Administration
`
`• MYRBETRIQ:
`
`
`o Adult patients: Swallow MYRBETRIQ whole with water. Do not
`
`
`
`
`
`chew, divide, or crush. Take with or without food. (2.7)
`
`
`Pediatric patients: Swallow MYRBETRIQ whole with water. Do
`
`
`
`
`o
`not chew, divide, or crush. Take with food. (2.7)
`
`
`
`• MYRBETRIQ Granules:
`
`
`Pediatric patients: Take MYRBETRIQ Granules prepared as an
`
`
`
`
`o
`extended-release oral suspension. Take with food. (2.7)
`
`
`
`
`--------------------- DOSAGE FORMS AND STRENGTHS -------------------­
`
`
`
`
`Extended-release tablets: 25 mg and 50 mg (3)
`
`
`
`
`•
`For extended-release oral suspension: 8 mg/mL of mirabegron after
`
`
`
`
`•
`reconstitution (3)
`
`
`
`
`•
`
`
`•
`
`
`------------------------------ CONTRAINDICATIONS ----------------------------­
`
`
`
`
`Hypersensitivity to mirabegron or any inactive ingredients. (4)
`
`
`
`----------------------- WARNINGS AND PRECAUTIONS ---------------------­
`
`
`
`
`Increases in Blood Pressure: Can increase blood pressure in adult or
`
`
`
`
`•
`pediatric patients. Periodically monitor blood pressure, especially in
`
`
`hypertensive patients. MYRBETRIQ/MYRBETRIQ Granules are not
`
`
`
`
`recommended in patients with severe uncontrolled hypertension. (5.1)
`
`
`
`
`Urinary Retention in Patients With Bladder Outlet Obstruction and in
`
`
`
`Patients Taking Muscarinic Antagonist Drugs for Overactive Bladder:
`Administer with caution in these patients because of risk of urinary
`
`
`
`
`retention. (5.2)
`
`Angioedema: Angioedema of the face, lips, tongue, and/or larynx has
`
`
`been reported with mirabegron. (5.3, 6.2)
`
`
`
`
`------------------------------ ADVERSE REACTIONS ----------------------------­
`
`
`
`
`• Most commonly reported adverse reactions with MYRBETRIQ
`
`
`
`monotherapy in adult patients with OAB (> 2% and > placebo) were
`
`
`
`
`
`
`hypertension, nasopharyngitis, urinary tract infection, and headache.
`
`
`(6.1)
`
`• Most commonly reported adverse reactions with MYRBETRIQ, in
`
`
`
`combination with solifenacin succinate in adult patients with OAB
`
`
`
`
`(> 2% and > placebo and > comparator), were dry mouth, urinary tract
`
`
`
`
`infection, constipation, and tachycardia. (6.1)
`
`• Most commonly reported adverse reactions with
`
`
`MYRBETRIQ/MYRBETRIQ Granules in pediatric patients with NDO
`
`
`
`
`(≥ 3%) were UTI, nasopharyngitis, constipation, 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 ----------------------------­
`
`
`
`
`Drugs Metabolized by CYP2D6: Mirabegron is a 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)
`
`Digoxin: When initiating a combination of mirabegron and digoxin with
`
`or without solifenacin succinate, use the lowest dose of digoxin; monitor
`
`
`
`serum digoxin concentrations to titrate digoxin dose to desired clinical
`
`
`
`effect. (7.2, 12.3)
`
`
`
`•
`
`
`See 17 for PATIENT COUNSELING INFORMATION and FDA-
`
`
`
`approved patient labeling.
`
`
`
`Revised: 3/2021
`
`
`
` HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`
`
` These highlights do not include all the information needed to use
`MYRBETRIQ®/MYRBETRIQ® GRANULES safely and effectively. See
`
`
`
`full prescribing information for MYRBETRIQ/MYRBETRIQ
`
`
`GRANULES.
`
`
`MYRBETRIQ (mirabegron extended-release tablets), for oral use
`
`
`
`MYRBETRIQ GRANULES (mirabegron for extended-release oral
`
`
`
`
`suspension)
`
`Initial U.S. Approval: 2012
`
`
`-------------------------- RECENT MAJOR CHANGES -------------------------­
`
`
`
`
`Indications and Usage (1.2)
`M/YYYY
`
`
`Dosage and Administration (2)
`M/YYYY
`
`
`Warnings and Precautions, Increase in Blood Pressure (5.1)
`M/YYYY
`
`
`
`
`
`
`
`
`
`
`--------------------------- INDICATIONS AND USAGE -------------------------­
`
`
`
`MYRBETRIQ is a beta-3 adrenergic agonist indicated for the treatment of:
`
`
`Overactive bladder (OAB) in adult patients with symptoms of urge
`•
`
`
`
`urinary incontinence, urgency, and urinary frequency, either alone or in
`
`
`combination with the muscarinic antagonist solifenacin succinate. (1.1)
`Neurogenic detrusor overactivity (NDO) in pediatric patients aged
`
`
`
`3 years and older and weighing 35 kg or more. (1.2)
`
`
`
`
`
`
`MYRBETRIQ Granules is a beta-3 adrenergic agonist indicated for the
`
`
`
`
`treatment of NDO in pediatric patients aged 3 years and older. (1.2)
`
`
`
`
`---------------------- DOSAGE AND ADMINISTRATION ---------------------­
`
`
`
`
`• MYRBETRIQ and MYRBETRIQ Granules are two different products
`
`
`
`
`and they are not substitutable on a milligram-per-milligram basis. Select
`
`
`
`
`
`the recommended product (MYRBETRIQ or MYRBETRIQ Granules)
`
`
`based on the indication and patient’s weight. Do not combine
`
`
`
`
`MYRBETRIQ and MYRBETRIQ Granules to achieve the total dose. A
`
`
`
`recommended dosage for MYRBETRIQ Granules for adults has not
`
`
`
`been determined. (2.1)
`
`
`OAB in Adults
`
`The recommended starting dose of MYRBETRIQ is 25 mg orally once
`
`
`•
`daily, either alone or in combination with solifenacin succinate 5 mg
`
`
`
`
`
`orally once daily. (2.2)
`
`
`After 4 to 8 weeks, the MYRBETRIQ dose may be increased to 50 mg
`
`
`
`orally once daily. (2.2)
`
`
`NDO in Pediatric Patients 3 Years and Older
`
`
`Pediatric Patients weighing less than 35 kg: Use MYRBETRIQ
`
`
`
`
`
`•
`Granules: The recommended starting dose of MYRBETRIQ Granules is
`
`
`
`weight-based and administered as an extended-release oral suspension
`
`
`
`
`once daily. After 4 to 8 weeks, increase to the lowest effective dose
`
`
`without exceeding the maximum recommended dose. (2.3)
`
`
`
`
`Pediatric Patients weighing 35 kg or more: Use MYRBETRIQ or
`
`
`
`
`MYRBETRIQ Granules:
`
`The recommended starting dosage of MYRBETRIQ is 25 mg
`
`
`o
`orally once daily. After 4 to 8 weeks, the MYRBETRIQ dose may
`
`
`
`
`
`be increased to 50 mg orally once daily. (2.3)
`
`
`
`
`
`The recommended starting dosage of MYRBETRIQ Granules,
`
`administered as an extended-release oral suspension, is 6 mL
`
`
`(48 mg) orally once daily. After 4 to 8 weeks, increase to a
`
`
`
`
`maximum dosage of MYRBETRIQ Granules 10 mL (80 mg)
`
`
`
`
`
`orally once daily (2.3)
`
`Adult or Pediatric Patients with Renal or Hepatic Impairment: Refer to the full
`
`
`prescribing information for recommended dosage. (2.4, 2.5)
`
`
`
`
`Preparation for MYRBETRIQ Granules: Refer to the full prescribing
`
`
`
`
`information. (2.6)
`
`
`
`
`•
`
`
`•
`
`
`•
`
`
`o
`
`Reference ID: 4768327
`
`

