Vibegron

Breast Feeding; Lactation; Milk, Human; Adrenergic beta-3 Receptor Agonists

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P273, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 36 reports by companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Vibegron, like other beta-adrenergic agents, is rarely associated with serum ALT or alkaline phosphatase elevations. In large randomized, placebo-controlled trials, serum aminotransferase elevations arose in less than 1% of treated participants, rates that were similar to patients receiving placebo and comparator agents such as tolterodine. In the registration trials of vibegron and since its approval and more widescale use, there have been no reports of clinically apparent liver injury.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Vibegron

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

G - Genito urinary system and sex hormones

QG - Genito urinary system and sex hormones

Vibegron selectivity for beta-3 adrenergic receptors is >9000 times higher than for β1AR or β2AR. Vibegron improves clinical symptoms of overactive bladder by increasing bladder capacity without affecting bladder contraction. It significantly increases the functional bladder volume in a dose-dependent manner, which results in prolongation of the interval between voids. In clinical studies, vibegron inhibited detrusor bladder contractions in a concentration-dependent manner, reduced voiding pressure, and increased bladder compliance. In Japanese clinical studies comprising patients with overactive bladder, vibegron significantly improved the frequency of micturition, urgency, and urgency incontinence episodes.

Overactive bladder is characterized by symptoms of urge urinary incontinence, urgency, and urinary frequency. Bladder filling and emptying are regulated by the coordinated communication between sympathetic and parasympathetic systems. Bladder filling occurs via parasympathetic inhibition and the sympathetic hypogastric nerve releasing norepinephrine, which acts on beta-adrenergic receptors responsible for mediating detrusor muscle relaxation. Symptoms of overactive bladder are thought to be caused by the deterioration of the sensory connections between the bladder, spinal cord and brain, leading to changes in the lower urinary tract and abnormal bladder sensations of the urge to void at small bladder volumes. Beta-3 adrenergic receptors (β3ARs) are expressed in the kidneys and lower urinary tract, including ureters, urethra, prostate, and bladder. Vibegron is a selective agonist at β3AR. One vibegron binds to the receptor, β3AR is stimulated and undergoes a conformation change and activates adenylyl cyclases (AC), which promotes the formation of cyclic adenosine monophosphate (cAMP). Increased intracellular cAMP concentration leads to the activation of cAMP-dependent protein kinase A (PKA), which subsequently phosphorylates myosin light chains that are responsible for inhibiting the interaction of actin with myosin dependent on calcium – calmodulin complex. In clinical trials, vibegron increased cAMP levels in a dose-proportional manner. There is evidence that β3AR agonists may also work via sensory mechanisms without directly affecting detrusor muscle motor function.