Betmiga

1 

ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Betmiga 25 mg prolonged-release tablets 
Betmiga 50 mg prolonged-release tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Betmiga 25 mg prolonged-release tablets 
Each tablet contains 25 mg of mirabegron. 
 
Betmiga 50 mg prolonged-release tablets 
Each tablet contains 50 mg of mirabegron. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Prolonged-release tablet. 
 
Betmiga 25 mg tablets 
Oval, brown tablet, debossed with the company logo and “325” on the same side. 
 
Betmiga 50 mg tablets 
Oval, yellow tablet, debossed with the company logo and “355” on the same side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as 
may occur in adult patients with overactive bladder (OAB) syndrome. 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults (including elderly patients) 
The recommended dose is 50 mg once daily 
 
Special populations 

Renal and hepatic impairment 

Betmiga has not been studied in patients with end stage renal disease (GFR < 15 mL/min/1.73 m2 or 
patients requiring haemodialysis) or severe hepatic impairment (Child-Pugh Class C) and it is 
therefore not recommended for use in these patient populations (see sections 4.4 and 5.2). 
 
The following table provides the daily dosing recommendations for subjects with renal or hepatic 
impairment in the absence and presence of strong CYP3A inhibitors (see sections 4.4, 4.5 and 5.2). 
 



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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 
Renal impairment(1) Mild 50 mg 25 mg 

Moderate 50 mg 25 mg 
Severe 25 mg Not recommended 

Hepatic impairment(2) Mild 50 mg 25 mg 
Moderate 25 mg Not recommended 

1. Mild: GFR 60 to 89 mL/min/1.73 m2; moderate: GFR 30 to 59 mL/min/1.73 m2; severe: GFR 
15 to 29 mL/min/1.73 m2. 

2. Mild: Child-Pugh Class A; Moderate: Child-Pugh Class B. 
3. Strong CYP3A inhibitors see section 4.5 
 
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. 
 
4.3 Contraindications 
 
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
- Severe uncontrolled hypertension defined as systolic blood pressure ≥ 180 mm Hg and/or diastolic 

blood pressure ≥ 110 mm Hg. 
 
4.4 Special warnings and precautions for use 
 
Renal impairment 
 
Betmiga has not been studied in patients with end stage renal disease (GFR < 15 mL/min/1.73 m2 or 
patients requiring haemodialysis) and, therefore, it is not recommended for use in this patient 
population. Data are limited in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2); 
based on a pharmacokinetic study (see section 5.2) a dose reduction to 25 mg is recommended in this 
population. This medicinal product is not recommended for use in patients with severe renal 
impairment (GFR 15 to 29 mL/min/1.73 m2) concomitantly receiving strong CYP3A inhibitors (see 
section 4.5). 
 
Hepatic impairment 
 
Betmiga 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. This medicinal product is not 
recommended for use in patients with moderate hepatic impairment (Child-Pugh B) concomitantly 
receiving strong CYP3A inhibitors (see section 4.5). 
 
Hypertension 
 
Mirabegron can increase blood pressure. Blood pressure should be measured at baseline and 
periodically during treatment with mirabegron, especially in hypertensive patients. 
 



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Data are limited in patients with stage 2 hypertension (systolic blood pressure ≥ 160 mm Hg or 
diastolic blood pressure ≥ 100 mm Hg). 
 
Patients with congenital or acquired QT prolongation 
 
Betmiga, at therapeutic doses, has not demonstrated clinically relevant QT prolongation in clinical 
studies (see section 5.1). 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 Betmiga; however, Betmiga should 
be administered with caution to patients with clinically significant BOO. Betmiga should also be 
administered with caution to patients taking antimuscarinic medicinal products for the treatment of 
OAB. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
In vitro data 
 
Mirabegron is transported and metabolised through multiple pathways. Mirabegron is a substrate for 
cytochrome P450 (CYP) 3A4, CYP2D6, butyrylcholinesterase, uridine 
diphospho-glucuronosyltransferases (UGT), the efflux transporter P-glycoprotein (P-gp) and the influx 
organic cation transporters (OCT) OCT1, OCT2, and OCT3. Studies of mirabegron using human liver 
microsomes and recombinant human CYP enzymes showed that mirabegron is a moderate and 
timedependent inhibitor of CYP2D6 and a weak inhibitor of CYP3A. Mirabegron inhibited 
P-gp-mediated drug transport at high concentrations. 
 
