MIRABEGRON SANDOZ

2). 2).

Table 1:

Daily dosing recommendations for subjects with renal or hepatic impairment in the absence and presence of strong CYP3A inhibitors Strong CYP3A inhibitors(3) Without inhibitor With inhibitor Mild 50 mg 25 mg Moderate 50 mg 25 mg Renal impairment(1) Severe 25 mg Not recommended Mild 50 mg 25 mgHepatic impairment(2) Moderate 25 mg Not recommended 1.

73 m2. 2.

Mild:

Child-Pugh Class A; Moderate: Child-Pugh Class B. 3. 5 Gender No dose adjustment is necessary according to gender. Paediatric population The safety and efficacy of mirabegron in children below 18 years of age have not yet been established.

No data are available. Method of administration 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.

Summary of the safety profile The safety of mirabegron was evaluated in 8433 patients with OAB, of which 5648 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 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 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 Infections and infestations Urinary tract Vaginal infection Psychiatric disorders Insomnia* Confusion al state* Nervous system disorders Headache* Dizziness* Eye disorders Eyelid oedema Cardiac disorders Tachycardia Palpitation Atrial Vascular disorders Hypertensive crisis* Gastrointestinal disorders Nausea* Constipation * Diarrhoea* Dyspepsia Gastritis Lip oedema Skin and subcutaneous tissue disorders Urticaria Rash Rash macular Rash papular Leukocytoclastic vasculitis Purpura Angioedema* MedDRA System organ class Common Uncommon Rare Very rare Not known (cannot be estimated from the Musculoskeletal and connective tissue disorders Joint swelling Renal and urinary Urinary retention* Reproductive system and breast disorders Vulvovaginal pruritus Investigations Blood pressure increased GGT increased AST *observed during post-marketing experience Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

73 m2 or patients requiring haemodialysis) and, therefore, it is not recommended for use in this patient population. 2) a dose reduction to 25 mg 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 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).

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.

Mirabegron should also be administered with caution to patients taking antimuscarinic medicinal products for the treatment of OAB.

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