Vibegron

• Overactive Bladder
• Urge Urinary Incontinence
• Urinary Frequency and Urgency

Vibegron is a beta-3 adrenergic receptor agonist used to treat overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. It provides an alternative mechanism to anticholinergic medications, potentially offering better tolerability with fewer cognitive and dry mouth side effects.

Mechanism of Action

Vibegron works through selective receptor activation in the bladder:

• Beta-3 adrenergic agonist: Selectively activates beta-3 adrenergic receptors in the bladder detrusor muscle
• Detrusor relaxation: Causes smooth muscle relaxation during the bladder storage phase
• Increases bladder capacity: Allows greater urine volumes before urgency sensation
• Reduces involuntary contractions: Decreases detrusor overactivity
• Minimal anticholinergic effects: Avoids dry mouth, constipation, and cognitive impairment associated with antimuscarinics

This mechanism offers particular advantages for elderly patients who may be more susceptible to anticholinergic side effects.

Available Formulations

Vibegron is available as oral tablets:

• 75 mg tablets (Gemtesy)

Medical Uses

FDA-Approved Indication:

• Treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency

Vibegron is appropriate for patients who have not responded to or cannot tolerate anticholinergic OAB medications.

Dosing Guidelines

Adults (Overactive Bladder):

• 75 mg once daily with or without food
• Swallow tablets whole, or crush and mix with applesauce for immediate administration

Administration:

• Take at approximately the same time each day
• If crushing tablet, consume mixture within 10 minutes
• No dose titration required

Important Safety Information

Contraindications:

• Known hypersensitivity to vibegron or any excipient

Warnings and Precautions:

• Urinary retention: Use with caution in patients with bladder outlet obstruction or taking antimuscarinics for OAB
• Patients taking digoxin: Monitor digoxin concentrations; vibegron increases digoxin levels
• Hypertension: Monitor blood pressure, especially in hypertensive patients
• Prostatic hyperplasia: Use with caution; may mask symptoms of BPH progression

Drug Interactions

• Digoxin: Vibegron increases digoxin exposure by approximately 20%; measure serum digoxin before starting vibegron and monitor periodically
• UGT1A1 substrates: Vibegron inhibits UGT1A1; may increase concentrations of drugs metabolized by this enzyme
• Other OAB medications: Concomitant use with antimuscarinics may increase risk of urinary retention
• CYP3A4 inhibitors/inducers: Vibegron is partially metabolized by CYP3A4 but no dose adjustment recommended
• Anticoagulants: No significant interaction with warfarin

Special Populations

• Renal Impairment: No dose adjustment for eGFR ≥15 mL/min; not recommended for eGFR <15 mL/min or patients on dialysis
• Hepatic Impairment: No dose adjustment for mild-moderate impairment (Child-Pugh A or B); avoid in severe impairment (Child-Pugh C)
• Elderly: No dose adjustment needed; favorable side effect profile may benefit elderly patients
• Pregnancy: No human data available; use only if benefit outweighs potential risk
• Lactation: Unknown if excreted in breast milk; consider benefit-risk
• Pediatric: Safety and efficacy not established in patients <18 years
• Males with BPH: Use with caution; not studied specifically in this population