Vibegron is an oral selective beta-3 adrenergic receptor (beta-3 AR) agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urinary urgency, and urinary frequency in adults. Like mirabegron, vibegron relaxes detrusor smooth muscle and increases bladder capacity, reducing incontinence. In studies for OAB, vibegron was associated with a reduction in the average daily number of micturitions and the number of urge urinary incontinence episodes. Beta-3 ARs are usually well-tolerated by patients and offer an alternative for patients experiencing intolerance to selective bladder antimuscarinics. Per guidelines for non-neurogenic OAB, either bladder-specific antimuscarinics or beta-3 ARs may be used as a second-line to behavioral interventions. Clinicians may consider combination therapy with an antimuscarinic and beta-3 AR for patients refractory to monotherapy with either an antimuscarinic or beta-3 AR alone. As with other agents, monitoring for urinary retention is necessary. Vibegron was FDA-approved in December 2020.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-May administer tablet with or without food.
-Have patient swallow the tablet whole with a glass of water.
-Alternatively, the tablet may be crushed, mixed with a tablespoon (approximately 15 mL) of applesauce, and taken immediately with a glass of water.
Headache was reported in 4% of adult patients during vibegron clinical trials.
Diarrhea (2.2%), nausea (2.2%), xerostomia (less than 2%), and constipation (less than 2%) were reported in adult patients receiving vibegron monotherapy during vibegron clinical trials. Constipation has also been reported during worldwide postmarketing experience with vibegron.
Naso-pharyngitis (2.8%) and bronchitis (2.9%) were reported in adult patients receiving vibegron monotherapy during clinical trials. Upper respiratory tract infection (2%) and urinary tract infection (6.6%) were also reported in treated patients.
Increased urine volume and urinary retention were each reported in less than 2% of adult patients receiving vibegron monotherapy during clinical trials. Urinary retention has been reported in association with vibegron use in worldwide postmarketing experience.
Hot flushes/hot flashes were reported in less than 2% of adult patients receiving vibegron monotherapy during clinical trials.
Pruritus, rash, drug eruption, and eczema (atopic dermatitis) have been noted in postmarketing reports from use of vibegron worldwide. Angioedema has been reported postmarketing with another beta-3 receptor agonist, mirabegron. If a serious hypersensitivity reaction to vibegron occurs, discontinue the drug and institute appropriate therapy.
Vibegron is contraindicated in patients with known vibegron hypersensitivity or hypersensitivity to any components of the product.
Vibegron should be administered with caution in patients with clinically significant bladder outlet obstruction (BOO), urinary tract obstruction, or with risk factors for bladder obstruction or urinary retention. The risk of urinary retention may be increased in patients with BOO and in patients taking anticholinergic medications for the treatment of overactive bladder (OAB). Monitor these patients for signs and symptoms of urinary retention and discontinue vibegron treatment in patients who develop urinary retention.
Vibegron is not recommended for use in patients with end-stage renal disease (eGFR less than 15 mL/min/1.73m2) or renal failure (with or without dialysis) as this drug has not been studied in this population. No dosage adjustments are needed for patients with mild, moderate, or severe renal impairment (eGFR 15 to less than 90 mL/min/1.73 m2).
Vibegron is not recommended for use in patients with severe hepatic disease or impairment (Child-Pugh C) as the drug has not been studied in this population. No dosage adjustments are needed in patients with mild to moderate hepatic impairment (Child-Pugh A and B).
There are no available data on vibegron use during human pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, no effects on embryofetal development were observed after administration of vibegron during the period of organogenesis at exposures of approximately 275- to 285-fold greater than clinical exposure at the recommended daily vibegron dose. Delayed fetal skeletal ossification was observed at approximately 898-fold clinical exposure, in the presence of maternal toxicity. In other animal studies during pregnancy and lactation, no effects on offspring were observed at 89-fold clinical exposure. Developmental toxicity was observed in offspring at approximately 458-fold clinical exposure, in the presence of maternal toxicity.
There are no data on the presence of vibegron in human breast milk, the effects of the drug on the breastfed infant, or the effects on milk production. When a single oral dose of radiolabeled vibegron was administered postnatally in animal studies, radioactivity was observed in milk. When a drug is present in animal milk, it is likely present in human milk. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for vibegron and any potential adverse effects on the breastfed infant from vibegron of from the underlying maternal condition.
During clinical trials, no overall differences in safety or effectiveness of vibegron have been observed between geriatric patients 65 years of age and older and younger adult patients. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs), such as the elderly. According to the OBRA guidelines, assessment of the underlying causes and identification of the type/category of urinary incontinence needs to be documented prior to or soon after the time of initiating treatment with a urinary incontinence medication such as mirabegron. These medications have specific and limited indications based on the cause and categorization of incontinence. Patients should be assessed periodically for medication effects on urinary incontinence as well as lower urinary tract symptoms and treatment tolerability.
The safety and effectiveness of vibegron in pediatric patients less than 18 years of age have not been established. Therefore, use of vibegron is not recommended in adolescents, children or infants.
For the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urinary urgency, and urinary frequency:
Oral dosage:
Adults: 75 mg PO once daily.
Maximum Dosage Limits:
-Adults
75 mg/day PO.
-Geriatric
75 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Mild to moderate hepatic impairment (Child-Pugh A and B): No dosage adjustment is needed.
