Mirabegron

• Overactive Bladder
• Urge Urinary Incontinence
• Neurogenic Detrusor Overactivity

Mirabegron is a selective beta-3 adrenergic receptor agonist used to treat overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. It represents an alternative mechanism to antimuscarinics for OAB treatment.

Mechanism of Action

Mirabegron activates beta-3 adrenergic receptors in the detrusor muscle of the bladder:

• Beta-3 receptors are the predominant beta-adrenoceptor subtype in the bladder
• Activation causes detrusor muscle relaxation during the storage phase
• Relaxation increases bladder capacity and reduces urgency
• Does not block muscarinic receptors, avoiding anticholinergic side effects

This mechanism is particularly advantageous for patients who cannot tolerate or have contraindications to antimuscarinics.

Available Formulations

Mirabegron is available as extended-release tablets (Myrbetriq):

• 25 mg tablets
• 50 mg tablets

Also available as:

• Granules for oral suspension: 8 mg/mL (for pediatric use)

Tablets should be swallowed whole with water; do not crush, chew, or divide.

Medical Uses

FDA-Approved Indications:

• Overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency in adults
• Neurogenic detrusor overactivity (NDO) in pediatric patients 3 years and older

May be used alone or in combination with the antimuscarinic solifenacin (Vesicare) for enhanced efficacy.

Dosing Guidelines

Adults with OAB:

• Starting dose: 25 mg once daily
• May increase to 50 mg once daily based on efficacy and tolerability

Pediatric NDO (≥3 years):

• Weight-based dosing using granules or tablets
• 11-22 kg: 24 mg once daily (may increase to 48 mg)
• 22-35 kg: 32 mg once daily (may increase to 64 mg)
• ≥35 kg: 40 mg once daily (may increase to 80 mg)

Important Safety Information

Contraindications:

• Known hypersensitivity to mirabegron

Warnings and Precautions:

• Hypertension: Can increase blood pressure; measure before starting and monitor periodically
• Urinary retention: Use with caution in patients with bladder outlet obstruction or taking antimuscarinics
• Angioedema: Discontinue immediately if occurs
• CYP2D6 drug interactions: Mirabegron inhibits CYP2D6

Blood Pressure Monitoring: Check blood pressure before starting treatment and monitor periodically, especially in hypertensive patients.

Drug Interactions

CYP2D6 Substrates:

• Metoprolol: Exposure increased; use lowest metoprolol dose and monitor
• Desipramine: Exposure increased 3.4-fold; use lower desipramine doses
• Thioridazine: Use not recommended (QT prolongation risk)

Other Interactions:

• Digoxin: Exposure increased; use lowest digoxin dose and monitor levels
• Warfarin: Monitor INR more frequently initially

Special Populations

• Hepatic Impairment:
  • Mild: No adjustment needed
  • Moderate (Child-Pugh B): Do not exceed 25 mg daily
  • Severe (Child-Pugh C): Not recommended
• Renal Impairment:
  • eGFR 15-29 mL/min: Do not exceed 25 mg daily
  • eGFR <15 or ESRD: Not recommended
• Pregnancy: Limited data; use only if benefit outweighs risk
• Elderly: No dose adjustment required