`

`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
`1 INDICATIONS AND USAGE
`
`1.1 Adult Overactive Bladder (OAB)
`
`1.2 Pediatric Neurogenic Detrusor Overactivity (NDO)
`
`2 DOSAGE AND ADMINISTRATION
`
`2.1 Important Dosage Information
`
`2.2 Recommended Dosage for Adult Patients with OAB
`
`
`
`2.3 Recommended Dosage for Pediatric Patients Aged 3 Years and Older
`
`
`
`
`
`with NDO
`2.4 Recommended Dosage in Adult Patients with Renal or Hepatic
`
`
`
`
`Impairment
`2.5 Recommended Dosage in Pediatric Patients with Renal or Hepatic
`
`
`
`Impairment
`
`2.6 Preparation and Storage Instructions for MYRBETRIQ Granules
`
`
`2.7 Administration Instructions
`
`
`2.8 Missed Dose
`
`
`3 DOSAGE FORMS AND STRENGTHS
`
`4 CONTRAINDICATIONS
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Increases in Blood Pressure
`5.2 Urinary Retention in Patients with Bladder Outlet Obstruction and in
`
`
`
`Patients Taking Muscarinic Antagonist Medications for OAB
`
`
`5.3 Angioedema
`
`5.4 Patients Taking Drugs Metabolized by CYP2D6
`
`
`
`6 ADVERSE REACTIONS
`
`6.1 Clinical Trials Experience
`
`
`6.2 Postmarketing Experience
`
`7 DRUG INTERACTIONS
`
`7.1 Drugs Metabolized by CYP2D6
`
`
`7.2 Digoxin
`
`7.3 Warfarin
`
`
`
`
`8 USE IN SPECIFIC POPULATIONS
`
`
`8.1 Pregnancy
`
`8.2 Lactation
`
`8.4 Pediatric Use
`
`8.5 Geriatric Use
`
`8.6 Renal Impairment
`
`
`8.7 Hepatic Impairment
`
`10 OVERDOSAGE
`
`11 DESCRIPTION
`
`12 CLINICAL PHARMACOLOGY
`
`12.1 Mechanism of Action
`
`12.2 Pharmacodynamics
`
`12.3 Pharmacokinetics
`
`13 NONCLINICAL TOXICOLOGY
`
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`
`
`14 CLINICAL STUDIES
`
`14.1 MYRBETRIQ Monotherapy for Adult OAB
`
`14.2 MYRBETRIQ Combination Therapy for Adult OAB
`
`14.3 MYRBETRIQ/MYRBETRIQ Granules for Pediatric Neurogenic
`
`
`
`Detrusor Overactivity (NDO)
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`16.1 MYRBETRIQ (mirabegron extended-release tablets)
`
`16.2 MYRBETRIQ Granules (mirabegron for extended-release oral
`
`
`
`suspension)
`
`17 PATIENT COUNSELING INFORMATION
`
`
`
`*Sections or subsections omitted from the full prescribing information are not listed.
`
`
`
`
` FULL PRESCRIBING INFORMATION
`
`
` 1 INDICATIONS AND USAGE
` 1.1 Adult Overactive Bladder (OAB)
`
` MYRBETRIQ Monotherapy
`
`
`
` MYRBETRIQ® is indicated for the treatment of OAB in adult patients with symptoms of urge urinary incontinence,
`
`
`
` urgency, and urinary frequency.
`
`
`
`
`
`
`
`
`
` MYRBETRIQ Combination Therapy with Solifenacin Succinate
`
`
`
`
`MYRBETRIQ, in combination with the muscarinic antagonist solifenacin succinate, is indicated for the treatment of OAB
`
`
`in adult patients with symptoms of urge urinary incontinence, urgency, and urinary frequency.
`
`
`
` 1.2 Pediatric Neurogenic Detrusor Overactivity (NDO)
`
`
`
` MYRBETRIQ Granules
`
` MYRBETRIQ® Granules is indicated for the treatment of NDO in pediatric patients aged 3 years and older.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`MYRBETRIQ
`
`MYRBETRIQ is indicated for the treatment of NDO in pediatric patients aged 3 years and older and weighing 35 kg
`
`
`
`
`
`or more.
`
`
`Reference ID: 4768327
`
`

`

`
`
` 2 DOSAGE AND ADMINISTRATION
` 2.1 Important Dosage Information
`
`
` MYRBETRIQ and MYRBETRIQ Granules are two different products and they are not substitutable on a milligram-per­
