Mirabegron
Tablet, Film Coated, Extended Release · Oral
Uses
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.
Dosage and administration
2 DOSAGE & ADMINISTRATION MYRBETRIQ and mirabegron for extended-release oral suspension are two different products and they are not substitutable on a milligram-per-milligram basis. Select the recommended product (MYRBETRIQ or mirabegron for extended-release oral suspension) based on the indication and patient’s weight. Do not combine MYRBETRIQ and mirabegron for extended-release oral suspension to achieve the total dose. A recommended dosage for mirabegron for extended-release oral suspension for adults has not been determined. ( 2.1 ) NDO in Pediatric Patients 3 Years and Older Pediatric Patients weighing less than 35 kg: Use mirabegron for extended-release oral suspension: The recommended starting dose of mirabegron for extended-release oral suspension 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 mirabegron for extended-release oral suspension: The recommended starting dosage of mirabegron for extended-release oral suspension, 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 mirabegron for extended-release oral suspension 10 mL (80 mg) orally once daily ( 2.3 ) Pediatric Patients with Renal or Hepatic Impairment : Refer to the full prescribing information for recommended dosage. ( 2.5 ) Preparation for Mirabegron for Extended-Release Oral Suspension : Refer to the full prescribing information. ( 2.6 ) Administration Mirabegron for Extended-Release Oral Suspension: Pediatric patients: Take mirabegron for extended-release oral suspension prepared as an extended-release oral suspension. Take with food. ( 2.7 ) 2.1 Important Dosage Information MYRBETRIQ and mirabegron for extended-release oral suspension are two different products and they are not substitutable on a milligram-per-milligram basis: Select the recommended product (MYRBETRIQ or Mirabegron for extended-release oral suspension) based on the indication and patient’s weight [see Indications and Usage ( 1 ) and Dosage and Administration ( 2.3 , 2.5 )]. Do not combine MYRBETRIQ and mirabegron for extended-release oral suspension to achieve the total dose. A recommended dosage for mirabegron for extended-release oral suspension for adults has not been determined. 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 Mirabegron for extended-release oral suspension) based on the patient’s weight. Pediatric Patients weighing less than 35 kg: Use Mirabegron for Extended-Release Oral Suspension The recommended starting and maximum doses of mirabegron for extended-release oral suspension, 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: Mirabegron for Extended-Release Oral Suspension 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 Starting Dose Maximum Volume 11 kg to less than 22 kg 3 mL (24 mg) 6 mL (48 mg) 22 kg to less than 35 kg 4 mL (32 mg) 8 mL (64 mg) Greater than or equal to 35 kg Refer to information in next section Pediatric Patients weighing 35 kg or more: Use MYRBETRIQ or Mirabegron for Extended-Release Oral Suspension The recommended starting dosage of mirabegron for extended-release oral suspension is 6 mL (48 mg) orally once daily. If needed, increase to a maximum dosage of mirabegron for extended-release oral suspension 10 mL (80 mg) orally once daily after 4 to 8 weeks. For administration instructions, see Dosage and Administration ( 2.7 ) . 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 mirabegron for extended-release oral suspension) based on the patient’s weight. Pediatric Patients Weighing Less Than 35 kg with Renal or Hepatic Impairment: Use Mirabegron for Extended-Release Oral Suspension Dosage in Pediatric Patients with Renal Impairment The recommended dosage of mirabegron for extended-release oral suspension 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: Mirabegron for Extended-Release Oral Suspension Recommended Dosage in Pediatric Patients Aged 3 Years and Older Weighing Less Than 35 kg with Renal Impairment (Administered Orally Once Daily) Estimated GFR1 Body Weight Range Starting Dose Maximum Dose eGFR 30 to 89 mL/min/1.73 m 2 11 kg to less than 22 kg 3 mL (24 mg) 6 mL (48 mg) 22 kg to less than 35 kg 4 mL (32 mg) 8 mL (64 mg) eGFR 15 to 29 mL/min/1.73 m 2 11 kg to less than 22 kg 3 mL (24 mg) 3 mL (24 mg) 22 kg to less than 35 kg 4 mL (32 mg) 4 mL (32 mg) eGFR < 15 mL/min/1.73 m 2 or undergoing dialysis Use is Not Recommended 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 mirabegron for extended-release oral suspension 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 ).
