MIRBERON ER 50MG TABLETS

Indications

• Overactive bladder (OAB) symptoms
• Urinary urgency
• Urinary frequency
• Urge incontinence

Dosage

Children: Safety and efficacy in children have not been established; refer to the BNF for Children for further guidance.

Adults: The recommended dose for adults is 60 mg once daily. For patients with renal impairment, dose adjustments may be required.

Mechanism of action

Mirabegron acts as a potent and selective agonist of the beta-3 adrenergic receptors. Upon activation, these receptors relax the detrusor smooth muscle during the storage phase of the bladder fill-void cycle, which enhances the bladder's storage capacity and alleviates feelings of urinary urgency and frequency.

Pharmacodynamics

The pharmacologic effects of mirabegron include the relaxation of bladder smooth muscle, which allows for increased capacity and relief from urgency. Unlike anticholinergic medications, mirabegron does not significantly impact the mean maximum flow rate or detrusor pressure in patients with lower urinary tract symptoms or bladder outlet obstruction (BOO). However, it can increase blood pressure and heart rate in a dose-dependent manner, warranting caution in patients with severely uncontrolled hypertension or those at risk for cardiovascular events.

Pharmacokinetics

Mirabegron is well-absorbed after oral administration, with peak plasma concentrations typically occurring within 3 to 4 hours. It undergoes extensive hepatic metabolism primarily via CYP2D6, with renal excretion of metabolites. The half-life of mirabegron is approximately 50 hours, allowing for once-daily dosing. Its pharmacokinetics may be affected by renal and hepatic function, requiring caution and possible dose adjustments in patients with varying degrees of impairment.

Adverse effects

• Hypertension
• Urinary retention
• Tachycardia
• Headache
• Dry mouth
• Nausea
• Diarrhea
• Constipation
• Dizziness
• Fatigue

Interactions

• Digoxin (moderate - increases exposure)
• Eliglustat (moderate - increases exposure)
• Aliskiren (unknown - increases exposure)
• Fexofenadine (unknown - increases exposure)
• Metoprolol (unknown - increases exposure)
• Cobicistat (unknown - increases exposure)
• Colchicine (unknown - increases exposure)
• Everolimus (unknown - increases exposure)
• Edoxaban (unknown - increases exposure)
• Idelalisib (unknown - increases exposure)

Precautions

• History of QT-interval prolongation
• Severe uncontrolled hypertension
• Bladder outlet obstruction (BOO)
• Hepatic impairment
• Renal impairment

Pregnancy

Manufacturer advises caution due to potential toxicity in animal studies.

Breast-feeding

Manufacturer advises caution, no information available on excretion in breast milk.

Storage

Store at room temperature, protect from moisture and light.

Formulations

• Modified-release capsules
• Tablets

Mechanism of action

Mirabegron is a potent and selective agonist of beta-3 adrenergic receptors. The activation of beta-3 receptors relaxes detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle, which increases the bladder's storage capacity thereby alleviating feelings of urgency and frequency.

Pharmacodynamics

Mirabegron exerts its pharmacologic effects by forcing bladder smooth muscle to relax, thereby expanding its capacity and relieving urgency. Mirabegron does not appear to adversely affect the mean maximum flow rate or mean detrusor pressure at maximum flow rate in patients with lower urinary tract symptoms and bladder outlet obstruction (BOO), but should be used with in patients with BOO due to reports of significant urinary retention. Furthermore, mirabegron increases both blood pressure and heart rate in a dose-dependent manner and should therefore be used with caution in patients with severely uncontrolled hypertension or others for whom these increases may prove dangerous.