`milligram basis:
`
`
`
`
`
`
`
`
`
`
`• Select the recommended product (MYRBETRIQ or MYRBETRIQ Granules) based on the indication and patient’s
`
`
`
`
`
`
`weight [see Indications and Usage (1) and Dosage and Administration (2.2, 2.3, 2.4, 2.5)].
`
`• Do not combine MYRBETRIQ and MYRBETRIQ Granules to achieve the total dose.
`
`
`
`• A recommended dosage for MYRBETRIQ Granules for adults has not been determined.
`
`
`
`
`
`
`
`
`
`
` 2.2 Recommended Dosage for Adult Patients with OAB
` MYRBETRIQ Monotherapy
`
`
`The recommended starting dosage of MYRBETRIQ is 25 mg orally once daily. If needed, increase to the maximum
`
`
`
`
`
`
`dosage of MYRBETRIQ 50 mg orally once daily after 4 to 8 weeks. For administration instructions, see Dosage and
`
`
`
`
`
`
`
`
`
`Administration (2.7).
`
`
`
`
`
`MYRBETRIQ Combination Therapy with Solifenacin Succinate
`
`
`The recommended starting dosage for combination treatment is MYRBETRIQ 25 mg orally once daily and solifenacin
`
`
`
`
`
`
`
`succinate 5 mg orally once daily. If needed, increase to the maximum dosage of MYRBETRIQ 50 mg orally once daily
`
`
`
`
`
`
`
`after 4 to 8 weeks. Refer to the Prescribing Information for solifenacin succinate for additional information. For
`
`
`
`
`
`
`administration instructions, see Dosage and Administration (2.7).
`
`
`
`
`
`
`
`
`
` 2.3 Recommended Dosage for Pediatric Patients Aged 3 Years and Older with NDO
`
` For pediatric patients 3 years of age and older, select the appropriate product (MYRBETRIQ or MYRBETRIQ Granules)
`
`
`
`
`based on the patient’s weight.
`
`
`
`
`Pediatric Patients weighing less than 35 kg: Use MYRBETRIQ Granules
`
`
`
`The recommended starting and maximum doses of MYRBETRIQ Granules, administered as extended-release oral
`
`
`
`
`
`suspension once daily [see Dosage and Administration (2.6)], are shown in Table 1. The recommended dosages are
`
`
`
`
`
`
`
`
`
`determined based on patient weight. Evaluate patients periodically for potential dosage adjustment. For administration
`
`
`
`instructions, see Dosage and Administration (2.7).
`
`
`
`
`Table 1: MYRBETRIQ Granules Recommended Dosage for Pediatric Patients Aged 3 Years and Older Weighing
`
`
`
`
`
`
`
`
`Less Than 35 kg as an Extended-Release Oral Suspension (Administered Orally Once Daily)
`
`
`
`
`
`
`
`
`
`
` Body Weight Range
`
` 11 kg to less than 22 kg
`
`
`
`
`
` 22 kg to less than 35 kg
`
`
` Greater than or equal to 35 kg
`
`
`
`
`
`
`
` Maximum Volume
`
` Starting Dose
`
`
`
`
` 6 mL (48 mg)
`
` 3 mL (24 mg)
`
`
`
`
` 8 mL (64 mg)
`
`
`
`
` 4 mL (32 mg)
`
`
`
` Refer to information in next section
`
`
`
`
`
`
`
`
`
`
`
` Pediatric Patients weighing 35 kg or more: Use MYRBETRIQ or MYRBETRIQ Granules
`The recommended starting dosage of MYRBETRIQ is 25 mg orally once daily. If needed, increase to a maximum dosage
`
`
`
`
`
`of MYRBETRIQ 50 mg orally once daily after 4 to 8 weeks. For administration instructions, see Dosage and
`
`
`
`
`
`
`Administration (2.7).
`
`The recommended starting dosage of MYRBETRIQ Granules is 6 mL (48 mg) orally once daily. If needed, increase to a
`
`
`
`maximum dosage of MYRBETRIQ Granules 10 mL (80 mg) orally once daily after 4 to 8 weeks. For administration
`
`
`
`
`instructions, see Dosage and Administration (2.7).
`
`
`
`Reference ID: 4768327
`
`

