Combination Treatment
It is indicated as monotherapy or in combination with the antimuscarinic solifenacin succinate for the treatment of OAB symptoms of urge urinary incontinence, urgency, and urinary frequency1
A β3-AR agonist combined with an antimuscarinic targets 2 different receptor pathways within the urinary bladder1,8
Co-administration of Myrbetriq with solifenacin succinate was evaluated in a 12-week, double-blind, randomized, placebo-controlled, parallel group, multicenter clinical trial in adult patients with OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency (SYNERGY Study; NCT01972841).1,9
Myrbetriq combined with solifenacin succinate showed measurable reduction in incontinence episodes per 24 hours1,9
Co-Primary Endpoint
Adjusted change from baseline to end of treatment (Week 12) in mean number of incontinence episodes per 24 hours1
The first statistical comparison within the pre-specified sequential testing was between the solifenacin 5 mg and mirabegron 50 mg group and its monotherapy components for incontinence. While the 5 + 50 mg group was superior to solifenacin 5 mg for incontinence, superiority versus mirabegron 50 mg could not be demonstrated (p=0.052). Therefore, the primary objective for the 5 + 50 mg therapy was not met. Because the null hypothesis for this test could not be rejected, the subsequent hypotheses for mean number of micturitions per 24 hours and mean volume voided per micturition could not be tested. Also, no hypothesis testing could be performed for the 5 + 25 mg group. Although formal hypothesis testing could not continue, nominal p values were assigned.1,9
a Combination therapy (25 mg/5 mg) demonstrated significant improvement vs Myrbetriq 25 mg (-0.34*, p=0.001†).
b Combination therapy (25 mg/5 mg) did not demonstrate significant improvement vs solifenacin succinate 5 mg (-0.25*, p=0.072†).
c Combination therapy (50 mg/5 mg) did not demonstrate significant improvement vs Myrbetriq 50 mg (-0.23*, p=0.052).
d Combination therapy (50 mg/5 mg) demonstrated significant improvement vs solifenacin succinate 5 mg (-0.20*, p=0.033).
*Adjusted mean difference.
†Nominal p values.
CI=confidence interval; EoT=end of treatment.
Myrbetriq combined with solifenacin succinate showed meaningful reduction in micturition frequency per 24 hours1,9
Co-Primary Endpoint
Adjusted change from baseline to end of treatment (Week 12) in mean number of micturitions per 24 hours1
a Combination therapy (25 mg/5 mg) demonstrated significant improvement vs Myrbetriq 25 mg (-0.48*, p=0.001†).
b Combination therapy (25 mg/5 mg) demonstrated significant improvement vs solifenacin succinate 5 mg (-0.29*, p=0.040†).
c Combination therapy (50 mg/5 mg) demonstrated significant improvement vs Myrbetriq 50 mg (-0.56*, p<0.001†).
d Combination therapy (50 mg/5 mg) demonstrated significant improvement vs solifenacin succinate 5 mg (-0.39*, p=0.006†).
*Adjusted mean difference.
†Nominal p values.
CI=confidence interval; EoT=end of treatment.
Myrbetriq combined with solifenacin succinate increased the mean volume voided per micturition1,9
Secondary Endpoint
Adjusted change from baseline to end of treatment (Week 12) in mean volume voided per micturition1
a Combination therapy (25 mg/5 mg) demonstrated significant improvement vs Myrbetriq 25 mg (21.52*, p<0.001†).
b Combination therapy (25 mg/5 mg) did not demonstrate significant improvement vs solifenacin succinate 5 mg (3.85*, p=0.219†).
c Combination therapy (50 mg/5 mg) demonstrated significant improvement vs Myrbetriq 50 mg (17.74*, p<0.001†).
d Combination therapy (50 mg/5 mg) demonstrated significant improvement vs solifenacin succinate 5 mg (8.75*, p=0.005†).
*Adjusted mean difference.
†Nominal p values.
CI=confidence interval; EoT=end of treatment.