Dosage forms and strengths
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 )
Contraindications
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 )
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 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 )] .
Side effects
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. Mirabegron for Pediatric Neurogenic Detrusor Overactivity (NDO) The safety of mirabegron was evaluated in a 52-week, open-label, baseline-controlled, multicenter, dose titration study (Study 9) [see Clinical Studies ( 14.3 )]. The study included 86 pediatric patients 3 to 17 years of age with neurogenic detrusor overactivity (NDO); 55% were female, 72% were White. Treatment was initiated at the weight-based starting recommended dose and was increased to a dose equivalent of MYRBETRIQ 50 mg daily dose in adults by Week 8. Subsequent to the dose titration period, patients continued their optimized dose for the duration of the 52-week study (mean exposure duration 303 days, range 1 to 390 days). The most commonly reported adverse reactions were UTI, nasopharyngitis, constipation, and headache. Table 12 lists the adverse reactions that were reported in 2% or more of patients treated with mirabegron in Study 9. Table 12: Percentages of Patients with Adverse Reactions Reported in ≥ 2% of Patients 3 to 17 Years of Age with Neurogenic Detrusor Overactivity (NDO) Treated with Mirabegron in Study 9 Adverse Reaction Percentage (%) of Patients Reporting Adverse Reactions N=86 Number of Patients 51 (59.3) Urinary Tract Infection 1 24.4 Nasopharyngitis 5.8 Constipation 4.7 Headache 3.5 Nausea 2.3 Gastroenteritis 2.3 Rhinitis 2.3 Cough 2.3 1. Includes any recorded UTI while patient was on treatment with mirabegron. Increased Blood Pressure in Pediatric Patients with NDO Treated with Mirabegron: Mean systolic and diastolic blood pressures increased in Study 9 by 4.3 mm Hg and 1.7 mm Hg, respectively, in patients less than 12 years of age on mirabegron at a dose equivalent of MYRBETRIQ 50 mg daily dose in adults. The blood pressure increases were larger in patients less than 8 years of age with mean systolic and diastolic blood pressure increases of 5.9 mm Hg and 2.3 mm Hg, respectively. Ten (24%) patients less than 12 years of age who were normotensive at baseline had at least one blood pressure measured at or above the 95th percentile for age, sex, and stature during Study 9. Stage 1 hypertension, defined as repeated blood pressure measurements at or above the 95th percentile for age, sex, and stature, was sustained in six of these 10 patients (60%) at the end of the study. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of mirabegron. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following events have been reported in association with mirabegron use in worldwide postmarketing experience: Cardiac disorders : atrial fibrillation Gastrointestinal disorders: nausea, constipation, diarrhea Nervous system disorders : dizziness, headache There have been postmarketing reports of confusion, hallucinations, insomnia, and anxiety in patients taking mirabegron. The majority of these patients had pre-existing medical conditions or concomitant medications that may cause confusion, hallucinations, insomnia, and anxiety. A causal relationship between mirabegron and these disorders has not been established. Skin and subcutaneous tissue disorders : angioedema of the face, lips, tongue, and larynx, with or without respiratory symptoms [see Warnings and Precautions ( 5.3 )] ; pruritus Renal and urinary disorders : urinary retention [see Warnings and Precautions ( 5.2 )]
Drug interactions
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. ( 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 ) 7.1 Drugs Metabolized by CYP2D6 Since mirabegron is a moderate CYP2D6 inhibitor, the systemic exposure of drugs metabolized by CYP2D6 enzyme is increased when coadministered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary when mirabegron is coadministered with these drugs, especially with narrow therapeutic index CYP2D6 substrates [see Warnings and Precautions ( 5.4 ) and Clinical Pharmacology ( 12.3 )] . 7.2 Digoxin When given in combination, 100 mg mirabegron increased mean digoxin C max from 1.01 to 1.3 ng/mL (29%) and AUC from 16.7 to 19.3 ng.h/mL (27%). Concomitant administration of 0.25 mg digoxin with a combination of 5 mg solifenacin and 50 mg mirabegron increased digoxin AUC tau and C max by approximately 10% and 14%, respectively. For patients who are initiating a combination of mirabegron and digoxin, the lowest dose for digoxin should initially be considered. Serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect [see Clinical Pharmacology ( 12.3 )] . 7.3 Warfarin The mean C max of S - and R -warfarin was increased by approximately 4% and AUC by approximately 9% when administered as a single dose of 25 mg after multiple doses of 100 mg mirabegron. Following a single dose administration of 25 mg warfarin, mirabegron had no effect on the warfarin pharmacodynamic endpoints such as International Normalized Ratio (INR) and prothrombin time. However, the effect of mirabegron on multiple doses of warfarin and on warfarin pharmacodynamic end points such as INR and prothrombin time has not been fully investigated [see Clinical Pharmacology ( 12.3 )] .