`

`
`
`
`
` 2.4 Recommended Dosage in Adult Patients with Renal or Hepatic Impairment
`
` Dosage in Adults with Renal Impairment
`The recommended dosage of MYRBETRIQ (administered orally once daily) in adult patients with renal impairment is
`
`
`
`
`
`described in Table 2 [see Use in Specific Populations (8.6)]. For administration instructions, see Dosage and
`
`
`
`Administration (2.7).
`
`
`
`Table 2: MYRBETRIQ Recommended Dosage in Adult Patients with Renal Impairment (Administered Orally
`
`
`
`
`
`
`Once Daily)
`
`
`Estimated GFR1
`
`
`
`
` eGFR 30 to 89 mL/min/1.73 m2
`
`
` eGFR 15 to 29 mL/min/1.73 m2
`
`
` eGFR < 15 mL/min/1.73 m2 or requiring dialysis
`
`
`
`
` 1. Estimated GFR using the modification of diet in renal disease (MDRD) formula
`
`
`
`
`
`
`
` Starting Dose
`
`
` 25 mg
`
` 25 mg
`
`
`
` Maximum Dose
`
`
` 50 mg
`
` 25 mg
`
`
`
`
` Not recommended
`
` Dosage in Adults with Hepatic Impairment
`
`The recommended dosage of MYRBETRIQ (administered orally once daily) in adult patients with hepatic impairment is
`
`
`
`described in Table 3 [see Use in Specific Populations (8.7)]. For administration instructions, see Dosage and
`
`
`
`
`Administration (2.7).
`
`Table 3: MYRBETRIQ Recommended Dosage in Adult Patients with Hepatic Impairment (Administered Orally
`
`
`
`
`
`
`Once Daily)
`
`
`
`
` Hepatic Impairment Classification
`
` Child-Pugh Class A (Mild hepatic impairment)
`
`
` Child-Pugh Class B (Moderate hepatic impairment)
`
` Child-Pugh Class C (Severe hepatic impairment)
`
`
` Starting Dose
`
`
` 25 mg
`
` 25 mg
`
`
`
` Maximum Dose
`
`
` 50 mg
`
` 25 mg
`
`
`
`
` Not Recommended
`
`
`
`
`
` 2.5 Recommended Dosage in Pediatric Patients with Renal or Hepatic Impairment
` For pediatric patients 3 years of age and older, select the appropriate product (MYRBETRIQ or MYRBETRIQ Granules)
`
`
`
`based on the patient’s weight.
`
`
`
`
`Pediatric Patients Weighing Less Than 35 kg with Renal or Hepatic Impairment: Use MYRBETRIQ Granules
`
`
`
`
`Dosage in Pediatric Patients with Renal Impairment
`
`
`The recommended dosage of MYRBETRIQ Granules in pediatric patients with renal impairment (administered orally
`
`
`
`once daily) is described in Table 4 [see Use in Specific Populations (8.6)]. For administration instructions, see Dosage
`
`
`
`
`
`
`
`
`
`
`and Administration (2.7).
`
`Table 4: MYRBETRIQ Granules Recommended Dosage in Pediatric Patients Aged 3 Years and Older Weighing
`
`
`
`
`
`
`
`
`Less Than 35 kg with Renal Impairment (Administered Orally Once Daily)
`
`
`
`
`
`
`
`
`
` Starting Dose Maximum Dose
`
`
` Body Weight Range
`
` 3 mL (24 mg)
`
`
`
`
`
` 6 mL (48 mg)
`
` 11 kg to less than 22 kg
`
`
`
`
` 4 mL (32 mg)
`
`
`
` 8 mL (64 mg)
`
`
`
`
` 22 kg to less than 35 kg
`
`
`
` 3 mL (24 mg)
`
`
`
` 3 mL (24 mg)
`
`
`
` 11 kg to less than 22 kg
`
`
`
`
`
`
` eGFR 15 to 29 mL/min/1.73 m2
`
` 4 mL (32 mg)
`
`
`
` 4 mL (32 mg)
`
`
`
` 22 kg to less than 35 kg
`
`
`
`
` Use is Not Recommended
`
` eGFR < 15 mL/min/1.73 m2 or undergoing dialysis
`
`
`
`
`
` 1. Estimate GFR using a validated eGFR estimating equation for the pediatric age range of the approved indication.
`
`
`
`
`Estimated GFR1
`
`
`
` eGFR 30 to 89 mL/min/1.73 m2
`
`
`
`
`
`
`
`Reference ID: 4768327
`
`

