BETMIGA™ (mirabegron) is indicated for symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with overactive bladder (OAB) syndrome. Treatment of neurogenic
detrusor overactivity (NDO) in paediatric patients aged 3 to less than 18 years.1

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BETMIGA is a selective and potent beta 3-adrenoceptor agonist established in clinical practice for more than a decade for the treatment of patients with overactive bladder (OAB).1 

BETMIGA was approved by EMA in 2012.1

EFFICACY

BETMIGA significantly reduces incontinence episodes vs. placebo1,2

This graph shows improvements in micturitions in the SCORPIO trial. The x-axis represents time from baseline to week 12, and the y-axis represents the mean change from baseline. The graph compares three groups: Betmiga 50mg, placebo, and Tolterodine ER 4mg. Betmiga 50mg shows a significant improvement in micturitions over the 12-week period compared with placebo. Figure adapted from Khullar et al. 2013.

BETMIGA significantly reduces micturition frequency vs. placebo1,2

This graph shows improvements in incontinence episodes in the SCORPIO trial. The x-axis represents time from baseline to week 12, and the y-axis represents the mean change from baseline. The graph compares three groups: Betmiga 50mg, placebo, and Tolterodine ER 4mg. Betmiga 50mg shows a significant improvement in incontinence episodes over the 12-week period compared with placebo. Figure adapted from Khullar et al. 2013.

PRACTICAL USE AND SAFETY

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How to initiate treatments for OAB

For adults (including elderly patients) with OAB the recommended dose is BETMIGA 50 mg once daily. The tablet is to be taken with liquids, swallowed whole and is not to be chewed, divided, or crushed. It may be taken with or without food.1

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Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients.1


Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg.1

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Adverse events

Like all medicines, BETMIGA can cause adverse reactions although not everybody gets them. Common adverse reactions (≥1/100 to <1/10) are urinary tract infection, headache*, dizziness*, tachycardia, nausea*, constipation* and diarrhoea*.1 (*=observed during post-marketing surveillance.)

NB: Follow-up consultations can improve the persistence to the overactive bladder treatment.3

ELDERLY PATIENTS

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The prevalence of OAB increases with age, affecting approximately 30% of individuals >65 years of age4 which makes the study design of the PILLAR study very relevant for clinical practice. The PILLAR study is a phase IV study comparing flexibly dosed (25–50 mg) BETMIGA* versus placebo in elderly patients with OAB and urgency incontinence.5

The patient population represents a subpopulation of the patients in the randomised placebo-controlled trials described in BETMIGA SmPC and comprises elderly patients, including those aged 75 years and older, having several comorbidities and concomitant medications. A patient group who is often underrepresented in clinical trials.

Relevant patient population for 
clinical practice

Baseline5

  • ≥65 years (28% ≥75 years)
  • Comorbidities: mean 8.2 (hypertension 58%; osteoarthritis 36%)
  • Polypharmacy: mean 6.5 concomitant medications
  • Mild or moderate cognitive impairment in 25% (by the MoCA test6)
  • OAB wet

BETMIGA was well tolerated5

  • Findings were consistent with the known BETMIGA safety profile1
  • Overall TEAE rates were similar in both groups, see table 1 below
  • The most common TEAEs in BETMIGA-treated patients were urinary tract infection, headache and diarrhoea





Improvements in OAB symptoms5

Statistically significant improvements in primary endpoints from baseline to EOT, BETMIGA (n=437) vs placebo (n=430)

  • Mean number of micturitions/24h/Age≥65: Difference (SE): –0.7 (0.2); 95% CI: –1.0, –0.3; p<0.001
  • Mean number of incontinence episodes/24h/Age≥65: Difference (SE): –0.6 (0.1); 95% CI: –0.8, 
–0.3; p<0.001
  • Findings were consistent with Phase 3 trials7

No relevant change in cognitive function5

  • No statistically relevant change in cognitive function as measured by the MoCA
  • From baseline to EOT, with adjusted mean (SE) changes of –0.1 (0.1) points for placebo and –0.2 (0.1) for BETMIGA 
Tabel1

Table 1. Adapted from Wagg A, et al, 2020. Incidences of TEAEs were similar in both groups (safety analysis set).


*The recommended BETMIGA dose for adults based on the SmPC is 50 mg daily, whereas patients in this study initially received 25 mg daily and only increased their dose to 50 mg after Week 4 or 8 based on individual efficacy/tolerability and investigator discretion.

 

MoCA=The Montreal Cognitive Assessment; EOT=End of Treatment; SE=Standard Error; TEAE=Treatment Emergent Adverse Event

PAEDIATRIC PATIENTS WITH NDO

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Indication: Treatment of neurogenic detrusor overactivity (NDO) in paediatric patients aged 3 to less than 18 years.1

Neurogenic detrusor overactivity is defined as involuntary detrusor contractions during bladder filling, where a relevant neurological cause is present. The most common cause of NDO is congenital spinal defects; other causes include spinal cord injuries or central nervous system abnormalities.8

A main objective for treatment is to maintain low bladder pressure during storage and voiding in order to avoid associated complications such as urinary tract infections, bladder stones, fibrosis, trabeculation, and autonomic dysreflexia.8

The NDO indication for paediatric patients is based on reference 8: Baka-Ostrowska M, Bolong DT, Persu C, et al. Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study. Neurourol Urodyn. 2021;40(6):1490-1499.

