Gemtesa (Vibegron) Cannot Be Given Twice Daily
Gemtesa is FDA-approved and should only be administered as one 75 mg tablet once daily, and there is no evidence or indication to support twice-daily dosing. 1
FDA-Approved Dosing
The official FDA labeling is unequivocal about dosing frequency 1:
- Single dose: 75 mg orally once daily with or without food 1
- Administration: Swallow whole with water, or may be crushed and mixed with applesauce 1
- No dose escalation or frequency increase is recommended or approved 1
Why Once-Daily Dosing Is Sufficient
The pharmacologic profile of vibegron supports once-daily administration 2, 3:
- Vibegron is a highly selective β3-adrenergic receptor agonist that increases bladder capacity and reduces urgency 2, 3
- The drug demonstrated significant efficacy at 75 mg once daily in the pivotal EMPOWUR trial, with reductions in micturitions (1.8 episodes/day vs 1.3 for placebo, p<0.001) and urge incontinence episodes (2.0 episodes/day vs 1.4 for placebo, p<0.0001) 4
- Phase IIb dose-ranging studies evaluated 50 mg and 100 mg once-daily doses, both showing efficacy, with the 75 mg dose selected for approval 5, 6
Clinical Evidence Base
All published clinical trials used once-daily dosing 5, 4, 6:
- The EMPOWUR trial (n=1,518) used 75 mg once daily for 12 weeks with superior efficacy over placebo 4
- Japanese phase 3 trial (n=1,232) tested 50 mg and 100 mg once daily, not divided doses 6
- Phase IIb international trial evaluated 3,15,50, and 100 mg doses, all administered once daily 5
Safety Considerations
Twice-daily dosing would constitute off-label use without supporting data 1:
- No safety data exist for doses exceeding 75 mg daily or for divided dosing 1, 4
- The drug has a favorable safety profile at approved dosing, with adverse event discontinuation rates of only 1.7% (similar to placebo at 1.1%) 4
- Urinary retention risk may increase with higher exposures, particularly in patients with bladder outlet obstruction or those taking antimuscarinics 1
Alternative Strategies for Inadequate Response
If once-daily vibegron provides insufficient symptom control 7, 3:
- Consider combination therapy with an alpha-blocker (in males with BPH) rather than increasing vibegron frequency 7, 1
- Evaluate for antimuscarinic combination if storage symptoms persist, though this increases urinary retention risk 1, 5
- Reassess the diagnosis to exclude other causes of persistent symptoms 1
- Consider alternative β3-agonist (mirabegron) or switching to antimuscarinic therapy 3