Mirabegron - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Increases in Blood Pressure: Can increase blood pressure in adult or pediatric patients.

Periodically monitor blood pressure, especially in hypertensive patients.

Mirabegron extended-release tablets 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. ( 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 ] .

In two, randomized, placebo-controlled, healthy adult volunteer studies, mirabegron 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, mirabegron, taken as monotherapy, 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 mirabegron.

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 99 th percentile plus 5 mm Hg for age, sex, and stature using appropriate reference values [see Adverse Reactions ] .

5.2 Urinary Retention in Patients with Bladder Outlet Obstruction and in Patients Taking Muscarinic Antagonist Medications for OAB In patients taking mirabegron, 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, mirabegron should still be administered with caution to patients with clinically significant BOO.

For example, monitor these patients for signs and symptoms of urinary retention.

Mirabegron should also be administered with caution to patients taking muscarinic antagonist medications for the treatment of OAB [see Clinical Pharmacology ] .

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 ].

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 and Clinical Pharmacology ] .