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 two years and older.

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 tollerance. 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 Results

FDA approval of Vesicare was based upon four 12-week multi-center, double-blind, placebo-controlled, parallel-group studies. The studies enrolled a total of 3027 subjects with at least a 3 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) endpoints.

The FDA approval of VESIcare LS for use in pediatric patients with NDO was based on two clinical trials with a total of 95 pediatric NDO patients, ages two to 17 years old. The studies were designed to measure (as a primary efficacy endpoint) the maximum amount of urine the bladder could hold after 24 weeks of treatment. In the first study, 17 patients ages 2 to less 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 five 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.

Side Effects

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

Dry mouth

Constipation

Blurred Vission

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.

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.

Literature References

Cardozo L, Lisec M, Millard R, et al. Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder. Journal of Urology 2004 Nov;172(5 Pt 1):1919-24.

Smulders RA, Krauwinkel WJ, Swart PJ, Huang M. Pharmacokinetics and safety of solifenacin succinate in healthy young men. Journal of Clinical Pharmacology 2004 Sep;44(9):1023-33.

Ohtake A, Ukai M, Hatanaka T,et al. In vitro and in vivo tissue selectivity profile of solifenacin succinate (YM905) for urinary bladder over salivary gland in rats. European Journal of Pharmacology 2004 May 25;492(2-3):243-50.