Introduction
Gemtesa (vibegron) is a novel beta-3 adrenergic agonist approved by the FDA in December 2020 for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. It represents a significant advancement in OAB management as the first new beta-3 agonist approved in nearly a decade, offering an alternative mechanism of action to antimuscarinic agents.
Mechanism of Action
Vibegron is a selective beta-3 adrenergic receptor agonist that works by relaxing the detrusor smooth muscle of the bladder during the storage phase. Activation of beta-3 receptors stimulates adenylate cyclase, increasing cyclic adenosine monophosphate (cAMP) production, which leads to bladder relaxation and increased bladder capacity. This mechanism reduces involuntary detrusor contractions, thereby decreasing urinary urgency, frequency, and incontinence episodes.
Indications
Gemtesa is indicated for the treatment of overactive bladder (OAB) with symptoms of:
- Urge urinary incontinence
- Urgency
- Urinary frequency
Dosage and Administration
Standard adult dosage: 75 mg orally once daily with or without food Administration: Tablet should be swallowed whole with water Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary for mild to moderate impairment; not studied in severe hepatic impairment
- Geriatric patients: No dosage adjustment necessary
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of 1-3 hours; bioavailability approximately 45% Distribution: Protein binding is approximately 71%; volume of distribution is approximately 134 L Metabolism: Primarily metabolized via glucuronidation (UGT1A1, UGT1A9, UGT2B7) and oxidation (CYP3A4) Elimination: Half-life approximately 22 hours; excreted primarily in feces (60%) and urine (40%)Contraindications
- Known hypersensitivity to vibegron or any component of the formulation
Warnings and Precautions
Hypertension: Monitor blood pressure, especially in patients with uncontrolled hypertension Urinary Retention: Use with caution in patients with bladder outlet obstruction Pregnancy: No human data; use only if potential benefit justifies potential risk Lactation: Not known if excreted in human milk; consider developmental and health benefits versus potential risk Pediatric Use: Safety and effectiveness not establishedDrug Interactions
Strong CYP3A inhibitors: (e.g., ketoconazole, clarithromycin) - May increase vibegron exposure; monitor for increased adverse effects P-glycoprotein substrates: (e.g., digoxin) - May increase concentrations of these drugs; monitor digoxin levels when co-administered Warfarin: No clinically significant interaction observedAdverse Effects
Most common adverse reactions (≥2% and greater than placebo):- Headache (8.6%)
- Nasopharyngitis (5.0%)
- Diarrhea (3.5%)
- Nausea (3.2%)
- Upper respiratory tract infection (2.8%)
- Urinary tract infection (2.5%)
- Hypertension (0.5%)
- Headache (0.4%)
- Atrial fibrillation (0.1%)
Monitoring Parameters
- Blood pressure at baseline and periodically during treatment
- OAB symptom improvement (voiding diary)
- Adverse effects (headache, gastrointestinal symptoms)
- Renal and hepatic function in patients with pre-existing conditions
- Signs of urinary retention
Patient Education
- Take once daily with or without food
- Swallow tablet whole with water
- May take several weeks to notice full therapeutic effects
- Report persistent headache, increased blood pressure, or difficulty urinating
- Maintain adequate fluid intake unless contraindicated
- Notify healthcare provider of all medications being taken
- Seek medical attention for symptoms of allergic reaction
References
1. FDA Prescribing Information: Gemtesa (vibegron) tablets. December 2020. 2. Staskin D, Frankel J, Varano S, et al. International Phase III, Randomized, Double-Blind, Placebo and Active Controlled Study to Evaluate the Safety and Efficacy of Vibegron in Patients with Symptoms of Overactive Bladder: EMPOWUR. J Urol. 2020;204(2):316-324. 3. Yoshida M, Takeda M, Gotoh M, et al. Efficacy and safety of vibegron in Japanese patients with overactive bladder: A randomized, double-blind, placebo-controlled, phase III study. Low Urin Tract Symptoms. 2021;13(4):487-496. 4. Chapple CR, Cruz F, Cardozo L, et al. Vibegron for the treatment of overactive bladder: A comprehensive review of the evidence. Ther Adv Urol. 2021;13:17562872211094950. 5. Coyne KS, Sexton CC, Thompson CL, et al. The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study. BJU Int. 2009;104(3):352-360.