Gemtesa (Vibegron) for Overactive Bladder
Gemtesa (vibegron) is dosed at 75 mg orally once daily, taken with or without food, and represents a preferred second-line pharmacologic option for overactive bladder after behavioral therapies, particularly advantageous over antimuscarinics due to its superior side effect profile and lack of cognitive risks. 1
Indications
Gemtesa is FDA-approved for two specific populations:
- Adults with overactive bladder presenting with urge urinary incontinence, urgency, and urinary frequency 1
- Adult males with OAB and benign prostatic hyperplasia who are already on BPH pharmacological therapy 1
Dosing and Administration
The standard dose is 75 mg once daily, which requires no titration or dose adjustment. 1
- Tablets should be swallowed whole with water 1
- May be taken with or without food 1
- For patients with swallowing difficulties, tablets may be crushed and mixed with approximately 15 mL of applesauce, taken immediately with water 1
Treatment Algorithm Position
First-Line: Behavioral Therapies
Begin with behavioral interventions including bladder training, delayed voiding, pelvic floor muscle training, fluid management, and weight loss 2
Second-Line: Pharmacologic Management
Beta-3 agonists like vibegron are now preferred before antimuscarinic medications due to their favorable side effect profile 2. This represents an important shift in the treatment paradigm, as the 2015 AUA/SUFU guidelines positioned antimuscarinics and beta-3 agonists as equivalent options 3, but more recent guidance prioritizes beta-3 agonists first 2.
Combination Therapy Considerations
- Behavioral therapy may be combined with vibegron for enhanced efficacy 3, 2
- Combination of vibegron with an antimuscarinic medication may be considered for inadequate monotherapy response 2
- Vibegron has been studied safely in combination with tolterodine 4, 5
Efficacy Profile
Vibegron demonstrates rapid onset with significant improvements as early as week 2 that are sustained long-term. 5, 6
Key efficacy outcomes at 12 weeks include:
- Reduction in daily micturitions with sustained benefit through 52 weeks (least squares mean change -2.4) 5, 6
- Reduction in urge urinary incontinence episodes with 61% of patients achieving ≥75% reduction and 40.8% achieving complete dryness at 52 weeks 5
- Reduction in urgency episodes maintained throughout treatment 5, 6
- Improvements in quality of life measures 6
Special Population: Elderly Patients
Vibegron is particularly advantageous for patients aged ≥65 years, as it does not carry the cognitive impairment or dementia risk associated with antimuscarinics. 2
In patients ≥65 years:
- Significant improvements in all OAB symptoms (micturitions, UUI episodes, urgency) versus placebo (P < 0.0001 to P < 0.01) 7
- 50% achieved ≥75% reduction in UUI episodes versus 29.8% with placebo 7
- Maintained efficacy in patients ≥75 years 7
- Low cardiovascular adverse event rates (<2%) similar to placebo 7
Safety Profile and Warnings
Critical Safety Concerns
Monitor for urinary retention, particularly in patients with bladder outlet obstruction or those taking concomitant antimuscarinic medications. 1
- Discontinue immediately if urinary retention develops 1
Angioedema can occur hours after first dose or after multiple doses and may be life-threatening. 1
- Immediately discontinue if tongue, hypopharynx, or laryngeal involvement occurs 1
- Contraindicated in patients with known hypersensitivity to vibegron 1
Common Adverse Events
The most frequently reported adverse events (>5%) include:
- Hypertension (8.8%) 5
- Urinary tract infection (6.6%) 5
- Headache (5.5%) 5
- Nasopharyngitis (4.8%) 5
- Notably, dry mouth occurs in only 1.8% of patients versus 5.2% with tolterodine 5
Cardiovascular Safety
A dedicated ambulatory blood pressure monitoring study demonstrated no clinically meaningful effects on blood pressure or heart rate. 6
- Hypertension rates in elderly patients (≥65 years) were 1.2% with vibegron versus 3.1% with placebo 7
Key Advantages Over Antimuscarinics
- No cytochrome P450 enzyme interactions, making it safer for patients on polypharmacy 8
- No anticholinergic cognitive effects or dementia risk 2, 6
- Lower dry mouth incidence (1.8% vs 5.2% with tolterodine) 5
- Single daily dose with no titration required 8
- High beta-3 receptor selectivity 8
Clinical Pitfalls to Avoid
- Do not abandon beta-3 agonist therapy if one antimuscarinic previously failed; vibegron has a different mechanism and may still be effective 3
- Exercise particular caution when combining with antimuscarinics due to increased urinary retention risk 1
- Do not use in patients with known hypersensitivity to vibegron due to angioedema risk 1
- Monitor elderly patients for hypertension, though rates remain low 7