pyrimidinones and mirabegron

In the absence of head-to-head trials, we performed an indirect treatment comparison of the β. PubMed, Embase, and Cochrane Library were searched for articles related to phase 3, double-blind, controlled trials of vibegron 75 mg and mirabegron 25/50 mg in patients with OAB. Efficacy outcomes included change from baseline at weeks 4, 12, and 52 in mean daily number of total urinary incontinence episodes and micturitions and mean volume voided/micturition. Effect size was computed as placebo-subtracted change from baseline (weeks 4, 12) or active control (tolterodine)-subtracted change from baseline (week 52) for each treatment group. Adverse events (AEs) are presented descriptively.. After removal of duplicates, 49 records were identified, and after screening 9 met inclusion criteria for analysis. Vibegron showed significantly greater reduction in mean daily number of total incontinence episodes than mirabegron 25 mg at week 4, mirabegron 50 mg (weeks 4, 52), and tolterodine (weeks 4, 12) (P < 0.05, each) and significantly greater improvement in volume voided versus mirabegron 25 mg (week 12), mirabegron 50 mg (weeks 12, 52), and tolterodine (week 4) (P < 0.05, each). Confidence intervals of point estimates overlapped zero for all other comparisons of vibegron and mirabegron (25 or 50 mg) or tolterodine, indicating no significant differences between treatments for these time/endpoints. Urinary tract infection, hypertension, and dry mouth were the most commonly occurring AEs for vibegron, mirabegron, and tolterodine, respectively, in the short-term trials; hypertension was the most commonly occurring AE with all three treatments in the long-term trials.. Vibegron was associated with significant improvement in total incontinence episodes versus mirabegron at 4 and 52 weeks and volume voided at 12 and 52 weeks. Improvement in micturitions was similar between vibegron and mirabegron or tolterodine. Incidence of AEs was generally comparable between vibegron and mirabegron.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Clinical Trials, Phase III as Topic; Double-Blind Method; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Vibegron is a very selective new β3-adrenergic receptor agonist introduced recently to clinical practice for OAB patients, which offers an alternative option for to antimuscarinic drugs.. This review presents the current knowledge concerning the mechanism of action, pharmacokinetics, and pharmacodynamics of vibegron. Moreover, it presents an overview of preclinical and phase II and phase III clinical studies on the efficacy, tolerability, and safety of this agent in patients suffering from OAB.. Clinical studies confirmed efficacy and safety of vibegron in OAB patients. Vibegron differ from well-known mirabegron with regards to its pharmacological profile because it is metabolized independently from CYP3A4, 2D6, or 2C9 and therefore is less likely to cause a drug-drug interaction. Moreover, since this drug does not penetrate the blood-brain barrier, it could become the drug of choice in OAB patients with cognitive impairment. These properties have paved the way in near future for better-tailored treatments for OAB patients.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

Overactive bladder syndrome (OAB) is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency incontinence, in the absence of urinary tract infection or other obvious pathology. In this review, we focus on recent advances in the management of OAB. We examine the evidence on the effect of anticholinergic load on OAB patients. Advances in medical treatment include a new beta-3 agonist, vibegron, which is thought to have fewer drug interactions than mirabegron. Treatment of genitourinary syndrome of the menopause with oestrogens and ospemifene have also shown promise for OAB. Botulinum toxin has been shown to be an effective treatment option. We discuss the new implantable neuromodulators that are on the market as well as selective bladder denervation and laser technology.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Botulinum Toxins; Denervation; Drug Implants; Humans; Laser Therapy; Pyrimidinones; Pyrrolidines; Tamoxifen; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive

This paper discusses the recent evidence supporting beta 3 adrenergic agonists as the preferred pharmacological management of overactive bladder syndrome.. Mirabegron has a similar efficacy profile to first-line antimuscarinics with favorable adverse effects profile. Treatment of OAB with beta-3 adrenergic agonist should be favored in patients at higher risk of anticholinergic adverse events. The efficacy and tolerability of beta-3 adrenergic agonists are consistently reported in older OAB patients, whether used alone or with other antimuscarinics. Mirabegron is cost-effective in treating OAB unless the symptoms were severe or refractory. Combination therapy of mirabegron and other pharmacotherapy has proven to be efficient in controlling OAB symptoms without inducing serious add-on adverse effects. While beta-3 adrenergic agonists bear favorable advantages in OAB treatment, physicians should perform a thorough and careful pre-treatment planning to optimize treatment benefits and adherence.

