Mirabegron

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. • Neurogenic detrusor overactivity (NDO) in pediatric patients aged 3 years and older and weighing 35 kg or more. MYRBETRIQ Granules is a beta-3 adrenergic agonist indicated for the treatment of NDO in pediatric patients aged 3 years and older.

Mirabegron is an agonist of the human beta-3 adrenergic receptor (AR) as demonstrated by in vitro laboratory experiments using the cloned human beta-3 AR. Mirabegron relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of beta-3 AR which increases bladder capacity. Although mirabegron showed very low intrinsic activity for cloned human beta-1 AR and beta-2 AR, results in humans indicate that beta-1 AR stimulation occurred at a mirabegron dose of 200 mg.

2 DOSAGE AND A DM INISTRATION • 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. 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. • After 4 to 8 weeks, the MYRBETRIQ dose may be increased to 50 mg orally once daily.

MYRBETRIQ/MYRBETRIQ Granules is contraindicated in patients with known hypersensitivity reactions to mirabegron or any inactive ingredients of the tablet or oral suspension. Hypersensitivity to mirabegron or any inactive ingredients.

• 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. • 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. • Angioedema: Angioedema of the face, lips, tongue, and/or larynx has been reported with mirabegron.

The following adverse reactions are discussed in more detail in other sections of the labeling. • Hypertension • Urinary Retention • Angioedema • Most commonly reported adverse reactions with MYRBETRIQ monotherapy in adult patients with OAB (> 2% and > placebo) were hypertension, nasopharyngitis, urinary tract infection, and headache. • 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. • Most commonly reported adverse reactions with MYRBETRIQ/MYRBETRIQ Granules in pediatric patients with NDO (≥ 3%) were UTI, nasopharyngitis, constipation, and headache.

Drug interaction studies were conducted in adult patients to investigate the effect of coadministered drugs on the pharmacokinetics of mirabegron and the effect of mirabegron on the pharmacokinetics of coadministered drugs (e.g., ketoconazole, rifampin, solifenacin succinate, tamsulosin, and oral contraceptives). No dose adjustment is recommended when these drugs are coadministered with mirabegron. The following are drug interactions for which monitoring is recommended: • 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.

Store and Dispense Store at 20°C to 25°C (68°F to 77°F) with excursions permitted from 15°C to 30°C (59°F to 86°F). logo.jpg logo.jpg MYRBETRIQ Granules (mirabegron for extended-release oral suspension) MYRBETRIQ Granules (mirabegron for extended-release oral suspension) is supplied as granules in bottles with a child-resistant cap packaged in an aluminum pouch with desiccant. After reconstitution with 100 mL water, the oral suspension is pale brownish yellow to yellow with 8 mg/mL of mirabegron. 1 Carton Containing 1 Bottle NDC 0469-5020-99 Store and Dispense Store MYRBETRIQ Granules at 20°C to 25°C (68°F to 77°F) with excursions permitted from 15°C to 30°C (59°F to 86°F).