`

` Dosage in Pediatric Patients with Hepatic Impairment
`
`
`The recommended dosage of MYRBETRIQ Granules in pediatric patients with hepatic impairment (administered orally
`
`
`once daily) is described in Table 5 [see Use in Specific Populations (8.7)]. For administration instructions, see Dosage
`
`
`
`
`
`
`
`
`
`and Administration (2.7).
`
`Table 5: MYRBETRIQ Granules Recommended Dosage in Pediatric Patients Aged 3 Years and Older Weighing
`
`
`
`
`
`
`
`Less Than 35 kg with Hepatic Impairment (Administered Orally Once Daily)
`
`
`
`
`
`Hepatic Impairment Classification
`
` Child-Pugh Class A (Mild hepatic impairment)
`
`
`
`
` Child-Pugh Class B (Moderate hepatic impairment)
` Child-Pugh Class C (Severe hepatic impairment)
`
`
`
`
`
`
` Starting Dose Maximum Dose
`
`
` Body Weight Range
`
` 3 mL (24 mg)
`
`
`
`
`
` 6 mL (48 mg)
`
` 11 kg to less than 22 kg
`
`
`
`
` 4 mL (32 mg)
`
`
`
` 8 mL (64 mg)
`
`
`
`
` 22 kg to less than 35 kg
`
`
`
` 3 mL (24 mg)
`
`
`
` 3 mL (24 mg)
`
`
`
` 11 kg to less than 22 kg
`
`
`
`
` 4 mL (32 mg)
`
`
`
` 4 mL (32 mg)
`
`
`
` 22 kg to less than 35 kg
`
`
`
` Use is Not Recommended
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Pediatric Patients weighing 35 kg or more with renal or hepatic impairment: Use MYRBETRIQ or MYRBETRIQ
`Granules
`
`Dosage in Pediatric Patients with Renal Impairment
`
`
`The recommended dosage of MYRBETRIQ in pediatric patients with renal impairment weighing 35 kg or more
`
`
`
`
`(administered orally once daily) is described in Table 2 (above). Note that the dosage is the same as for adult patients with
`
`
`
`
`
`renal impairment [see Dosage and Administration (2.4) and Use in Specific Populations (8.6)]. For administration
`
`
`
`instructions, see Dosage and Administration (2.7).
`
`
`
`
`The recommended dosage of MYRBETRIQ Granules in pediatric patients with renal impairment weighing 35 kg or more
`
`
`
`
`
`
`(administered orally once daily) is described in Table 6 [see Use in Specific Populations (8.6)]. For administration
`
`
`instructions, see Dosage and Administration (2.7).
`
`
`
`
`Table 6: MYRBETRIQ Granules Recommended Dosage in Pediatric Patients Aged 3 Years and Older with Renal
`
`
`
`
`
`
`
`
`Impairment Weighing 35 kg or More (Administered Orally Once Daily)
`
`
`
`
`
` Estimated GFR1
`
` Maximum Dose
`
` Starting Dose
`
`
`
`
`
` 10 mL (80 mg)
` 6 mL (48 mg)
`
`
`
`
`
`
` eGFR 30 to 89 mL/min/1.73 m2
`
`
`
` 6 mL (48 mg)
`
`
` 6 mL (48 mg)
`
`
`
`
` eGFR 15 to 29 mL/min/1.73 m2
` Use is Not Recommended
`
` eGFR < 15 mL/min/1.73 m2 or undergoing dialysis
`
`
`
`
`
`
` 1. Estimate GFR using a validated eGFR estimating equation for the pediatric age range of the approved indication.
`
`
` Dosage in Pediatric Patients with Hepatic Impairment
`
`
`The recommended dosage of MYRBETRIQ in pediatric patients with hepatic impairment weighing 35 kg or more
`
`
`
`
`
`(administered orally once daily) is described in Table 3 (above). Note that the dosage is the same as for adult patients with
`
`
`
`
`
`hepatic impairment [see Dosage and Administration (2.4) and Use in Specific Populations (8.6)]. For administration
`
`
`
`instructions, see Dosage and Administration (2.7).
`
`
`
`
`The recommended dosage of MYRBETRIQ Granules in pediatric patients with hepatic impairment weighing 35 kg or
`
`
`
`
`
`more (administered orally once daily) is described in Table 7 [see Use in Specific Populations (8.7)]. For administration
`
`
`
`
`
`
`
`
`instructions, see Dosage and Administration (2.7).
`
`
`
`
`Table 7: MYRBETRIQ Granules Recommended Dosage in Pediatric Patients Aged 3 Years and Older with
`
`
`
`
`
`
`
`
`
`Hepatic Impairment Weighing 35 kg or More (Administered Orally Once Daily)
`
`
`
`
`
`
` Hepatic Impairment Classification
`
`
`
` Child-Pugh Class A (Mild hepatic impairment)
`
` Child-Pugh Class B (Moderate hepatic impairment)
`
` Child-Pugh Class C (Severe hepatic impairment)
`
`
`
`
`
` Maximum Dose
`
` Starting Dose
`
`
`
`
` 10 mL (80 mg)
` 6 mL (48 mg)
`
`
`
`
` 6 mL (48 mg)
`
`
` 6 mL (48 mg)
`
`
` Use is Not Recommended
`
`
`Reference ID: 4768327
`
`