Myrbetriq add-on therapy was evaluated in a 12-week, double-blind, randomized, active-controlled, multicenter clinical trial in incontinent OAB patients who received solifenacin succinate for 4 weeks and required additional relief for their OAB symptoms (BESIDE; NCT01908829).1,10
Myrbetriq added on to solifenacin succinate showed meaningful reduction in incontinence episodes per 24 hours1,10
Primary Endpoint
Adjusted change from baseline to end of treatment (Week 12) in mean number of incontinence
episodes per 24 hours1
a Add-on therapy demonstrated significant improvement vs solifenacin succinate 5 mg (p=0.001).
CI=confidence interval; EoT=end of treatment.
*Patients in the add-on therapy treatment group received Myrbetriq 25 mg and solifenacin succinate 5 mg for 4 weeks. The Myrbetriq dose was increased to 50 mg after Week 4.1
Myrbetriq added on to solifenacin succinate showed meaningful reduction in micturition frequency per 24 hours1
Secondary Endpoint
Adjusted change from baseline to end of treatment (Week 12) in mean number of micturitions per 24 hours1,10
a Add-on therapy demonstrated significant improvement vs solifenacin succinate 5 mg (p<0.001).
CI=confidence interval; EoT=end of treatment.
*Patients in the add-on therapy treatment group received Myrbetriq 25 mg and solifenacin succinate 5 mg for 4 weeks. The Myrbetriq dose was increased to 50 mg after Week 4.1
Myrbetriq added on to solifenacin succinate increased the mean volume voided per micturition1
Secondary Endpoint
Adjusted change from baseline to end of treatment (Week 12) in mean volume voided per micturition1,10
a Add-on therapy demonstrated significant improvement vs solifenacin succinate 5 mg (p<0.001).
CI=confidence interval; EoT=end of treatment.
*Patients in the add-on therapy treatment group received Myrbetriq 25 mg and solifenacin succinate 5 mg for 4 weeks. The Myrbetriq dose was increased to 50 mg after Week 4.1
Evaluated in adult patients with overactive bladder (OAB) in three 12‑week trials and a 1‑year safety study1
Percent of patients with adverse reactions derived from all adverse events >placebo and
comparator (at same dose level) rate and reported by ≥1% of patients treated with combination
therapy in Studies 5, 6 and 7*†
*Adverse reactions occurring in patients treated with co-administration of Myrbetriq and solifenacin succinate in Study 7, that included a 4-week initial treatment period with Myrbetriq 25 mg + solifenacin succinate 5 mg, are included in the Myrbetriq 50 mg + solifenacin succinate 5 mg group.
†Study 5=SYMPHONY (NCT01340027); Study 6=SYNERGY (NCT01972841); Study 7=BESIDE (NCT01908829).
‡Includes any recorded treatment-emergent UTI.
Percent of patients with adverse reactions derived from all adverse events exceeding
comparator rate and reported ≥2% of patients treated with combination therapy in Study 8*
*Study 8=SYNERGY II (NCT02045862).10
†Includes any recorded treatment-emergent UTI.
ABPM=ambulatory blood pressure monitoring; BOO=bladder outlet obstruction; SBP/DBP=systolic blood pressure/diastolic blood pressure; UTI=urinary tract infection.
Percent of patients with adverse reactions derived from all adverse events >placebo and
comparator (at same dose level) rate and reported by ≥1% of patients treated with combination
therapy in Studies 5, 6 and 7*†
*Adverse reactions occurring in patients treated with co-administration of Myrbetriq and solifenacin succinate in Study 7, that included a 4-week initial treatment period with Myrbetriq 25 mg + solifenacin succinate 5 mg, are included in the Myrbetriq 50 mg + solifenacin succinate 5 mg group.
†Study 5=SYMPHONY (NCT01340027); Study 6=SYNERGY (NCT01972841); Study 7=BESIDE (NCT01908829).
‡Includes any recorded treatment-emergent UTI.
Percent of patients with adverse reactions derived from all adverse events exceeding
comparator rate and reported ≥2% of patients treated with combination therapy in Study 8*
*Study 8=SYNERGY II (NCT02045862).10
†Includes any recorded treatment-emergent UTI.
ABPM=ambulatory blood pressure monitoring; BOO=bladder outlet obstruction; SBP/DBP=systolic blood pressure/diastolic blood pressure; UTI=urinary tract infection.
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® (mirabegron extended-release tablets) 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.