What is the role of Mirabegron (beta-3 adrenergic agonist) in the treatment of Benign Prostatic Hyperplasia (BPH) patients?

Mirabegron in BPH Patients

Mirabegron is effective and safe for treating overactive bladder (OAB) symptoms in men with BPH, particularly when storage symptoms (urgency, frequency, urge incontinence) persist despite or alongside alpha-blocker therapy. 1

Primary Indication and Mechanism

• Mirabegron is FDA-approved specifically for overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults 2
• The drug works as a beta-3 adrenergic agonist, relaxing the detrusor muscle during bladder filling without affecting voiding function 1
• Importantly, mirabegron also relaxes prostatic smooth muscle directly, providing dual benefit in BPH patients 3

Clinical Evidence in BPH Population

Monotherapy Efficacy

• In men with BPH-related OAB symptoms, mirabegron demonstrated 85.2% efficacy for newly diagnosed patients and 61.6% efficacy for those unresponsive to antimuscarinics 4
• Mirabegron improves not only storage symptoms but also voiding symptoms in men with BPH, with significant reductions in IPSS scores 4
• Post-void residual volumes remain stable (no significant increase from baseline), addressing a key safety concern in men with bladder outlet obstruction 4

Combination Therapy with Alpha-Blockers

• The 2023 European Association of Urology guidelines support combination therapy of mirabegron with tamsulosin for men with persistent OAB symptoms despite alpha-blocker monotherapy 1
• The MATCH and PLUS trials demonstrated that adding mirabegron to tamsulosin significantly improved OAB symptoms without increasing urinary retention risk 1
• This combination addresses both the obstructive component (via alpha-blocker) and storage symptoms (via mirabegron) 1

Dosing Strategy

• Start with mirabegron 25 mg once daily, particularly in older patients (≥65 years) with multiple comorbidities 5, 6
• Can titrate to 50 mg once daily if inadequate response after 4-8 weeks 7
• The 25 mg dose has demonstrated particular safety and efficacy in elderly patients with comorbidities 1

Safety Profile in BPH Patients

Cardiovascular Monitoring

• Monitor blood pressure at baseline and during initial treatment, especially in hypertensive patients 1, 5
• Cardiovascular safety analysis shows no significant concerns with mirabegron treatment 1, 6
• Pulse rate increases are minimal at therapeutic doses (25-50 mg) and not associated with increased cardiovascular adverse events 7

Urinary Retention Risk

• Advise patients to discontinue if worsening voiding symptoms or urinary stream occurs after initiation 5
• Regular re-evaluation of post-void residual volume is recommended by EAU guidelines, particularly in the first 4-8 weeks 5
• The incidence of urinary retention is low (8.4% adverse event rate overall, with no serious events related to retention) 4

Treatment Algorithm for BPH with OAB Symptoms

1. If patient on alpha-blocker with persistent storage symptoms: Add mirabegron 25-50 mg once daily 1

2. If patient has both voiding and storage symptoms, treatment-naïve: Consider combination therapy from the start (alpha-blocker + mirabegron) 1

3. If inadequate response to mirabegron + alpha-blocker after 6 months: Consider triple therapy by adding antimuscarinic (solifenacin 5 mg) to mirabegron 1, 5, 6

4. If patient cannot tolerate antimuscarinics: Mirabegron is the preferred alternative, with superior tolerability profile 1, 8

Advantages Over Antimuscarinics in BPH

• No anticholinergic side effects (dry mouth, constipation, cognitive impairment), which are particularly problematic in elderly men with BPH 8
• Better adherence and persistence compared to antimuscarinics 1
• Does not worsen voiding symptoms or significantly increase post-void residual 4
• May actually improve voiding symptoms through prostatic smooth muscle relaxation 3

Common Pitfalls to Avoid

• Do not withhold mirabegron solely due to concerns about urinary retention—evidence shows it is safe in men with BPH when monitored appropriately 4, 9
• Do not use mirabegron as monotherapy for significant voiding symptoms—it should be combined with alpha-blockers in men with both obstructive and storage symptoms 1
• Avoid starting at 50 mg in elderly patients or those with multiple comorbidities—begin with 25 mg 5, 6