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warnings and cautions
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. ( 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, 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 (6....
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adverse reactions
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 )] Most commonly reported adverse reactions with mirabegron 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 mirabegron in pediatric patients with NDO (≥ 3%) were UTI, nasopharyngitis, constipation, and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 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. Mirabegron 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), mirabegron was evaluated for safety in 2,736 patients [see Clinical Studies ( 14.1 )]. Study 1 also included an active control. For the combined Studies 1, 2, and 3,432 patients received mirabegron 25 mg, 1,375 received mirabegron 50 mg, and 929 received mirabegron 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). Mirabegron was also evaluated for safety in 1,632 patients who received mirabegron 50 mg once daily (n=812 patients) or mirabegron 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 mirabegron in a previous 12-week study. In Study 4, 1385 patients received mirabegron continuously for at least 6 months, 1,311 patients received mirabegron for at least 9 months, and 564 patients received mirabegron 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,...
adverse reactions table
Table 3: Percentages of Patients with Adverse Reactions, Derived from All Adverse Events, Exceeding Placebo Rate and Reported in ≥ 1% of OAB Patients Treated with mirabegron 25 mg or 50 mg Once Daily in Studies 1, 2, and 3 Adverse Reaction Placebo (%) Mirabegron 25 mg (%) Mirabegron 50 mg (%) Number of Patients 1380 432 1375 Hypertension * 7.6 11.3 7.5 Nasopharyngitis 2.5 3.5 3.9 Urinary Tract Infection 1.8 4.2 2.9 Headache 3.0 2.1 3.2 Constipation 1.4 1.6 1.6 Upper Respiratory Tract Infection 1.7 2.1 1.5 Arthralgia 1.1 1.6 1.3 Diarrhea 1.3 1.2 1.5 Tachycardia 0.6 1.6 1.2 Abdominal Pain 0.7 1.4 0.6 Fatigue 1.0 1.4 1.2 *Includes reports of blood pressure above the normal range, and BP increased from baseline, occurring predominantly in subjects with baseline hypertension.