What do we know and not know about mirabegron, a novel β3 agonist, in the treatment of overactive bladder?

Abstract

Anticholinergic drugs should remain the first-line pharmacologic treatment for OAB until head-to-head comparative study eventually shows that mirabegron has equivalent or superior efficacy. However, it seems logical to use mirabegron as second-line treatment of OAB in patients who are poor responders or intolerant to anticholinergics.

The Role of Mirabegron in Overactive Bladder: A Systematic Review and Meta-Analysis

“…Mirabegron as a beta-3 adrenoceptor agonist is approved in the USA, Japan, EU and Canada for the symptomatic treatment of OAB syndrome [16,20,21]. …”

Mirabegron in the treatment of overactive bladder

“…Furthermore, mirabegron causes clinical benefit without significant AEs in those patients who have been previously treated with AMs [65] or who were unresponsive to these drugs [66]. Current literature shows that mirabegron causes less dry mouth, constipation, urinary retention, or blurred vision than tolterodine, and interestingly the incidence of dry mouth, which is the most frequent AE with AM treatment, was similar to placebo, 50 and 100 mg mirabegron [73]. However, no study has still compared the clinical efficacy of mirabegron with other AMs in the treatment of OAB, but only in the Phase III study by Khullar et al tolterodine was included as active control [56].…”

“…First, this agent shows a good safety profile in terms of neurological AEs, while AMs are frequently associated with headache, somnolence, and cognitive impairment; this is due to the activity of AMs on muscarinic receptors (M 1 -M 5 ), all of which are expressed in brain tissue, and the possibility of blood--brain barrier penetration (with the exception of trospium chloride). Thus, future research should focus on the assessment of mirabegron concentrations in the central nervous system, clinical evaluation of neurocognition and memory, since b 3 -AR mRNA has been observed in discrete regions of the human brain (such as hippocampus, hypothalamus, amygdala, and cerebral cortex) [73,74]. If the neurological advantages are confirmed, mirabegron may become a first-line option for the treatment of patients with cognitive impairment.…”

“…However, this potential advantage of mirabegron in the elderly population should be balanced against the risk of cardiovascular AEs, in particular in women; on the other hand, also AMs may also cause QT prolongation and increase HR and the CV risk due to drug--drug interactions in patients with OAB [75]. The second advantage is that in animal studies mirabegron decreases the frequency of rhythmic bladder contractions during the filling phase without suppressing amplitude during micturition [73,[76][77][78]. This may be of help for treating OAB associated with bladder outlet obstruction diminishing the risk of voiding difficulties in comparison with AMs [73].…”

Improving Outcomes in Patients With Refractory Idiopathic and Neurogenic Detrusor Overactivity: Management Strategies

“…70 The incidence of dry mouth associated with mirabegron is similar to that with placebo and is reportedly 3-fold lower than that with tolterodine. 71,72 The most common side effect is dose-related elevation in blood pressure, which occurs in 7.5% to 11.3% of patients. 73 Mirabegron is taken once daily and can be used as a primary treatment or add-on therapy with an antimuscarinic in OAB.…”