Use in specific populations
8.1 Pregnancy Risk Summary There are no studies with the use of mirabegron in pregnant women or adolescents to inform a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. Mirabegron administration to pregnant animals during organogenesis resulted in reversible skeletal variations (in rats) at 22-fold (via AUC) the maximum recommended human dose (MRHD) of 50 mg/day and decreased fetal body weights (in rabbits) at 14-fold the MRHD. At maternally-toxic exposures in rats (96-fold), decreased fetal weight and increased fetal mortality were observed and, in rabbits (36-fold), cardiac findings (fetal cardiomegaly and fetal dilated aortae) were observed [see Data ] . The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects or miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. Data Animal Data No embryo-fetal lethality or morphological fetal developmental abnormalities were produced in pregnant rats following daily oral administration of mirabegron during the period of organogenesis (Days 7 to 17 of gestation) at 0, 10, 30, 100, or 300 mg/kg, doses which were associated with systemic exposures (AUC) 0, 1, 6, 22, and 96-fold the MRHD. Skeletal variations (wavy ribs, delayed ossification) were observed in fetuses at doses 22-fold the systemic exposure at the MRHD and were reversible during development. Exposures 96-fold the MRHD were maternally-toxic (mortality, decreased body weight gain) and associated with fetal growth reduction. Pregnant rabbits were treated with daily oral doses of mirabegron at 0, 3, 10, or 30 mg/kg/day during the period of organogenesis (Days 6 to 20 of gestation), which resulted in plasma exposures that were 0, 1, 14, or 36-fold the MRHD based on AUC. At 10 mg/kg/day (14-fold the MRHD) and higher, fetal body weights were reduced. At 30 mg/kg/day, maternal toxicity (increased heart rate, mortality, reduced body weight gain, reduced food consumption) occurred, and fetal deaths, fetal cardiomegaly and fetal dilated aortae were observed at systemic exposure levels (AUC) 36-fold the MRHD. In a pre- and postnatal developmental study, rats were treated with daily oral doses of mirabegron at 0, 10, 30, or 100 mg/kg/day (0, 1, 6, or 22-fold the MRHD) from day 7 of gestation until day 20 after birth. Decreased maternal body weight was observed along with decreased pup survival in the first few days after birth (92.7% survival) compared to the control group (98.8% survival), at 100 mg/kg/day (22-fold the MRHD). Pup body weight gain was reduced until postnatal day 7 but not further affected throughout the remainder of the lactation period. In utero and lactational exposure did not affect developmental milestones, behavior, or fertility of offspring. No effects were observed at 30 mg/kg/day. 8.2 Lactation Risk Summary There are no data on the presence of mirabegron in human milk, the effects on the breastfed child, or the effects on milk production. Mirabegron-related material was present in rat milk and in the stomach of nursing pups following administrations of a single 10 mg/kg oral dose of 14 C-labeled mirabegron to lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mirabegron and any potential adverse effects on the breastfed child from mirabegron or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness have been established only for the following pediatric indications: Mirabegron for extended-release oral suspension: Treatment of neurogenic detrusor overactivity (NDO) in pediatric patients 3 years of age and older. The safety and effectiveness of mirabegron in pediatric patients aged 3 years and older have been established for the treatment of neurogenic detrusor overactivity (NDO) and the information on this use is discussed throughout the labeling. Use of mirabegron for this indication is supported by evidence from a 52-week, open-label, baseline-controlled, multicenter, dose titration trial in pediatric patients 3 years of age and older with NDO (Study 9) [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.3 )] . Results showed an improvement from baseline in maximum cystometric (bladder) capacity (MCC) with mirabegron use [see Clinical Studies ( 14.3 )] . The most commonly reported adverse reactions in Study 9 (≥3%) were UTI, nasopharyngitis, constipation, and headache. Increased mean systolic and diastolic blood pressures with use of mirabegron occurred in patients less than 12 years of age with larger increases in patients younger than 8 years of age [see Adverse Reactions ( 6.1 )] . Take mirabegron with food to reduce potential exposure-related risks, such as increased heart rate, as predicted by modeling of vital signs data in Study 9 [see Clinical Pharmacology ( 12.3 )] . 