What is the recommended treatment and dosage for overactive bladder using beta-3 adrenergic agonists, such as mirabegron (mirabegron)?

Beta-3 Adrenergic Agonist Treatment for Overactive Bladder

Mirabegron should be started at a dose of 25 mg orally once daily for overactive bladder, with the option to increase to 50 mg once daily after 4-8 weeks if needed and tolerated, while monitoring blood pressure before and during treatment. 1, 2

Mirabegron Dosage and Administration

• Starting dose: 25 mg orally once daily 1, 2
• Dose adjustment: May increase to 50 mg once daily after 4-8 weeks if needed 1, 2
• Administration:
  • For adults: Take with or without food, swallow tablets whole with water (do not chew, divide, or crush) 2
  • For pediatric patients: Take with food, swallow tablets whole with water 2

Patient Selection and Advantages of Mirabegron

Mirabegron offers significant advantages over traditional antimuscarinic medications:

• Different side effect profile compared to anticholinergics 1
• Lower risk of cognitive side effects and dry mouth 1
• Only 2.8% of patients report dry mouth with mirabegron compared to 8.6% with tolterodine ER 3
• Particularly beneficial for patients who cannot tolerate antimuscarinic side effects 4

Contraindications and Dose Adjustments

• Contraindicated in: 1, 2
  • Severe uncontrolled hypertension
  • Severe hepatic impairment
  • End-stage renal disease
• Dose adjustments required for: 1, 2
  • Severe renal failure
  • Moderate hepatic failure

Monitoring and Safety Considerations

• Blood pressure monitoring: Regular monitoring is essential, especially in patients with pre-existing hypertension 1, 2
• Urinary retention: Use with caution in patients with bladder outlet obstruction or those taking muscarinic antagonists 2
• Drug interactions: 2
  • Mirabegron is a CYP2D6 inhibitor - monitor patients taking medications metabolized by CYP2D6
  • When used with digoxin, start with lowest digoxin dose and monitor serum concentrations

Treatment Algorithm for Overactive Bladder

1. First-line treatment:

   • Behavioral therapies (bladder training, delayed voiding, pelvic floor muscle training, fluid management, weight loss) 1

2. Second-line treatment (if behavioral therapies insufficient):

   • Antimuscarinic medications (solifenacin 5mg daily recommended as first choice) OR
   • Mirabegron 25 mg daily (especially for patients concerned about dry mouth, cognitive effects) 1

3. Dose adjustment:

   • If response inadequate after 4-8 weeks, increase mirabegron to 50 mg daily 1, 2

4. For refractory cases:

   • Consider combination therapy with mirabegron plus solifenacin 5mg 1
   • Third-line options: intradetrusor onabotulinumtoxinA injections, peripheral tibial nerve stimulation, sacral neuromodulation 1

Common Adverse Effects

• Hypertension
• Nasopharyngitis
• Urinary tract infection
• Headache 2, 5

Clinical Efficacy

Clinical trials have demonstrated that mirabegron significantly reduces:

• Incontinence episodes per 24 hours
• Micturition episodes per 24 hours
• Urgency episodes
• Nocturia 5, 6

Additionally, mirabegron increases the volume of urine voided per micturition and improves health-related quality of life 3, 5.

Important Caveats

• Mirabegron carries a low risk of QT interval prolongation 3
• Angioedema of the face, lips, tongue, and/or larynx has been reported 2
• Monitor for urinary retention, especially in patients with bladder outlet obstruction 1, 2
• Extended-release tablets must be swallowed whole and not crushed or chewed 2
• Mirabegron extended-release tablets and mirabegron granules are not substitutable on a milligram-per-milligram basis 2