In vivo data 
 
Drug-drug interactions 
The effect of co-administered medicinal products on the pharmacokinetics of mirabegron and the 
effect of mirabegron on the pharmacokinetics of other medicinal products was studied in single and 
multiple dose studies. Most drug-drug interactions were studied using a dose of 100 mg mirabegron 
given as oral controlled absorption system (OCAS) tablets. Interaction studies of mirabegron with 
metoprolol and with metformin used mirabegron immediate-release (IR) 160 mg. 
 
Clinically relevant drug interactions between mirabegron and medicinal products that inhibit, induce 
or are a substrate for one of the CYP isozymes or transporters are not expected except for the 
inhibitory effect of mirabegron on the metabolism of CYP2D6 substrates. 
 
Effect of enzyme inhibitors 

Mirabegron exposure (AUC) was increased 1.8-fold in the presence of the strong inhibitor of 
CYP3A/P-gp ketoconazole in healthy volunteers. No dose-adjustment is needed when Betmiga is 
combined with inhibitors of CYP3A and/or P-gp. However, in patients with mild to moderate renal 
impairment (GFR 30 to 89 mL/min/1.73 m2) or mild hepatic impairment (Child-Pugh Class A) 
concomitantly receiving strong CYP3A inhibitors, such as itraconazole, ketoconazole, ritonavir and 
clarithromycin, the recommended dose is 25 mg once daily with or without food (see section 4.2). 
Betmiga is not recommended in patients with severe renal impairment 
(GFR 15 to 29 mL/min/1.73 m2) or patients with moderate hepatic impairment (Child-Pugh Class B) 
concomitantly receiving strong CYP3A inhibitors (see sections 4.2 and 4.4). 



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Effect of enzyme inducers 

Substances that are inducers of CYP3A or P-gp decrease the plasma concentrations of mirabegron. No 
dose adjustment is needed for mirabegron when administered with therapeutic doses of rifampicin or 
other CYP3A or P-gp inducers. 
 
Effect of CYP2D6 polymorphism 
CYP2D6 genetic polymorphism has minimal impact on the mean plasma exposure to mirabegron (see 
section 5.2). Interaction of mirabegron with a known CYP2D6 inhibitor is not expected and was not 
studied. No dose adjustment is needed for mirabegron when administered with CYP2D6 inhibitors or 
in patients who are CYP2D6 poor metabolisers. 
 
Effect of mirabegron on CYP2D6 substrates 
In healthy volunteers, the inhibitory potency of mirabegron towards CYP2D6 is moderate and the 
CYP2D6 activity recovers within 15 days after discontinuation of mirabegron. Multiple once daily 
dosing of mirabegron IR resulted in a 90% increase in Cmax and a 229% increase in AUC of a single 
dose of metoprolol. Multiple once daily dosing of mirabegron resulted in a 79% increase in Cmax and a 
241% increase in AUC of a single dose of desipramine. 
 
Caution is advised if mirabegron is co-administered with medicinal products with a narrow therapeutic 
index and significantly metabolised by CYP2D6, such as thioridazine, Type 1C antiarrhythmics (e.g., 
flecainide, propafenone) and tricyclic antidepressants (e.g., imipramine, desipramine). Caution is also 
advised if mirabegron is co-administered with CYP2D6 substrates that are individually dose titrated. 
 
Effect of mirabegron on transporters 
Mirabegron is a weak inhibitor of P-gp. Mirabegron increased Cmax and AUC by 29% and 27%, 
respectively, of the P-gp substrate digoxin in healthy volunteers. For patients who are initiating a 
combination of mirabegron and digoxin, the lowest dose for digoxin should be prescribed initially. 
Serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain 
the desired clinical effect. The potential for inhibition of P-gp by mirabegron should be considered 
when Betmiga is combined with sensitive P-gp substrates e.g. dabigatran. 
 
Other interactions 

No clinically relevant interactions have been observed when mirabegron was co-administered with 
therapeutic doses of solifenacin, tamsulosin, warfarin, metformin or a combined oral contraceptive 
medicinal product containing ethinylestradiol and levonorgestrel. Dose-adjustment is not 
recommended. 
 
Increases in mirabegron exposure due to drug-drug interactions may be associated with increases in 
pulse rate. 
 
4.6 Fertility, pregnancy and lactation 
 
Woman of childbearing potential 
 
Betmiga is not recommended in women of childbearing potential not using contraception. 
 
Pregnancy 
 
There are limited amount of data from the use of Betmiga in pregnant women. Studies in animals have 
shown reproductive toxicity (see section 5.3). This medicinal product is not recommended during 
pregnancy. 
 



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Breast-feeding 
 
Mirabegron is excreted in the milk of rodents and therefore is predicted to be present in human milk 
(see section 5.3). No studies have been conducted to assess the impact of mirabegron on milk 
production in humans, its presence in human breast milk, or its effects on the breast-fed child. 
 