8.6 Renal Impairment Mirabegron have not been studied in patients with End-Stage Renal Disease (eGFR < 15 mL/min/1.73 m 2 ) or patients requiring hemodialysis and, therefore, is not recommended for use in these patient populations. No dose adjustment is necessary in patients with mild or moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m 2 ). In pediatric patients with severe renal impairment, the daily dose of mirabegron should not exceed the recommended starting dose [see Clinical Pharmacology ( 12.3 )] . 8.7 Hepatic Impairment Mirabegron have not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and, therefore, is not recommended for use in this patient population. No dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh Class A).
Pregnancy
8.1 Pregnancy Risk Summary There are no studies with the use of mirabegron in pregnant women or adolescents to inform a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes. Mirabegron administration to pregnant animals during organogenesis resulted in reversible skeletal variations (in rats) at 22-fold (via AUC) the maximum recommended human dose (MRHD) of 50 mg/day and decreased fetal body weights (in rabbits) at 14-fold the MRHD. At maternally-toxic exposures in rats (96-fold), decreased fetal weight and increased fetal mortality were observed and, in rabbits (36-fold), cardiac findings (fetal cardiomegaly and fetal dilated aortae) were observed [see Data ] . The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects or miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. Data Animal Data No embryo-fetal lethality or morphological fetal developmental abnormalities were produced in pregnant rats following daily oral administration of mirabegron during the period of organogenesis (Days 7 to 17 of gestation) at 0, 10, 30, 100, or 300 mg/kg, doses which were associated with systemic exposures (AUC) 0, 1, 6, 22, and 96-fold the MRHD. Skeletal variations (wavy ribs, delayed ossification) were observed in fetuses at doses 22-fold the systemic exposure at the MRHD and were reversible during development. Exposures 96-fold the MRHD were maternally-toxic (mortality, decreased body weight gain) and associated with fetal growth reduction. Pregnant rabbits were treated with daily oral doses of mirabegron at 0, 3, 10, or 30 mg/kg/day during the period of organogenesis (Days 6 to 20 of gestation), which resulted in plasma exposures that were 0, 1, 14, or 36-fold the MRHD based on AUC. At 10 mg/kg/day (14-fold the MRHD) and higher, fetal body weights were reduced. At 30 mg/kg/day, maternal toxicity (increased heart rate, mortality, reduced body weight gain, reduced food consumption) occurred, and fetal deaths, fetal cardiomegaly and fetal dilated aortae were observed at systemic exposure levels (AUC) 36-fold the MRHD. In a pre- and postnatal developmental study, rats were treated with daily oral doses of mirabegron at 0, 10, 30, or 100 mg/kg/day (0, 1, 6, or 22-fold the MRHD) from day 7 of gestation until day 20 after birth. Decreased maternal body weight was observed along with decreased pup survival in the first few days after birth (92.7% survival) compared to the control group (98.8% survival), at 100 mg/kg/day (22-fold the MRHD). Pup body weight gain was reduced until postnatal day 7 but not further affected throughout the remainder of the lactation period. In utero and lactational exposure did not affect developmental milestones, behavior, or fertility of offspring. No effects were observed at 30 mg/kg/day.
