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MYRBETRIQ ® (mirabegron) extended-release tablets,
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use MYRBETRIQ ® safely and effectively. See full prescribing information for MYRBETRIQ ®.
MYRBETRIQ ® (mirabegron) extended-release tablets, for oral use
Initial U.S. Approval: 2012
RECENT MAJOR CHANGES
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Contraindications ( 4) 07/2015
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Warnings and Precautions ( 5.3) 07/2015
INDICATIONS AND USAGE
MYRBETRIQ® is a beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency (1).
DOSAGE AND ADMINISTRATION
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Recommended starting dose is 25 mg once daily, with or without food ( 2.1).
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25 mg is effective within 8 weeks. Based on individual efficacy and tolerability, may increase dose to 50 mg once daily ( 2.1, 14).
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Swallow whole with water, do not chew, divide or crush ( 2.1).
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Patients with Severe Renal Impairment or Patients with Moderate Hepatic Impairment: Maximum dose is 25 mg once daily ( 2.2, 8.6, 8.7, 12.3).
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Patients with End Stage Renal Disease (ESRD) or Patients with Severe Hepatic Impairment: Not recommended ( 2.2, 8.6, 8.7, 12.3).
DOSAGE FORMS AND STRENGTHS
Extended-release tablets: 25 mg and 50 mg (3)
CONTRAINDICATIONS
Hypersensitivity reactions (4)
WARNINGS AND PRECAUTIONS
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Increases in Blood Pressure: MYRBETRIQ ® 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 ( 5.1).
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Urinary Retention in Patients With Bladder Outlet Obstruction and in Patients Taking Antimuscarinic Drugs for Overactive Bladder: Administer with caution in these patients because of risk of urinary retention ( 5.2).
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Angioedema: Angioedema of the face, lips, tongue and/or larynx has been reported with MYRBETRIQ ® ( 5.3, 6.2).
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Patients Taking Drugs Metabolized by CYP2D6: MYRBETRIQ ® is a moderate inhibitor of CYP2D6. Appropriate monitoring is recommended and dose adjustment may be necessary for narrow therapeutic index CYP2D6 substrates ( 5.4, 7.1, 12.3).
ADVERSE REACTIONS
Most commonly reported adverse reactions (> 2% and > placebo) were hypertension, nasopharyngitis, urinary tract infection and headache (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
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Drugs Metabolized by CYP2D6 (e.g., Metoprolol and Desipramine): Mirabegron is CYP2D6 inhibitor and when used concomitantly with drugs metabolized by CYP2D6, especially narrow therapeutic index drugs, appropriate monitoring and possible dose adjustment of those drugs may be necessary ( 5.4, 7.1, 12.3).
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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 ( 7.2, 12.3).
USE IN SPECIFIC POPULATIONS
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Pregnancy: Use only if the benefit to the mother outweighs the potential risk to the fetus ( 8.1).
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Nursing mothers: MYRBETRIQ ® is predicted to be excreted in human milk and is not recommended for use by nursing mothers ( 8.3).
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Pediatric use: The safety and effectiveness of MYRBETRIQ ® in pediatric patients have not been established ( 8.4).
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Geriatric use: No dose adjustment is recommended for elderly patients ( 8.5).
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 11/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
MYRBETRIQ® is a beta-3 adrenergic agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Information
The recommended starting dose of MYRBETRIQ® is 25 mg once daily with or without food. MYRBETRIQ® 25 mg is effective within 8 weeks. Based on individual patient efficacy and tolerability the dose may be increased to 50 mg once daily [see Clinical Studies (14)].
MYRBETRIQ® should be taken with water, swallowed whole and should not be chewed, divided, or crushed.
3 DOSAGE FORMS AND STRENGTHS
MYRBETRIQ® extended-release tablets are supplied in two different strengths as described below:
• 25 mg oval, brown, film coated tablet, debossed with the  (Astellas logo) and “325”
• 50 mg oval, yellow, film coated tablet, debossed with the (Astellas logo) and “355”
4 CONTRAINDICATIONS
MYRBETRIQ® is contraindicated in patients who have known hypersensitivity reactions to mirabegron or any component of the tablet [see Adverse Reactions (6.1, 6.2)].
5 WARNINGS AND PRECAUTIONS
5.1 Increases in Blood Pressure
MYRBETRIQ® can increase blood pressure. 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 greater than or equal to 180 mm Hg and/or diastolic blood pressure greater than or equal to 110 mm Hg) [see Clinical Pharmacology (12.2)].
In two, randomized, placebo-controlled, healthy volunteer studies, MYRBETRIQ® was associated with dose-related increases in supine blood pressure. In these studies, at the maximum recommended dose of 50 mg, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mm Hg greater than placebo.
In contrast, in OAB patients in clinical trials, the mean increase in systolic and diastolic blood pressure at the maximum recommended dose of 50 mg was approximately 0.5 - 1 mm Hg greater than placebo. Worsening of pre-existing hypertension was reported infrequently in MYRBETRIQ® patients.
5.2 Urinary Retention in Patients with Bladder Outlet Obstruction and in Patients Taking Antimuscarinic Medications for OAB
Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medications for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in MYRBETRIQ® patients; however, MYRBETRIQ® should be administered with caution to patients with clinically significant BOO. MYRBETRIQ® should also be administered with caution to patients taking antimuscarinic medications for the treatment of OAB [see Clinical Pharmacology (12.2)].
5.3 Angioedema
Angioedema of the face, lips, tongue, and/or larynx has been reported with MYRBETRIQ®. In some cases angioedema occurred after the first dose. 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 initiate appropriate therapy and/or measures necessary to ensure a patent airway [see Adverse Reactions (6.2)].
5.4 Patients Taking Drugs Metabolized by CYP2D6
Since mirabegron is a moderate CYP2D6 inhibitor, the systemic exposure to CYP2D6 substrates such as metoprolol and desipramine is increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary, especially with narrow therapeutic index drugs metabolized by CYP2D6, such as thioridazine, flecainide, and propafenone [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In three, 12 week, double-blind, placebo-controlled, safety and efficacy studies in patients with overactive bladder (Studies 1, 2, and 3), MYRBETRIQ® was eva luated for safety in 2736 patients [see Clinical Studies (14)]. Study 1 also included an active control. For the combined Studies 1, 2, and 3, 432 patients received MYRBETRIQ® 25 mg, 1375 received MYRBETRIQ® 50 mg, and 929 received MYRBETRIQ® 100 mg once daily. In these studies, the majority of the patients were Caucasian (94%), and female (72%) with a mean age of 59 years (range 18 to 95 years).
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