Betmiga should not be administered during breast-feeding. 
 
Fertility 
 
There were no treatment-related effects of mirabegron on fertility in animals (see section 5.3). The 
effect of mirabegron on human fertility has not been established. 
 
4.7 Effects on ability to drive and use machines 
 
Betmiga has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety of Betmiga 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 Betmiga 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 Betmiga 50 mg during the three 
12-week phase 3 double blind, placebo controlled studies are tachycardia and urinary tract infections. 
The frequency of tachycardia was 1.2% in patients receiving Betmiga 50 mg. Tachycardia led to 
discontinuation in 0.1% patients receiving Betmiga 50 mg. The frequency of urinary tract infections 
was 2.9% in patients receiving Betmiga 50 mg. Urinary tract infections led to discontinuation in none 
of the patients receiving Betmiga 50 mg. Serious adverse reactions included atrial fibrillation (0.2%). 
 
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. 
 



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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   

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 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Mirabegron has been administered to healthy volunteers at single doses up to 400 mg. At this dose, 
adverse events reported included palpitations (1 of 6 subjects) and increased pulse rate exceeding 
100 beats per minute (bpm) (3 of 6 subjects). Multiple doses of mirabegron up to 300 mg daily for 
10 days showed increases in pulse rate and systolic blood pressure when administered to healthy 
volunteers. 



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Treatment for overdose should be symptomatic and supportive. In the event of overdose, pulse rate, 
blood pressure, and ECG monitoring is recommended. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Urologicals, urinary antispasmodics ATC code: G04BD12. 
 
Mechanism of action 
 
Mirabegron is a potent and selective beta 3-adrenoceptor agonist. Mirabegron showed relaxation of 
bladder smooth muscle in rat and human isolated tissue, increased cyclic adenosine monophosphate 
(cAMP) concentrations in rat bladder tissue and showed a bladder relaxant effect in rat urinary bladder 
function models. Mirabegron increased mean voided volume per micturition and decreased the 
frequency of non-voiding contractions, without affecting voiding pressure, or residual urine in rat 
models of bladder overactivity. In a monkey model, mirabegron showed decreased voiding frequency. 
These results indicate that mirabegron enhances urine storage function by stimulating 
beta 3-adrenoceptors in the bladder. 
 
During the urine storage phase, when urine accumulates in the bladder, sympathetic nerve stimulation 
predominates. Noradrenaline is released from nerve terminals, leading predominantly to beta 
adrenoceptor activation in the bladder musculature, and hence bladder smooth muscle relaxation. 
During the urine voiding phase, the bladder is predominantly under parasympathetic nervous system 
control. Acetylcholine, released from pelvic nerve terminals, stimulates cholinergic M2 and M3 
receptors, inducing bladder contraction. The activation of the M2 pathway also inhibits 
beta 3-adrenoceptor induced increases in cAMP. Therefore beta 3-adrenoceptor stimulation should not 
interfere with the voiding process. This was confirmed in rats with partial urethral obstruction, where 
mirabegron decreased the frequency of non-voiding contractions without affecting the voided volume 
per micturition, voiding pressure, or residual urine volume. 
 
Pharmacodynamic effects 
 
Urodynamics 

Betmiga at doses of 50 mg and 100 mg once daily for 12 weeks in men with lower urinary tract 
symptoms (LUTS) and bladder outlet obstruction (BOO) showed no effect on cystometry parameters 
and was safe and well tolerated. The effects of mirabegron on maximum flow rate and detrusor 
pressure at maximum flow rate were assessed in this urodynamic study consisting of 200 male patients 
with LUTS and BOO. Administration of mirabegron at doses of 50 mg and 100 mg once daily for 
12 weeks did not adversely affect the maximum flow rate or detrusor pressure at maximum flow rate. 
In this study in male patients with LUTS/BOO, the adjusted mean (SE) change from baseline to end of 
treatment in post void residual volume (mL) was 0.55 (10.702), 17.89 (10.190), 30.77 (10.598) for the 
placebo, mirabegron 50 mg and mirabegron 100 mg treatment groups. 
 
Effect on QT interval 
Betmiga at doses of 50 mg or 100 mg had no effect on the QT interval individually corrected for heart 
rate (QTcI interval) when evaluated either by sex or by the overall group. 
 
