MIRABEGRON STADA

Posology Overactive bladder Adults (including elderly patients) The recommended dose is 50 mg once daily Neurogenic detrusor overactivity in the paediatric population Paediatric patients 3 to less than 18 years of age with NDO may be administered mirabegron prolonged-release products based on the body weight of the patient.

Prolonged-release tablets may be administered to patients weighing 35 kg or more. Alternative formulations are recommended for patients below 35 kg. Patients administered 6 ml oral suspension dose may be switched to 25 mg tablet dose and patients administered 10 ml oral suspension dose may be switched to 50 mg tablet dose.

The recommended starting dose of mirabegron is 25 mg once daily with food. If needed, the dose may be increased to a maximum dose of 50 mg once daily with food after 4 to 8 weeks. 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.

Patients requiring the 25 mg dose should be advised to use other medicinal products containing mirabegron 25 mg available on the market. The tablet of 50 mg is not intended to be divided to obtain the 25 mg dose. Missed dose Patients should be instructed to take any missed doses, unless more than 12 hours have passed since the missed dose.

If more than 12 hours have passed, the missed dose can be skipped, and the next dose should be taken at the usual time. 2). 2).

Table 1:

Daily dosing recommendations for adult OAB patients with renal or hepatic impairment Parameter Classification Dose (mg) Mild/Moderate* 50 Severe** 25Renal impairment(1) ESRD Not recommended Mild* 50 Moderate** 25Hepatic impairment(2) Severe Not recommended 1.

73 m2. 2.

Mild:

Child-Pugh Class A; Moderate: Child-Pugh Class B; Severe: Child-Pugh Class C. * In patients with mild to moderate renal impairment or mild hepatic impairment concomitantly receiving strong CYP3A inhibitors, the recommended dose is no more than 25 mg.

** Not recommended for use in patients with severe renal impairment or moderate hepatic impairment concomitantly receiving strong CYP3A inhibitors. 2).

Summary of the safety profile The safety of mirabegron was evaluated in 8 433 adult patients with OAB, of which 5 648 received at least one dose of mirabegron in the phase 2/3 clinical program, and 622 patients received mirabegron for at least 1 year (365 days).

In the three 12-week phase 3 double blind, placebo controlled studies, 88% of the patients completed treatment with this medicinal product, and 4% of the patients discontinued due to adverse events. Most adverse reactions were mild to moderate in severity.

The most common adverse reactions reported for adult patients treated with mirabegron 50 mg during the three 12-week phase 3 double blind, placebo controlled studies are tachycardia and urinary tract infections. 2% in patients receiving mirabegron 50 mg.

1% patients receiving mirabegron 50 mg. 9% in patients receiving mirabegron 50 mg. Urinary tract infections led to discontinuation in none of the patients receiving mirabegron 50 mg. 2%). Adverse reactions observed during the 1-year (long term) active controlled (muscarinic antagonist) study were similar in type and severity to those observed in the three 12-week phase 3 double blind, placebo controlled studies.

Tabulated list of adverse reactions The table below reflects the adverse reactions observed with mirabegron in adults with OAB in the three 12-week phase 3 double blind, placebo controlled studies. The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000) and not known (cannot be established from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. MedDRA System organ class Common Uncommon Rare Very rare Not known (cannot be estimated from the available data) Infections and infestations Urinary tract infection Vaginal infection Cystitis Psychiatric disorders Insomnia* Confusional state* Nervous system disorders Headache* Dizziness* Eye disorders Eyelid oedema Cardiac disorders Tachycardia Palpitation Atrial fibrillation Vascular disorders Hypertensive crisis* Gastrointestinal disorders Nausea* Constipation* Diarrhoea* Dyspepsia Gastritis Lip oedema Hepatobiliary disorders GGT increased AST increased ALT increased Skin and subcutaneous tissue disorders Urticaria Rash Rash macular Rash papular Pruritus Leukocytoclastic vasculitis Purpura Angioedema* Musculoskeletal and connective tissue disorders Joint swelling Renal and urinary disorders Urinary retention* Reproductive system and breast disorders Vulvovaginal pruritus Investigations Blood pressure increased, GGT increased, AST increased, ALT increased *observed during post-marketing experience Paediatric population The safety of mirabegron tablets and oral suspension was evaluated in 86 paediatric patients aged 3 to less than 18 years with neurogenic detrusor overactivity in a 52- week, open-label, baseline-controlled, multicentre, dose titration study.

73 m2 or patients requiring haemodialysis) and, therefore, it is not recommended for use in this patient population. 2) a dose of 25 mg once daily is recommended in this population. 5). Hepatic impairment Mirabegron has not been studied in patients with severe hepatic impairment (Child- Pugh Class C) and, therefore, it is not recommended for use in this patient population.

5). Hypertension Overactive bladder in adults Mirabegron can increase blood pressure. Blood pressure should be measured at baseline and periodically during treatment with mirabegron, especially in hypertensive patients. Data are limited in patients with stage 2 hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg).

Neurogenic detrusor overactivity in the paediatric population Mirabegron can increase blood pressure in 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 with mirabegron. 1). However, since patients with a known history of QT prolongation or patients who are taking medicinal products known to prolong the QT interval were not included in these studies, the effects of mirabegron in these patients is unknown.

Caution should be exercised when administering mirabegron in these patients. Patients with bladder outlet obstruction and patients taking antimuscarinics medicinal products for OAB Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medicinal products for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron.

A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients treated with mirabegron; however, mirabegron should be administered with caution to patients with clinically significant BOO.

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