What is the role of Mirabegron (beta-3 adrenergic agonist) in treating overactive bladder symptoms in males?

Mirabegron in Males with Overactive Bladder

Mirabegron is an effective and well-tolerated treatment option for overactive bladder symptoms in males, with demonstrated efficacy and a favorable safety profile compared to antimuscarinics, particularly regarding dry mouth and other anticholinergic side effects. 1

FDA-Approved Indication

• Mirabegron is FDA-approved for treating overactive bladder (OAB) in adult patients with symptoms of urge urinary incontinence, urgency, and urinary frequency 2
• The medication works as a beta-3 adrenergic receptor agonist that relaxes detrusor smooth muscle during bladder storage, increasing bladder capacity without impairing voiding 2

Dosing Recommendations for Males

• Start with 25 mg orally once daily, which can be increased to 50 mg once daily after 4-8 weeks if needed 1, 2
• The 25 mg starting dose is particularly appropriate for older males (≥65 years) with multiple comorbidities 3
• Tablets should be swallowed whole with water (with or without food in adults) and must not be chewed, divided, or crushed 2

Efficacy in Male Populations

• Multiple phase III randomized controlled trials demonstrate significant improvements in micturition frequency, urgency incontinence, and urgency episodes as early as week 4, with sustained benefits throughout treatment 1, 4
• Real-world data shows that approximately two-thirds of male patients (66.7%) maintain therapy for more than 3 months, with 47.5% continuing for 6+ months 5
• Therapeutic effects are similar between male and female patients, with no statistical difference in symptom improvement or drug persistence rates 5

Critical Safety Consideration: Bladder Outlet Obstruction

• Mirabegron should be administered with caution in males with clinically significant bladder outlet obstruction (BOO) due to risk of urinary retention 2
• A urodynamic study in 200 males with lower urinary tract symptoms and BOO showed that mirabegron did not adversely affect maximum flow rate or detrusor pressure at maximum flow rate after 12 weeks 1, 2
• However, regular monitoring of post-void residual volume is advised, and patients should discontinue if worsening voiding symptoms or urinary stream occurs 3, 6

Blood Pressure Monitoring

• Periodically monitor blood pressure, especially during initial treatment, as mirabegron can cause dose-dependent increases 2
• At the 50 mg dose, maximum mean increases in supine systolic/diastolic blood pressure were approximately 4.0/1.6 mm Hg greater than placebo 2
• Mirabegron is not recommended in patients with severe uncontrolled hypertension 2
• Real-world data shows elevated blood pressure occurs in approximately 2.8% of patients 5

Safety Profile Advantages Over Antimuscarinics

• The incidence of dry mouth with mirabegron is similar to placebo and three to fivefold less than tolterodine extended-release 4 mg 4
• Mirabegron has a favorable profile regarding constipation and CNS effects compared to antimuscarinics 7
• Most common adverse events are hypertension (dose-dependent), nasopharyngitis, and urinary tract infection 2, 4
• Overall side effect rate is approximately 10.2%, with only 4.5% discontinuing due to adverse effects 5

Combination Therapy for Inadequate Response

• For males with inadequate response to mirabegron monotherapy after 6 months, consider combination therapy with an antimuscarinic agent like solifenacin 3
• The SYNERGY study demonstrated that mirabegron 25 mg + solifenacin 5 mg or mirabegron 50 mg + solifenacin 5 mg combinations provide improved efficacy without significant safety concerns compared to monotherapy 1, 3

Special Populations

Elderly Males

• Mirabegron 25 mg demonstrates safety and therapeutic efficacy in older patients (≥65 years) with multiple comorbidities 1, 3
• No dose adjustment is necessary based on age alone, though the 25 mg starting dose is preferred 3

Renal Impairment

• No dose adjustment needed for mild-moderate renal impairment (eGFR 30-89 mL/min/1.73 m²) 2
• In severe renal impairment (eGFR 15-29 mL/min/1.73 m²), do not exceed 25 mg daily 2
• Not recommended for end-stage renal disease or hemodialysis patients 2

Hepatic Impairment

• In moderate hepatic impairment (Child-Pugh Class B), do not exceed 25 mg daily 2
• Not recommended for severe hepatic impairment (Child-Pugh Class C) 2

Common Pitfalls to Avoid

• Do not use mirabegron as a substitute for addressing bladder outlet obstruction in males with significant BOO—evaluate and treat the obstruction appropriately 2
• Do not crush or divide tablets, as this destroys the extended-release formulation 2
• Do not neglect blood pressure monitoring, particularly in the first few months of therapy 2
• Do not assume treatment failure too early—therapeutic effects may continue to improve through 12-24 weeks 5