A thorough QT (TQT) study (n = 164 healthy male and n = 153 healthy female volunteers with a mean 
age of 33 years) evaluated the effect of repeat oral dosing of mirabegron at the indicated dose (50 mg 
once daily) and two supra-therapeutic doses (100 and 200 mg once daily) on the QTcI interval. The 
supra-therapeutic doses represent approximately 2.6- and 6.5-fold the exposure of the therapeutic dose, 
respectively. A single 400 mg dose of moxifloxacin was used as a positive control. Each dose level of 
mirabegron and moxifloxacin was evaluated in separate treatment arms each including placebo-control 
(parallel cross-over design). For both males and females administered mirabegron at 50 mg and 



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100 mg, the upper bound of the one-sided 95% confidence interval did not exceed 10 msec at any time 
point for the largest time-matched mean difference from placebo in the QTcI interval. In females 
administered mirabegron at the 50 mg dose, the mean difference from placebo on QTcI interval at 
5 hours post dose was 3.67 msec (upper bound of the one-sided 95% CI 5.72 msec). In males, the 
difference was 2.89 msec (upper bound of the one-sided 95% CI 4.90 msec). At a mirabegron dose of 
200 mg, the QTcI interval did not exceed 10 msec at any time point in males, while in females the 
upper bound of the one-sided 95% confidence interval did exceed 10 msec between 0.5–6 hours, with 
a maximum difference from placebo at 5 hours where the mean effect was 10.42 msec (upper bound of 
the one-sided 95% CI 13.44 msec). Results for QTcF and QTcIf were consistent with QTcI. 
 
In this TQT study, mirabegron increased heart rate on ECG in a dose dependent manner across the 
50 mg to 200 mg dose range examined. The maximum mean difference from placebo in heart rate 
ranged from 6.7 bpm with mirabegron 50 mg up to 17.3 bpm with mirabegron 200 mg in healthy 
subjects. 
 
Effects on pulse rate and blood pressure in patients with OAB 
In OAB patients (mean age of 59 years) across three 12-week phase 3 double blind, placebo controlled 
studies receiving Betmiga 50 mg once daily, an increase in mean difference from placebo of 
approximately 1 bpm for pulse rate and approximately 1 mm Hg or less in systolic blood 
pressure/diastolic blood pressure (SBP/DBP) was observed. Changes in pulse rate and blood pressure 
are reversible upon discontinuation of treatment. 
 
Effect on intraocular pressure (IOP) 
Mirabegron 100 mg once daily did not increase IOP in healthy subjects after 56 days of treatment. In a 
phase 1 study assessing the effect of Betmiga on IOP using Goldmann applanation tonometry in 
310 healthy subjects, a dose of mirabegron 100 mg was non-inferior to placebo for the primary 
endpoint of the treatment difference in mean change from baseline to day 56 in subject-average IOP; 
the upper bound of the two-sided 95% CI of the treatment difference between mirabegron 100 mg and 
placebo was 0.3 mm Hg. 
 
Clinical efficacy and safety 
 
Efficacy of Betmiga was evaluated in three phase 3 randomized, double blind, placebo controlled, 12-
week studies for the treatment of overactive bladder with symptoms of urgency and frequency with or 
without incontinence. Female (72%) and male (28%) patients with a mean age of 59 years (range 18 –
 95 years) were included. The study population consisted of approximately 48% antimuscarinic 
treatment naïve patients as well as approximately 52% patients previously treated with antimuscarinic 
medicinal products. In one study, 495 patients received an active control (tolterodine prolonged release 
formulation). 
 
The co-primary efficacy endpoints were (1) change from baseline to end of treatment in mean number 
of incontinence episodes per 24 hours and (2) change from baseline to end of treatment in mean 
number of micturitions per 24 hours based on a 3-day micturition diary. Mirabegron demonstrated 
statistically significant larger improvements compared to placebo for both co-primary endpoints as 
well as secondary endpoints (see Tables 2 and 3). 
 



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Table 2: Co-primary and selected secondary efficacy endpoints at end of treatment for 
pooled studies 

Parameter 

Pooled studies 
(046, 047, 074) 

