What are the uses and dosing guidelines for Mirabegron (Beta-3 adrenergic agonist)?

Mirabegron Uses and Dosing

FDA-Approved Indications

Mirabegron is a beta-3 adrenergic agonist FDA-approved for two specific indications: overactive bladder (OAB) in adults with symptoms of urge urinary incontinence, urgency, and urinary frequency, and neurogenic detrusor overactivity (NDO) in pediatric patients aged 3 years and older weighing 35 kg or more. 1

Dosing Guidelines

Adult Overactive Bladder

• Start with 25 mg orally once daily, then increase to 50 mg once daily after 4-8 weeks if needed 1
• The 50 mg dose demonstrates superior efficacy with significant improvements in micturition frequency, incontinence episodes, and urgency as early as week 4 of treatment 2, 3
• Tablets should be swallowed whole with water (do not chew, divide, or crush) and can be taken with or without food 1

Pediatric Neurogenic Detrusor Overactivity (≥35 kg)

• Use the same dosing as adults: start 25 mg once daily, increase to 50 mg after 4-8 weeks if needed 1
• Pediatric patients must take tablets with food (unlike adults who can take with or without food) 1

Dose Adjustments for Renal Impairment

• eGFR 30-89 mL/min/1.73 m²: Start 25 mg, maximum 50 mg daily 1
• eGFR 15-29 mL/min/1.73 m²: Start 25 mg, maximum 25 mg daily (do not increase) 1
• eGFR <15 mL/min/1.73 m² or dialysis: Not recommended 1

Dose Adjustments for Hepatic Impairment

• Child-Pugh Class A (mild): Start 25 mg, maximum 50 mg daily 1
• Child-Pugh Class B (moderate): Start 25 mg, maximum 25 mg daily (do not increase) 1
• Child-Pugh Class C (severe): Not recommended 1

Clinical Efficacy

Monotherapy Benefits

• Mirabegron 50 mg and 100 mg produce dose-dependent reductions in micturition frequency (2.1-2.2 episodes/24h vs 1.4 with placebo), with improvements evident by week 4 and maintained throughout 12-month treatment 2, 3
• Significant improvements occur in incontinence episodes, urgency episodes, volume voided per micturition, and nocturia compared to placebo 4
• The 25 mg dose is particularly effective and safe in older patients (≥65 years) with multiple comorbidities 5, 6

Combination Therapy

For patients with inadequate response to monotherapy, combination with solifenacin 5 mg provides superior efficacy compared to either drug alone. 7, 8

• Mirabegron 50 mg + solifenacin 5 mg is statistically superior to both monotherapies for reducing urinary incontinence episodes, urgency episodes, and nocturia 7, 5
• Effect sizes for combination therapy (0.65-0.95) exceed those of monotherapy (0.36-0.56 for various measures) 7
• The SYNERGY trials demonstrated this combination's safety over 12 months, though treatment-emergent adverse events were slightly higher (49%) than monotherapy (41-44%) 7

Safety Profile and Monitoring

Common Adverse Events

• Most frequent adverse events (>2% and exceeding placebo) are hypertension, nasopharyngitis, urinary tract infection, and headache 1, 2
• Dry mouth incidence is similar to placebo and 3-5 fold less than tolterodine ER 4 mg, making mirabegron valuable for patients who discontinued antimuscarinics due to this side effect 2

Critical Monitoring Requirements

• Monitor blood pressure periodically, especially in hypertensive patients and during initial treatment 6, 1
• Mirabegron is not recommended in severe uncontrolled hypertension 1
• For men with lower urinary tract symptoms, regularly re-evaluate symptoms and post-void residual volume 6
• Discontinue if worsening voiding symptoms or urinary stream occurs after initiation 6

Important Warnings

• Risk of urinary retention in patients with bladder outlet obstruction or those taking antimuscarinic drugs concomitantly—use with caution 1
• Angioedema of face, lips, tongue, and/or larynx has been reported 1
• Contraindicated in patients with hypersensitivity to mirabegron or any inactive ingredients 1

Drug Interactions

• Mirabegron is a CYP2D6 inhibitor—when used with drugs metabolized by CYP2D6 (especially narrow therapeutic index drugs), appropriate monitoring and dose adjustment may be necessary 1
• Propensity for drug interactions is generally low due to multiple metabolic and excretory pathways 9

Missed Dose Instructions

• Take missed doses as soon as remembered, unless more than 12 hours have passed 1
• If more than 12 hours have passed, skip the missed dose and take the next dose at the usual time 1