Vibegron is a β3-adrenergic receptor agonist approved by the U.S. FDA on December 23, 2020, for the treatment of overactive bladder (OAB) syndrome. symptoms such as urgency, frequency, and urge urinary incontinence. Marketed under the brand name Gemtesa (75 mg once daily), it works by relaxing the bladder muscle to increase storage capacity. Approved based on the EMPOWUR Phase 3 trial, vibegron offers effective symptom relief with a favorable safety profile and minimal anticholinergic side effects.
BRAND NAMES
Gemtesa (U.S.): Treatment of overactive bladder (OAB) to reduce urgency, frequency, and urge incontinence.
Beova (Japan): Treatment of overactive bladder (OAB) to alleviate urinary urgency, increased frequency, and incontinence.
MECHANISM OF ACTION
Vibegron selectively activates β₃-adrenergic receptors on detrusor smooth muscle, stimulating adenylate cyclase to raise intracellular cAMP. This leads to protein kinase A–mediated opening of potassium channels and reduced calcium influx, relaxing the bladder wall during filling, increasing capacity, and reducing urgency and frequency without significant cardiovascular or anticholinergic effects.
PHARMACOKINETICS
Absorbtion
Vibegron is rapidly absorbed after oral administration, reaching peak plasma concentrations within 1 to 3 hours, with an absolute bioavailability of approximately 57%.
Distribution
It is highly protein-bound (~98%) and has a large volume of distribution (~165 L), indicating extensive tissue distribution.
Metabolism
Vibegron undergoes minimal metabolism, primarily through glucuronidation and oxidation, and does not significantly interact with major cytochrome P450 enzymes, reducing the risk of drug-drug interactions.
Elimination
It is eliminated mainly unchanged via feces (~59%) and urine (~20%), with a long terminal half-life of about 68 hours, supporting once-daily dosing. Food has no clinically meaningful effect on its pharmacokinetics, and no dose adjustment is necessary in elderly patients or those with mild to moderate renal or hepatic impairment.
DOSAGE AND ADMINISTRATION
Vibegron should be taken orally at a dose of 75 mg once daily, with or without food, swallowed whole or crushed and mixed with a tablespoon of applesauce; dose adjustments are not needed for mild to moderate renal or hepatic impairment, but it should be avoided in severe cases, and patients should be monitored for urinary retention and potential interactions, especially with digoxin.
DRUG INTERACTIONS
- CYP2D6 Inhibition: May increase levels of drugs like metoprolol, desipramine, dextromethorphan.
- P-gp Inhibition: Can raise levels of drugs like digoxin, dabigatran.
- With Anticholinergics: Increases risk of urinary retention and dry mouth.
- Hypertension Risk: May slightly increase blood pressure; use cautiously with antihypertensives.
- No Major CYP450 Interactions: Minimal interaction with most common drugs.
SIDE EFFECTS
- Headache
- Nasopharyngitis (common cold symptoms)
- Dry mouth (less common than with antimuscarinics)
- Increased blood pressure (rare)
- Constipation (rare)
TOXICITY
Vibegron is generally well tolerated, and no severe toxic effects have been reported at therapeutic doses. Animal studies show that very high doses can cause:
- Increased heart rate
- Elevated blood pressure
- Mild liver enzyme changes
