Dosing & Administration

GO with a once-daily OAB treatment option1

Dosing: Monotherapy

The recommended starting dose of Myrbetriq® (mirabegron) is 25 mg orally, once daily1

MYRBETRIQ (mirabegron) dosing options: based on individual patient efficacy and tolerability, the dose may be increased MYRBETRIQ (mirabegron) dosing options: based on individual patient efficacy and tolerability, the dose may be increased
Tablet is not actual size
  • Based on individual patient efficacy and tolerability, the dose may be increased to 50 mg, once daily.1
  • For treating the symptoms of OAB, Myrbetriq 25 mg was effective within 8 weeks and Myrbetriq 50 mg was effective within 4 weeks.1
  • Efficacy of both 25 mg and 50 mg doses of Myrbetriq was maintained through the 12‑week treatment period.1
  • Myrbetriq can be taken with or without food.1
  • Myrbetriq should be taken with water, swallowed whole, and should not be chewed, divided, or crushed.1

Dose adjustments in special populations1

  • The daily dose of Myrbetriq should not exceed 25 mg once daily in the following populations:
    • Patients with severe renal impairment (CLcr 15 to 29 mL/min or eGFR 15 to 29 mL/min/1.73 m2).
    • Patients with moderate hepatic impairment (Child‑Pugh Class B).
  • Myrbetriq is not recommended for use in patients with End‑Stage Renal Disease (ESRD) or in patients with severe hepatic impairment (Child‑Pugh Class C).
  • No dose adjustment is necessary for the elderly.
  • The safety and effectiveness of Myrbetriq in pediatric patients have not been established.
Female Myrbetriq patient

Drug‑to‑Drug Interactions

Drug interaction studies were conducted to investigate the effect of co-administered drugs on the pharmacokinetics of mirabegron and the effect of mirabegron on the pharmacokinetics of co‑administered drugs. No dose adjustment is recommended when these drugs are co‑administered with Myrbetriq® (mirabegron):

  • Ketoconazole
  • Rifampin
  • Solifenacin succinate*
  • Tamsulosin*
  • Metformin
  • Oral contraceptives

*Although no dosage adjustment is recommended with solifenacin succinate or tamsulosin based on the lack of pharmacokinetic interaction, Myrbetriq should be administered with caution to patients taking muscarinic antagonist medications for the treatment of overactive bladder (OAB) and in patients with clinically significant bladder outlet obstruction (BOO) because of the risk of urinary retention.

The following are drug interactions for which monitoring is recommended:

Drugs Metabolized by CYP2D6

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.

Digoxin

When initiating a combination of Myrbetriq and digoxin, prescribe the lowest dose of digoxin; monitor serum digoxin concentrations to titrate digoxin dose to desired clinical effect.

Warfarin

  • Following a single‑dose administration of 25 mg warfarin, Myrbetriq had no effect on the warfarin pharmacodynamic endpoints such as International Normalized Ratio (INR) and prothrombin time (PT).
  • The effect of Myrbetriq on multiple doses of warfarin and on warfarin pharmacodynamic endpoints
    (INR and PT) has not been fully investigated.

INDICATIONS AND USAGE

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.

IMPORTANT SAFETY INFORMATION

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).

References

1. Myrbetriq [Prescribing Information]. Northbrook, IL: Astellas Pharma US, Inc.

Important Safety Information,
Indications and Usage

INDICATIONS AND USAGE

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.

IMPORTANT SAFETY INFORMATION

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).