Mirabegron: uses, appearance and warnings

Mirabegron for extended-release oral suspension is a beta-3 adrenergic agonist indicated for the treatment of NDO in pediatric patients aged 3 years and older. ( 1.2 ) 1.2 Pediatric Neurogenic Detrusor Overactivity (NDO) Mirabegron for Extended-Release Oral Suspension Mirabegron for extended-release oral suspension is indicated for the treatment of NDO in pediatric patients aged 3 years and older.

Mirabegron for extended-release oral suspension: Each bottle is filled with approximately 8.3 g of yellowish to brownish colored granular powder filled in amber colored PET bottle, which contain 830 mg of mirabegron. After reconstitution with 100 mL water, the oral suspension is pale yellow to brownish yellow with 8 mg/mL of mirabegron. For extended-release oral suspension: 8 mg/mL of mirabegron after reconstitution ( 3 )

16.2 Mirabegron for Extended-Release Oral Suspension Mirabegron for extended-release oral suspension is supplied as granules in bottles with a child- resistant cap packaged in an aluminum pouch with desiccant. Each bottle is filled with approximately 8.3 g of yellowish to brownish colored granular powder, which contain 830 mg of mirabegron. After reconstitution with 100 mL water, the oral suspension is pale yellow to brownish yellow with 8 mg/mL of mirabegron. 1 Carton Containing 1 Bottle NDC 67877-890-88 Store and Dispense Store mirabegron for extended-release oral suspension 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) [see USP Controlled Room Temperature]. 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.

Mirabegron for extended-release oral suspension is contraindicated in patients with known hypersensitivity reactions to mirabegron or any inactive ingredients of the oral suspension [see Adverse Reactions ( 6.1 , 6.2 )]. Hypersensitivity to mirabegron or any inactive ingredients. ( 4 )

Increases in Blood Pressure: Can increase blood pressure in adult or pediatric patients. Periodically monitor blood pressure, especially in hypertensive patients. Mirabegron is 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 ) 5.1 Increases in Blood Pressure Increases in Blood Pressure in Adults Mirabegron can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients. Mirabegron 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 Mirabegron 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. Mirabegron 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 mirabegron. 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 mirabegron 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 mirabegron is a moderate CYP2D6 inhibitor, the systemic exposure to CYP2D6 substrates is increased when coadministered with mirabegron. 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 )] .

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 )] Most commonly reported adverse reactions with mirabegron in pediatric patients with NDO (≥ 3%) were UTI, nasopharyngitis, constipation, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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. …

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) [see Clinical Pharmacology ( 12.3 )] . 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. …