Mirabegron

Generic Name: Mirabegron
Brand Names: Myrbetriq, Betmiga
Drug Class: Beta-3 adrenergic receptor agonist
Formulation: Extended-release oral tablets

---

Mechanism of Action
Mirabegron selectively stimulates beta-3 adrenergic receptors found in the detrusor muscle of the bladder. Activation of these receptors relaxes the detrusor during the storage phase of the micturition cycle. This leads to increased bladder capacity and a reduction in symptoms associated with overactive bladder, including urgency, frequency, and urge incontinence. It does not possess significant antimuscarinic activity, which differentiates it from traditional OAB medications.

---

Indications

Adults:

• Overactive bladder (OAB) with symptoms of urgency, urinary frequency, and urge incontinence.

Pediatric (age ≥3 years):

• Neurogenic detrusor overactivity (NDO), as monotherapy or in combination with other treatments.

---

Dosage and Administration

Adults:

• Initial dose: 25 mg once daily

• May increase to 50 mg once daily based on response and tolerability

• Should be swallowed whole with water and not chewed, crushed, or divided

• Can be taken with or without food

Pediatric Patients (age ≥3 years):

• Dose is weight-based and formulation may include oral suspension

• Requires specialist dosing and careful titration

Dose Adjustments:

• Severe renal impairment: Do not exceed 25 mg/day

• Moderate hepatic impairment: Do not exceed 25 mg/day

• Contraindicated in end-stage renal disease and severe hepatic impairment

---

Pharmacokinetics

• Absorption: Oral bioavailability is approximately 30–35%, increased with higher doses

• Time to Peak Plasma Concentration: Approximately 3.5 hours post-dose

• Protein Binding: ~70%

• Metabolism: Primarily via amide hydrolysis and glucuronidation; minor metabolism through CYP2D6 and CYP3A4

• Half-Life: 50 hours

• Elimination: Excreted mainly in urine (~55%) and feces (~35%)

---

Contraindications

• Severe uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥110 mmHg)

• Known hypersensitivity to mirabegron or any component of the formulation

• Avoid use in patients with severe hepatic or renal dysfunction not suitable for dosing

---

Warnings and Precautions

• Hypertension: Increases in blood pressure have been observed; regular monitoring is recommended especially in patients with pre-existing hypertension

• Urinary Retention: Risk is increased in patients with bladder outlet obstruction or those taking antimuscarinic drugs concomitantly

• Angioedema: Rare but serious, may occur after the first dose and requires immediate discontinuation

• Hepatic and Renal Impairment: Adjust dose accordingly and monitor function periodically

• QT Prolongation: Use caution in patients with known QT prolongation or those on medications known to prolong the QT interval

---

Adverse Effects

Very Common (>10%):

• Hypertension

Common (1–10%):

• Urinary tract infection

• Nasopharyngitis

• Headache

• Constipation

• Tachycardia

• Back pain

• Dry mouth

• Nausea

• Dizziness

Uncommon (<1%):

• Palpitations

• Abdominal pain

• Blurred vision

• Rash

• Fatigue

• Insomnia

• Angioedema

• Elevated liver enzymes

Rare:

• Urinary retention

• Hypersensitivity reactions

• Severe cutaneous reactions (e.g., erythema multiforme)

---

Drug Interactions

• CYP2D6 Substrates: Mirabegron inhibits CYP2D6 and can increase plasma levels of drugs metabolized by this enzyme (e.g., metoprolol, desipramine, dextromethorphan, thioridazine). Use caution and consider monitoring when co-administered

• Digoxin: Increases digoxin exposure; initiate digoxin at lowest recommended dose and monitor

• Antimuscarinics: Additive risk of urinary retention when used concurrently with anticholinergic drugs such as tolterodine or solifenacin

• Drugs that prolong QT interval: Use caution in combination with other QT-prolonging agents

---

Use in Special Populations

Pregnancy:

• Limited data; use only if clearly needed

• Not teratogenic in animal studies but effects in humans are unknown

Lactation:

• Unknown whether excreted in human milk

• Consider benefit-risk assessment before use in breastfeeding

Geriatrics:

• No dose adjustment necessary, but monitor for blood pressure and cardiac side effects due to higher prevalence of comorbidities

Pediatrics:

• Approved for NDO in children aged 3 years and older; requires specialist dosing protocols and monitoring

---

Monitoring Recommendations

• Blood pressure before starting and periodically during treatment

• Signs of urinary retention, especially in those with risk factors

• Cardiac monitoring if used with QT-prolonging drugs

• Monitor for signs of hypersensitivity reactions, particularly angioedema

• In patients on CYP2D6 substrates, monitor for increased effects or toxicity

---

Patient Counseling Information

• Take at the same time each day, preferably with water

• Do not crush, chew, or split the tablet

• Inform physician of any signs of allergic reactions, urinary difficulty, or significant blood pressure changes

• Be aware that symptom improvement may take up to 8 weeks

• Report any unusual cardiac symptoms such as rapid heartbeat, palpitations, or fainting

---

Comparison to Other OAB Medications

• Compared to antimuscarinics (e.g., oxybutynin, tolterodine):

  • Lower risk of dry mouth, constipation, and cognitive side effects

  • Less likely to cause central nervous system effects in elderly

• Combined use: May be prescribed with solifenacin for enhanced efficacy in refractory cases

---

Storage and Stability

• Store below 30°C (86°F)

• Protect from moisture and light

• Keep in original packaging until use

• Keep out of reach of children