Dosage and administration

Only for administration to patients weighing 35 kg or more. Starting dose is 25 mg once daily with food. The tablet is to be taken with liquids, swallowed whole, and is not to be chewed, divided, or crushed. The dose may be increased to a maximum dose of 50 mg once daily with food after 4 to 8 weeks if needed. During long‑term therapy, patients should be periodically evaluated for treatment continuation and for potential dose adjustment, at least annually or more frequently if indicated.1

Mirabegron may increase blood pressure in paediatric patients. Blood pressure increases may be larger in children (ages 3 to under 12) compared to adolescents (ages 12 to under 18). Blood pressure should be measured at baseline and regularly monitored during treatment with mirabegron.1

 

For dosing recommendations for children and adolescents with impaired kidney or liver function, see Table 2 in the SmPC.1

 

Adverse events


In the paediatric patients with NDO, no severe adverse reactions were reported.1,8 The most commonly reported adverse reactions observed in the paediatric population were urinary tract infection, constipation, and nausea.1 Overall, the safety profile in children and adolescents is similar to that observed in adults.1

 

Contraindications


Hypersensitivity to the active substance(s) or to any of the excipients. Severe uncontrolled hypertension defined as systolic blood pressure ≥ 180 mm Hg and/or diastolic blood pressure ≥ 110 mm Hg.1

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REFERENCES:

1. BETMIGA SmPC 08.2024. 2. Khullar V, Amarenco G, Angulo JC, et al. Efficacy and tolerability of mirabegron, a beta(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial. Eur Urol. 2013;63(2):283-295 (Study 046 in SmPC). 3. Ali M, Grogan S, Powell S, et al. Qualitative analysis of factors influencing patient persistence and adherence to prescribed overactive bladder medication in UK primary care. Adv ther. 2019;36:3110-22. 4. Nitti VW, Khullar V, van Kerrebroeck P, et al. Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomised, double-blind, placebo-controlled, phase III studies. Int J Clin Pract. 2013;67(7):619-632. 5. Wagg A, Staskin D, Engel E, et al. Efficacy, safety, and tolerability of mirabegron in patients aged ≥65 year with overactive bladder wet: a phase IV, double-blind, randomized, placebo-controlled study (PILLAR). Eur Urol. 2020;77:211-220. 6. Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695-699. 7. Wagg A, Cardozo L, Nitti VW, et al. The efficacy and tolerability of the beta3-adrenoceptor agonist mirabegron for the treatment of symptoms of overactive bladder in older patients. Age Ageing. 2014;43:666-675. 8. Baka-Ostrowska M, Bolong DT, Persu C, et al. Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study. Neurourol Urodyn. 2021;40(6):1490-1499.

COMPULSORY INFORMATION

BETMIGA™ (mirabegron) 25 and 50 mg prolonged-release tablets

Pharmacotherapeutic group: Urologicals, urinary antispasmodics (G04BD12).
Therapeutic indications: Symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with overactive bladder (OAB) syndrome. Treatment of neurogenic detrusor overactivity (NDO) in paediatric patients aged 3 to less than 18 years.
*Posology and administration: For adults with OAB (≥ 18 years and elderly): 50 mg once daily, with or without food. For paediatric patients 3 to less than 18 years of age with NDO: Only for administration to patients weighing 35 kg or more. Starting dose is 25 mg once daily with food. The dose may be increased to a maximum dose of 50 mg once daily with food after 4 to 8 weeks if needed. For patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2) or with moderate hepatic impairment (Child-Pugh Class B), a maximum dose of 25 mg is recommended.
To be taken with liquids, swallowed whole and is not to be chewed, divided, or crushed.
Contraindications: Hypersensitivity to the active substance(s) or to any of the excipients.
Severe uncontrolled hypertension defined as systolic blood pressure ≥ 180 mm Hg and/or diastolic blood pressure ≥ 110 mm Hg
*Special warnings and precautions for use: Renal and hepatic impairment: Betmiga has not been studied in patients with end stage renal disease (GFR < 15 mL/min/1.73 m2), patients requiring haemodialysis or patients with severe hepatic impairment (Child-Pugh Class C) and it is therefore not recommended for use in these patient populations. Betmiga is not recommended for use in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2) or patients with moderate hepatic impairment (Child-Pugh B) concomitantly receiving strong CYP3A inhibitors. Hypertension: Can increase blood pressure in both adults and paediatric patients. Blood pressure increases may be larger in children (3 to less than 12 years of age) than in adolescents (12 to less than 18 years of age). Blood pressure should be measured at baseline and periodically during treatment, especially in hypertensive patients. Administer with caution to patients with congenital or acquired QT prolongation, patients with clinically significant bladder outlet obstruction and patients on antimuscarinic treatment of OAB. Pregnancy, lactation and fertility: Is not recommended in women of childbearing potential not using contraception, nor during pregnancy or breast feeding. The effect of mirabegron on human fertility has not been established.
*Undesirable effects: The most common (< 10 %) adverse drug reactions (ADRs) are tachycardia, urinary tract infection, headache, dizziness, nausea, constipation and diarrhoea. Insomnia and confusional state have been reported at an unknown frequency. Overall, the safety profile in children and adolescents is similar to that observed in adults. In the paediatric patients with NDO, no severe adverse reactions have been reported. The most commonly reported adverse reactions observed in the paediatric population are urinary tract infection, constipation, and nausea.
Marketing authorisation holder: Astellas Pharma Europe B.V., The Netherlands.
Country specific information
Sweden: Status of the product: Rx. Reimbursement: Only reimbursed for patients that have tried but cannot tolerate antimuscarinic pharmaceuticals. Local representative: Astellas Pharma AB, Tel: +46 (0)40 650 15 00. For more information, pack size and price see www.fass.se.

Based on the authorised summary of product characteristics (SmPC) dated 22 August 2024.

*The section has been rewritten and/or abbreviated compared to the authorised SmPC.

The SmPC can be ordered free of charge from the local representative.