How should mirabegron be dosed and monitored in adults with overactive bladder, particularly in the setting of renal impairment or uncontrolled hypertension, and what are its common adverse effects, drug interactions, and alternative therapies?

Mirabegron Dosing and Monitoring in Overactive Bladder

Standard Dosing

Start mirabegron at 25 mg orally once daily, then increase to 50 mg once daily after 4–8 weeks if symptom control remains inadequate. 1, 2

• Efficacy becomes evident as early as week 4, with sustained benefits throughout treatment. 1, 3
• The 50 mg dose demonstrates superior efficacy compared to 25 mg for reducing incontinence episodes, urgency, and micturition frequency. 3, 4

Dosing in Renal Impairment

For patients with eGFR 30–89 mL/min/1.73 m², start at 25 mg daily with a maximum dose of 50 mg daily. 2

• Mirabegron exposure (AUC) increases by 31%, 66%, and 118% in mild, moderate, and severe renal impairment, respectively. 5
• Peak concentrations (Cmax) rise by 6%, 23%, and 92% across these same categories. 5
• Despite increased exposure, the pharmacokinetic overlap with healthy subjects is substantial, and changes in mild-to-moderate impairment are unlikely to be clinically significant. 5
• Mirabegron is contraindicated in severe renal impairment (eGFR <30 mL/min/1.73 m²) due to the 118% increase in drug exposure. 5

Dosing in Hepatic Impairment

For patients with Child-Pugh Class A (mild hepatic impairment), start at 25 mg daily with a maximum dose of 50 mg daily. 2

• Mirabegron exposure increases by 19% and 65% in mild and moderate hepatic impairment, respectively. 5
• Peak concentrations increase by 9% in mild impairment but 175% in moderate impairment. 5
• Mirabegron is contraindicated in moderate-to-severe hepatic impairment (Child-Pugh Class B or C) due to the marked increase in Cmax. 5

Management in Uncontrolled Hypertension

Mirabegron is contraindicated in patients with severe uncontrolled hypertension. 1

• Monitor blood pressure periodically, especially during the initial treatment phase, as mirabegron causes dose-dependent increases in systolic blood pressure. 1, 2
• Hypertension is one of the most common adverse events (>2% incidence) reported with mirabegron. 2, 3
• For patients with controlled hypertension, mirabegron can be used safely with appropriate blood pressure monitoring. 1

Common Adverse Effects

The most frequently reported adverse events include:

• Hypertension, urinary tract infection, headache, and nasopharyngitis (each occurring in >2% of patients). 1, 2, 3
• Dry mouth occurs at rates similar to placebo—three to fivefold lower than tolterodine extended-release 4 mg—making mirabegron particularly valuable for patients who discontinued antimuscarinics due to this side effect. 3, 6
• Rare but serious adverse effects include angioedema (face, lips, tongue, larynx), cardiac arrhythmias, kidney stones, and serious skin reactions. 2

Monitoring Requirements

Implement the following monitoring protocol:

• Blood pressure: Check at baseline and periodically during treatment, with heightened vigilance in hypertensive patients and during the first 8 weeks. 1, 2
• Post-void residual (PVR) volume: Assess in male patients or those with obstructive symptoms, history of urinary retention, or neurologic diagnoses before starting therapy. 1, 7
• Discontinue mirabegron if patients develop worsening voiding symptoms or deteriorating urinary stream after initiation. 1
• Re-evaluate lower urinary tract symptoms regularly, particularly in men who may be prone to voiding dysfunction. 1

Drug Interactions

Mirabegron has minimal clinically significant drug interactions:

• Co-administration with solifenacin does not alter the pharmacokinetics of either drug, allowing safe concurrent use without dose adjustments. 2
• Protein binding (~71%) is not altered by renal or hepatic impairment. 5

Alternative Therapies

Behavioral Therapies (First-Line)

All patients must begin with behavioral interventions before or alongside pharmacotherapy, as these approaches demonstrate efficacy equal to antimuscarinic medications. 7

• Bladder training, pelvic floor muscle training, and fluid management should be offered to all patients. 7
• Weight loss in obese patients reduces incontinence episodes by up to 47%. 7

Antimuscarinic Alternatives (Second-Line)

If mirabegron is contraindicated or not tolerated, consider the following antimuscarinics:

• Tolterodine extended-release 4 mg once daily offers comparable efficacy to immediate-release formulations with better tolerability and fewer anticholinergic side effects. 7, 6
• Solifenacin 5 mg once daily is effective and particularly useful if combination therapy becomes necessary later. 2, 7
• Fesoterodine provides superior efficacy to tolterodine in patients ≥80 years (number needed to benefit = 18 for continence). 7
• Beta-3 agonists like mirabegron are typically preferred before antimuscarinics due to lower cognitive risk, especially in elderly patients or those with cognitive concerns. 7

Combination Therapy

For patients with inadequate response to mirabegron 25–50 mg monotherapy after 6 months, add solifenacin 5 mg once daily. 1, 2

• The combination of mirabegron 25 mg or 50 mg plus solifenacin 5 mg demonstrates statistically superior efficacy compared to either monotherapy for reducing incontinence episodes, urgency, and nocturia. 1, 2
• Adverse events (dry mouth, constipation, dyspepsia) increase slightly with combination therapy compared to monotherapy. 2
• Do not use combination therapy as first-line treatment; reserve it for patients refractory to monotherapy. 2

Third-Line Options

For patients failing behavioral and pharmacologic therapy, consider:

• Intradetrusor onabotulinumtoxinA injections (requires ability to perform self-catheterization if needed). 7
• Sacral neuromodulation (durable effects but requires surgical procedure). 7
• Peripheral tibial nerve stimulation (less invasive but requires ongoing office visits). 7

Special Population Considerations

Elderly Patients (≥65 Years)

Mirabegron 25 mg is particularly effective and safe in older patients with multiple comorbidities, making it an appropriate starting dose in this population. 1, 2

• Efficacy is maintained in patients ≥65 and ≥75 years. 3, 8
• Baseline hypertension and diabetes are more frequent in older age groups, necessitating careful cardiovascular assessment before initiation. 8

Frail Patients

Exercise extreme caution in frail patients (those with mobility deficits, unexplained weight loss, weakness, or cognitive deficits) due to a lower therapeutic index with all OAB medications. 7

• Beta-3 agonists remain preferred over antimuscarinics because they do not increase cognitive impairment risk. 7

Male Patients

Before starting mirabegron in men, assess for bladder outlet obstruction (PVR ≥250 mL or maximum flow rate <10 mL/s). 7

• If obstruction is present, initiate an alpha-blocker as first-line therapy rather than mirabegron or antimuscarinic monotherapy. 7
• Regularly re-evaluate symptoms and post-void residual volume in men. 1

Common Pitfalls to Avoid

• Do not skip behavioral therapy: Failing to optimize bladder training, pelvic floor exercises, and fluid management before starting medications is a common error. 7
• Do not abandon antimuscarinic therapy after one agent fails: Switch to a different antimuscarinic or to mirabegron rather than discontinuing the class entirely. 7
• Do not use antimuscarinics in patients with contraindications: Avoid in narrow-angle glaucoma, impaired gastric emptying, or history of urinary retention. 7
• Do not ignore cognitive risks: Antimuscarinics carry potential cumulative, dose-dependent risk for dementia and cognitive impairment, particularly in elderly patients. 7
• Do not use combination therapy as first-line: Reserve mirabegron plus solifenacin for patients refractory to monotherapy. 2