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Mirabegron: Drug information

Mirabegron: Drug information
(For additional information see "Mirabegron: Patient drug information" and see "Mirabegron: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Myrbetriq
Brand Names: Canada
  • Myrbetriq
Pharmacologic Category
  • Beta3 Agonist
Dosing: Adult
Overactive bladder

Overactive bladder:

Note: May be used as monotherapy or in combination with an antimuscarinic agent (Ref).

Oral: Initial: 25 mg once daily. May increase to 50 mg once daily after 4 to 8 weeks based on response and tolerability.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

Note: eGFR may be estimated using the MDRD equation for dosage adjustment purposes (manufacturer’s labeling).

eGFR ≥30 mL/minute/1.73 m2: Oral: No dosage adjustment necessary.

eGFR 15 to <30 mL/minute/1.73 m2: Oral: Do not exceed 25 mg once daily.

eGFR <15 mL/minute/1.73 m2: Oral: Not recommended (has not been studied).

Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (large Vd and moderately high protein binding) (Ref):

Oral: Not recommended (has not been studied).

Peritoneal dialysis: Unlikely to be dialyzed (large Vd and relatively high protein binding) (Ref):

Oral: Not recommended (has not been studied).

CRRT: Unlikely to be dialyzed (large Vd and relatively high protein binding) (Ref):

Oral: Not recommended (has not been studied) (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Unlikely to be dialyzed (large Vd and relatively high protein binding) (Ref):

Oral: Not recommended (has not been studied) (Ref).

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate impairment (Child-Pugh class B): Do not exceed 25 mg once daily.

Severe impairment (Child-Pugh class C): Not recommended (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Mirabegron: Pediatric drug information")

Dosage guidance:

Dosage form information: Extended-release tablets and extended-release granules are not bioequivalent and cannot be substituted on a mg:mg basis; do not combine dosage forms to achieve a specific dose.

Neurogenic detrusor overactivity

Neurogenic detrusor overactivity:

Children ≥3 years and Adolescents: Note: Appropriate dosage form dependent on patient weight.

11 to <22 kg: Oral: Granules: Initial: 24 mg once daily; after 4 to 8 weeks of therapy, may increase dose if needed up to a maximum daily dose: 48 mg/day once daily.

22 to <35 kg: Oral: Granules: Initial: 32 mg once daily; after 4 to 8 weeks of therapy, may increase dose if needed up to a maximum daily dose: 64 mg/day once daily.

≥35 kg: Oral:

Granules: Initial: 48 mg once daily; after 4 to 8 weeks of therapy, may increase dose if needed up to a maximum daily dose: 80 mg/day once daily.

Tablets: Initial: 25 mg once daily; after 4 to 8 weeks of therapy, may increase dose if needed up to a maximum daily dose: 50 mg/day once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Children ≥3 years and Adolescents: Oral:

eGFR 30 to 89 mL/minute/1.73 m2: No dosage adjustment necessary (regardless of patient weight or dosage form).

eGFR 15 to 29 mL/minute/1.73 m2:

11 to <22 kg: Granules: Do not exceed 24 mg once daily.

22 to <35 kg: Granules: Do not exceed 32 mg once daily.

≥35 kg:

Granules: Do not exceed 48 mg once daily.

Tablets: Do not exceed 25 mg once daily.

eGFR <15 mL/minute/1.73 m2: Not recommended (has not been studied).

Hemodialysis: Not recommended (has not been studied).

Dosing: Hepatic Impairment: Pediatric

Children ≥3 years and Adolescents: Oral:

Mild impairment (Child-Pugh class A): No dosage adjustment necessary (regardless of weight or dosage form).

Moderate impairment (Child-Pugh class B):

11 to <22 kg: Granules: Do not exceed 24 mg once daily.

22 to <35 kg: Granules: Do not exceed 32 mg once daily.

≥35 kg:

Granules: Do not exceed 48 mg once daily.

Tablets: Do not exceed 25 mg once daily.

Severe impairment (Child-Pugh class C): Not recommended (has not been studied).

