Mirabegron is a novel β3-adrenergic receptor agonist developed for the treatment of overactive bladder (OAB) syndrome. It offers an alternative therapeutic approach by relaxing the detrusor muscle, thereby increasing bladder storage capacity and reducing symptoms such as urinary urgency, frequency, and incontinence. It was first approved in Japan in July 2011, followed by regulatory approvals in the United States (FDA) in June 2012, the European Union (EMA) in December 2012, and subsequently in several other countries worldwide.
BRAND NAMES
Myrbetriq: Myrbetriq (Mirabegron) prescribed for overactive bladder. It works by relaxing the bladder muscle and is typically taken once daily, starting at 25 mg and can be increased to 50 mg if needed.
Betanis: Betanis (Mirabegron) used in Japan to treat overactive bladder by relaxing the bladder muscle. It’s taken once daily, starting at 25 mg, and can be increased to 50 mg based on response.
Miragron: Miragron is an Indian brand of mirabegron used to treat overactive bladder. It is taken once daily as a 25 mg extended-release tablet, which can be increased to 50 mg based on patient response.
MECHANISM OF ACTION
- It selectively activates β3-adrenergic receptors predominantly found in the detrusor muscle of the urinary bladder.
- Activation of β3 receptors causes the detrusor smooth muscle to relax during the bladder’s storage phase in the fill-void cycle.
- This relaxation increases bladder capacity and reduces the urgency and frequency of urination, which helps in treating overactive bladder (OAB) symptoms such as urgency, frequency, and urge incontinence.
PHARMACOKINETICS
Absorption
Mirabegron is well absorbed orally, with a bioavailability of approximately 29% to 35% due to first-pass metabolism.
Distribution
It exhibits a large volume of distribution of approximately 1670 liters, reflecting extensive distribution throughout body tissues. Approximately 71% to 72% bound to plasma proteins.
Metabolism
Mainly metabolized in the liver via multiple pathways including CYP3A4, CYP2D6, and other non-CYP enzymes
Elimination
Ranges from 50 to 60 hours, allowing once-daily dosing. The drug is mainly eliminated as metabolites, with about 55% excreted through urine and 34% through feces.
DOSAGE AND ADMINISTRATION
Mirabegron is administered orally, starting at 25 mg once daily, with the possibility of increasing to 50 mg once daily based on clinical response and tolerability; it can be taken with or without food, and dose modifications are recommended for patients with moderate to severe renal or hepatic impairment to minimize the risk of adverse effects, with treatment duration tailored according to symptom control.
DRUG INTERACTIONS
- Inhibits CYP2D6, increasing levels of drugs like metoprolol and desipramine.
- May raise digoxin plasma concentrations — monitor levels.
- Additive bladder relaxation effects with anticholinergic agents.
- Increased risk of hypertension with thiazide diuretics — monitor blood pressure.
- Caution when used with beta-blockers due to cardiovascular effects.
CONTRAINDICATIONS
- Hypersensitivity to mirabegron or any of its components
- Severe uncontrolled hypertension (e.g., blood pressure >180/110 mmHg)
- Urinary retention (due to risk of worsening retention)
- Severe liver impairment (Child-Pugh class C)
- Patients with bladder outlet obstruction without catheterization
SIDE EFFECTS
- Hypertension
- Headache
- Nasopharyngitis (common cold symptoms)
- Urinary tract infection
- Dizziness
- Gastrointestinal symptoms (nausea, constipation)
- Dry mouth (less common than with anticholinergics)
- Increased heart rate (tachycardia)
TOXICITY
- Overdose of mirabegron may cause elevated blood pressure, tachycardia, and palpitations due to excessive β3-adrenergic stimulation.
- There is no specific antidote; treatment is mainly supportive and symptomatic, focusing on monitoring cardiovascular status and managing blood pressure.
- Use caution in patients with cardiovascular disease during overdose situations.