Pediatric use
8.4 Pediatric Use The safety and effectiveness have been established only for the following pediatric indications: Mirabegron for extended-release oral suspension: Treatment of neurogenic detrusor overactivity (NDO) in pediatric patients 3 years of age and older. The safety and effectiveness of mirabegron in pediatric patients aged 3 years and older have been established for the treatment of neurogenic detrusor overactivity (NDO) and the information on this use is discussed throughout the labeling. Use of mirabegron for this indication is supported by evidence from a 52-week, open-label, baseline-controlled, multicenter, dose titration trial in pediatric patients 3 years of age and older with NDO (Study 9) [see Adverse Reactions ( 6.1 ), Clinical Studies ( 14.3 )] . Results showed an improvement from baseline in maximum cystometric (bladder) capacity (MCC) with mirabegron use [see Clinical Studies ( 14.3 )] . The most commonly reported adverse reactions in Study 9 (≥3%) were UTI, nasopharyngitis, constipation, and headache. Increased mean systolic and diastolic blood pressures with use of mirabegron occurred in patients less than 12 years of age with larger increases in patients younger than 8 years of age [see Adverse Reactions ( 6.1 )] . Take mirabegron with food to reduce potential exposure-related risks, such as increased heart rate, as predicted by modeling of vital signs data in Study 9 [see Clinical Pharmacology ( 12.3 )] .
Overdosage
Mirabegron has been administered to healthy volunteers at single doses up to 400 mg. At this dose, adverse events reported included palpitations (1 of 6 subjects) and increased pulse rate exceeding 100 beats per minute (bpm) (3 of 6 subjects). Multiple doses of mirabegron up to 300 mg daily for 10 days showed increases in pulse rate and systolic blood pressure when administered to healthy volunteers. Treatment for overdosage should be symptomatic and supportive. In the event of overdosage, pulse rate, blood pressure and ECG monitoring is recommended.
Description
Mirabegron for extended-release oral suspension are beta-3 adrenergic agonists. The chemical name of mirabegron is 2-(2-aminothiazol-4-yl)-N-[4-(2-{[(2R)-2-hydroxy-2- phenylethyl]amino}ethyl)phenyl]acetamide having an molecular formula of C 21 H 24 N 4 O 2 S and a molecular weight of 396.51. The structural formula of mirabegron is: Mirabegron is a white to off white solid. It is soluble in methanol and dimethyl sulfoxide, practically insoluble in water. Each bottle of mirabegron for extended-release oral suspension contains approximately 8.3 g of granules, which contain 830 mg of mirabegron, and the following inactive ingredients: acesulfame potassium, colloidal silicon dioxide, ethyl paraben, hydrochloric acid, hypromellose, mannitol, methyl paraben, simethicone, sodium polystyrene sulfonate, talc, xanthan gum. After reconstituted with 100 mL water, the suspension contains 8 mg/mL of mirabegron. mirabegron-stru
Mechanism of action
12.1 Mechanism of Action 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.
How supplied
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.
Patient information
Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information). Increases in Blood Pressure Inform patients and/or their caregivers that mirabegron may increase blood pressure. Advise patients, especially patients with hypertension, to periodically monitor their blood pressure and report increased measurement to their health care provider [see Warnings and Precautions ( 5.1 )] . Urinary Retention Inform patients and/or their caregivers that MYRBETRIQ may cause urinary retention in adult patients with bladder outlet obstruction and in patients taking muscarinic antagonist medications for the treatment of OAB. Advise patients to contact their physician if they experience these effects while taking MYRBETRIQ [see Warnings and Precautions ( 5.2 )] . Angioedema Inform patients and/or their caregivers that mirabegron may cause angioedema. Advise patients and/or their caregivers to promptly discontinue mirabegron and seek medical attention if angioedema associated with the upper airway swelling occurs as this may be life-threatening [see Warnings and Precautions ( 5.3 )]. Drug Interactions Advise patients to report their use of any other prescription or nonprescription medications or dietary supplements because co-administration with mirabegron may require a dose adjustment and/or increased monitoring of these drugs [see Drug Interactions ( 7 )]. Administration Instructions Mirabegron for Extended-Release Oral Suspension Advise pediatric patients and/or their caregivers to use an appropriate measuring device and instructions for measuring the correct dose of mirabegron for extended-release oral suspension. Instruct patients or their caregivers that patients should take mirabegron for extended-release oral suspension orally within 1 hour after preparation with food once daily and not save the dose for later. The bottle should be shaken for 1 minute each day if the suspension will not be used for 2 or more days. When ready to use, shake the bottle vigorously for 1 minute then let it stand until the foam on top of the suspension is gone (approximately 1 to 2 minutes). Missed Dose Instruct patients and/or their caregivers 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. Manufactured by: Alkem Laboratories Ltd., Mumbai - 400 013, INDIA. Distributed by: Ascend Laboratories, LLC Bedminster, NJ 07921 All other trademarks are the property of their respective owners.