`

`
`
`
`
`
` 2.6 Preparation and Storage Instructions for MYRBETRIQ Granules
`
` The required dose for MYRBETRIQ Granules (mirabegron for extended-release oral suspension) is calculated based on
`
`the weight of the patient. Prepare oral suspension at the time of dispensing.
`
`
`
`
`
`
`
`
`
`
`Keep the bottle in the pouch up until the time of reconstitution.
`
`
`
`
`• Discard the pouch and desiccant prior to reconstitution. Do not dispense.
`
`
`
`• Tap the closed bottle several times to loosen the granules.
`
`
`• Measure 100 mL of water, add the total amount to the bottle, and immediately shake vigorously for 1 minute, then
`
`
`
`
`
`
`
`let it stand for 10 to 30 minutes. Shake vigorously again for 1 minute.
`
`
`
`
`
`If granules have not dispersed, shake vigorously for another 1 minute.
`
`
`
`
`
`
`•
`• Record the 28-day expiration date on the container and carton based on the reconstitution date.
`
`
`
`
`• Give the patient an appropriate dosing device.
`
`
`• Store the reconstituted suspension at 20°C to 25°C (68°F to 77°F) for up to 28 days.
`
`
`
`
`
`
`
`
`• Discard the unused portion after 28 days [see How Supplied/Storage and Handling (16.2)].
`
`
`
`
`
`
`
`After reconstitution with 100 mL water, the suspension contains 8 mg/mL of mirabegron.
`
`
`
`
`
`
` 2.7 Administration Instructions
`
`
`
`
` Administration instructions for MYRBETRIQ and MYRBETRIQ Granules differ based on the patient population.
`
`
`
`
`
`
`
`
`
`
`
`MYRBETRIQ
`
`
`Adult patients: Swallow MYRBETRIQ whole with water. Do not chew, divide, or crush. Take with or without food.
`
`
`
`
`
`Pediatric patients: Swallow MYRBETRIQ whole with water. Do not chew, divide, or crush. Take with food [see Use in
`
`
`
`
`
`Specific Populations (8.4)].
`
`
`
`MYRBETRIQ Granules
`
`
`Adult patients: A recommended dosage for MYRBETRIQ Granules for adults has not been determined.
`
`
`
`
`
`
`
`
`Pediatric patients: Take MYRBETRIQ Granules prepared as an extended-release oral suspension [see Dosage and
`
`
`
`
`Administration (2.6)]. Take with food to reduce potential exposure-related risks [see Use in Specific Populations (8.4)].
`
`
`
`
`
`
` 2.8 Missed Dose
`
`
` Instruct patients to take any missed doses as soon as they remember, unless more than 12 hours have passed since the
`
`
`missed dose. If more than 12 hours have passed, the missed dose can be skipped, and the next dose should be taken at the
`
`
`
`
`
`
`usual time.
`
` 3 DOSAGE FORMS AND STRENGTHS
`
` MYRBETRIQ (mirabegron extended-release tablets) are supplied in two different strengths as described below:
`
`
`
`
`
`
`
` • 25 mg oval, brown, film-coated tablet, debossed with the
`
`
`
`
`
`
`• 50 mg oval, yellow, film-coated tablet, debossed with the
`
`
`
`(Astellas logo) and “325”
`
`
`(Astellas logo) and “355”
`
`
`
`
`
`
`
`
`MYRBETRIQ Granules (mirabegron for extended-release oral suspension): Each bottle is filled with approximately 8.3 g
`
`
`
`
`
`
`
`
`
`
`
`of yellowish white granules, which contain 830 mg of mirabegron. After reconstitution with 100 mL water, the oral
`
`
`
`
`
`suspension is pale brownish yellow to yellow with 8 mg/mL of mirabegron.
`
` 4 CONTRAINDICATIONS
`
`
`
`
` MYRBETRIQ/MYRBETRIQ Granules is contraindicated in patients with known hypersensitivity reactions to mirabegron
`
` or any inactive ingredients of the tablet or oral suspension [see Adverse Reactions (6.1, 6.2)].
`
`
`
`Reference ID: 4768327
`
`

