What is the recommended treatment and dosage of Vibegron (beta-3 adrenergic agonist) for overactive bladder?

Vibegron Treatment for Overactive Bladder

The recommended treatment for overactive bladder is vibegron 75 mg administered orally once daily, which has demonstrated significant efficacy in reducing micturitions, urgency episodes, and urge incontinence episodes with a favorable safety profile compared to antimuscarinic agents. 1, 2

Mechanism and Dosage

• Vibegron is a beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults 1
• The FDA-approved dose is 75 mg taken orally once daily, with the tablet swallowed whole with water or crushed and mixed with applesauce 1
• As a beta-3 adrenergic receptor agonist, vibegron works through a different mechanism than antimuscarinic agents, providing efficacy without significant anticholinergic side effects 2

Efficacy

• In the phase III EMPOWUR trial, vibegron 75 mg once daily demonstrated statistically significant reductions in:
  • Daily micturitions (-1.8 episodes per day vs -1.3 for placebo, p<0.001) 2
  • Urge incontinence episodes (-2.0 episodes per day vs -1.4 for placebo, p<0.0001) 2
  • Urgency episodes and increased volume per micturition (p<0.01) 2
• Efficacy is maintained long-term, with improvements sustained through 52 weeks of treatment 3
• Significant improvements are observed as early as week 2 of treatment 4

Safety Profile

• Vibegron is well-tolerated with a favorable safety profile compared to antimuscarinic agents 2, 3
• Common adverse events include headache, urinary tract infection, nasopharyngitis, diarrhea, nausea, and upper respiratory tract infection 1
• Incidence of dry mouth is lower with vibegron compared to antimuscarinic agents like tolterodine (1.8% vs 5.2%) 3
• Cardiovascular safety is favorable, with hypertension rates similar to placebo (1.7% for both) 2
• No clinically meaningful effects on blood pressure or heart rate have been observed 5

Special Populations

• Vibegron has demonstrated efficacy and safety in older adults (≥65 and ≥75 years), an important consideration as OAB is common in this population 4
• In patients aged ≥65 years, vibegron showed significant improvements in daily micturitions (p<0.0001), UUI episodes (p<0.001), and urgency episodes (p<0.01) 4
• Not recommended for patients with end-stage renal disease with or without hemodialysis 1
• Not recommended for patients with severe hepatic impairment 1

Treatment Algorithm

1. First-line therapy: Behavioral interventions (bladder training, pelvic floor exercises, fluid management) 6
2. Second-line therapy: Pharmacological treatment with vibegron 75 mg once daily 1, 2
3. For inadequate response: Consider combination therapy with vibegron plus an antimuscarinic agent 7
4. Monitor: Regular assessment of symptom improvement and potential adverse effects 8

Important Considerations

• Vibegron offers advantages over antimuscarinic agents, particularly for elderly patients, due to its lower risk of anticholinergic side effects like dry mouth, constipation, and cognitive impairment 6, 4
• Monitor for urinary retention, especially in patients with bladder outlet obstruction or those taking muscarinic antagonists 1
• If taking digoxin, measure serum digoxin concentrations before initiating vibegron and monitor to titrate digoxin dose to desired clinical effect 1
• Discontinue vibegron if angioedema of the face and/or larynx develops 1

Comparative Efficacy

• The AUA/SUFU guidelines support the use of β3-adrenoceptor agonists like vibegron as an effective treatment option for OAB 8
• Vibegron has demonstrated efficacy similar to mirabegron, another β3-adrenoceptor agonist, but with potentially fewer drug interactions 9, 10
• Compared to antimuscarinic agents, vibegron shows similar efficacy with fewer anticholinergic side effects 2, 3