Topics: Acetanilides; Adrenergic alpha-1 Receptor Antagonists; Adrenergic beta-3 Receptor Agonists; Cholinergic Antagonists; Cost-Benefit Analysis; Humans; Muscarinic Antagonists; Phosphodiesterase Inhibitors; Pyrimidinones; Pyrrolidines; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To compare the efficacy and safety of mirabegron versus vibegron in postmenopausal women with treatment-naïve overactive bladder (OAB).. We conducted a prospective randomized controlled study of women with treatment-naïve OAB. The patients received mirabegron or vibegron at 50 mg daily for 12 weeks by a stratified randomized method. The OAB symptom score (OABSS) and quality of life (QOL) index were evaluated before and 4 and 12 weeks after the treatment. The patients' 3-day voiding diary and postvoided residual urine volumes were evaluated before and 12 weeks after the treatment.. Of 213 patients initially enrolled in this study, 199 patients were randomized to the mirabegron group (n = 97) or vibegron group (n = 102). Twelve weeks after the treatment, OABSS, QOL index, the numbers of micturition, urgency episodes, incontinence episodes, and voided volume per 24 hours were significantly improved compared with the baseline in both groups, and there was no significant difference in the rate of change in both groups. The postvoid residual urine volume was not significantly different in the 2 groups at 12 weeks. Discontinuation because of adverse effects was observed in 6.2% of patients in the mirabegron group and 6.8% in the vibegron group, with no significant difference between 2 groups.. Both mirabegron at 50 mg and vibegron at 50 mg improved OAB symptoms and the parameters of voiding diary equally in postmenopausal women with treatment naïve OAB.

Topics: Acetanilides; Aged; Aged, 80 and over; Female; Humans; Middle Aged; Prospective Studies; Pyrimidinones; Pyrrolidines; Quality of Life; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) is associated with physical, emotional, and financial burden. After failed conservative measures, second-line therapy includes medications, such as antimuscarinics and beta-3 adrenergic receptor (β3AR) agonists. Antimuscarinics are most commonly prescribed but have systemic side effects that lead to poor compliance. β3AR agonists include mirabegron and vibegron. Mirabegron is a first-generation β3AR agonist that is effective for frequency, urgency urinary incontinence (UUI) and urgency, but has interactions with cytochrome P450 enzymes (CYPs) and cardiovascular sequelae. Vibegron is a second-generation β3AR agonist that is highly selective and does not interact with CYPs. It is effective for reducing UUI episodes and daily micturition number and has a favorable side effect profile.. Clinical background, pharmacology, and clinical studies for vibegron.. Vibegron is a welcomed addition to the OAB therapeutic landscape. This single dose, once daily option is effective, especially for patients with wet OAB, with a favorable side effect profile. Sub-analyses of patients ≥ 65 years have shown continued efficacy and safety. The few drug interactions are of benefit, especially for older patients with polypharmacy. As long-term data accrues, vibegron has the potential to drive the OAB therapeutic market.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Muscarinic Antagonists; Pyrimidinones; Pyrrolidines; Receptors, Adrenergic, beta-3; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To compare the 1-year continuation rate and discontinuation factors between vibegron and mirabegron in patients with neurogenic and nonneurogenic overactive bladder.. Continuation or discontinuation of the target drugs and reasons for discontinuation as well as patients' grounds and adverse effects were evaluated retrospectively from the medical records between September 2018 and December 2020. After selecting patients according to the inclusion and exclusion criteria, 180 cases taking mirabegron and 132 taking vibegron were adjusted for intergroup variability by propensity score matching. We performed Cox proportional hazards regression for the 1-year continuation rate and Fine-Gray proportional hazards regression for the 1-year cumulative incidence of discontinuation events. Subgroup analysis was also performed for the background factors related to the 1-year continuation rate.. The 1-year continuation rate was 83.8% for vibegron and 58.2% for mirabegron, and the hazard ratio was 0.32 (95% CI: 0.18-0.57, P < .001) as for an incidence of discontinuation events of vibegron against mirabegron. The incidence of discontinuation due to an inadequate efficacy was 8.7% for vibegron and 29.1% for mirabegron, and similarly the hazard ratio was 0.26 (95% CI: 0.12-0.55, P < .001). The subgroup analysis indicated a similar tendency in each subgroup except for that of catheterization, and there was no significant interaction between the groups.. It is suggested that vibegron is superior to mirabegron in the continuity of administration in neurogenic and nonneurogenic overactive bladder populations without catheterization with fewer discontinuations due to inadequate efficacy.

Topics: Acetanilides; Hospitals; Humans; Japan; Pyrimidinones; Pyrrolidines; Retrospective Studies; Thiazoles; Treatment Outcome