increase in the volume voided per micturition was significantly greater with VESIcare 5 mg (32.3 mL; p < 0.001) and VESIcare 10 mg (42.5 mL; p < 0.001) compared with placebo (8.5 mL).

The results for the primary and secondary endpoints in the four individual 12-week clinical studies of VESIcare are reported in Tables 2 through 5.

Table 2. Mean Change from Baseline to Endpoint for VESIcare (5 mg and 10 mg daily) and Placebo: 905-CL-015

Parameter	Placebo (N=253) Mean (SE)	VESIcare 5 mg (N=266) Mean (SE)	VESIcare 10 mg (N=264) Mean (SE)
Urinary Frequency (Number of Micturitions/24 hours)*
Baseline	12.2 (0.26)	12.1 (0.24)	12.3 (0.24)
Reduction	1.2 (0.21)	2.2 (0.18)	2.6 (0.20)
P value vs. placebo		< 0.001	< 0. 001
Number of Incontinence Episodes/24 hours**
Baseline	2.7 (0.23)	2.6 (0.22)	2.6 (0.23)
Reduction	0.8 (0.18)	1.4 (0.15)	1.5 (0.18)
P value vs. placebo		< 0.01	< 0.01
Volume Voided per micturition [mL]**
Baseline	143.8 (3.37)	149.6 (3.35)	147.2 (3.15)
Increase	7.4 (2.28)	32.9 (2.92)	39.2 (3.11)
P value vs. placebo		< 0.001	< 0.001
* Primary endpoint ** Secondary endpoint

Table 3. Mean Change from Baseline to Endpoint for VESIcare (5 mg and 10 mg daily) and Placebo: 905-CL-018

Parameter	Placebo (N=281) Mean (SE)	VESIcare 5 mg (N=286) Mean (SE)	VESIcare 10 mg (N=290) Mean (SE)
Urinary Frequency (Number of Micturitions/24 hours)*
Baseline	12.3 (0.23)	12.1 (0.23)	12.1 (0.21)
Reduction	1.7 (0.19)	2.4 (0.17)	2.9 (0.18)
P value vs. placebo		< 0.001	< 0. 001
Number of Incontinence Episodes/24 hours**
Baseline	3.2 (0.24)	2.6 (0.18)	2.8 (0.20)
Reduction	1.3 (0.19)	1.6 (0.16)	1.6 (0.18)
P value vs. placebo		< 0.01	0.016
Volume Voided per micturition [mL]**
Baseline	147.2 (3.18)	148.5 (3.16)	145.9 (3.42)
Increase	11.3 (2.52)	31.8 (2.94)	36.6 (3.04)
P value vs. placebo		< 0.001	< 0.001
* Primary endpoint ** Secondary endpoint

Table 4. Mean Change from Baseline to Endpoint for VESIcare (10 mg daily) and Placebo: 905-CL-013

Parameter	Placebo (N=309) Mean (SE)	VESIcare 10 mg (N=306) Mean (SE)
Urinary Frequency (Number of Micturitions/24 hours)*
Baseline	11.5 (0.18)	11.7 (0.18)
Reduction	1.5 (0.15)	3.0 (0.15)
P value vs. placebo		< 0. 001
Number of Incontinence Episodes/24 hours**
Baseline	3.0 (0.20)	3.1 (0.22)
Reduction	1.1 (0.16)	2.0 (0.19)
P value vs. placebo		< 0.001
Volume Voided per micturition [mL]**
Baseline	190.3 (5.48)	183.5 (4.97)
Increase	2.7 (3.15)	47.2 (3.79)
P value vs. placebo		< 0.001
* Primary endpoint ** Secondary endpoint

Table 5. Mean Change from Baseline to Endpoint for VESIcare (10 mg daily) and Placebo: 905-CL-014

