Myrbetriq - Drug Monograph

Introduction

Myrbetriq (mirabegron) is a prescription medication approved by the FDA in 2012 for the treatment of overactive bladder (OAB) syndrome. It represents the first in a new class of medications called beta-3 adrenergic receptor agonists, offering an alternative mechanism of action to traditional antimuscarinic agents for OAB management.

Mechanism of Action

Mirabegron works as a selective beta-3 adrenergic receptor agonist. It stimulates beta-3 adrenergic receptors in the detrusor smooth muscle of the bladder, which leads to:

• Bladder relaxation during the storage phase
• Increased bladder capacity
• Reduction in involuntary detrusor contractions
• Decreased urinary urgency and frequency

Unlike antimuscarinic agents, mirabegron does not affect muscarinic receptors, resulting in a different side effect profile with potentially fewer anticholinergic effects.

Indications

FDA-approved indications:

• Treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency

Off-label uses (not FDA-approved):

• Neurogenic detrusor overactivity
• Pediatric voiding dysfunction (limited evidence)

Dosage and Administration

• Initial dose: 25 mg once daily
• May increase to 50 mg once daily after 4-8 weeks based on efficacy and tolerability

• Oral administration with water
• Should be swallowed whole; do not crush, chew, or divide tablets
• May be taken with or without food

• Renal impairment:

- Mild to moderate (CrCl 30-89 mL/min): No dosage adjustment necessary - Severe (CrCl 15-29 mL/min): Maximum dose 25 mg daily - End-stage renal disease (CrCl <15 mL/min): Not recommended

• Hepatic impairment:

- Mild to moderate (Child-Pugh A and B): Maximum dose 25 mg daily - Severe (Child-Pugh C): Not recommended

• Geriatric patients: No dosage adjustment required based on age alone
• Pediatric patients: Safety and effectiveness not established

Pharmacokinetics

• Oral bioavailability: approximately 29-35%
• Tmax: approximately 3.5 hours
• Food does not significantly affect absorption

• Protein binding: approximately 71%
• Steady-state concentrations reached within 7 days
• Volume of distribution: approximately 1670 L

• Primarily metabolized via multiple pathways including:

- Hydrolysis (urease-mediated) - Glucuronidation (UGT2B7, UGT1A3) - Oxidation (CYP2D6, CYP3A4)

• Multiple metabolites, most inactive

• Half-life: approximately 50 hours
• Excretion: primarily urine (55%) and feces (34%)
• Less than 5% excreted unchanged in urine

Contraindications

• Known hypersensitivity to mirabegron or any component of the formulation
• Uncontrolled hypertension (due to potential blood pressure effects)
• Severe hepatic impairment (Child-Pugh Class C)
• End-stage renal disease (CrCl <15 mL/min) or requiring dialysis
• Concomitant use with strong CYP2D6 inhibitors in patients with pre-existing hypertension or hepatic/renal impairment

Warnings and Precautions

• May increase blood pressure; monitor regularly
• Use with caution in patients with hypertension
• Consider alternative therapy in uncontrolled hypertension

• Use with caution in patients with bladder outlet obstruction
• May increase risk of urinary retention

• Rare cases reported; discontinue immediately if angioedema occurs

• Avoid use in patients with known QT prolongation
• Use with caution with other drugs that prolong QT interval

• Pregnancy Category C: Use only if potential benefit justifies potential risk
• Not recommended during breastfeeding

Drug Interactions

• Increased mirabegron exposure
• Examples: paroxetine, bupropion, fluoxetine, quinidine
• Monitor for increased adverse effects

• Mirabegron may increase concentrations of CYP2D6 substrates
• Examples: metoprolol, desipramine, dextromethorphan
• Monitor for substrate-specific effects

• May increase digoxin concentrations
• Monitor digoxin levels and clinical response

• Possible increased INR; monitor coagulation parameters

Adverse Effects

• Hypertension (11.5%)
• Nasopharyngitis (4.2%)
• Urinary tract infection (4.0%)
• Headache (3.9%)
• Constipation (2.3%)

• Tachycardia
• Angioedema
• Urinary retention
• Increased intraocular pressure
• QT interval prolongation

Monitoring Parameters

• Blood pressure
• Heart rate
• Renal function (serum creatinine, CrCl)
• Hepatic function (LFTs)
• Medication review for potential interactions

• Blood pressure at regular intervals
• Symptom assessment (voiding diary)
• Adverse effect monitoring
• Renal and hepatic function in impaired patients
• OAB symptom improvement

Patient Education

• Take once daily with water
• Swallow tablet whole; do not crush or chew
• May take with or without food
• If missed dose, take as soon as remembered unless close to next dose

• Bladder training exercises
• Pelvic floor muscle exercises (Kegels)
• Fluid management strategies
• Dietary modifications (avoid bladder irritants)

• Report any swelling of face, lips, or tongue immediately
• Monitor blood pressure regularly
• Report rapid heartbeat, dizziness, or vision changes
• Inform all healthcare providers of Myrbetriq use
• Notify provider if pregnancy is planned or occurs

• Improvement may take several weeks
• Maximum benefit may require 8-12 weeks
• Report lack of improvement or worsening symptoms

References

1. FDA Prescribing Information: Myrbetriq (mirabegron). Revised 2022. 2. Chapple CR, et al. Mirabegron in overactive bladder: a review of efficacy, safety, and tolerability. Neurourol Urodyn. 2014;33(1):17-30. 3. Nitti VW, et al. Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies. Int J Clin Pract. 2013;67(7):619-632. 4. American Urological Association. Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline (2019). 5. Krauwinkel W, et al. Pharmacokinetic properties of mirabegron, a β3-adrenoceptor agonist: results from two phase I, randomized, multiple-dose studies in healthy young and elderly men and women. Clin Ther. 2012;34(10):2144-2160. 6. Rosa GM, et al. Cardiovascular safety of β3-adrenoceptor agonists for the treatment of patients with overactive bladder syndrome. Eur Urol. 2016;69(2):311-323.