What is the starting dose of mirabegron for overactive bladder, and how should it be modified in patients with moderate (creatinine clearance 15–30 mL/min) or severe (creatinine clearance <15 mL/min) renal impairment or combined renal and hepatic impairment?

Mirabegron Starting Dosage

The recommended starting dose of mirabegron for overactive bladder is 25 mg orally once daily, which can be increased to 50 mg once daily after 4 to 8 weeks if needed. 1

Standard Dosing in Adults with Normal Organ Function

• Begin with mirabegron 25 mg once daily, taken orally with or without food. 1
• After 4 to 8 weeks, if symptom control is inadequate, increase to the maximum dose of 50 mg once daily. 1
• Swallow tablets whole with water; do not chew, divide, or crush. 1

Dosing in Renal Impairment

For patients with moderate renal impairment (eGFR 30–89 mL/min/1.73 m²):

• Start with 25 mg once daily. 1
• Maximum dose is 50 mg once daily. 1

For patients with severe renal impairment (eGFR 15–29 mL/min/1.73 m²):

• Start with 25 mg once daily. 1
• Maximum dose remains 25 mg once daily—do not increase beyond this. 1

For patients with end-stage renal disease (eGFR <15 mL/min/1.73 m² or requiring dialysis):

• Mirabegron is not recommended. 1

The rationale for dose limitation in severe renal impairment is that mirabegron AUC and Cmax increase by 118% and 92%, respectively, in patients with severe renal dysfunction, though these changes showed high variability and significant overlap with healthy subjects. 2

Dosing in Hepatic Impairment

For patients with mild hepatic impairment (Child-Pugh Class A):

• Start with 25 mg once daily. 1
• Maximum dose is 50 mg once daily. 1

For patients with moderate hepatic impairment (Child-Pugh Class B):

• Start with 25 mg once daily. 1
• Maximum dose remains 25 mg once daily—do not increase beyond this. 1

For patients with severe hepatic impairment (Child-Pugh Class C):

• Mirabegron is not recommended. 1

Pharmacokinetic data show that mirabegron AUC and Cmax increase by 65% and 175%, respectively, in patients with moderate hepatic impairment, justifying the dose cap at 25 mg. 2

Combined Renal and Hepatic Impairment

For patients with both moderate renal impairment (eGFR 30–89 mL/min/1.73 m²) and mild hepatic impairment (Child-Pugh Class A):

• Start with 25 mg once daily. 1
• Maximum dose is 50 mg once daily. 1

For patients with severe renal impairment (eGFR 15–29 mL/min/1.73 m²) OR moderate hepatic impairment (Child-Pugh Class B), regardless of the other organ function:

• Start with 25 mg once daily. 1
• Do not exceed 25 mg once daily. 1

For patients with end-stage renal disease (eGFR <15 mL/min/1.73 m²) OR severe hepatic impairment (Child-Pugh Class C):

• Do not use mirabegron. 1

Clinical Context and Monitoring

• Mirabegron demonstrates efficacy as early as week 4, with sustained benefits throughout treatment for reducing micturition frequency, urgency incontinence, and urgency episodes. 3
• Monitor blood pressure periodically, especially during initial treatment, as mirabegron can cause dose-dependent increases in systolic blood pressure. 4
• The most common adverse events include hypertension, urinary tract infection, and headache. 4
• Mirabegron has a significantly lower incidence of dry mouth compared to antimuscarinics, making it particularly valuable for patients who discontinued antimuscarinic therapy due to intolerable anticholinergic side effects. 3, 5

Common Pitfalls to Avoid

• Do not start at 50 mg in patients with any degree of renal or hepatic impairment—always begin at 25 mg and assess tolerability before considering dose escalation. 1
• Do not exceed 25 mg daily in patients with eGFR 15–29 mL/min/1.73 m² or Child-Pugh Class B hepatic impairment, even if symptoms persist, as higher doses significantly increase drug exposure. 1, 2
• Do not use mirabegron in patients with eGFR <15 mL/min/1.73 m² or Child-Pugh Class C, as safety and efficacy have not been established and drug accumulation is substantial. 1
• Always combine pharmacotherapy with behavioral interventions (bladder training, pelvic floor exercises, fluid management) for optimal outcomes. 6