Placebo Mirabegron 
50 mg 

Mean number of incontinence episodes per 24 hours (FAS-I) (Co-primary) 
n 878 862 
Mean baseline 2.73 2.71 
Mean change from baseline† -1.10 -1.49 
Mean difference from placebo† (95% CI) -- -0.40 (-0.58, -0.21) 
 p-value -- < 0.001# 
Mean number of micturitions per 24 hours (FAS) (Co-primary) 
n 1328 1324 
Mean baseline 11.58 11.70 
Mean change from baseline† -1.20 -1.75 
Mean difference from placebo† (95% CI) -- -0.55 (-0.75, -0.36) 
 p-value -- < 0.001# 
Mean volume voided (mL) per micturition (FAS) (Secondary) 
n 1328 1322 
Mean baseline 159.2 159.0 
Mean change from baseline† 9.4 21.4 
Mean difference from placebo† (95% CI) -- 11.9 (8.3, 15.5) 
 p-value -- < 0.001# 
Mean level of urgency (FAS) (Secondary) 
n 1325 1323 
Mean baseline 2.39 2.42 
Mean change from baseline† -0.15 -0.26 
Mean difference from placebo† (95% CI) -- -0.11 (-0.16, -0.07) 
 p-value -- < 0.001# 
Mean number of urgency incontinence episodes per 24 hours (FAS-I) (Secondary) 
n 858 834 
Mean baseline 2.42 2.42 
Mean change from baseline† -0.98 -1.38 
Mean difference from placebo† (95% CI) -- -0.40 (-0.57, -0.23) 
 p-value -- < 0.001# 
Mean number of episodes with urgency grades 3 or 4 per 24 hours (FAS) (Secondary) 
n 1324 1320 
Mean baseline 5.61 5.80 
Mean change from baseline† -1.29 -1.93 
Mean difference from placebo† (95% CI) -- -0.64 (-0.89, -0.39) 
 p-value -- < 0.001# 
Treatment satisfaction – visual analogue scale (FAS) (Secondary) 
n 1195 1189 
Mean baseline 4.87 4.82 
Mean change from baseline† 1.25 2.01 
Mean difference from placebo† (95% CI) -- 0.76 (0.52, 1.01) 
 p-value -- < 0.001* 
Pooled studies consisted of studies 046 (Europe/Australia), 047 (North America [NA]) and 074 
(Europe/NA). 
† Least squares mean adjusted for baseline, gender, and study. 
* Statistically significantly superior compared to placebo at the 0.05 level without multiplicity 
adjustment. 
# Statistically significantly superior compared to placebo at the 0.05 level with multiplicity 
adjustment. 



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FAS: Full analysis set, all randomized patients who took at least 1 dose of double blind study drug and 
who had a micturition measurement in the baseline diary and at least 1 post-baseline visit diary with a 
micturition measurement. 
FAS-I: Subset of FAS who also had at least 1 incontinence episode in the baseline diary. 
CI: Confidence Interval 
 
Table 3: Co-primary and selected secondary efficacy endpoints at end of treatment for 

studies 046, 047 and 074 

Parameter 
Study 046 Study 047 Study 074 

Placebo Mirabegron 
50 mg 

Tolterodine 
ER 4 mg 

Placebo Mirabegron 
50 mg 

Placebo Mirabegron 
50 mg 

Mean number of incontinence episodes per 24 hours (FAS-I) (Co-primary) 
n 291 293 300 325 312 262 257 
Mean 
baseline 2.67 2.83 2.63 3.03 2.77 2.43 2.51 

Mean 
change 
from 
baseline† 

-1.17 -1.57 -1.27 -1.13 -1.47 -0.96 -1.38 

Mean 
difference 
from 
placebo† 

-- -0.41 -0.10 -- -0.34 -- -0.42 

95% 
Confidence 
Interval 

-- (-0.72, -0.09) (-0.42, 0.21) -- (-0.66, -0.03) -- (-0.76, -0.08) 

p-value -- 0.003# 0.11 -- 0.026# -- 0.001# 
Mean number of micturitions per 24 hours (FAS) (Co-primary) 
n 480 473 475 433 425 415 426 
Mean 
baseline 11.71 11.65 11.55 11.51 11.80 11.48 11.66 

Mean 
change 
from 
baseline† 

-1.34 -1.93 -1.59 -1.05 -1.66 -1.18 -1.60 

Mean 
difference 
from 
placebo† 

-- -0.60 -0.25 -- -0.61 -- -0.42 

95% 
Confidence 
Interval 

-- (-0.90, -0.29) (-0.55, 0.06) -- (-0.98, -0.24) -- (-0.76, -0.08) 

p-value -- < 0.001# 0.11 -- 0.001# -- 0.015# 
Mean volume voided (mL) per micturition (FAS) (Secondary) 
n 480 472 475 433 424 415 426 
Mean 
baseline 156.7 161.1 158.6 157.5 156.3 164.0 159.3 

Mean 
change 
from 
baseline† 

12.3 24.2 25.0 7.0 18.2 8.3 20.7 

Mean 
difference 
from 
placebo† 

-- 11.9 12.6 -- 11.1 -- 12.4 



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Parameter 
Study 046 Study 047 Study 074 

