When to prescribe Mirabegron (beta-3 adrenergic agonist) for overactive bladder?

When to Prescribe Mirabegron for Overactive Bladder

Prescribe mirabegron as second-line pharmacologic therapy for overactive bladder when first-line behavioral interventions (bladder training for urgency incontinence or pelvic floor muscle training for stress incontinence) have failed after 8-12 weeks, or as an alternative to antimuscarinics when patients cannot tolerate their side effects. 1

First-Line Treatment Requirements

Before considering mirabegron, patients must attempt appropriate behavioral therapy:

• Bladder training for urgency urinary incontinence (8-12 weeks trial) 1
• Pelvic floor muscle training (PFMT) for stress urinary incontinence 1
• Combined PFMT with bladder training for mixed urinary incontinence 1
• Weight loss and exercise for obese women with urinary incontinence 1

These behavioral interventions are effective, have minimal adverse effects, and cost less than pharmacologic therapy. 1

When to Initiate Mirabegron

Primary Indications

Start mirabegron 25 mg once daily when:

• Behavioral therapy has been unsuccessful after adequate trial (8-12 weeks) 1
• Patient has urgency urinary incontinence with symptoms of urgency and urinary frequency 2
• Patient cannot tolerate antimuscarinic side effects (dry mouth, constipation, blurred vision, cognitive impairment) 1
• Patient has failed one antimuscarinic medication trial (4-8 weeks) due to inadequate efficacy or unacceptable adverse effects 1

Dosing Strategy

• Initial dose: 25 mg orally once daily 2
• Dose escalation: May increase to 50 mg once daily after 4-8 weeks if symptom control is inadequate 2
• Administration: Take with or without food in adults; swallow whole, do not crush or chew 2

Advantages Over Antimuscarinics

Mirabegron offers a similar efficacy profile to antimuscarinics but with a relatively lower adverse event profile, particularly regarding anticholinergic side effects. 1

Key tolerability differences:

• Dry mouth: 0.5-2.1% with mirabegron vs 8.6% with tolterodine ER 3, 4
• Lower risk of constipation, blurred vision, and cognitive impairment compared to antimuscarinics 1, 5
• Most common adverse effects: nasopharyngitis, hypertension, urinary tract infection, headache (>2% incidence) 2, 6

Special Populations and Precautions

Elderly Patients (≥80 years)

• Start with 25 mg dose, which produces statistically significant improvements with acceptable adverse event rate (24.62%) 7, 8
• Use caution in frail patients with mobility deficits, unexplained weight loss, weakness, or cognitive deficits 1

Cardiovascular Considerations

• Monitor blood pressure periodically, especially during initial treatment, as mirabegron causes dose-dependent blood pressure increases 7, 8, 2
• Contraindicated in severe uncontrolled hypertension 7, 8, 2

Renal Impairment

• eGFR 30-89 mL/min/1.73 m²: Start 25 mg, may increase to 50 mg 2
• eGFR 15-29 mL/min/1.73 m²: Maximum dose 25 mg 2
• eGFR <15 mL/min/1.73 m² or dialysis: Not recommended 2

Hepatic Impairment

• Child-Pugh Class A (mild): Start 25 mg, may increase to 50 mg 2
• Child-Pugh Class B (moderate): Maximum dose 25 mg 2
• Child-Pugh Class C (severe): Not recommended 2

Urinary Retention Risk

• Administer with caution in patients with bladder outlet obstruction 2
• Monitor post-void residual volume, particularly in men with lower urinary tract symptoms 7

Combination Therapy Strategy

If monotherapy with mirabegron 50 mg provides inadequate response after 6 months, add solifenacin 5 mg once daily. 1, 7, 8

Two validated combination regimens:

• Mirabegron 25 mg + solifenacin 5 mg 1, 7, 8
• Mirabegron 50 mg + solifenacin 5 mg 1, 7, 8

Combination therapy demonstrates superior efficacy with effect sizes (0.65-0.95) exceeding monotherapy (0.36-0.56) for reducing incontinence episodes and micturitions. 1, 7, 8

Important caveat: Combination therapy carries slightly increased risk of dry mouth, constipation, dyspepsia, and urinary retention compared to monotherapy. 1, 7

Drug Interactions

• Mirabegron is a CYP2D6 inhibitor: Monitor and adjust doses of narrow therapeutic index drugs metabolized by CYP2D6 when used concomitantly 2

When to Refer to Specialist

Refer patients who remain refractory after:

• Adequate trial of behavioral therapy (8-12 weeks) 1
• Trial of at least one antimuscarinic or mirabegron (4-8 weeks) 1
• Failure may include lack of efficacy or intolerable adverse effects 1

Clinical Pearls

• Do not abandon beta-3 agonist therapy if one antimuscarinic fails—patients who experience inadequate control or unacceptable adverse effects with antimuscarinics may respond better to mirabegron 1
• Treatment persistence with mirabegron monotherapy: 68% at 3 months, 54.4% at 6 months, 39.4% at 12 months 9
• Treatment-naïve patients demonstrate better persistence than those previously treated with antimuscarinics 9
• Patients with severe baseline OAB symptoms more likely to require add-on therapy during follow-up 9