1. Clinical Overview
Mirabegron is a selective beta-3 adrenergic receptor agonist used primarily for the treatment of overactive bladder (OAB) syndrome. It works by relaxing the detrusor smooth muscle of the urinary bladder during the storage phase, increasing bladder capacity and reducing the frequency of involuntary detrusor contractions. It represents a significant advancement over antimuscarinic agents due to a different mechanism of action and a potentially more favorable side effect profile, particularly regarding dry mouth and constipation.
| Onset | Duration | Bioavailability |
|---|---|---|
| Clinical improvement in symptoms (reduction in micturition frequency and urgency episodes) is typically observed within 4-8 weeks of starting therapy. | Approximately 24 hours, supporting once-daily dosing. | Approximately 29-35% in healthy subjects. |
2. Mechanism of Action
Mirabegron is a potent and selective agonist for the human beta-3 adrenergic receptor (β3-AR). In the urinary bladder, stimulation of β3-ARs on the detrusor smooth muscle activates Gs proteins, leading to increased intracellular cyclic adenosine monophosphate (cAMP). Elevated cAMP activates protein kinase A (PKA), which results in relaxation of the detrusor muscle. This relaxation increases bladder storage capacity and reduces the frequency and intensity of involuntary bladder contractions (detrusor overactivity) that characterize OAB.
3. Indications & Uses
- Treatment of overactive bladder (OAB) syndrome with symptoms of urge urinary incontinence, urgency, and urinary frequency.
4. Dosage & Administration
Adult Dosage: The recommended starting dose is 25 mg once daily. Based on individual efficacy and tolerability, the dose may be increased to 50 mg once daily after 4-8 weeks.
Administration: Swallow the tablet whole with a glass of water, with or without food. Do not crush, split, or chew. Should be taken at approximately the same time each day.
5. Side Effects
Common side effects may include:
- Hypertension (elevated blood pressure)
- Nasopharyngitis (common cold)
- Urinary tract infection
- Headache
- Constipation
- Tachycardia (increased heart rate)
- Dizziness
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Digoxin | Mirabegron increases digoxin plasma concentration (AUC) by approximately 27%. Risk of digoxin toxicity. | Major |
| Metoprolol, Propranolol (CYP2D6 substrates) | Mirabegron may increase plasma concentrations of these drugs. Monitor for increased beta-blockade effects (bradycardia, hypotension). | Moderate |
| Ketoconazole, Itraconazole, Clarithromycin (Strong CYP3A4 inhibitors) | Increase mirabegron exposure. In patients with normal renal/hepatic function, monitor for increased side effects. In patients with renal/hepatic impairment, co-administration is contraindicated. | Major |
| Rifampicin (Strong CYP3A4 inducer) | Decreases mirabegron exposure, potentially reducing efficacy. | Moderate |
| Warfarin | No significant pharmacokinetic interaction. However, monitor INR as a precaution due to potential pharmacodynamic effects on BP/HR. | Minor |
| Other antihypertensives | Mirabegron may attenuate the blood pressure-lowering effect. Monitor blood pressure regularly. | Moderate |
7. Patient Counselling
- DO take the tablet exactly as prescribed, at the same time each day.
- DO inform your doctor about all other medicines you are taking, including herbal supplements.
- DO have your blood pressure and heart rate monitored regularly, especially if you have hypertension.
- DO NOT stop taking the medicine suddenly without consulting your doctor.
- DO NOT crush, chew, or split the tablet.
- DO NOT start this medication if you are pregnant, planning pregnancy, or breastfeeding without discussing with your doctor.
8. Toxicology & Storage
Overdose: Expected symptoms are related to excessive pharmacodynamic effects: severe tachycardia, palpitations, hypertension, headache, nausea, and vomiting. QT interval prolongation may occur.
Storage: Store at room temperature (15°C to 30°C). Protect from moisture. Keep in the original blister pack until use. Keep out of reach and sight of children.