Adverse Reactions (Significant): Considerations
Angioedema

Angioedema of the face, lips, tongue, and/or larynx has been reported with use of mirabegron (Ref); mirabegron-associated angioedema may be life-threatening. Angioedema may be reversible following discontinuation of mirabegron (Ref).

Mechanism: Not clearly established; likely nonallergic (ie, bradykinin-mediated) (Ref).

Onset: Varied; cases have occurred hours after the first dose or after multiple doses.

Cardiovascular effects

Dose-related cardiovascular effects have been described with use of mirabegron, including hypertension, tachycardia, and palpitations (Ref). Changes in cardiovascular parameters associated with mirabegron do not appear to confer an increased risk for adverse cardiovascular events (eg, stroke, myocardial infarction) (Ref). Symptoms may improve or resolve following discontinuation (Ref). Exacerbation of preexisting hypertension has been infrequently reported.

Oftentimes, increases in blood pressure and heart rate are not clinically significant (eg, systolic blood pressure increased ~3.5/1.5 mm Hg; heart rate increased <5 beats per minute [bpm] following mirabegron 50 mg) (Ref). In pediatric patients, increases in blood pressure are larger in younger children (ages 3 to <12 years) as compared to older children and adolescents (ages 12 to <18 years). When administered at supratherapeutic doses (ie, 200 mg/day), QTc prolongation was observed (Ref); however, use of therapeutic doses does not appear to increase the risk of QT prolongation (Ref). Mirabegron does not differ with regards to risk of cardiovascular adverse effects when compared to antimuscarinic agents (eg, solifenacin) (Ref).

Mechanism: Dose-related; related to the pharmacologic action. In addition to β3-adrenoreceptor (AR) stimulation, mirabegron stimulates β1-AR at high doses which may result in positive chronotropic effects, including increased systolic blood pressure and heart rate and decreased stroke volume (Ref).

Onset: Varied. Cardiovascular effects were evident during the first month of treatment (Ref); an ascending-dose study in healthy volunteers noted changes in blood pressure and heart rate within 3 hours of administration (Ref). In one trial, palpitations developed between 45 minutes and 10 days of initiation of therapy (Ref).

Risk factors:

• Increased blood pressure:

- Prior history of hypertension (use is not recommended in adult patients with severe uncontrolled hypertension [SBP ≥180 and/or DBP ≥110 mm Hg])

- Younger children (ages 3 to <12 years) as compared to older children and adolescents (ages 12 to <18 years) (use is not recommended in any pediatric patient with severe uncontrolled hypertension ([SBP and/or DBP >99th percentile plus 5 mm Hg for age, sex, and stature])

• QT prolongation:

- History of QT interval prolongation or concomitant medications known to prolong the QT interval (Ref)

Urinary retention

Use of mirabegron may result in urinary retention, especially in patients with bladder outlet obstruction, benign prostatic hyperplasia (BPH), and/or with use of concomitant muscarinic antagonists (eg, solifenacin, tolterodine) (Ref). However, in a pooled 12-week analysis of phase III clinical trials, the incidence of urinary retention was negligible in patients treated with mirabegron and changes in postvoid residual volume (PVR) were similar to placebo (Ref). In addition, patients receiving mirabegron with risk factors for urinary retention (eg, males, presence of lower urinary tract symptoms, concomitant use of antimuscarinic agents) have been shown to have a low rate of urinary retention or changes in PVR (Ref).

Mechanism: Unknown; must also consider the impact of concomitant medications and patient-specific risk factors (Ref).

Risk factors:

• Bladder outlet obstruction

• BPH (Ref)

• History of PVR >200 mL (Ref)

• Concomitant use of antimuscarinic agents (eg, solifenacin)

• Increasing age (eg, risk increases with age ≥40 years) (Ref)

• Males (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%: Cardiovascular: Hypertension (8% to 11%) (table 1)

Mirabegron: Adverse Reaction: Hypertension

Drug (Mirabegron)

Comparator (Active Control)

Placebo

Dose

Indication

Number of Patients (Mirabegron)

Number of Patients (Active Control)

Number of Patients (Placebo)

