Myrbetriq was evaluated in three 12-week, double-blind, randomized, placebo-controlled,
parallel group, multicenter clinical trials in patients with overactive bladder with symptoms
of urge urinary incontinence, urgency, and urinary frequency (Studies 1, 2, and 3).1
Required patients to have symptoms of overactive bladder ≥3 months, ≥8 micturitions per day, and ≥3 episodes of urgency with or without incontinence over a 3-day period1
The majority of patients were Caucasian (94%) and female (72%), with a mean age of 59
years (range 18-95 years)1
The population included both treatment-naive patients who had not received prior
antimuscarinic pharmacotherapy for overactive bladder (48%) and those who had
received prior antimuscarinic pharmacotherapy for OAB (52%)1
Study 1: Myrbetriq 50 mg, placebo, or an active control once daily
Study 2: Myrbetriq 50 mg or placebo once daily
Study 3: Myrbetriq 25 mg, Myrbetriq 50 mg, or placebo once daily
Efficacy demonstrated in three 12-week, double-blind, placebo-controlled Phase III studies1
Fewer episodes of
incontinence
Reduced micturition
frequency
Greater volume
voided
Mean change from baseline to end treatment (Week 12) in number of incontinence episodes per 24 hours (Full Analysis Set-Incontinence
[FAS-I])1-5*†‡
The efficacy of Myrbetriq 25 mg and 50 mg was maintained through the 12-week treatment period.1
Mean change from baseline to end of treatment (Week 12) in number of micturitions per 24 hours1-5*
The efficacy of Myrbetriq 25 mg and 50 mg was maintained through the 12-week treatment period.1
Mean change from baseline to end of treatment (Week 12) in volume of urine (mL) voided per micturition1-5*
*Adjusted mean for baseline, gender, and geographic region. †Statistically significant vs placebo at the 0.05 level with multiplicity adjustment. ‡Myrbetriq 25 mg did not demonstrate statistical significance for change in volume voided per micturition.
*Of 5648 patients who received Myrbetriq monotherapy in the Phase II and III studies for OAB, 2029 (35.9%) were 65 years of age or older, and 557 (9.9%) were 75 years of age or older. All patients were ≥18 years of age.1
†The Cmax and area under curve (AUC) of Myrbetriq following multiple oral doses in elderly volunteers (≥65 years) were similar to those in younger volunteers (18 to 45 years).1
Efficacy demonstrated in a double-blind, randomized, placebo-controlled, parallel-group, multicenter Phase IV study8
After a 2-week placebo run-in period, those who entered the 12-week treatment period were randomized to Myrbetriq 25 mg or placebo and were given the option to increase to 50 mg at Week 4 or Week 8 based on individual efficacy, tolerability, and investigator discretion.
This study was designed to detect a difference between placebo and total mirabegron groups and not for each individual mirabegron dosing group.
Change from baseline to end of treatment (EoT) in mean number of urinary incontinence episodes per 24 hours8
Change from baseline to EoT in the mean number of micturitions per 24 hours8
Change from baseline to EoT in mean volume voided per micturition8
MYRBETRIQ® (mirabegron extended-release tablets), either alone or in combination with the muscarinic antagonist solifenacin succinate, is indicated for the treatment of overactive bladder (OAB) in adult patients with symptoms of urge urinary incontinence, urgency, and urinary frequency.
MYRBETRIQ is contraindicated in patients with known hypersensitivity reactions to mirabegron or any inactive ingredients of the tablet.
MYRBETRIQ monotherapy or in combination with solifenacin succinate can increase blood pressure in adults. Periodic blood pressure determinations are recommended, especially in hypertensive patients. MYRBETRIQ is not recommended for use in patients with severe uncontrolled hypertension (defined as systolic blood pressure ≥ 180mm Hg and/or diastolic blood pressure ≥ 110mm Hg). Worsening of pre-existing hypertension was reported infrequently in patients taking MYRBETRIQ.
