Uroben XR50 mg

Established (FDA-Approved) Indications

• Overactive bladder (OAB) in adults — for the treatment of symptoms of urge urinary incontinence, urgency, and urinary frequency. Uroben XR may be used as monotherapy or in combination with the anticholinergic agent solifenacin succinate when monotherapy with either agent provides inadequate control of symptoms.
• Neurogenic detrusor overactivity (NDO) in pediatric patients 3 years of age and older — Uroben XR extended-release tablets (patients weighing ≥35 kg) or oral suspension granules (patients weighing ≥11 kg) are approved for this indication, generally used together with clean intermittent catheterization.

Not an Approved Use

Uroben XR is not approved for treatment of overactive bladder in pediatric patients (its pediatric approval is limited to neurogenic detrusor overactivity) and is not indicated for stress urinary incontinence.

Each tablet of Mirabegron extended-release formulation typically contains Mirabegron as the active pharmaceutical ingredient, along with excipients that permit controlled/extended release of the drug. Oral suspension granule formulations of Mirabegron are also available for patients unable to swallow tablets. Exact strengths and excipients vary by manufacturer/brand.

Uroben XR is a selective beta-3 adrenergic receptor agonist indicated for the treatment of overactive bladder and, in pediatric patients, neurogenic detrusor overactivity. It represents a mechanistically distinct alternative to the anticholinergic (antimuscarinic) class of drugs traditionally used for overactive bladder, and is often chosen for patients who cannot tolerate anticholinergic side effects such as dry mouth and constipation.

Uroben XR is administered orally, once daily, as an extended-release tablet or oral suspension, and works by relaxing the detrusor (bladder) smooth muscle during the bladder-filling phase, thereby increasing bladder capacity.

Beta-3 adrenergic receptor agonist; urinary antispasmodic / overactive bladder agent.

Mirabegron is a selective agonist of the beta-3 adrenergic receptor, which is the predominant beta-adrenoceptor subtype expressed in human detrusor smooth muscle. Activation of beta-3 receptors by Mirabegron stimulates adenylate cyclase, increasing intracellular cyclic AMP, which produces relaxation of the detrusor muscle during the storage (filling) phase of the micturition cycle without affecting normal voiding contractions. This mechanism increases bladder capacity and reduces episodes of urgency, frequency, and urge incontinence, and is distinct from the antimuscarinic mechanism used by other overactive bladder drugs.

Pharmacokinetics: Mirabegron is absorbed after oral administration with peak plasma concentrations reached in approximately 3.5 hours; absolute bioavailability increases with dose. It is extensively distributed and approximately 71% protein-bound. Metabolism occurs via multiple pathways including CYP3A4- and CYP2D6-mediated oxidation, amide hydrolysis, and glucuronidation; no single pathway predominates. Mirabegron is also a moderate inhibitor of CYP2D6. Elimination occurs via both renal and hepatic routes, with an elimination half-life of approximately 50 hours.

Uroben XR extended-release tablets should be taken orally, once daily, with or without food, swallowed whole with liquid — do not chew, divide, or crush the tablet. The oral suspension (granules) should be prepared and administered per the manufacturer's instructions, generally with food.

CYP2D6 Substrates (Clinically Significant)

Uroben XR is a moderate inhibitor of the CYP2D6 enzyme. Co-administration with drugs that are CYP2D6 substrates, particularly those with a narrow therapeutic index, can increase their plasma concentrations and requires caution and dose adjustment/monitoring. Examples include certain tricyclic antidepressants (e.g., desipramine, imipramine), some antipsychotics (e.g., thioridazine), and some beta-blockers (e.g., metoprolol).

Digoxin

Co-administration of Uroben XR with digoxin increases digoxin exposure. When starting Uroben XR in a patient already taking digoxin, the lowest dose of digoxin should be used initially, with serum digoxin concentrations monitored and the digoxin dose titrated as needed.

Other Overactive Bladder Medications (Anticholinergics)

Concurrent use of Uroben XR with anticholinergic medications for overactive bladder (e.g., solifenacin) is an approved combination but increases the risk of urinary retention; see Precautions and Warnings.

Warfarin

Uroben XR has shown minimal effect on the pharmacodynamics of warfarin in single-dose studies; data with repeated dosing are limited, so monitoring is reasonable when initiating combination therapy.

The following side effects have been reported with Uroben XR in clinical trials.

