M-beg

Approved Indications

• Overactive Bladder (OAB) with symptoms of:
• Urgency
• Urge urinary incontinence
• Increased urinary frequency
  Indicated in adults and pediatric patients ≥3 years of age and weighing ≥35 kg.
• Neurogenic Detrusor Overactivity (NDO) in pediatric patients aged 3 years and older, either alone or in combination with solifenacin.

Clinically Accepted Off-label Uses

• Benign Prostatic Hyperplasia (BPH):
  As adjunct to α-blockers in men with persistent storage symptoms.
• Stress Urinary Incontinence (investigational use):
  Occasionally evaluated in women with mixed incontinence.

Adults with Overactive Bladder

• Initial dose: 25 mg orally once daily.
• Maintenance dose: May increase to 50 mg once daily based on patient response and tolerability.
• Route: Oral, with or without food.
• Form: Extended-release tablets.

Pediatric Patients (≥3 years and ≥35 kg)

• Weight-based dosing:
• 35–50 kg: 25 mg once daily
• 50 kg: 50 mg once daily
• Oral Suspension (Granules) may be used if tablets are not suitable.

Renal Impairment

• Moderate impairment (eGFR 30–59 mL/min/1.73 m²):
  Max dose: 25 mg once daily.
• Severe impairment (eGFR 15–29):
  Not recommended unless benefit outweighs risk.
• End-stage renal disease (eGFR <15 or on dialysis):
  Not recommended.

Hepatic Impairment

• Mild impairment (Child-Pugh A):
  Max 50 mg once daily.
• Moderate impairment (Child-Pugh B):
  Max 25 mg once daily.
• Severe impairment (Child-Pugh C):
  Not recommended.

Elderly

• No dose adjustment necessary, but monitor for blood pressure elevations.

Mirabegron is a β3-adrenergic receptor agonist. In the detrusor muscle of the bladder, stimulation of β3 receptors leads to relaxation of the bladder during the storage phase, thereby increasing bladder capacity without impairing voiding. Unlike antimuscarinics, mirabegron does not inhibit acetylcholine at muscarinic receptors, and thus reduces the likelihood of anticholinergic side effects such as dry mouth and constipation. This makes it a preferred option in patients who cannot tolerate or have contraindications to antimuscarinics.

• Absorption:
  Peak plasma concentrations achieved in 3.5 hours (Tmax).
  Food may increase systemic exposure but does not require dosage adjustment.
• Bioavailability:
  29% (25 mg) to 35% (50 mg); dose-dependent.
• Distribution:
  Volume of distribution ~1670 L.
  Plasma protein binding ~71%.
• Metabolism:
  Primarily metabolized by CYP3A4, with minor contribution from CYP2D6, along with UGT and esterases.
• Half-life:
  ~50 hours (long terminal half-life allows once-daily dosing).
• Elimination:
  55% excreted in urine (unchanged and metabolites), 34% in feces.

• Pregnancy:
  No FDA pregnancy category assigned.
  Animal studies showed no major teratogenic effects, but limited human data. Use only if clearly needed.
• Lactation:
  Unknown whether mirabegron is excreted in human milk.
  A decision should be made to discontinue drug or breastfeeding based on benefit-risk assessment.

• Primary Class:
  β3-Adrenergic Receptor Agonist
• Subclass:
  Urinary Antispasmodic Agent

• Known hypersensitivity to mirabegron or any of its excipients
• Severe uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥110 mmHg)
• End-stage renal or severe hepatic impairment

• Hypertension:
  Can increase blood pressure; monitor regularly, especially in those with preexisting hypertension.
• Urinary Retention:
  Risk is increased in patients with bladder outlet obstruction or those taking anticholinergics concurrently.
• QT Prolongation:
  Use caution in patients with known QT prolongation or those on QT-prolonging drugs.
• Angioedema:
  Rare cases reported. Discontinue immediately if symptoms occur.
• Hepatic and Renal Impairment:
  Requires dose adjustments or avoidance in moderate to severe impairment.

Common

• Cardiovascular: Hypertension, tachycardia
• Gastrointestinal: Constipation, dry mouth, nausea
• Nervous system: Headache, dizziness
• Urinary: Urinary tract infections, dysuria

Serious or Rare

• Urinary retention
• Atrial fibrillation
• Angioedema
• QT prolongation
• Hypersensitivity reactions

• CYP2D6 substrates (e.g., metoprolol, desipramine):
  Mirabegron inhibits CYP2D6, increasing plasma levels of co-administered drugs.
• CYP3A4 inhibitors (e.g., ketoconazole):
  May increase mirabegron levels—monitor for adverse effects.
• Antimuscarinics (e.g., solifenacin):
  Combination may increase risk of urinary retention—monitor closely.
• Digoxin:
  Caution advised. Start digoxin at lowest dose and monitor serum levels.

• FDA Pediatric Approval (2021–2022):
  Approved for neurogenic detrusor overactivity in children ≥3 years.
• AUA Guidelines (2023):
  Endorses mirabegron as a first-line or adjunct option for OAB, especially in those intolerant to antimuscarinics.
• Combination Therapy:
  Fixed-dose combination of mirabegron + solifenacin recommended for patients with suboptimal response to monotherapy.

• Temperature:
  Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Humidity & Light:
  Protect from excessive moisture. No special light protection needed.
• Handling Precautions:
  Do not crush or chew extended-release tablets.
  Oral suspension must be shaken well before each use (if prepared from granules).
• Reconstitution Needs:
  Oral suspension should be stored in original container and discarded 60 days after preparation.