What is the appropriate dosing, contraindications, monitoring, and precautions for mirabegron in adults with overactive bladder, including elderly patients or those with moderate renal or hepatic impairment?

Mirabegron Dosing and Management for Overactive Bladder

Dosing Recommendations

Start mirabegron at 25 mg orally once daily, and increase to 50 mg once daily after 4-8 weeks if needed for symptom control. 1

Standard Adult Dosing

• Initial dose: 25 mg once daily 1
• Titration: May increase to 50 mg once daily after 4-8 weeks 1
• Maximum dose: 50 mg once daily 1
• Administration: Swallow tablets whole with water; do not chew, divide, or crush; may take with or without food 1

Dosing in Special Populations

Renal Impairment:

• eGFR 30-89 mL/min/1.73 m²: Start 25 mg, maximum 50 mg daily 2, 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

Hepatic Impairment:

• Child-Pugh Class A (mild): Start 25 mg, maximum 50 mg daily 2, 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

Elderly Patients (≥65 years):

• Mirabegron 25 mg is particularly effective and safe in older patients with multiple comorbidities 2, 3
• Standard dosing applies, but 25 mg may provide adequate symptom control without requiring titration 3
• Baseline hypertension and diabetes are more frequent in this population, requiring closer monitoring 4

Contraindications

Absolute Contraindications:

• Hypersensitivity to mirabegron or any inactive ingredients 1
• Severe uncontrolled hypertension 3, 1

Relative Contraindications/Use with Caution:

• Bladder outlet obstruction (risk of urinary retention) 1
• Concurrent use with muscarinic antagonists (increased urinary retention risk) 1

Monitoring Requirements

Blood Pressure Monitoring

Periodically monitor blood pressure, especially during initial treatment and in hypertensive patients, as mirabegron causes dose-dependent blood pressure increases. 2, 3, 1

• Monitor at baseline and regularly during treatment 2
• Particular attention needed in patients with pre-existing hypertension 3
• Hypertension is one of the most common adverse events (>2%) 2, 1

Urinary Function Monitoring

• Regular re-evaluation of lower urinary tract symptoms and post-void residual volume, especially in men 3
• Advise patients to discontinue if worsening voiding symptoms or deteriorating urinary stream occurs after initiation 3
• Monitor for urinary retention, particularly in patients with bladder outlet obstruction or those on antimuscarinics 1

Laboratory and Other Monitoring

• No routine laboratory monitoring required beyond standard clinical assessment 2
• Monitor for signs of angioedema (face, lips, tongue, larynx) 2, 1

Common Adverse Events

Most frequently reported (>2%):

• Hypertension 2, 1, 4
• Urinary tract infection 2, 1, 4
• Headache 2, 1, 4
• Nasopharyngitis 1, 4, 5

Key Safety Advantage:

• Dry mouth incidence similar to placebo (0.5-2.1%) and 3-5 fold lower than tolterodine 6, 5
• This represents a major advantage over antimuscarinics, as dry mouth is the most common reason for treatment discontinuation 6

Serious but Rare Adverse Effects

• Angioedema of face, lips, tongue, and/or larynx 2, 1
• Cardiac arrhythmias 2
• Kidney stones 2
• Serious skin reactions 2

Important Drug Interactions

CYP2D6 Substrates:

• Mirabegron is a moderate CYP2D6 inhibitor 1
• When used with CYP2D6-metabolized drugs (especially narrow therapeutic index drugs), appropriate monitoring and dose adjustment may be necessary 1

Digoxin:

• When initiating mirabegron with digoxin, use the lowest digoxin dose and monitor serum concentrations 1
• Titrate digoxin to desired clinical effect based on monitoring 1

Combination Therapy Considerations

For patients inadequately responding to monotherapy after 6 months:

• Consider combination with solifenacin 5 mg once daily 2, 3
• Two validated regimens: mirabegron 25 mg + solifenacin 5 mg OR mirabegron 50 mg + solifenacin 5 mg 2, 3
• Combination shows superior efficacy for reducing incontinence episodes, urgency episodes, and nocturia compared to either monotherapy 2
• Do not use combination therapy as first-line treatment; reserve for patients refractory to monotherapy 2
• Combination increases rates of dry mouth, constipation, dyspepsia, and urinary retention compared to monotherapy 2
• No pharmacokinetic interactions between solifenacin and mirabegron, allowing safe concurrent use without dose adjustments 2

Clinical Efficacy

Mirabegron demonstrates significant improvements as early as week 4 and sustained throughout treatment:

• Number needed to treat (NNT) for continence: 12 7
• Number needed to treat (NNT) for urinary incontinence improvement: 9 7
• Significant reductions in micturition frequency, urgency incontinence, urgency episodes, and nocturia 4, 6, 5
• Increased voided volume per micturition 6, 5
• Improved health-related quality of life 6, 8

Key Clinical Pitfalls to Avoid

• Do not crush, chew, or divide extended-release tablets 1
• Do not skip blood pressure monitoring, especially in hypertensive patients 2, 3
• Do not ignore worsening voiding symptoms after initiation—discontinue if this occurs 3
• Do not use in severe uncontrolled hypertension 1
• Do not exceed maximum doses in renal or hepatic impairment 1
• Avoid compounding anticholinergic burden in elderly patients already on anticholinergic medications—mirabegron is preferred in this scenario 7