`

`
`
` 5 WARNINGS AND PRECAUTIONS
` 5.1 Increases in Blood Pressure
`
` Increases in Blood Pressure in Adults
`
`MYRBETRIQ/MYRBETRIQ Granules can increase blood pressure. Periodic blood pressure determinations are
`
`
`
`recommended, especially in hypertensive patients. MYRBETRIQ/MYRBETRIQ Granules 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 adult 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 adult OAB patients in clinical trials, MYRBETRIQ, taken as monotherapy or in combination with
`
`
`solifenacin succinate 5 mg, the mean increase in systolic and diastolic blood pressure at the maximum recommended
`
`
`
`
`mirabegron dose of 50 mg was approximately 0.5 to 1 mm Hg greater than placebo. Worsening of pre-existing
`
`
`
`
`
`
`hypertension was reported infrequently in patients taking MYRBETRIQ.
`
`
`
`
`Increases in Blood Pressure in Pediatric Patients 3 Years and Older
`
`
`MYRBETRIQ/MYRBETRIQ Granules can increase blood pressure in pediatric patients. Blood pressure increases may be
`
`
`
`
`
`
`
`larger in children (3 to less than 12 years of age) than in adolescents (12 to less than 18 years of age). Periodic blood
`
`
`
`
`
`
`
`
`
`pressure determinations are recommended. MYRBETRIQ/MYRBETRIQ Granules is not recommended for use in
`
`
`
`
`pediatric patients with severe uncontrolled hypertension, defined as a systolic and/or diastolic blood pressure above the
`
`
`
`
`
` 99th percentile plus 5 mm Hg for age, sex, and stature using appropriate reference values [see Adverse Reactions (6.1)].
`
`
`
`
`
`
`5.2 Urinary Retention in Patients with Bladder Outlet Obstruction and in Patients Taking Muscarinic
` Antagonist Medications for OAB
`
`
`
`
` In patients taking MYRBETRIQ, urinary retention has been reported to occur 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 [see Clinical
`
`
`
`Pharmacology (12.2)].
`
`
`
`
`
` 5.3 Angioedema
`
`
`
` Angioedema of the face, lips, tongue, and/or larynx has been reported with MYRBETRIQ/MYRBETRIQ Granules. In
` some cases, angioedema occurred after the first dose, however, 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/MYRBETRIQ Granules and provide
`
`
`
`
`
` 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 MYRBETRIQ/MYRBETRIQ Granules is a moderate CYP2D6 inhibitor, the systemic exposure to CYP2D6
` substrates is increased when coadministered with MYRBETRIQ/MYRBETRIQ Granules. Therefore, appropriate
`
`
`
`
`
`
` monitoring and dose adjustment may be necessary, especially with narrow therapeutic index drugs metabolized by
` CYP2D6 [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
`
`
`
`
`
`Reference ID: 4768327
`
`

