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 patients with OAB with symptoms of urge urinary incontinence, urgency, and urinary frequency (SYNERGY Study; NCT01972841).
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; NCT 01908829).
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
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
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 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).9
‡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).9
‡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
How can your patients save on combination therapy?
With the Momentum program, eligible patients can
save up to*:
The Momentum program offers savings for eligible patients being treated with Myrbetriq and VESIcare together, totalling up to $840 each (or $1680 combined) for 12 Myrbetriq and VESIcare prescriptions. Any out-of-pocket costs for your patient’s first prescription owed to their insurance company will be paid through the Momentum Program. See eligibility restrictions, terms and conditions below. Offer valid for prescriptions of one month only.
Eligibility Restrictions,*Patient is responsible for the first $20 per month and any differential over $90 on a Myrbetriq prescription, as well as the first $20 per month and any differential over $90 on a VESIcare prescription.
Myrbetriq® (mirabegron), a beta-3 adrenergic agonist, is indicated as monotherapy or in combination with the muscarinic antagonist solifenacin succinate for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Do not use Myrbetriq® (mirabegron) in patients who have known hypersensitivity reactions to mirabegron or any component of the tablet.
Solifenacin succinate is contraindicated in patients with urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and in patients with hypersensitivity to the product.
Myrbetriq alone or in combination with solifenacin succinate can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients. Myrbetriq is not recommended for use in severe uncontrolled hypertensive patients (defined as systolic blood pressure ≥ 180mm Hg and/or diastolic blood pressure ≥ 110mm Hg). Worsening of hypertension was reported infrequently in Myrbetriq clinical trial patients with OAB.
In patients taking Myrbetriq, urinary retention has been reported in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medications for the treatment of OAB. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in Myrbetriq patients; however, Myrbetriq and solifenacin succinate 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 antimuscarinic medications for the treatment of OAB, including solifenacin succinate.
Angioedema of the face, lips, tongue and/or larynx has been reported with Myrbetriq and with solifenacin succinate. Cases of angioedema 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/or solifenacin succinate and initiate appropriate therapy and/or measures necessary to ensure a patent airway.
Solifenacin succinate should be administered with caution to patients with decreased gastrointestinal motility, controlled narrow-angle glaucoma or reduced renal or hepatic function. Doses of solifenacin succinate higher than 5mg are not recommended in patients with severe renal impairment, moderate hepatic impairment, or when administered with ketoconazole or other potent CYP3A4 inhibitors. Use of solifenacin succinate in patients with severe hepatic impairment is not recommended.
Anticholinergic central nervous system (CNS) effects have been reported with solifenacin succinate use, including headache, confusion, hallucinations and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing dose, and be advised not to drive or operate heavy machinery until they know how solifenacin succinate affects them. If a patient experiences these effects, dose reduction or drug discontinuation should be considered.
Since Myrbetriq is a moderate CYP2D6 inhibitor, the systemic exposure to CYP2D6 substrates such as metoprolol and desipramine 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, such as thioridazine, flecainide, and propafenone.
In solifenacin succinate monotherapy studies, for the 5mg dose one serious adverse event (angioneurotic edema) was reported. For the 10mg dose, three intestinal serious adverse events were reported (one fecal impaction, one colonic obstruction and one intestinal obstruction).
In clinical trials, the most commonly reported adverse reactions (> 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 (> 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, constipation, diarrhea, and dizziness.
Please see accompanying complete Prescribing Information for Myrbetriq® (mirabegron) and VESIcare® (solifenacin succinate).
Myrbetriq® (mirabegron), a beta-3 adrenergic agonist, is indicated as monotherapy or in combination with the muscarinic antagonist solifenacin succinate for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.
Do not use Myrbetriq® (mirabegron) in patients who have known hypersensitivity reactions to mirabegron or any component of the tablet.
Solifenacin succinate is contraindicated in patients with urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and in patients with hypersensitivity to the product.
Myrbetriq alone or in combination with solifenacin succinate can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients. Myrbetriq is not recommended for use in severe uncontrolled hypertensive patients (defined as systolic blood pressure ≥ 180mm Hg and/or diastolic blood pressure ≥ 110mm Hg). Worsening of hypertension was reported infrequently in Myrbetriq clinical trial patients with OAB.
In patients taking Myrbetriq, urinary retention has been reported in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medications for the treatment of OAB. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in Myrbetriq patients; however, Myrbetriq and solifenacin succinate 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 antimuscarinic medications for the treatment of OAB, including solifenacin succinate.
Angioedema of the face, lips, tongue and/or larynx has been reported with Myrbetriq and with solifenacin succinate. Cases of angioedema 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/or solifenacin succinate and initiate appropriate therapy and/or measures necessary to ensure a patent airway.
Solifenacin succinate should be administered with caution to patients with decreased gastrointestinal motility, controlled narrow-angle glaucoma or reduced renal or hepatic function. Doses of solifenacin succinate higher than 5mg are not recommended in patients with severe renal impairment, moderate hepatic impairment, or when administered with ketoconazole or other potent CYP3A4 inhibitors. Use of solifenacin succinate in patients with severe hepatic impairment is not recommended.
Anticholinergic central nervous system (CNS) effects have been reported with solifenacin succinate use, including headache, confusion, hallucinations and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing dose, and be advised not to drive or operate heavy machinery until they know how solifenacin succinate affects them. If a patient experiences these effects, dose reduction or drug discontinuation should be considered.
Since Myrbetriq is a moderate CYP2D6 inhibitor, the systemic exposure to CYP2D6 substrates such as metoprolol and desipramine 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, such as thioridazine, flecainide, and propafenone.
In solifenacin succinate monotherapy studies, for the 5mg dose one serious adverse event (angioneurotic edema) was reported. For the 10mg dose, three intestinal serious adverse events were reported (one fecal impaction, one colonic obstruction and one intestinal obstruction).
In clinical trials, the most commonly reported adverse reactions (> 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 (> 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, constipation, diarrhea, and dizziness.
Please see accompanying complete Prescribing Information for Myrbetriq® (mirabegron) and VESIcare® (solifenacin succinate).