Parameter	Placebo (N=295) Mean (SE)	VESIcare 10 mg (N=298) Mean (SE)
Urinary Frequency (Number of Micturitions/24 hours)*
Baseline	11.8 (0.18)	11.5 (0.18)
Reduction	1.3 (0.16)	2.4 (0.15)
P value vs. placebo		< 0. 001
Number of Incontinence Episodes/24 hours**
Baseline	2.9 (0.18)	2.9 (0.17)
Reduction	1.2 (0.15)	2.0 (0.15)
P value vs. placebo		< 0.001
Volume Voided per micturition [mL]**
Baseline	175.7 (4.44)	174.1 (4.15)
Increase	13.0 (3.45)	46.4 (3.73)
P value vs. placebo		< 0.001
* Primary endpoint ** Secondary endpoint

Last updated on RxList: 1/8/2009

Patients should be informed that antimuscarinic agents such as VESIcare have been associated with constipation and blurred vision. Patients should be advised to contact their physician if they experience severe abdominal pain or become constipated for 3 or more days. Because VESIcare may cause blurred vision, patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug's been determined. Heat prostration (due to decreased sweating) can occur when anticholinergic drugs, such as VESIcare, are used in a hot environment. Patients should read the patient leaflet entitled “Patient Information VESIcare” before starting therapy with VESIcare.

Last updated on RxList: 1/8/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

SOLIFENACIN - ORAL

(soul-lee-fen-A-sin)

COMMON BRAND NAME(S): Vesicare

USES: This medication is used to treat an overactive bladder. By relaxing the muscles in the bladder, solifenacin improves your ability to control your urination. It helps to reduce leaking of urine, feelings of needing to urinate right away, and frequent trips to the bathroom. This medication belongs to the class of drugs known as antispasmodics.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using solifenacin and each time you get a refill. If you have any questions regarding the information, consult your doctor or pharmacist.

Take this medication by mouth, with or without food, usually once a day, or as directed by your doctor. Swallow this medication whole with a full glass of liquid.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day. Dosage is based on your medical condition (especially kidney and liver disease), response to therapy, and use of certain interacting medicines. Consult your doctor or pharmacist for more details.

Do not increase your dose or take this medication more often without your doctor's approval. Your condition will not improve any faster and the risk of serious side effects may be increased.

Inform your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: Dry mouth, constipation, stomach upset, stomach pain, blurred vision, dry eyes, or unusual tiredness/weakness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water or use a saliva substitute.

To prevent constipation, maintain a diet adequate in fiber, drink plenty of water, and exercise. If you become constipated, consult your pharmacist for help in choosing a laxative (e.g., stimulant-type with stool softener).

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: severe stomach/abdominal pain, constipation for 3 or more days, difficulty urinating, signs of kidney infection (e.g., burning/painful urination, lower back pain, fever).

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking solifenacin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: problems emptying your bladder (urinary retention), severe blockage of stomach/intestines (gastric retention), a certain eye condition (uncontrolled narrow angle glaucoma), severe liver disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: other bladder problems (e.g., bladder outflow obstruction), stomach/intestinal disease (e.g., ulcerative colitis), slowed movement of stomach/intestines, severe constipation, controlled narrow angle glaucoma, kidney disease, liver disease, enlarged prostate, a certain muscle disease (myasthenia gravis).

This drug may cause blurred vision; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.

This medication can cause decreased sweating. Avoid becoming overheated in hot weather, saunas, or during exercise or other strenuous activities since heatstroke may occur.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be more sensitive to this drug.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Due to the potential risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because very serious interactions may occur: pramlintide.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting solifenacin.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: potassium tablets/capsules, other drugs that can cause dry mouth and constipation (e.g., anticholinergic medications such as atropine, antihistamines including diphenhydramine and scopolamine, other antispasmodics including dicyclomine, belladonna alkaloids), drugs affecting liver enzymes that remove solifenacin from your body (such as azole antifungals including itraconazole; macrolide antibiotics including erythromycin; cimetidine; rifamycins including rifabutin; St. John's wort; certain anti-seizure medicines including carbamazepine).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include fast/irregular heartbeat, agitation.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised August 2008 Copyright(c) 2008 First DataBank, Inc.