What is the recommended dosing, contraindications, and monitoring for Mirabegron in adults with overactive bladder, including dose adjustments for renal or hepatic impairment and precautions in uncontrolled hypertension?

Mirabegron Dosing and Clinical Management

Recommended Dosing

For adults with overactive bladder, start mirabegron 25 mg orally once daily, which can be increased to 50 mg once daily after 4–8 weeks if needed for symptom control. 1, 2

• The 25 mg starting dose is particularly appropriate for older patients (≥65 years) with multiple comorbidities, demonstrating both safety and therapeutic efficacy in this population. 1, 2
• Efficacy is typically evident within 8 weeks of initiating therapy. 1
• The medication should be taken as an extended-release tablet once daily. 3

Dose Adjustments for 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. 1

• Mirabegron is contraindicated in severe renal impairment (eGFR <30 mL/min/1.73 m²) per FDA labeling. 3

Dose Adjustments for 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. 1

• Mirabegron is contraindicated in moderate to severe hepatic impairment (Child-Pugh Class B or C). 3

Contraindications

Mirabegron is absolutely contraindicated in patients with severe uncontrolled hypertension. 2, 3

Additional contraindications include:

• Severe renal impairment (eGFR <30 mL/min/1.73 m²) 3
• Moderate to severe hepatic impairment (Child-Pugh Class B or C) 3
• End-stage renal disease 3

Blood Pressure Monitoring Requirements

Monitor blood pressure periodically, especially during the initial treatment period and in patients with pre-existing hypertension, as mirabegron can cause dose-dependent blood pressure increases. 1, 2

• In patients with well-controlled hypertension, mirabegron is generally safe, though approximately 6.5% may experience blood pressure elevation requiring discontinuation. 4
• Home blood pressure monitoring can aid in earlier detection of worsening control in the small segment of patients who develop hypertension. 4
• The risk of hypertension as an adverse event is not statistically higher than with antimuscarinic agents. 5

Use in Patients with Controlled Hypertension

Mirabegron can be used in patients with well-controlled hypertension, but requires vigilant blood pressure monitoring. 4

• In a retrospective study of 46 women with well-controlled hypertension, only 3 patients (6.5%) experienced blood pressure increases requiring discontinuation. 4
• The majority of hypertensive patients (78.2%) experienced no side effects at all. 4
• When blood pressure elevation occurs, discontinue mirabegron immediately; additional antihypertensive agents are typically not needed. 4

Additional Monitoring Parameters

For male patients or those with obstructive symptoms, regularly re-evaluate lower urinary tract symptoms and post-void residual (PVR) volume. 2

• Advise patients to discontinue medication if worsening voiding symptoms or deteriorating urinary stream occurs after initiation. 2
• Mirabegron can cause urinary retention, particularly in patients with bladder outlet obstruction or those taking concurrent antimuscarinic medications. 3

Common Adverse Events

The most frequently reported adverse events (>2%) include:

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

Serious but Rare Adverse Effects

Be alert for angioedema of the face, lips, tongue, and/or larynx, which requires immediate discontinuation. 1

Other serious adverse effects include:

• Cardiac arrhythmias 1
• Kidney stones 1
• Serious skin reactions 1

Combination Therapy Strategy

For patients with inadequate response to mirabegron monotherapy after 6 months, consider combination therapy with solifenacin 5 mg once daily. 1, 2

• The combination of mirabegron 25–50 mg plus solifenacin 5 mg demonstrates statistically superior efficacy compared to either monotherapy for reducing incontinence episodes, urgency episodes, and nocturia. 1
• Combination therapy shows slightly increased rates of dry mouth, constipation, dyspepsia, and urinary retention compared to monotherapy. 1
• Do not use combination therapy as first-line treatment; reserve it specifically for patients refractory to monotherapy. 1
• Co-administration has no significant pharmacokinetic interactions, allowing safe concurrent use without dose adjustments. 1

Treatment Context and Algorithm

Always initiate behavioral therapies (bladder training, pelvic floor muscle training, fluid management) before or alongside mirabegron, as these interventions provide efficacy comparable to pharmacotherapy. 6

• Mirabegron is a second-line pharmacologic option after behavioral therapies. 6
• Beta-3 agonists like mirabegron are typically preferred before antimuscarinics due to lower cognitive risk concerns, especially in elderly patients. 6
• Mirabegron has a superior tolerability profile with significantly lower incidence of dry mouth and constipation compared to antimuscarinics. 6, 7, 8

Special Population Considerations

In frail elderly patients (those with mobility deficits, unexplained weight loss, weakness, or cognitive deficits), exercise extreme caution with mirabegron due to a lower therapeutic index, though it remains preferable to antimuscarinics for cognitive safety. 6

• Mirabegron demonstrates maintained efficacy in patients aged ≥75 years with statistically significant reductions in incontinence episodes and micturition frequency. 2
• The medication is generally well tolerated in elderly patients with multiple comorbidities. 2, 7

Drug Interactions

Mirabegron is a moderate CYP2D6 inhibitor and can increase exposure to drugs metabolized by this pathway (e.g., metoprolol, desipramine, flecainide). 3

• Monitor patients taking CYP2D6 substrates, particularly those with narrow therapeutic indices. 3
• Mirabegron may increase digoxin levels; monitor digoxin concentrations when initiating or adjusting mirabegron. 3
• No clinically significant interaction with warfarin has been demonstrated. 3

Common Pitfalls to Avoid

• Do not prescribe mirabegron to patients with uncontrolled hypertension without first achieving blood pressure control. 2, 3
• Do not fail to monitor blood pressure during initial treatment, especially in patients with pre-existing hypertension. 1, 2
• Do not use combination therapy as first-line treatment; always trial monotherapy first. 1
• Do not abandon mirabegron after inadequate response without first attempting dose escalation to 50 mg or adding solifenacin. 1, 2
• Do not neglect behavioral therapies; always combine pharmacotherapy with bladder training and pelvic floor exercises. 6