In patients taking MYRBETRIQ, urinary retention has been reported in patients with bladder outlet obstruction (BOO) and in patients taking muscarinic antagonist medications for the treatment of OAB. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients treated with mirabegron; however, MYRBETRIQ should still be administered with caution to patients with clinically significant BOO. For example, monitor these patients for signs and symptoms of urinary retention. MYRBETRIQ should also be administered with caution to patients taking muscarinic antagonist medications for the treatment of OAB, including solifenacin succinate.
Angioedema of the face, lips, tongue and/or larynx has been reported with MYRBETRIQ. In some cases, angioedema occurred after the first dose. Cases have been reported to occur hours after the first dose or after multiple doses. Angioedema, associated with upper airway swelling, may be life threatening. If involvement of the tongue, hypopharynx, or larynx occurs, promptly discontinue MYRBETRIQ and initiate appropriate therapy and/or measures necessary to ensure a patent airway.
Since MYRBETRIQ is a moderate CYP2D6 inhibitor, the systemic exposure to CYP2D6 substrates is increased when co‐administered with MYRBETRIQ. Therefore, appropriate monitoring and dose adjustment may be necessary, especially with narrow therapeutic index drugs metabolized by CYP2D6.
In clinical trials, the most commonly reported adverse reactions in adults (> 2% and > placebo) for MYRBETRIQ 25mg and 50mg versus placebo, respectively, were hypertension (11.3%, 7.5% vs. 7.6%), nasopharyngitis (3.5%, 3.9% vs. 2.5%), urinary tract infection (4.2%, 2.9% vs. 1.8%), and headache (2.1%, 3.2% vs. 3.0%).
In clinical trials, the most commonly reported adverse reactions in adults (> 2% and > placebo and > comparator) for MYRBETRIQ in combination with solifenacin succinate 25mg + 5mg and 50mg + 5mg versus MYRBETRIQ 25mg, MYRBETRIQ 50mg, solifenacin succinate 5mg, and placebo, respectively, were dry mouth (9.3%, 7.2% vs. 3.8%, 3.6%, 6.5%, 2.2%), urinary tract infection (7.0%, 4.0% vs. 4.0%, 4.2%, 3.6%, 5.3%), constipation (4.2%, 3.9% vs. 1.2%, 2.8%, 2.4%, 1.2%), and tachycardia (2.2%, 0.9% vs. 1.6%, 1.6%, 0.7%, 0.8%).
In postmarketing experience with mirabegron, the following events have also occurred: atrial fibrillation, nausea, diarrhea, and dizziness.
Please refer to prescribing information for solifenacin succinate when prescribing MYRBETRIQ in combination with solifenacin succinate.
1. Myrbetriq [package insert]. Northbrook, IL: Astellas Pharma US, Inc. 2. Khullar V, Amarenco G, Angulo JC, et al. Efficacy and tolerability of mirabegron, a β3-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial. Eur Urol 2013;63(2):283-95. 3. Nitti VW, Auerbach S, Martin N, Calhoun A, Lee M, Herschorn S. Results of a randomized phase III trial of mirabegron in patients with overactive bladder. J Urol 2013;189(4):1388-95. 4. Astellas. Myrbetriq. Data on File. 5. Herschorn S, Barkin J, Castro-Diaz D, et al. A phase III, randomized, double-blind, parallel-group, placebo-controlled, multicentre study to assess the efficacy and safety of the β3 adrenoceptor agonist, mirabegron, in patients with symptoms of overactive bladder. Urology 2013;82(2):313-20. Erratum in: Urology 2013;82(6):1457. 6. Coyne KS, Sexton CC, Vats V, Thompson C, Kopp ZS, Milsom I. National community prevalence of overactive bladder in the United States stratified by sex and age. Urology 2011;77(5):1081-7. 7. Wagg A, Cardozo L, Nitti VW, et al. The efficacy and tolerability of the β3-adrenoceptor agonist mirabegron for the treatment of symptoms of overactive bladder in older patients. Age Ageing 2014;43(5):666-75. 8. Wagg A, Staskin D, Engel E, Herschorn S, Kristy RM, Schermer CR. Efficacy, safety, and tolerability of mirabegron in patients aged ≥65yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR). Eur Urol 2020;77(2):211-20.