`

` 6 ADVERSE REACTIONS
`
` The following adverse reactions are discussed in more detail in other sections of the labeling.
`
`
`
`
`
`
`
` • Hypertension [see Warnings and Precautions (5.1)]
`
`
`
`• Urinary Retention [see Warnings and Precautions (5.2)]
`
`
`
`
`
`• Angioedema [see Warnings and Precautions (5.3)]
`
`
`
`
` 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.
`
`
`
` MYRBETRIQ Monotherapy for Adult OAB
`
`In three, 12-week, double-blind, placebo-controlled, safety and efficacy studies in patients with OAB (Studies 1, 2, and 3),
`
`MYRBETRIQ was evaluated for safety in 2736 patients [see Clinical Studies (14.1)]. 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).
`
`
`
`
`MYRBETRIQ was also evaluated for safety in 1632 patients who received MYRBETRIQ 50 mg once daily
`
`
`
`
`(n=812 patients) or MYRBETRIQ 100 mg (n=820 patients) in a 1-year, randomized, fixed-dose, double-blind, active-
`
`
`
`controlled, safety study in patients with OAB (Study 4). Of these patients, 731 received MYRBETRIQ in a previous 12­
`
`week study. In Study 4, 1385 patients received MYRBETRIQ continuously for at least 6 months, 1311 patients received
`
`
`
`
`
`MYRBETRIQ for at least 9 months, and 564 patients received MYRBETRIQ for at least 1 year.
`
`
`
`
`
`
`
`
`
`The most frequent adverse events (0.2%) leading to discontinuation in Studies 1, 2, and 3 for the 25 mg or 50 mg dose
`
`
`
`
`
`
`were nausea, headache, hypertension, diarrhea, constipation, dizziness, and tachycardia.
`
`
`Atrial fibrillation (0.2%) and prostate cancer (0.1%) were reported as serious adverse events by more than 1 patient and at
`
`
`
`
`
`a rate greater than placebo.
`
`
`Table 8 lists the adverse reactions, derived from all adverse events, that were reported in Studies 1, 2, and 3 at an
`
`
`
`
`
`incidence greater than placebo and in 1% or more of patients treated with MYRBETRIQ 25 mg or 50 mg once daily for
`
`
`
`up to 12 weeks. The most commonly reported adverse reactions (greater than 2% of MYRBETRIQ patients and greater
`
`
`
`
`
`
`than placebo) were hypertension, nasopharyngitis, urinary tract infection, and headache.
`
`
`
`
`Reference ID: 4768327
`
`

`

`
`
`
`
`
` Table 8: Percentages of Patients with Adverse Reactions, Derived from All Adverse Events, Exceeding Placebo
`
` Rate and Reported in ≥ 1% of OAB Patients Treated with MYRBETRIQ 25 mg or 50 mg Once Daily in Studies 1,
`
`
`
`
`
`
`
`
` 2, and 3
`
`
`
`
`
`
` MYRBETRIQ 50 mg
`
` MYRBETRIQ 25 mg
`Placebo
`
`
`
`Adverse Reaction
`
`(%)
`(%)
`(%)
`
`
`
`
` Number of Patients
`1375
`432
`1380
`
`
`
`
` Hypertension1
`
`
` 7.5
`
` 11.3
`
` 7.6
` Nasopharyngitis
`
`
` 3.9
`
` 3.5
`
` 2.5
` Urinary Tract Infection
`
`
` 2.9
`
` 4.2
`
` 1.8
`
` Headache
`
` 3.2
`
` 2.1
`
` 3.0
` Constipation
`
`
` 1.6
`
` 1.6
`
` 1.4
` Upper Respiratory Tract
`
` 1.5
`
` 2.1
`
` 1.7
`
` Infection
`
` Arthralgia
`
` 1.3
`
` 1.6
`
` 1.1
`
` Diarrhea
`
` 1.5
`
` 1.2
`
` 1.3
` Tachycardia
`
` 1.2
`
` 1.6
`
` 0.6
`
`
` 0.6
`
` 1.4
`
` 0.7
` Abdominal Pain
`
`
` 1.2
`
` 1.4
`
` 1.0
`
` Fatigue
`
` Includes reports of blood pressure above the normal range, and BP increased from baseline, occurring predominantly in subjects with baseline
`
` 1.
`
` hypertension.
`
`
`
`
`
`
`
` Other adverse reactions reported by less than 1% of patients treated with MYRBETRIQ in Studies 1, 2, or 3 included:
`
`
`
`
`
` Cardiac disorders: palpitations, blood pressure increased [see Clinical Pharmacology (12.2)]
`
`Eye disorders: glaucoma [see Clinical Pharmacology (12.2)]
`
`
`Gastrointestinal disorders: dyspepsia, gastritis, abdominal distension
`
`
`Infections and Infestations: sinusitis, rhinitis
`
`Investigations: GGT increased, AST increased, ALT increased, LDH increased
`
`
`Renal and urinary disorders: nephrolithiasis, bladder pain
`
`
`
`Reproductive system and breast disorders: vulvovaginal pruritus, vaginal infection
`
`
`
`Skin and subcutaneous tissue disorders: urticaria, leukocytoclastic vasculitis, rash, pruritus, purpura, lip edema
`
`
`
`
`Table 9 lists the rates of the most commonly reported adverse reactions, derived from all adverse event