Placebo Mirabegron 
50 mg 

Tolterodine 
ER 4 mg 

Placebo Mirabegron 
50 mg 

Placebo Mirabegron 
50 mg 

95% 
Confidence 
Interval 

-- (6.3, 17.4) (7.1, 18.2) -- (4.4, 17.9) -- (6.3, 18.6) 

p-value -- < 0.001# < 0.001* -- 0.001# -- < 0.001# 
Mean level of urgency (FAS) (Secondary) 
n 480 472 473 432 425 413 426 
Mean 
baseline 2.37 2.40 2.41 2.45 2.45 2.36 2.41 

Mean 
change 
from 
baseline† 

-0.22 -0.31 -0.29 -0.08 -0.19 -0.15 -0.29 

Mean 
difference 
from 
placebo† 

-- -0.09 -0.07 -- -0.11 -- -0.14 

95% 
Confidence 
Interval 

-- (-0.17, -0.02) (-0.15, 0.01) -- (-0.18, -0.04) -- (-0.22, -0.06) 

p-value -- 0.018* 0.085 -- 0.004* -- < 0.001‡ 
Mean number of urgency incontinence episodes per 24 hours (FAS-I) (Secondary) 
n 283 286 289 319 297 256 251 
Mean 
baseline 2.43 2.52 2.37 2.56 2.42 2.24 2.33 

Mean 
change 
from 
baseline† 

-1.11 -1.46 -1.18 -0.89 -1.32 -0.95 -1.33 

Mean 
difference 
from 
placebo† 

-- -0.35 -0.07 -- -0.43 -- -0.39 

95% 
Confidence 
Interval 

-- (-0.65, -0.05) (-0.38, 0.23) -- (-0.72, -0.15) -- (-0.69, -0.08) 

p-value -- 0.003* 0.26 -- 0.005* -- 0.002‡ 
Mean number of episodes with urgency grades 3 or 4 per 24 hours (FAS) (Secondary) 
n 479 470 472 432 424 413 426 
Mean 
baseline 5.78 5.72 5.79 5.61 5.90 5.42 5.80 

Mean 
change 
from 
baseline† 

-1.65 -2.25 -2.07 -0.82 -1.57 -1.35 -1.94 

Mean 
difference 
from 
placebo† 

-- -0.60 -0.42 -- -0.75 -- -0.59 

95% 
Confidence 
Interval 

-- (-1.02, -0.18) (-0.84, -0.00) -- (-1.20, -0.30) -- (-1.01, -0.16) 

p-value -- 0.005* 0.050* -- 0.001* -- 0.007‡ 



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Parameter 
Study 046 Study 047 Study 074 

Placebo Mirabegron 
50 mg 

Tolterodine 
ER 4 mg 

Placebo Mirabegron 
50 mg 

Placebo Mirabegron 
50 mg 

Treatment satisfaction – visual analogue scale (FAS) (Secondary) 
n 428 414 425 390 387 377 388 
Mean 
baseline 4.11 3.95 3.87 5.5 5.4 5.13 5.13 

Mean 
change 
from 
baseline† 

1.89 2.55 2.44 0.7 1.5 1.05 1.88 

Mean 
difference 
from 
placebo† 

-- 0.66 0.55 -- 0.8 -- 0.83 

95% 
Confidence 
Interval 

-- (0.25, 1.07) (0.14, 0.95) -- (0.4, 1.3) -- (0.41, 1.25) 

p-value -- 0.001* 0.008* -- < 0.001* -- < 0.001* 
† Least squares mean adjusted for baseline, gender and geographical region. 
* Statistically significantly superior compared with placebo at the 0.05 level without multiplicity 
adjustment. 
# Statistically significantly superior compared with placebo at the 0.05 level with multiplicity 
adjustment. 
‡ Not statistically significantly superior compared to placebo at the 0.05 level with multiplicity 
adjustment. 
FAS: Full analysis set, all randomized patients who took at least 1 dose of double blind study drug and 
who had a micturition measurement in the baseline diary and at least 1 post-baseline visit diary with a 
micturition measurement. 
FAS-I: Subset of FAS who also had at least 1 incontinence episode in the baseline diary. 
 
Betmiga 50 mg once daily was effective at the first measured time point of week 4, and efficacy was 
maintained throughout the 12-week treatment period. A randomized, active controlled, long term study 
demonstrated that efficacy was maintained throughout a 1-year treatment period. 
 
Subjective improvement in health-related quality of life measurements 
In the three 12-week phase 3 double blind, placebo controlled studies, treatment of the symptoms of 
OAB with mirabegron once daily resulted in a statistically significant improvement over placebo on 
the following health-related quality of life measures: treatment satisfaction and symptom bother. 
 
Efficacy in patients with or without prior OAB antimuscarinic therapy 
Efficacy was demonstrated in patients with and without prior OAB antimuscarinic therapy. In addition 
mirabegron showed efficacy in patients who previously discontinued OAB antimuscarinic therapy due 
to insufficient effect (see Table 4). 
 



