Mirabegron 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 mirabegron for this indication were established in three 12-week randomized, double-blind, placebo-controlled studies in patients with symptoms of urinary frequency, urgency, and/or urge incontinence that had persisted for at least 3 months. Patients (mean age of 59 years) were required to have at least 8 micturitions per day and at least 3 episodes of urgency with or without incontinence over a 3-day period; 52% of these patients had received prior treatment with antimuscarinic agents for overactive bladder symptoms. In all studies, the primary efficacy outcome was the change from baseline to end of treatment in the mean number of micturitions and also the mean number of incontinence episodes per 24 hours. In the first 2 studies, patients were randomized to receive mirabegron 50 or 100 mg once daily or placebo. In the first study, a group of patients also was randomized to an active control arm with an antimuscarinic agent (i.e., tolterodine 4 mg extended-release tablets once daily); however, the study design did not allow for a direct comparison between mirabegron and tolterodine. In the third study, patients were randomized to receive mirabegron 25 or 50 mg once daily or placebo. Although mirabegron dosages of 25, 50, and 100 mg were evaluated in clinical studies, only the 25- and 50-mg dosages were considered for Food and Drug Administration (FDA) approval for the management of overactive bladder.
In the first 2 studies, mirabegron 50 mg daily was more effective than placebo in reducing the number of micturitions and incontinence episodes per 24 hours; mirabegron 50 mg daily also was more effective than placebo in increasing the volume of urine voided per micturition. In these 2 studies, urinary frequency was decreased from baseline by 1.66-1.93 or 1.05-1.34 micturitions per 24 hours; urge incontinence episodes were decreased from baseline by 1.47-1.57 or 1.13-1.17 occurrences per 24 hours; and urine volume voided per micturition was increased by 18.2-24.2 or 7-12.3 mL per micturition in patients receiving mirabegron or placebo, respectively. In the third study, mirabegron 25 or 50 mg daily was more effective than placebo in reducing the number of micturitions and incontinence episodes per 24 hours; urinary frequency was decreased from baseline by 1.6-1.65 or 1.18, and urge incontinence episodes were decreased from baseline by 1.36-1.38 or 0.96 in patients receiving mirabegron or placebo, respectively. Efficacy in treating the symptoms of overactive bladder was observed within 4 or 8 weeks in patients receiving mirabegron at a daily dosage of 50 or 25 mg, respectively; efficacy of both dosages was maintained throughout the 12-week treatment period.
In another randomized, double-blind, active-controlled study, patients received mirabegron 50 or 100 mg or tolterodine 4 mg extended-release tablets once daily for 12 months. These patients were required to have at least 8 micturitions per day and at least 3 episodes of urgency over a 3-day period. Mirabegron and the active control tolterodine improved symptoms of overactive bladder from the first measured time point of 4 weeks; efficacy was maintained throughout the 12-month treatment period.
In addition to objective improvements, a beneficial effect on quality-of-life scores has been demonstrated with mirabegron. Clinical study data indicate that treatment with mirabegron was associated with improvements in quality-of-life aspects related to severity measures, symptom severity, coping, concern, sleep, and treatment satisfaction.
Antimuscarinic agents (e.g., darifenacin, fesoterodine, oxybutinin, solifenacin, tolterodine) are considered first-line drugs for the treatment of overactive bladder. Mirabegron may be an appropriate alternative in patients with overactive bladder in whom antimuscarinic agents are ineffective or cannot be tolerated because of adverse anticholinergic effects (e.g., dry mouth and constipation). Mirabegron also may be considered for the management of overactive bladder in geriatric patients or patients with Alzheimer's disease, who may be more sensitive to anticholinergic effects and potential effects on cognition associated with antimuscarinic agents.