What is Vibegron (beta-3 adrenergic agonist) used for?

Vibegron for Overactive Bladder Treatment

Vibegron is a selective β3-adrenergic receptor agonist used to treat overactive bladder (OAB) in adults, specifically targeting symptoms of urge urinary incontinence, urgency, and urinary frequency. 1

Mechanism of Action

Vibegron works by activating β3-adrenergic receptors in the bladder, which increases bladder capacity by relaxing the detrusor smooth muscle during bladder filling. 1 This mechanism differs fundamentally from anticholinergic medications, offering an alternative pathway for symptom control. 2

Clinical Indications and Efficacy

Vibegron is indicated as second-line pharmacologic therapy for OAB after behavioral interventions have been attempted. 3 The medication demonstrates significant improvements in:

• Reduction in daily micturition episodes (mean difference -0.77 episodes/day compared to placebo) 4
• Decrease in urgency episodes (mean difference -0.77 episodes/day) 4
• Reduction in urgency incontinence episodes (mean difference -0.50 episodes/day) 4
• Increased voided volume per micturition (mean difference +22.22 mL) 4

The efficacy profile is particularly notable for patients with "wet OAB" (those with incontinence episodes), where vibegron shows robust clinical benefit. 5

Dosing and Administration

The standard dose is 75 mg once daily, taken orally. 1 The medication can be taken with or without food, as high-fat meals do not significantly affect pharmacokinetics. 1 If needed, the tablet can be crushed and mixed with applesauce without clinically relevant changes in drug absorption. 1

Special Populations

Elderly Patients

No dose adjustment is required for geriatric patients, and vibegron has demonstrated continued efficacy and safety in patients ≥65 years of age. 1, 5 This is particularly advantageous given the high prevalence of OAB in older adults. 1

Renal Impairment

No dose adjustment is needed for mild, moderate, or severe renal impairment (eGFR 15 to <90 mL/min/1.73 m²). 1 However, vibegron is not recommended for patients with eGFR <15 mL/min/1.73 m² or those on hemodialysis, as it has not been studied in this population. 1

Hepatic Impairment

No dose adjustment is required for mild to moderate hepatic impairment (Child-Pugh A and B). 1 Vibegron is not recommended for severe hepatic impairment (Child-Pugh C) due to lack of data. 1

Safety Profile and Monitoring

Vibegron demonstrates a favorable safety profile with low rates of drug-related adverse events (5.4-7.6%, similar to placebo at 5.1%). 6 Key safety considerations include:

• No clinically significant blood pressure changes in controlled studies, even in patients with pre-existing hypertension 1
• No QT interval prolongation at doses up to 5.3 times the approved dose 1
• Minimal drug interactions due to lack of significant CYP450 enzyme involvement 5
• Low incidence of dry mouth compared to anticholinergics 4

Drug Interactions

The primary interaction of clinical relevance is with digoxin, where vibegron increases digoxin Cmax by 21% and AUC by 11%. 1 This is generally not clinically significant but warrants awareness in patients on digoxin therapy. 1

Treatment Algorithm Position

According to AUA/SUFU guidelines, vibegron fits into the following treatment sequence:

1. First-line: Behavioral therapies (bladder training, fluid management, pelvic floor exercises) 3
2. Second-line: Pharmacologic management with β3-adrenergic agonists (including vibegron) or antimuscarinics, which may be combined with behavioral therapies 3
3. For refractory cases: Consider combination therapy with an antimuscarinic agent if monotherapy with vibegron is inadequate after appropriate trial duration 3

Advantages Over Other β3-Agonists

Vibegron demonstrates superior real-world adherence and persistence compared to mirabegron and anticholinergics. 7 Specifically:

• Higher mean proportion of days covered (0.67 vs. 0.64 for mirabegron, 0.67 vs. 0.58 for anticholinergics) 7
• Longer median persistence (171 days vs. 128 days for mirabegron, 172 days vs. 91 days for anticholinergics) 7
• Minimal CYP450 interactions, unlike mirabegron which interacts with CYP enzymes 5

Common Pitfalls to Avoid

• Do not use in patients with eGFR <15 mL/min/1.73 m² or severe hepatic impairment (Child-Pugh C), as safety and efficacy are not established 1
• Monitor digoxin levels if co-administering, though clinical significance is typically minimal 1
• Allow adequate trial duration (typically 4-8 weeks) before deeming treatment ineffective 3
• Consider combination therapy with antimuscarinics for patients with inadequate response to monotherapy rather than abandoning β3-agonist therapy entirely 3

Quality of Life Impact

Vibegron significantly improves quality of life measures with high patient satisfaction scores, addressing not just symptom frequency but the overall burden of OAB on daily functioning. 6