What is the recommended treatment for chronic urinary urgency, specifically using Myrbetriq (mirabegron)?

Treatment of Chronic Urinary Urgency with Myrbetriq (Mirabegron)

Mirabegron is an effective first-line pharmacological treatment for chronic urinary urgency associated with overactive bladder, with a starting dose of 25 mg once daily that can be increased to 50 mg after 4-8 weeks if symptom control is inadequate. 1

Initial Dosing Strategy

• Start with mirabegron 25 mg orally once daily, which is the FDA-approved starting dose for adults with overactive bladder 1
• This lower starting dose is particularly appropriate for elderly patients (≥80 years) with multiple comorbidities, producing statistically significant improvements in voiding symptoms and quality of life with an acceptable adverse event rate of 24.62% 2
• After 4-8 weeks, if symptom control remains inadequate, increase to the maximum dose of 50 mg once daily 1

Monitoring Requirements

Blood pressure monitoring is essential because mirabegron causes dose-dependent blood pressure increases 2:

• Monitor blood pressure periodically, especially during initial treatment 2
• Mirabegron is contraindicated in severe uncontrolled hypertension 2, 1
• For men with lower urinary tract symptoms, regularly re-evaluate post-void residual volume due to urinary retention risk 2

Efficacy Expectations

Mirabegron demonstrates clinically meaningful benefits 3, 4:

• Significant reductions in incontinence episodes per 24 hours are evident as early as week 4 4
• Reduces micturition frequency by approximately 2.1 episodes per 24 hours compared to 1.4 with placebo 5
• Increases volume voided per micturition and reduces urgency episodes 3
• Improvements in quality of life and treatment satisfaction are consistently demonstrated 3, 4

Combination Therapy for Refractory Cases

If monotherapy with mirabegron fails after 6 months, add solifenacin 5 mg once daily to create combination therapy 6, 2:

• The SYNERGY I/II and BESIDE trials provide the strongest evidence for combining solifenacin 5 mg with mirabegron (25 mg or 50 mg) 6
• Combination therapy was statistically superior to either monotherapy for decreasing incontinence episodes (p<0.001 vs mirabegron; p=0.002 vs solifenacin) and micturitions (p<0.001 vs mirabegron; p=0.004 vs solifenacin) over 12 months 6
• Effect sizes for combination therapy (0.85-0.95) exceeded those of monotherapy (0.36-0.56) 6

Combination Therapy Caveats

Be aware that combination therapy increases certain adverse events 6, 2:

• Dry mouth, constipation, and dyspepsia are slightly increased compared to monotherapy 6
• Urinary retention events are reported more frequently with combination therapy 6
• Treatment-emergent adverse events occur in 49% with combination versus 41% with mirabegron alone 6

Common Adverse Effects

The most frequently reported adverse reactions with mirabegron monotherapy (>2% and greater than placebo) are 1:

• Hypertension
• Nasopharyngitis
• Urinary tract infection
• Headache

Importantly, dry mouth incidence with mirabegron 50 mg (2.8% over 12 months) is substantially lower than tolterodine ER 4 mg (8.6%), making it advantageous for patients who discontinued antimuscarinics due to this bothersome side effect 3, 4

Dosage Adjustments for Special Populations

Renal Impairment 1:

• eGFR 30-89 mL/min/1.73 m²: Start 25 mg, maximum 50 mg daily
• eGFR 15-29 mL/min/1.73 m²: Start 25 mg, maximum 25 mg daily (do not increase)
• eGFR <15 mL/min/1.73 m² or dialysis: Not recommended

Hepatic Impairment 1:

• Child-Pugh Class A (mild): Start 25 mg, maximum 50 mg daily
• Child-Pugh Class B (moderate): Start 25 mg, maximum 25 mg daily (do not increase)
• Child-Pugh Class C (severe): Not recommended

Administration Instructions

• Swallow tablets whole with water—do not chew, divide, or crush 1
• Can be taken with or without food in adults 1
• Mirabegron is a CYP2D6 inhibitor, requiring appropriate monitoring and possible dose adjustment of concomitant drugs metabolized by CYP2D6, especially narrow therapeutic index drugs 1

Clinical Context

Mirabegron represents a mechanistically distinct alternative to antimuscarinic agents, working as a β3-adrenoceptor agonist that causes detrusor muscle relaxation 1, 7. This different mechanism accounts for its favorable tolerability profile, particularly the markedly lower incidence of dry mouth compared to antimuscarinics 3, 4. The drug has demonstrated efficacy even in patients who previously discontinued antimuscarinic therapy due to lack of efficacy or poor tolerability 4, 7.