Severe hepatic impairment (Child-Pugh C): Use is not recommended; vibegron has not been studied in this population.
Patients with Renal Impairment Dosing
eGFR 15 mL/minute/1.73 m2 or more: No dosage adjustment is needed.
eGFR 0 to 14 mL/minute/1.73 m2 (with or without hemodialysis): Use not recommended; vibegron has not been studied in this population.
*non-FDA-approved indication
Anticholinergics: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Atropine: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Atropine; Difenoxin: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Belladonna; Opium: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Benztropine: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Chlordiazepoxide; Clidinium: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Darifenacin: (Moderate) Vibegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as darifenacin, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Dicyclomine: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Digoxin: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing vibegron. Concurrent use may increase digoxin exposure. Concomitant administration of vibegron increased digoxin Cmax by 21% and AUC by 11%.
Diphenoxylate; Atropine: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Fesoterodine: (Moderate) Vibegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as fesoterodine, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Flavoxate: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Glycopyrrolate: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Glycopyrrolate; Formoterol: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Homatropine; Hydrocodone: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Hyoscyamine: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Indacaterol; Glycopyrrolate: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Methscopolamine: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Neostigmine; Glycopyrrolate: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Oxybutynin: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Propantheline: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Revefenacin: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Scopolamine: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Solifenacin: (Moderate) Vibegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as solifenacin, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Tolterodine: (Moderate) Vibegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as tolterodine, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Trihexyphenidyl: (Moderate) Vibegron should be administered with caution in patients taking anticholinergics because of potential for an increased risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Trospium: (Moderate) Vibegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as trospium, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Vibegron is a selective human beta-3 adrenergic receptor agonist. Activation of the beta-3 adrenergic receptor increases bladder capacity by relaxing the detrusor smooth muscle during bladder filling.
In a 4-week, randomized, placebo-controlled, ambulatory blood pressure study in patients with overactive bladder (n=200), daily treatment with vibegron 75 mg was not associated with clinically significant changes in blood pressure. Subjects enrolled in this study had a mean age of 59 years and 75% were female. Thirty-five percent of subjects had pre-existing hypertension at baseline and 29% of all subjects were taking at least 1 concomitant antihypertensive medication. Vibegron does not prolong the QT interval to any clinically relevant extent at a single dose 5.3 times the approved recommended dose.
Vibegron is administered orally. The mean apparent volume of distribution is 6,304 L. Human plasma protein binding is approximately 50%. The average blood-to-plasma concentration ratio is 0.9. Metabolism plays a minor role in the elimination of vibegron. CYP3A4 is the predominant enzyme responsible for in vitro metabolism. Following a radiolabeled dose, approximately 59% of the dose (54% unchanged) was recovered in feces and 20% (19% unchanged) in urine. The effective half-life of vibegron is 30.8 hours across all populations.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
In vitro, vibegron is a substrate of CYP3A4 and P-glycoprotein (P-gp). However, No clinically significant differences in vibegron pharmacokinetics were observed when used concomitantly with ketoconazole (P-gp and strong CYP3A4 inhibitor), diltiazem (P-gp and moderate CYP3A4 inhibitor), rifampin (strong CYP3A4 inducer), or tolterodine. Vibegron did not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4. Vibegron did not induce CYP1A2, CYP2B6, or CYP3A4. Vibegron did not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, or MATE2K at clinically relevant concentrations.
-Route-Specific Pharmacokinetics
Oral Route
Mean vibegron Cmax and AUC increased in a greater than dose-proportional manner up to 600 mg (8 times the approved recommended dose). Steady-state concentrations are achieved within 7 days of once daily dosing. The mean accumulation ration was 1.7 for the Cmax and 2.4 for the AUC. The median Tmax is approximately 1 to 3 hours. Oral administration of a 75 mg vibegron tablet crushed and mixed with 15 mL of applesauce resulted in no clinically relevant changes in vibegron pharmacokinetics when compared to the administration of an intact tablet. No clinically significant pharmacokinetic differences were observed after administration of vibegron with a high-fat meal.
-Special Populations
Hepatic Impairment
No clinically significant differences in the pharmacokinetics of vibegron were observed based on moderate (Child-Pugh B) hepatic impairment. The effect of severe hepatic impairment (Child-Pugh C) on vibegron pharmacokinetics has not been studied; use in this population is not recommended.
Renal Impairment
No clinically significant differences in the pharmacokinetics of vibegron were observed based on mild (eGFR 60 to less than 90 mL/min/1.73 m2), moderate (eGFR 30 to less than 60 mL/min/1.73 m2), and severe (eGFR 15 to less than 30 mL/min/1.73 m2) renal impairment. The effect of more severe renal impairment (end-stage renal disease or eGFR less than 15 mL/min/1.73 m2) with or without hemodialysis on vibegron pharmacokinetics has not been studied; use in this population is not recommended.
Geriatric
No clinically significant differences in the pharmacokinetics of vibegron were observed based on age (18 to 93 years).
Gender Differences
No clinically significant differences in the pharmacokinetics of vibegron were observed based on sex.
Ethnic Differences
No clinically significant differences in the pharmacokinetics of vibegron were observed based on race/ethnicity (e.g., Japanese vs. non-Japanese).