14 

Table 4: Co-primary efficacy endpoints for patients with prior OAB antimuscarinic therapy 

Parameter 

Pooled studies 
(046, 047, 074) 

 
Study 046 

Placebo Mirabegron 
50 mg 

Placebo Mirabegron 
50 mg 

Tolterodine 
ER 4 mg 

 
Patients with prior OAB antimuscarinic therapy 
 
Mean number of incontinence episodes per 24 hours (FAS-I) 
n 518 506 167 164 160 
Mean baseline 2.93 2.98 2.97 3.31 2.86 
Mean change from baseline† -0.92 -1.49 -1.00 -1.48 -1.10 
Mean difference from placebo† -- -0.57 -- -0.48 -0.10 
 95% Confidence Interval -- (-0.81, -0.33) -- (-0.90, -0.06) (-0.52, 0.32) 
Mean number of micturitions per 24 hours (FAS) 
n 704 688 238 240 231 
Mean baseline 11.53 11.78 11.90 11.85 11.76 
Mean change from baseline† -0.93 -1.67 -1.06 -1.74 -1.26 
Mean difference from placebo† -- -0.74 -- -0.68 -0.20 
 95% Confidence Interval -- (-1.01, -0.47) -- (-1.12, -0.25) (-0.64, 0.23) 
 
Patients with prior OAB antimuscarinic therapy who discontinued due to insufficient effect 
 
Mean number of incontinence episodes per 24 hours (FAS-I) 
n 336 335 112 105 102 
Mean baseline 3.03 2.94 3.15 3.50 2.63 
Mean change from baseline† -0.86 -1.56 -0.87 -1.63 -0.93 
Mean difference from placebo† -- -0.70 -- -0.76 -0.06 
 95% Confidence Interval -- (-1.01, -0.38) -- (-1.32, -0.19) (-0.63, 0.50) 
Mean number of micturitions per 24 hours (FAS) 
n 466 464 159 160 155 
Mean baseline 11.60 11.67 11.89 11.49 11.99 
Mean change from baseline† -0.86 -1.54 -1.03 -1.62 -1.11 
Mean difference from placebo† -- -0.67 -- -0.59 -0.08 
 95% Confidence Interval -- (-0.99, -0.36) -- (-1.15, -0.04) (-0.64, 0.47) 
Pooled studies consisted of 046 (Europe/Australia), 047 (North America [NA]) and 074 (Europe/NA). 
† Least squares mean adjusted for baseline, gender, study, subgroup, and subgroup by treatment 
interaction for Pooled Studies and least squares mean adjusted for baseline, gender, geographical 
region, subgroup, and subgroup by treatment interaction for Study 046. 
FAS: Full analysis set, all randomized patients who took at least 1 dose of double blind study drug and 
who had a micturition measurement in the baseline diary and at least 1 post-baseline visit diary with a 
micturition measurement. 
FAS-I: Subset of FAS who also had at least 1 incontinence episode in the baseline diary. 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Betmiga in one or more subsets of the paediatric population in “Treatment of idiopathic overactive 
bladder” and “Treatment of neurogenic detrusor overactivity” (see section 4.2 for information on 
paediatric use). 
 



15 

5.2 Pharmacokinetic properties 
 
Absorption 
 
After oral administration of mirabegron in healthy volunteers mirabegron is absorbed to reach peak 
plasma concentrations (Cmax) between 3 and 4 hours. The absolute bioavailability increased from 29% 
at a dose of 25 mg to 35% at a dose of 50 mg. Mean Cmax and AUC increased more than dose 
proportionally over the dose range. In the overall population of males and females, a 2-fold increase in 
dose from 50 mg to 100 mg mirabegron increased Cmax and AUCtau by approximately 2.9- and 
2.6-fold, respectively, whereas a 4-fold increase in dose from 50 mg to 200 mg mirabegron increased 
Cmax and AUCtau by approximately 8.4- and 6.5-fold. Steady state concentrations are achieved within 
7 days of once daily dosing with mirabegron. After once daily administration, plasma exposure of 
mirabegron at steady state is approximately double that seen after a single dose. 
 
Effect of food on absorption 
 
Co-administration of a 50 mg tablet with a high-fat meal reduced mirabegron Cmax and AUC by 45% 
and 17%, respectively. A low-fat meal decreased mirabegron Cmax and AUC by 75% and 51%, 
respectively. In the phase 3 studies, mirabegron was administered with or without food and 
demonstrated both safety and efficacy. Therefore, mirabegron can be taken with or without food at the 
recommended dose. 
 