11%

N/A

8%

25 mg once daily

Overactive bladder

432

N/A

1,380

9%

10%

N/A

50 mg once daily

Overactive bladder

812

812

N/A

8%

N/A

8%

50 mg once daily

Overactive bladder

1,375

N/A

1,380

1% to 10%:

Cardiovascular: Tachycardia (1% to 2%) (table 2)

Mirabegron: Adverse Reaction: Tachycardia

Drug (Mirabegron)

Comparator (Solifenacin Succinate)

Placebo

Dose

Indication

Number of Patients (Mirabegron)

Number of Patients (Solifenacin Succinate)

Number of Patients (Placebo)

2%

0.7%

0.8%

25 mg once daily

Overactive bladder

500

1,288

510

2%

0.7%

0.8%

50 mg once daily

Overactive bladder

500

1,288

510

2%

N/A

0.6%

25 mg once daily

Overactive bladder

432

N/A

1,380

1%

N/A

0.6%

50 mg once daily

Overactive bladder

1,375

N/A

1,380

Gastrointestinal: Abdominal pain (1%), constipation (1% to 3%), diarrhea (2%), xerostomia (3% to 4%)

Genitourinary: Cystitis (2%), urinary tract infection (3% to 6%)

Infection: Influenza (3%)

Nervous system: Dizziness (1% to 3%), headache (2% to 4%)

Neuromuscular & skeletal: Arthralgia (2%), back pain (3%)

Respiratory: Nasopharyngitis (4%), sinusitis (3%)

<1%:

Cardiovascular: Atrial fibrillation, cerebrovascular accident, hypersensitivity angiitis, palpitations

Dermatologic: Genital pruritus, pruritus, skin rash, urticaria

Endocrine & metabolic: Increased gamma-glutamyl transferase, increased lactate dehydrogenase

Gastrointestinal: Abdominal distension, dyspepsia, gastritis

Genitourinary: Bladder pain, vaginal infection

Hematologic & oncologic: Malignant neoplasm of breast, malignant neoplasm of lung, malignant neoplasm of prostate, purpuric rash

Hepatic: Increased serum alanine aminotransferase, increased serum aspartate aminotransferase

Neuromuscular & skeletal: Osteoarthritis

Ophthalmic: Glaucoma

Renal: Nephrolithiasis

Respiratory: Rhinitis

Frequency not defined: Ophthalmic: Blurred vision, dry eye syndrome

Postmarketing:

Dermatologic: Serum sickness-like reaction (Tan 2019)

Gastrointestinal: Nausea

Genitourinary: Urinary retention (Nitti 2014)

Hypersensitivity: Angioedema (Davis 2019)

Nervous system: Anxiety, confusion, hallucination, insomnia

Contraindications

Hypersensitivity to mirabegron or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Severe uncontrolled hypertension (systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg); pregnancy

Warnings/Precautions

Concerns related to adverse effects:

• Angioedema: Immediately discontinue and institute supportive care if the tongue, hypopharynx, or larynx is involved.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment; dosage adjustment is required in patients with moderate hepatic impairment. Use is not recommended in severe hepatic impairment.

• Hypertension: Use with caution if used in patients with controlled and less severe hypertension; use is not recommended in patients with uncontrolled hypertension.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment is required in patients with severe renal impairment. Use is not recommended in ESRD.

Dosage form specific issues:

• Product interchangeability: ER granules and ER tablets are not interchangeable; do not combine products to achieve a total dose. Select appropriate product based on patient's indication and weight; ER granules are not approved for adult use (recommended dose not determined).

Warnings: Additional Pediatric Considerations

Increased blood pressure may occur in patients treated with mirabegron; increases are larger in younger children (ages 3 to <12 years) compared to older children and adolescents (12 to <18 years). Use is not recommended in pediatric patients with severe uncontrolled hypertension (SBP and/or DBP >99th percentile plus 5 mm Hg for age, sex, and stature).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension Reconstituted ER, Oral:

Myrbetriq: 8 mg/mL (100 mL) [contains ethylparaben, methylparaben]

Tablet Extended Release 24 Hour, Oral:

Myrbetriq: 25 mg, 50 mg

Generic Equivalent Available: US

No

Pricing: US

Suspension Reconstituted ER (Myrbetriq Oral)

8 mg/mL (per mL): $2.77

Tablet, 24-hour (Myrbetriq Oral)

25 mg (per each): $18.41

50 mg (per each): $18.41

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet Extended Release 24 Hour, Oral:

Myrbetriq: 25 mg, 50 mg

Administration: Adult

Oral: Administer tablet without regard to food; swallow whole with water; do not chew, divide, or crush.

Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. No IR formulation is available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.

Administration: Pediatric

Oral:

Granules: Administer with food. Before use, shake bottle for 1 minute, then let stand until foam has been dissipated (~1 to 2 minutes). Measure dose using an accurate measuring device; use dose within 1 hour of measuring. If mirabegron will not be used for ≥2 days, bottle should be shaken vigorously for 1 minute each day not used.

Tablets: Administer with food in pediatric patients. Swallow the tablet whole with water; do not chew, divide, or crush.

Missed dose: Administer dose as soon as remembered if ≤12 hours since missed dose; if >12 hours have passed, skip dose and administer next dose at usual time.

Use: Labeled Indications

Neurogenic detrusor overactivity: Treatment of neurogenic detrusor overactivity in pediatric patients ≥3 years of age (granules) and weighing ≥35 kg (tablets).

Overactive bladder: Treatment of overactive bladder in adults with symptoms of urinary frequency, urgency, or urge urinary incontinence as monotherapy or in combination with an antimuscarinic agent (AUA/SUFU [Gormley 2019]).

Metabolism/Transport Effects

Substrate of CYP2D6 (minor), CYP3A4 (minor), OCT1, OCT2, P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (moderate)

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Risk C: Monitor therapy

Amitriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Amitriptyline. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy

Amoxapine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amoxapine. Risk C: Monitor therapy

Amphetamines: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a moderate CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor therapy

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Risk C: Monitor therapy

Atomoxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Atomoxetine. Risk C: Monitor therapy

Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose when treating indications other than major depressive disorder. Risk C: Monitor therapy

Carvedilol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Risk C: Monitor therapy

ClomiPRAMINE: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of ClomiPRAMINE. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy

CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy

Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Mirabegron. Risk C: Monitor therapy

Desipramine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Desipramine. Risk C: Monitor therapy

Deutetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deutetrabenazine. Risk C: Monitor therapy

Dextromethorphan: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Dextromethorphan. Risk C: Monitor therapy

Digoxin: Mirabegron may increase the serum concentration of Digoxin. Management: Consider initiating the lowest dose of digoxin in patients beginning treatment with a combination of digoxin and mirabegron. Monitor digoxin concentrations and adjust the digoxin dose as needed. Risk D: Consider therapy modification

Doxepin (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Systemic). Risk C: Monitor therapy

Doxepin (Topical): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Doxepin (Topical). Risk C: Monitor therapy

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination

Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider therapy modification

Fesoterodine: Mirabegron may enhance the adverse/toxic effect of Fesoterodine. Mirabegron may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy

Flecainide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Flecainide. Risk C: Monitor therapy

Haloperidol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy

Iboga: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Iboga. Risk C: Monitor therapy

Iloperidone: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Iloperidone. Risk C: Monitor therapy

Imipramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Imipramine. Concentrations of desipramine may be increased. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Imipramine. Risk C: Monitor therapy

Indoramin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. Risk C: Monitor therapy

Lofepramine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor therapy

Mequitazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Mequitazine. Risk X: Avoid combination

Methadone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Methadone. Risk C: Monitor therapy

Metoclopramide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoclopramide. Risk C: Monitor therapy

Metoprolol: Mirabegron may diminish the antihypertensive effect of Metoprolol. Mirabegron may increase the serum concentration of Metoprolol. Risk C: Monitor therapy

Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy

Nortriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nortriptyline. Risk C: Monitor therapy

Oliceridine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Oliceridine. Risk C: Monitor therapy

Olmutinib: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy

PARoxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of PARoxetine. Risk C: Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy

Perphenazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Perphenazine. Risk C: Monitor therapy

