OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Vibegron – Gemtesa®

DRUG CLASS

Urologic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Vibegron	1190389-15-1	C26-H28-N4-O3

ANNOTATED BIBLIOGRAPHY

References updated: 10 July 2023

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Expert review of drug induced liver injury published in 1999 before the availability of beta-3 adrenergic receptor agonists and other drugs for overactive bladder syndrome such as tolterodine, mirabegron or vibegron).
• Westfall TC, Macarthur H, Westfall DP. Adrenergic agonists and antagonists. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 191-223.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2020/213006Orig1s000MedR.pdf

  (FDA website with product labels and FDA review of the safety and efficacy of vibegron based upon submission of data by the sponsor in support of its approval, mentions that in a large preregistration trial, ALT elevations above 3 times the upper limit of normal arose in 0.2% of 545 patients on vibegron and 0.3% of 540 receiving placebo, and there were no cases of liver test abnormalities accompanied by symptoms or jaundice and no hepatic serious adverse events).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none were attributed to mirabegron or vibegron).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol 2014; 13: 231-9. [PubMed: 24552865]

  (Systematic review of literature on drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases, none of which were attributed to urologic agent such as mirabegron, vibegron, or tolterodine).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-1352.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, no cases were attributed to a urologic agent such as mirabegron, vibegron or tolterodine).
• Thiagamoorthy G, Cardozo L, Srikrishna S. Drug therapy for an overactive bladder. Womens Health (Lond) 2015; 11: 445-8. [PubMed: 26238677]

  (Overactive bladder is defined as urinary urgency, usually with frequency and nocturia with or without incontinence in the absence of infection or other known cause, medical therapy being use of anticholinergics or beta-3 adrenergic receptor agonists such as mirabegron or vibegron which have fewer side effects than typical anticholinergics).
• Edmondson SD, Zhu C, Kar NF, Di Salvo J, Nagabukuro H, Sacre-Salem B, Dingley K, et al. Discovery of vibegron: a potent and selective β3 adrenergic receptor agonist for the treatment of overactive bladder. J Med Chem. 2016;59:609-23. [PubMed: 26709102]

  (Description of the development of a selective beta-2 adrenergic receptor agonist with in vitro activity against bladder smooth muscle and no structural evidence for hepatic toxicity [phospholipidosis]).
• Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN Jr. International phase III, randomized, double-blind, placebo and active controlled study to evaluate the safety and efficacy of vibegron in patients with symptoms of overactive bladder: EMPOWUR. J Urol. 2020;204:316-324. [PubMed: 32068484]

  (Among 1518 adults with overactive bladder treated with vibegron [75 mg], tolterodine [4 mg], or placebo once daily for 12 weeks, daily micturitions decreased by 1.8 episodes with the two medications vs 1.4 with placebo, while adverse events were uncommon [39% and 39% vs 33%] and ALT elevations were rare [0.2% and 0.2% vs 0.4%] and there were no hepatic severe adverse events or discontinuations).
• Vibegron (Gemtesa) for overactive bladder. Med Lett Drugs Ther. 2021;63(1623):67-69. [PubMed: 33976098]

  (Concise review of the mechanism of action, clinical efficacy, safety, and costs of vibegron shortly after its approval for use in the US, mentions adverse events of headache and nasopharyngitis, but urinary retention was uncommon [0.6% vs 0.4% with placebo]; no mention of ALT elevations or hepatotoxicity).
• Staskin D, Frankel J, Varano S, Shortino D, Jankowich R, Mudd PN Jr. Once-daily vibegron 75 mg for overactive bladder: long-term safety and efficacy from a double-blind extension study of the international phase 3 trial (EMPOWUR). J Urol. 2021;205:1421-1429. [PubMed: 33356445]

  (Among 506 patients completing the 12-week placebo-controlled trial of vibegron [Staskin 2020] who were continued on vibegron or tolterodine to week 52, improvements in numbers of micturitions and incontinence and urgency episodes were slightly greater with vibegron, while adverse event rates were similar and “changes in clinical laboratory parameters…were not considered clinically meaningful.”).
• Lacy BE, King J, Shortino D, Schaumburg C, Haag-Molkenteller C, Chey WD. Efficacy and safety of vibegron for the treatment of irritable bowel syndrome in women: Results of a randomized, double-blind, placebo-controlled phase 2 trial. Neurogastroenterol Motil. 2022;34(12):e14448. [PMC free article: PMC10078113] [PubMed: 35975404]

  (Among 222 adult women with diarrhea-predominant irritable bowel syndrome treated with vibegron [75 mg] or placebo once daily for 12 weeks, rates of improvements in abdominal pain and diarrhea were similar in the two groups as were overall adverse event rates [33% in both]; no mention of ALT elevations but there were no hepatic serious adverse events).
• Kinjo M, Masuda K, Nakamura Y, Miyakawa J, Tambo M, Fukuhara H. Comparison of mirabegron and vibegron in women with treatment-naive overactive bladder: A randomized controlled study. Urology. 2023;175:67-73. [PubMed: 36822245]

  (Among 199 adult women with overactive bladder syndrome treated with 50 mg of either mirabegron or vibegron daily for 12 weeks, response rates were similar in both groups as were overall rates of adverse event [17.5% vs 15.7%], discontinuations [6.2% vs 6.8%], constipation [10.3% vs 11.8%], dry mouth [both 1%], and rash [2% vs 1%]; no mention of ALT elevations or hepatotoxicity).
• Drugs for overactive bladder. Med Lett Drugs Ther. 2023;65:41-45. [PubMed: 36897601]

  (Concise review of drugs approved for therapy of overactive bladder in the US including anticholinergic agents [darifenacin, fesoterodine, oxbutynin, solifenacin, tolterodine and trospium] and beta-3 adrenergic receptor agonists [mirabegron and vibegron] including clinical efficacy, safety, and costs; no mention of ALT elevations or hepatotoxicity of any of the agent discussed).