General Information

Vesicare/VESIcare LS contains solifenacin, a competitive muscarinic receptor antagonist. Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of urinary bladder smooth muscle. Antagonism at these receptors has been shown to reduce tonus (elastic tension) of the urinary bladder and slow parasympathetic contractions.

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

VESIcare LS is specifically indicated for the treatment of neurogenic detrusor overactivity (NDO), a form of bladder dysfunction related to neurological impairment, in children ages 2 years of age and older.

Mechanism of Action

Solifenacin acts as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Its anticholinergic-parasympatholytic action reduces the tonus of smooth muscle in the bladder, effectively reducing the number of required voids, urge incontinence episodes, urge severity and improving retention, facilitating increased volume per void.

Side Effects

Adverse events associated with the use of Vesicare may include, but are not limited to, the following:

• Dry mouth
• Constipation
• Blurred vision
• Urinary retention
• Dry eyes

In addition, three serious intestinal complications (one fecal impaction, one colonic obstruction and one intestinal obstruction) and one case of angioneurotic edema occurred among patients taking Vesicare in clinical trials. There was not a significant difference in the incidence of serious adverse events between subjects taking the drug for 12 weeks and 12 months.

Dosing/Administration

Vesicare is administered via an oral tablet of 5 mg once daily, with a possible increase in dosage, to 10 mg once daily, in subjects experiencing good tolerance. Dosing should occur with liquids, and tablets should not be crushed or broken prior to administration.

VESIcare LS is supplied as a liquid oral suspension. The recommended starting and maximum VESIcare LS oral suspension doses are weight-based and are administered once daily. After administration of the recommended starting dose, the dose may be increased to the lowest effective dose but should not exceed the maximum recommended dose.

Clinical Trial Results

FDA approval of Vesicare was based upon four 12-week multicenter, double-blind, placebo-controlled, parallel-group studies. The studies enrolled 3,027 subjects with at least a three-month history of increased urinary frequency, urinary urgency and/or urge or mixed (predominantly urge) incontinence. Subjects in two of the trials received either 5 or 10 mg Vesicare or placebo once daily, and subjects in the other two received exclusively 10 mg or placebo once daily. All patients completing the 12-week studies were eligible to enter an open label long-term extension. All four trials found that Vesicare offered significantly better efficacy than placebo in both primary (mean change from baseline to 12 weeks in number of micturitions/24 hours) and secondary (including mean change from baseline to 12 weeks in number of incontinence episodes/24 hours, and mean volume voided per micturition) end points.

The FDA approval of VESIcare LS for use in pediatric patients with NDO was based on two clinical trials with 95 pediatric NDO patients, ages 2 to 17 years old. The studies were designed to measure (as a primary efficacy end point) the maximum amount of urine the bladder could hold after 24 weeks of treatment. In the first study, 17 patients ages 2 to younger than 5 years old were able to hold an average of 39 mL more urine than when the study began. In the second study, 49 patients ages 5 to 17 years were able to hold an average of 57 mL more urine than when the study began. Reductions in spontaneous bladder contractions, bladder pressure and number of incontinence episodes were also observed in both studies.