What is the role of mirabegron in treating overactive bladder?

Role of Mirabegron in Treating Urological Disorders of Bladder

Mirabegron is a beta-3 adrenergic agonist indicated as a second-line pharmacological treatment for overactive bladder (OAB) with a favorable cardiovascular safety profile and fewer side effects compared to antimuscarinic medications. 1

Indications and Mechanism of Action

• FDA-approved for:

  • Treatment of overactive bladder (OAB) in adults with symptoms of urge urinary incontinence, urgency, and urinary frequency
  • Neurogenic detrusor overactivity (NDO) in pediatric patients aged 3 years and older weighing 35 kg or more 2

• Mechanism: Targets β3-adrenoreceptors in the bladder, improving storage capacity without affecting voiding contractions 3

Treatment Algorithm for OAB

First-Line Treatment

• Behavioral therapies should be initiated first:
  • Pelvic floor muscle training
  • Bladder training
  • Fluid management (25% reduction in fluid intake)
  • Weight loss if applicable 1

Second-Line Treatment

• Pharmacological options:
  1. Antimuscarinic agents (e.g., solifenacin 5mg daily)
  2. Mirabegron - preferred in patients with:
     • Pre-existing cardiac conditions
     • Elderly patients (lower risk of cognitive side effects)
     • History of poor tolerability to antimuscarinics 1

Dosing and Administration

• Starting dose: 25 mg orally once daily
• May increase to 50 mg once daily after 4-8 weeks if needed and tolerated
• Administration:
  • Adults: Take with or without food
  • Pediatric patients: Take with food
  • Swallow tablets whole with water; do not chew, divide, or crush 2

Efficacy

• Significant improvements in key OAB symptoms:

  • Micturition frequency
  • Urgency incontinence episodes
  • Mean volume voided per micturition 4

• Benefits observed as early as 4 weeks and maintained throughout treatment 5

• Efficacy demonstrated in:

  • Treatment-naïve patients
  • Patients who previously discontinued antimuscarinic therapy
  • Patients ≥65 years of age 4, 6

Safety Profile and Adverse Events

• Most common adverse events:

  • Hypertension
  • Nasopharyngitis
  • Urinary tract infection
  • Headache 2, 4

• Key advantages over antimuscarinic agents:

  • Significantly lower incidence of dry mouth (similar to placebo)
  • Lower rates of constipation
  • Fewer CNS effects 4, 7

Special Considerations and Monitoring

• Blood pressure monitoring:

  • Regular monitoring recommended, especially in first few weeks
  • Not recommended in patients with severe uncontrolled hypertension 1, 2

• Use with caution in:

  • Patients with bladder outlet obstruction (risk of urinary retention)
  • Patients taking muscarinic antagonist drugs for OAB 2
  • Patients with renal or hepatic impairment (may require dose adjustment) 2

• Drug interactions:

  • Mirabegron is a CYP2D6 inhibitor - monitor when used with drugs metabolized by CYP2D6, especially those with narrow therapeutic index 2

Combination Therapy

• Combination of mirabegron plus solifenacin 5mg may be considered for patients who fail monotherapy
• Shows improved efficacy with additive effects for urgency urinary incontinence episodes, urgency episodes, and nocturia 1

Third-Line Options for Treatment Failures

For patients who fail behavioral and pharmacologic therapy (including mirabegron):

• OnabotulinumtoxinA injections
• Peripheral tibial nerve stimulation (PTNS)
• Sacral neuromodulation (SNS) 1

Clinical Pearls

• Complete symptom relief is unlikely in patients with severe baseline symptoms
• Patients refractory to behavioral and medical therapy should be evaluated by a specialist
• The low incidence of dry mouth with mirabegron (compared to antimuscarinics) may improve treatment adherence 1, 4
• Long-term safety and efficacy have been demonstrated in studies up to 12 months 4