Label text from the FDA structured product label by Ascend Laboratories, LLC (revised May 22, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Mirabegron in 17 products
Mirabegron NDC products (17)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 69238-2860 | Mirabegron 25 mg/1 Tablet, Film Coated, Extended Release | Amneal Pharmaceuticals NY LLC | ANDA |
| 69238-2861 | Mirabegron 50 mg/1 Tablet, Film Coated, Extended Release | Amneal Pharmaceuticals NY LLC | ANDA |
| 67877-890 | Mirabegron 8 mg/mL For Suspension, Extended Release | Ascend Laboratories, LLC | ANDA |
| 71335-2810 | Mirabegron 50 mg/1 Tablet, Film Coated, Extended Release | Bryant Ranch Prepack | ANDA |
| 71335-2809 | Mirabegron 25 mg/1 Tablet, Film Coated, Extended Release | Bryant Ranch Prepack | ANDA |
| 71335-2808 | Mirabegron 50 mg/1 Tablet, Film Coated, Extended Release | Bryant Ranch Prepack | ANDA |
| 71335-2807 | Mirabegron 25 mg/1 Tablet, Film Coated, Extended Release | Bryant Ranch Prepack | ANDA |
| 68180-152 | Mirabegron 50 mg/1 Tablet, Film Coated, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 68180-151 | Mirabegron 25 mg/1 Tablet, Film Coated, Extended Release | Lupin Pharmaceuticals, Inc. | ANDA |
| 67184-0571 | Mirabegron 25 mg/1 Tablet, Film Coated, Extended Release | Qilu Pharmaceutical Co., Ltd. | ANDA |
| 70518-4631 | Mirabegron 25 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-4665 | Mirabegron 50 mg/1 Tablet, Film Coated, Extended Release | REMEDYREPACK INC. | ANDA |
| 70518-4304 | Mirabegron 50 mg/1 Tablet, Extended Release | REMEDYREPACK INC. | ANDA |
| 70771-1752 | Mirabegron 25 mg/1 Tablet, Extended Release | Zydus Lifesciences Limited | ANDA |
| 70771-1753 | Mirabegron 50 mg/1 Tablet, Extended Release | Zydus Lifesciences Limited | ANDA |
| 70710-1159 | Mirabegron 25 mg/1 Tablet, Extended Release | Zydus Pharmaceuticals (USA) Inc. | ANDA |
| 70710-1160 | Mirabegron 50 mg/1 Tablet, Extended Release | Zydus Pharmaceuticals (USA) Inc. | ANDA |
Mirabegron recalls
- D-0745-2026 Aug 12, 2026 · Class II · Ongoing
CGMP: Due to Out of Specification (OOS) result for N-Nitroso Mirabegron impurity.
Frequently asked questions
What is Mirabegron used for?
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.
What are the side effects of Mirabegron?
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… See the full label for the complete list.
Who makes Mirabegron?
Mirabegron is listed by 8 labelers in the FDA NDC directory, including Amneal Pharmaceuticals NY LLC, Ascend Laboratories, LLC, Bryant Ranch Prepack, Lupin Pharmaceuticals, Inc..
Has Mirabegron been recalled?
The FDA enforcement database lists 1 recall for Mirabegron, most recently D-0745-2026 (class ii): CGMP: Due to Out of Specification (OOS) result for N-Nitroso Mirabegron impurity.