Common Side Effects (Monotherapy)

• Hypertension (increased blood pressure)
• Nasopharyngitis (common cold symptoms)
• Urinary tract infection
• Headache

Common Side Effects (Combination Therapy with Solifenacin)

• Dry mouth
• Constipation
• Tachycardia (fast heart rate)

Less Common but Serious Side Effects

• Urinary retention (see Precautions and Warnings)
• Angioedema of the face, lips, tongue, and/or larynx (see Precautions and Warnings)
• Atrial fibrillation (reported rarely)

Pregnancy

There are no adequate and well-controlled studies of Uroben XR in pregnant women, and available data are insufficient to establish a drug-associated risk of major birth defects or miscarriage. Animal reproduction studies have shown skeletal and cardiac findings at systemic exposures well above the human therapeutic exposure. Uroben XR should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; a physician should be consulted before use.

Lactation

There is no information on the presence of Uroben XR in human milk or its effects on the breastfed infant or on milk production; drug-related material has been detected in the milk of lactating animals. The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for Uroben XR and any potential adverse effects on the breastfed child. Consult a physician before use while breastfeeding.

Blood Pressure Increase / Hypertension

Uroben XR can increase blood pressure. It is not recommended for use in patients with severe uncontrolled hypertension (blood pressure ≥180/110 mmHg). Blood pressure should be measured at baseline and periodically during treatment, particularly in patients with pre-existing hypertension. This effect has also been observed in pediatric patients, in whom larger blood pressure increases have been reported, especially in children under 12 years of age.

Urinary Retention

Urinary retention has been reported in patients taking Uroben XR, particularly in patients with bladder outlet obstruction and in patients taking anticholinergic medications for overactive bladder concurrently with Uroben XR. Use Uroben XR with caution in patients with clinically significant bladder outlet obstruction and monitor for signs and symptoms of urinary retention, especially when used together with an anticholinergic OAB agent.

Angioedema

Angioedema of the face, lips, tongue, and/or larynx has been reported with Uroben XR, sometimes occurring after the first dose but also after multiple doses. If involvement of the tongue, hypopharynx, or larynx occurs, Uroben XR should be discontinued immediately and appropriate emergency therapy instituted.

Renal and Hepatic Impairment

Uroben XR requires dose adjustment in moderate renal or hepatic impairment and is not recommended in severe renal impairment (eGFR <15 mL/min/1.73m² or end-stage renal disease) or severe hepatic impairment (Child-Pugh C). See Dosage and Administration for details.

The highest single dose of Uroben XR studied in clinical trials (400 mg in healthy volunteers) was associated with palpitations and increases in heart rate, and higher doses could be expected to cause exaggerated increases in heart rate and blood pressure. In case of suspected overdose of Uroben XR, seek immediate medical attention or contact a poison control center. Management should be symptomatic and supportive, with monitoring of pulse rate, blood pressure, and ECG until the patient is stable.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal Impairment

No dose adjustment of Uroben XR is needed in mild-to-moderate renal impairment (eGFR 30–89 mL/min/1.73m²); maximum 25 mg daily in eGFR 15–29 mL/min/1.73m²; not recommended in eGFR <15 mL/min/1.73m² or end-stage renal disease. See Dosage and Administration.

Hepatic Impairment

No dose adjustment needed in mild hepatic impairment (Child-Pugh A); maximum 25 mg daily in moderate impairment (Child-Pugh B); not recommended in severe hepatic impairment (Child-Pugh C).

Elderly

No overall differences in safety or efficacy of Uroben XR were observed between elderly and younger adult patients in clinical trials, though greater sensitivity in some older individuals cannot be ruled out; use with routine monitoring of blood pressure.

Pediatric

Uroben XR is approved for neurogenic detrusor overactivity in children aged 3 years and older, with weight-based dosing. Safety and efficacy have not been established in children under 3 years of age, and Uroben XR is not approved for overactive bladder in the pediatric population.

The duration of treatment with Uroben XR should be individualized by the treating physician based on symptom response. Clinical response is typically assessed after 4–8 weeks, at which point the dose may be increased if tolerated and needed, or continued long-term for chronic overactive bladder symptom control. Periodic reassessment of continued need and blood pressure monitoring is recommended.

Beta-3 adrenergic receptor agonists; agents for urinary frequency and incontinence.

Mirabegron selectively stimulates beta-3 adrenergic receptors on detrusor smooth muscle, activating adenylate cyclase and increasing intracellular cyclic AMP, which relaxes the bladder during the filling/storage phase and increases bladder capacity, without impairing normal voiding.

Uroben XR is approved for the treatment of neurogenic detrusor overactivity in pediatric patients 3 years of age and older, weighing at least 11 kg (oral suspension granules) or at least 35 kg (extended-release tablets or granules), typically used together with clean intermittent catheterization. Dosing is weight-based and must be individualized by the treating physician. Safety and effectiveness of Uroben XR have not been established in children younger than 3 years, and Uroben XR is not approved for overactive bladder in children. Blood pressure increases have been observed more prominently in pediatric patients, especially those under 12 years, and periodic blood pressure monitoring is recommended.