Darifenacin hydrobromide is used in the management of overactive bladder for the relief of symptoms associated with voiding such as urge urinary incontinence, urgency, and frequency.
Safety and efficacy of darifenacin for this indication were established in four 12-week randomized, double-blind, placebo-controlled studies in more than 1400 patients with symptoms of urinary frequency, urgency, and/or urge or mixed incontinence that had persisted for at least 6 months. In these studies, darifenacin 7.5-15 mg daily was more effective than placebo in reducing the number of urge incontinence episodes per week, reducing the number of micturitions per 24 hours, and increasing the volume of urine voided per micturition. In the 3 fixed-dose studies, patients received darifenacin 7.5 or 15 mg once daily or placebo; in these studies, urge incontinence episodes were decreased from baseline by 8.1-11.4 or 5.9-9 occurrences per week, urinary frequency was decreased from baseline by 1.6-1.9 or 0.8-1.2 micturitions per 24 hours, and urine volume voided per micturition was increased by 14.9-30.9 or 4.6-7.6 mL per micturition in patients receiving darifenacin or placebo, respectively. In the flexible-dose study, patients received darifenacin 7.5 mg once daily (with the option to increase dosage to 15 mg once daily) or placebo; in this study, urge incontinence episodes were decreased from baseline by 8.2 or 6 occurrences per week, urinary frequency was decreased from baseline by 1.9 or 1 micturition per 24 hours, and urine volume voided per micturition was increased by 18.8 or 6.6 mL per micturition in patients receiving darifenacin or placebo, respectively. Among patients who required dosage escalation to 15 mg daily, clinical outcome achieved at 12 weeks was comparable to that achieved in patients who initially responded to the 7. 5-mg daily dosage. Reduction in the number of urge incontinence episodes was observed within the first 2 weeks of therapy, and this effect was sustained throughout the 12-week treatment period.
In addition to objective improvements, a beneficial effect on quality-of-life scores has been demonstrated with darifenacin. Data from a pooled analysis indicate that treatment with darifenacin 7.5 or 15 mg daily was associated with improvements in quality-of-life aspects related to incontinence impact, severity measures, emotions and role, and social and physical limitations. However, treatment did not improve aspects related to personal relationships, sleep and energy, or general health.
Limited data from a short-term (2-week) efficacy study in patients with overactive bladder indicate that extended-release darifenacin (15 mg once daily) may be as effective as immediate-release oxybutynin (5 mg 3 times daily) in reducing the frequency of urinary incontinence and the frequency and severity of urgency. However, the efficacy of extended-release oxybutynin and extended-release darifenacin has not been compared.