What is the appropriate dosing, contraindications, and adverse effects of mirabegron (Mirabefron) for treating overactive bladder?

Mirabegron for Overactive Bladder: Dosing, Contraindications, and Adverse Effects

Start mirabegron at 25 mg orally once daily, increase to 50 mg after 4–8 weeks if needed, and always combine with behavioral therapy (bladder training, pelvic floor exercises, fluid management) as first-line treatment. 1

Dosing Algorithm

Standard Adult Dosing

• Initial dose: 25 mg once daily 1
• Titration: Increase to 50 mg once daily after 4–8 weeks if symptom control is inadequate 1
• Maximum dose: 50 mg once daily 1
• Efficacy is typically evident by week 4, with sustained benefits throughout treatment 2, 3

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

Special Populations

• Elderly patients (≥65 years) with multiple comorbidities: 25 mg once daily is particularly effective and safe as a starting dose 4, 5
• Frail elderly patients (mobility deficits, weight loss, weakness, cognitive impairment): Use extreme caution with all OAB medications due to narrower therapeutic index, but mirabegron is preferred over antimuscarinics because it does not increase cognitive impairment risk 6

Contraindications

Absolute Contraindications

• Severe uncontrolled hypertension 4
• Severe hepatic impairment (Child-Pugh Class C) 1
• End-stage renal disease (eGFR <15 mL/min/1.73 m²) or dialysis 1

Key Advantage Over Antimuscarinics

Mirabegron can be safely used in patients with narrow-angle glaucoma, history of urinary retention, or impaired gastric emptying—all of which are contraindications to antimuscarinic agents. 6 This is because mirabegron lacks anticholinergic effects and works through β3-adrenergic receptor agonism rather than muscarinic receptor blockade.

Adverse Effects Profile

Most Common Adverse Events

The most frequently reported adverse events include: 4, 7, 2

• Hypertension (most common)
• Urinary tract infections
• Headache
• Nasopharyngitis

Cardiovascular Effects

• Dose-dependent increases in systolic blood pressure can occur 4
• Blood pressure monitoring is mandatory, especially during initial treatment and in patients with pre-existing hypertension 4
• Regular monitoring should continue throughout therapy 4

Anticholinergic Side Effects (Notably Absent)

Mirabegron has a markedly superior tolerability profile compared to antimuscarinics, with dry mouth incidence similar to placebo (0.5–2.1% vs 1.5% for placebo) and three- to fivefold lower than tolterodine 4 mg. 2, 3 This represents a major clinical advantage, as dry mouth is the most common reason for antimuscarinic discontinuation. 2

• Dry mouth: 0.5–2.1% (comparable to placebo) 3
• Constipation: Significantly lower than antimuscarinics 6, 8
• Cognitive impairment: No increased risk (unlike antimuscarinics) 6

Urinary Retention Risk

• Mirabegron does not cause urinary retention through anticholinergic mechanisms 6
• However, in elderly men, assess for bladder outlet obstruction (post-void residual ≥250 mL or maximum flow rate <10 mL/s) before initiating therapy 6
• If obstruction is present, start an α-blocker first rather than mirabegron monotherapy 6

Critical Monitoring Parameters

Before Initiating Therapy

• Baseline blood pressure measurement 4
• In men: Assess post-void residual volume to exclude bladder outlet obstruction 4, 6
• Renal function (eGFR) and hepatic function tests 1

During Treatment

• Regular blood pressure monitoring, especially in the first 4–8 weeks 4
• Re-evaluate lower urinary tract symptoms and post-void residual volume periodically 4
• Discontinue if worsening voiding symptoms or deteriorating urinary stream develops 4

Combination Therapy Strategy

For patients with inadequate response to mirabegron 25–50 mg monotherapy after 6 months, add solifenacin 5 mg once daily. 4, 6 The SYNERGY trials provide the strongest evidence for this specific combination, demonstrating improved efficacy without significant additional safety concerns. 4, 6

• Validated regimens: mirabegron 25 mg + solifenacin 5 mg OR mirabegron 50 mg + solifenacin 5 mg 4
• Combination therapy is superior to monotherapy for reducing incontinence episodes and micturitions 6
• Adverse events (dry mouth, constipation, dyspepsia) are slightly increased but remain acceptable 6

Common Pitfalls to Avoid

• Never prescribe mirabegron without concurrent behavioral therapy (bladder training, pelvic floor exercises, fluid management)—behavioral interventions are as effective as medications and must be first-line treatment 6
• Do not fail to monitor blood pressure, especially in hypertensive patients 4
• Do not overlook bladder outlet obstruction screening in elderly men before starting therapy 4, 6
• Do not discontinue after inadequate response without first attempting dose escalation to 50 mg or adding combination therapy with solifenacin 4, 6
• Do not use in severe hepatic impairment or end-stage renal disease 1

Long-Term Safety

Mirabegron has demonstrated sustained safety and efficacy for up to 12 months in clinical trials, with no new safety concerns emerging with extended use. 4, 7, 2 The SYNERGY II trial specifically evaluated 12-month outcomes, supporting long-term use. 4