Vibegron (Monograph)

Brand name: Gemtesa
Drug class: Selective beta-3 Adrenergic Agonists
Chemical name: (6S)-N-[4-[[(2S,5R)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl]methyl]phenyl]-4-oxo-7,8-dihydro-6H-pyrrolo[1,2-a]pyrimidine-6-carboxamide
Molecular formula: C₂₆H₂₈N₄O₃
CAS number: 1190389-15-1

Medically reviewed by Drugs.com on Jan 9, 2023. Written by ASHP.

Introduction

Vibegron is a selective β₃-adrenergic agonist.

Uses for Vibegron

Vibegron has the following uses:

Vibegron is a β₃-adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults.

Vibegron Dosage and Administration

General

Vibegron is available in the following dosage form(s) and strength(s):

Tablets: 75 mg.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• The recommended dose is one 75 mg tablet once daily.

• Swallow tablet whole with water.

• Tablet may be crushed and mixed with applesauce.

Cautions for Vibegron

Contraindications

Do not use if prior hypersensitivity reaction to vibegron or any components of the product.

Warnings/Precautions

Urinary Retention

Urinary retention has been reported in patients taking vibegron. The risk of urinary retention may be increased in patients with bladder outlet obstruction and also in patients taking muscarinic antagonist medications for the treatment of OAB. Monitor patients for signs and symptoms of urinary retention, particularly in patients with bladder outlet obstruction and patients taking muscarinic antagonist medications for the treatment of OAB. Discontinue vibegron in patients who develop urinary retention.

Specific Populations

Pregnancy

Risk Summary: There are no available data on vibegron use in pregnant women 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 following administration of vibegron during the period of organogenesis at exposures approximately 275- and 285-fold greater than clinical exposure at the recommended daily dose of vibegron, in rats and rabbits, respectively. Delayed fetal skeletal ossification was observed in rabbits at approximately 898-fold clinical exposure, in the presence of maternal toxicity. In rats treated with vibegron 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. No effects on offspring were observed at 89-fold clinical exposure.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Animal Data: In an embryo-fetal developmental toxicity study, pregnant rats were treated with daily oral doses of 0, 30, 100, 300, or 1000 mg/kg/day vibegron during the period of organogenesis (Days 6 to 20 of gestation). These doses were associated with systemic exposures (AUC) 0-, 9-, 89-, 275-, and 1867-fold higher, respectively, than in humans treated with the recommended daily dose of vibegron. No embryo-fetal developmental toxicity was observed at doses up to 300 mg/kg/day. Treatment with the high dose of 1000 mg/kg/day was discontinued due to maternal toxicity.

In an embryo-fetal developmental toxicity study, pregnant rabbits were treated with daily oral doses of 0, 30, 100, or 300 mg/kg/day vibegron during the period of organogenesis (Days 7 to 20 of gestation). These doses were associated with systemic exposures (AUC) 0-, 86-, 285-, and 898-fold higher, respectively, than in humans treated with the recommended daily dose of vibegron. No embryo-fetal developmental toxicity was observed at doses of vibegron up to 100 mg/kg/day. Maternal toxicity (decreased food consumption), reduced fetal body weight, and an increased incidence of delayed skeletal ossification, were observed at 300 mg/kg/day.

In a pre- and post-natal developmental toxicity study, pregnant or lactating rats were treated with daily oral doses of 0, 30, 100, or 500 mg/kg/day vibegron from day 6 of gestation through day 20 of lactation. These doses were associated with estimated systemic exposures (AUC) 0-, 9-, 89-, and 458-fold higher, respectively, than in humans treated with the recommended daily dose of vibegron. No developmental toxicity was observed in F1 offspring at doses up to 100 mg/kg/day. Maternal toxicity was observed during lactation (decreased body weight gain) at doses ≥100 mg/kg/day and during gestation (decreased body weight gain and food consumption) at 500 mg/kg/day. Developmental toxicity was observed in F1 offspring (increased stillborn index, lethality, reduced viability and weaning indices, decreased body weight and body weight gains, low physical development differentiation indices, and effects on sensory function and reflexes) at 500 mg/kg/day.

Lactation

Risk Summary: There are no data on the presence of vibegron in human 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 to postnatal nursing rats, radioactivity was observed in milk When a drug is present in animal milk, it is likely that the drug will be present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for vibegron and any potential adverse effects on the breastfed infant from vibegron or from the underlying maternal condition.

Animal Data: In a lactational transfer study, lactating rats were treated with a single oral dose of 10 mg/kg radiolabeled³H] vibegron on postpartum day 10. Levels of radioactivity were determined in milk and plasma collected at 1, 4, 12, and 24 after dosing. The C_max of total radioactivity in milk and plasma were observed at 9 and 2 hours after dosing, respectively, with a maximum milk-to-plasma concentration ratio of 2.2 observed at 12 hours after dosing. Vibegron elimination from milk showed a similar trend as that from plasma. The radioactivity concentration in milk at 24 hours after administration was approximately 25% of the C_max.

Pediatric Use

The safety and effectiveness of vibegron in pediatric patients have not been established.

Geriatric Use

Of 526 patients who received vibegron in the clinical studies for OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency, 242 (46%) were 65 years of age or older, and 75 (14%) were 75 years of age or older. No overall differences in safety or effectiveness of vibegron have been observed between patients 65 years of age and older and younger adult patients.

Renal Impairment

No dosage adjustment for vibegron is recommended for patients with mild, moderate, or severe renal impairment (eGFR 15 to <90 mL/min/1.73 m². Vibegron has not been studied in patients with eGFR <15 mL/min/1.73 m²(with or without hemodialysis) and is not recommended in these patients.

Hepatic Impairment

No dosage adjustment for vibegron is recommended for patients with mild to moderate hepatic impairment (Child-Pugh A and B). Vibegron has not be studied in patients with severe hepatic impairment (Child-Pugh C) and is not recommended in this patient population.

Common Adverse Effects

Most common adverse reactions (≥2%) reported with vibegron were headache, urinary tract infection, nasopharyngitis, diarrhea, nausea, and upper respiratory tract infection.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Digoxin: Measure serum digoxin concentrations before initiating vibegron. Monitor serum digoxin concentrations to titrate digoxin dose to desired clinical effect.

Actions

Mechanism of Action

Vibegron is a selective human β₃-adrenergic receptor agonist. Activation of the β₃-adrenergic receptor increases bladder capacity by relaxing the detrusor smooth muscle during bladder filling.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information).

• Inform patients that vibegron has been associated with urinary retention. Inform patients that the risk of urinary retention may be increased in patients taking muscarinic antagonist medications for the treatment of OAB. Instruct patients to contact their healthcare provider if they experience symptoms consistent with urinary retention while taking vibegron.

• Advise patients that vibegron tablets can be swallowed whole with a glass of water or may be crushed, mixed with a tablespoon of applesauce and taken immediately with a glass of water.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• How long does it take for Gemtesa (vibegron) to work?
• How does Gemtesa (vibegron) work?

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