Pimozide: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk C: Monitor therapy

Pitolisant: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pitolisant. Risk C: Monitor therapy

Propafenone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Risk C: Monitor therapy

Propranolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Risk C: Monitor therapy

Protriptyline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Protriptyline. Risk C: Monitor therapy

RisperiDONE: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy

Sertindole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Sertindole. Risk C: Monitor therapy

Solifenacin: Mirabegron may enhance the adverse/toxic effect of Solifenacin. Specifically, the risk of acute urinary retention may be enhanced. Risk C: Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives to the use of moderate CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with reduced clinical effectiveness of tamoxifen. Risk D: Consider therapy modification

Tamsulosin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy

Tetrabenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Risk C: Monitor therapy

Thioridazine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Thioridazine. Risk X: Avoid combination

Timolol (Systemic): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Timolol (Systemic). Risk C: Monitor therapy

TraMADol: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Moderate) may increase the serum concentration of TraMADol. Risk C: Monitor therapy

Trimipramine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Trimipramine. Risk C: Monitor therapy

Valbenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Valbenazine. Risk C: Monitor therapy

Vortioxetine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Vortioxetine. Risk C: Monitor therapy

Zuclopenthixol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy

Pregnancy Considerations

Adverse effects have been observed in some animal reproduction studies.

Breastfeeding Considerations

It is not known if mirabegron is present in breast milk. According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Monitor BP at baseline and then periodically during therapy (especially in patients with preexisting hypertension, even if controlled); postvoid residual urine volume at baseline and as clinically indicated thereafter (AUA [Lerner 2021]); signs and symptoms of urinary retention.

Mechanism of Action

Mirabegron, a beta-3 adrenergic receptor agonist, activates beta-3 adrenergic receptors in the bladder resulting in relaxation of the detrusor smooth muscle during the urine storage phase, thus increasing bladder capacity. At usual doses, mirabegron is believed to display selectivity for the beta-3 adrenergic receptor subtype compared to its affinity for the beta-1 and -2 adrenoceptor subtypes. Data have shown that beta-adrenoceptors, predominately the beta-3 subtype, mediate detrusor smooth muscle tone and promote the storage function of the human bladder.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Adults: Overactive bladder: Efficacy is seen within 8 weeks; steady state achieved within 7 days.

Absorption:

Adults: Tablets: No clinically significant differences with fed vs fasting administration.

Children ≥3 years and Adolescents:

Granules: Fasting AUC increased by 170% and Cmax increased by 80% compared to fed state.

Tablets: Fasting AUC increased by 120% compared to fed state.

Distribution:

Pediatric patients: Vz/F: Large mean range reported: 4,895 to 13,726 L.

Adults: Vss: ~1,670 L (following IV administration).

Protein binding: ~71%; binds mainly to albumin and alpha1-acid glycoprotein.

Metabolism: Extensive metabolism via multiple pathways (eg, dealkylation, oxidation, glucuronidation, amide hydrolysis) via multiple enzymes (eg, UGT, esterase, CYP3A4, CYP2D6); two major pharmacologically inactive metabolites produced.

Bioavailability: 29% to 35% (following 25 mg and 50 mg oral dosing, respectively); bioavailability is dose-dependent; Cmax and AUC are higher in females compared to males.

Half-life elimination:

Pediatric patients: ~26 to 31 hours.

Adults: ~50 hours.

Time to peak:

Children ≥3 years and Adolescents: Granules, Tablets: Fed-state: Median: 4 to 5 hours (single dose), 3 to 4 hours (steady-state; predicted).

Adults: Tablets: ~3.5 hours.

Excretion: Urine (radiolabeled drug: 55%; unchanged drug: ~25%); feces (radiolabeled drug: 34%; unchanged drug: 0%).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Following single dose administration of mirabegron 100 mg in adults with mild renal impairment (eGFR 60 to 89 mL/minute/1.73 m2 as estimated by modification of diet in renal disease), mean mirabegron Cmax and AUC were increased by 6% and 31% relative to adults with normal renal function. In adults with moderate renal impairment (eGFR 30 to 59 mL/minute/1.73 m2), Cmax and AUC were increased by 23% and 66%, respectively. In adults with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2), mean Cmax and AUC values were 92% and 118% higher compared with healthy subjects with normal renal function.

