Introduction
Vibegron is a novel beta-3 adrenergic receptor 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 with a distinct mechanism of action from previously available antimuscarinic agents.
Mechanism of Action
Vibegron selectively activates beta-3 adrenergic receptors in the detrusor smooth muscle of the urinary bladder. This receptor stimulation activates adenylate cyclase, increasing intracellular cyclic adenosine monophosphate (cAMP) levels. The resulting pathway leads to bladder smooth muscle relaxation during the storage phase, increasing bladder capacity and reducing involuntary detrusor contractions. Unlike antimuscarinic agents, vibegron does not affect muscarinic receptors, resulting in a favorable side effect profile with minimal anticholinergic effects.
Indications
- 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 Special populations:- Renal impairment: No dosage adjustment necessary in mild to moderate impairment. Not studied in severe renal impairment (CrCl <30 mL/min)
- Hepatic impairment: No dosage adjustment necessary in mild to moderate impairment. Not recommended in severe hepatic impairment (Child-Pugh Class C)
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of approximately 1 hour. Bioavailability is approximately 45%. Food does not significantly affect absorption. Distribution: Mean apparent volume of distribution is approximately 278 L. Protein binding is approximately 71-73%, primarily to albumin. Metabolism: Primarily metabolized via CYP3A4 and to a lesser extent by CYP2D6. The major metabolic pathways include oxidation, glucuronidation, and hydrolysis. Elimination: Mean elimination half-life is approximately 21 hours. Excretion occurs primarily via feces (60%) and urine (20%) as metabolites, with less than 1% excreted unchanged.Contraindications
- Known hypersensitivity to vibegron or any component of the formulation
Warnings and Precautions
- Urinary Retention: Use with caution in patients with clinically significant bladder outlet obstruction. Monitor for urinary retention
- Hypertension: May increase blood pressure. Monitor blood pressure periodically, especially in hypertensive patients
- Hepatic Impairment: Not recommended in severe hepatic impairment
- Pregnancy: No human data; use only if potential benefit justifies potential risk
- Lactation: No data on presence in human milk; exercise caution when administering to nursing women
Drug Interactions
Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin): May increase vibegron exposure. Monitor for increased adverse effects Strong CYP3A inducers (e.g., rifampin, carbamazepine): May decrease vibegron exposure. Monitor for reduced efficacy Digoxin: Vibegron may increase digoxin concentrations. Monitor digoxin levels and adjust dosage as needed P-glycoprotein substrates: May increase concentrations of narrow therapeutic index P-gp substratesAdverse Effects
Common adverse reactions (≥2% and greater than placebo):- Headache (8.5%)
- Nasopharyngitis (5.1%)
- Diarrhea (4.3%)
- Nausea (3.4%)
- Upper respiratory tract infection (2.6%)
- Hypertension (1.2%)
- Urinary tract infection (1.9%)
Monitoring Parameters
- Blood pressure at baseline and periodically during treatment
- Assessment of OAB symptom improvement
- Monitor for signs of urinary retention
- Evaluation for adverse effects, particularly gastrointestinal symptoms
- Renal and hepatic function in patients with pre-existing impairment
Patient Education
- Take medication once daily with or without food
- Report any significant increase in blood pressure to healthcare provider
- Inform healthcare provider of all medications being taken, including over-the-counter products
- Seek medical attention if experiencing difficulty urinating or complete inability to urinate
- May take several weeks to experience full therapeutic benefit
- Report persistent headache, nausea, or diarrhea
- Notify healthcare provider if pregnant, planning pregnancy, or breastfeeding
References
1. FDA prescribing information: Gemtesa (vibegron) tablets. December 2020. 2. Yoshida M, Takeda M, Gotoh M, et al. Efficacy and safety of vibegron in patients with overactive bladder: A randomized, double-blind, placebo-controlled, phase 3 study. Neurourol Urodyn. 2021;40(1):531-540. 3. 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 overactive bladder: EMPOWUR. J Urol. 2020;204(2):316-324. 4. 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. 5. Chapple CR, Cardozo L, Nitti VW, et al. Mirabegron in overactive bladder: a review of efficacy, safety, and tolerability. Neurourol Urodyn. 2014;33(1):17-30.