Hepatic impairment: Following single-dose administration of mirabegron 100 mg in adults with mild hepatic impairment (Child-Pugh class A), mean mirabegron Cmax and AUC were increased by 9% and 19% relative to adults with normal hepatic function. In adults with moderate hepatic impairment (Child-Pugh class B), mean Cmax and AUC values were 175% and 65% higher.

Sex: The Cmax and AUC of mirabegron were ~40% to 50% higher in adult females than in adult males. When corrected for differences in body weight, the mirabegron systemic exposure is 20% to 30% higher in adult females compared with adult males.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Betmiga;
  • (AR) Argentina: Urgistat | Uroval;
  • (AT) Austria: Betmiga;
  • (AU) Australia: Betmiga;
  • (BD) Bangladesh: Betmira er | Iragon | Mirabeg | Mirader | Mirasol xr | Utromeg;
  • (BE) Belgium: Betmiga;
  • (BG) Bulgaria: Betmiga;
  • (BR) Brazil: Myrbetric;
  • (CH) Switzerland: Betmiga;
  • (CO) Colombia: Betmiga | Myrbetric;
  • (CZ) Czech Republic: Betmiga;
  • (DE) Germany: Betmiga;
  • (DO) Dominican Republic: Urgistat;
  • (EE) Estonia: Betmiga;
  • (EG) Egypt: Atobegron | Betmiga | Bladogra | Uribladon xr;
  • (ES) Spain: Betmiga;
  • (FI) Finland: Betmiga;
  • (FR) France: Betmiga;
  • (GB) United Kingdom: Betmiga;
  • (GR) Greece: Betmiga;
  • (HK) Hong Kong: Betmiga;
  • (HR) Croatia: Betmiga;
  • (HU) Hungary: Betmiga;
  • (ID) Indonesia: Betmiga;
  • (IE) Ireland: Betmiga;
  • (IN) India: Betmiga | Bladmir | Exena | Megatas | Mira | Mirabet | Mirabig | Mirago | Mirakem | Miranix | Mirasmart | Miratas | Mirbeg | Vesibeta;
  • (IT) Italy: Betmiga;
  • (JO) Jordan: Betmiga;
  • (JP) Japan: Betanis;
  • (KE) Kenya: Betmiga;
  • (KR) Korea, Republic of: Betagron | Betmiga | Br mirabegron ir | Gitamiga sr | Liberon | Mira q ron | Mirabe sr | Mirabeg sr | Miraron | Ql pharma mirabegron | Rabegron | Rablon sr | Selebeta sr | Tamiga;
  • (KW) Kuwait: Betmiga;
  • (LB) Lebanon: Betmiga;
  • (LT) Lithuania: Betmiga;
  • (LU) Luxembourg: Betmiga;
  • (LV) Latvia: Betmiga;
  • (MA) Morocco: Betmiga;
  • (MX) Mexico: Myrbetric;
  • (MY) Malaysia: Betmiga;
  • (NL) Netherlands: Betmiga;
  • (NO) Norway: Betmiga;
  • (PE) Peru: Myrbetric;
  • (PH) Philippines: Betmiga;
  • (PK) Pakistan: Begron | Mibega | Mirabet | Mirexia xr;
  • (PL) Poland: Betmiga;
  • (PR) Puerto Rico: Myrbetriq;
  • (PT) Portugal: Betmiga;
  • (RO) Romania: Betmiga;
  • (RU) Russian Federation: Betmiga;
  • (SA) Saudi Arabia: Betmiga;
  • (SE) Sweden: Betmiga;
  • (SG) Singapore: Betmiga;
  • (SI) Slovenia: Betmiga;
  • (SK) Slovakia: Betmiga;
  • (TH) Thailand: Betmiga;
  • (TR) Turkey: Betmiga;
  • (TW) Taiwan: Betmiga;
  • (UA) Ukraine: Betmiga;
  • (ZA) South Africa: Betmiga
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