Distribution 
 
Mirabegron is extensively distributed. The volume of distribution at steady state (Vss) is approximately 
1670 L. Mirabegron is bound (approximately 71%) to human plasma proteins, and shows moderate 
affinity for albumin and alpha-1 acid glycoprotein. Mirabegron distributes to erythrocytes. In vitro 
erythrocyte concentrations of 14C-mirabegron were about 2-fold higher than in plasma. 
 
Biotransformation 
 
Mirabegron is metabolised via multiple pathways involving dealkylation, oxidation, (direct) 
glucuronidation, and amide hydrolysis. Mirabegron is the major circulating component following a 
single dose of 14C-mirabegron. Two major metabolites were observed in human plasma; both are 
phase 2 glucuronides representing 16% and 11% of total exposure. These metabolites are not 
pharmacologically active. 
 
Based on in vitro studies, mirabegron is unlikely to inhibit the metabolism of co-administered 
medicinal products metabolised by the following cytochrome P450 enzymes: CYP1A2, CYP2B6, 
CYP2C8, CYP2C9, CYP2C19 and CYP2E1 because mirabegron did not inhibit the activity of these 
enzymes at clinically relevant concentrations. Mirabegron did not induce CYP1A2 or CYP3A. 
Mirabegron is predicted not to cause clinically relevant inhibition of OCT-mediated drug transport. 
 
Although in vitro studies suggest a role for CYP2D6 and CYP3A4 in the oxidative metabolism of 
mirabegron, in vivo results indicate that these isozymes play a limited role in the overall elimination. 
In vitro and ex vivo studies have shown the involvement from butyrylcholinesterase, UGT and 
possibly alcohol dehydrogenase (ADH) in the metabolism of mirabegron, in addition to CYP3A4 and 
CYP2D6. 
 
CYP2D6 polymorphism 
In healthy subjects who are genotypically poor metabolisers of CYP2D6 substrates (used as a 
surrogate for CYP2D6 inhibition), mean Cmax and AUCinf of a single 160 mg dose of a mirabegron IR 
formulation were 14% and 19% higher than in extensive metabolisers, indicating that CYP2D6 genetic 
polymorphism has minimal impact on the mean plasma exposure to mirabegron. Interaction of 
mirabegron with a known CYP2D6 inhibitor is not expected and was not studied. No dose adjustment 
is needed for mirabegron when administered with CYP2D6 inhibitors or in patients who are CYP2D6 
poor metabolisers. 



16 

 
Elimination 
 
Total body clearance (CLtot) from plasma is approximately 57 L/h. The terminal elimination half-life 
(t1/2) is approximately 50 hours. Renal clearance (CLR) is approximately 13 L/h, which corresponds to 
nearly 25% of CLtot. Renal elimination of mirabegron is primarily through active tubular secretion 
along with glomerular filtration. The urinary excretion of unchanged mirabegron is dose-dependent 
and ranges from approximately 6.0% after a daily dose of 25 mg to 12.2% after a daily dose of 
100 mg. Following the administration of 160 mg 14C-mirabegron to healthy volunteers, approximately 
55% of the radiolabel was recovered in the urine and 34% in the faeces. Unchanged mirabegron 
accounted for 45% of the urinary radioactivity, indicating the presence of metabolites. Unchanged 
mirabegron accounted for the majority of the faecal radioactivity. 
 
Age 
 
The Cmax and AUC of mirabegron and its metabolites following multiple oral doses in elderly 
volunteers (≥ 65 years) were similar to those in younger volunteers (18–45 years). 
 
Gender 
 
The Cmax and AUC are approximately 40% to 50% higher in females than in males. Gender differences 
in Cmax and AUC are attributed to differences in body weight and bioavailability. 
 
Race 
 
The pharmacokinetics of mirabegron are not influenced by race. 
 
Renal impairment 
 
Following single dose administration of 100 mg Betmiga in volunteers with mild renal impairment 
(eGFR-MDRD 60 to 89 mL/min/1.73 m2), mean mirabegron Cmax and AUC were increased by 6% and 
31% relative to volunteers with normal renal function. In volunteers with moderate renal impairment 
(eGFR-MDRD 30 to 59 mL/min/1.73 m2), Cmax and AUC were increased by 23% and 66%, 
respectively. In volunteers with severe renal impairment (eGFR-MDRD 15 to 29 mL/min/1.73 m2), 
mean Cmax and AUC values were 92% and 118% higher. Mirabegron has not been studied in patients 
with end stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis). 
 
Hepatic impairment 
 
Following single dose administration of 100 mg Betmiga in volunteers with mild hepatic impairment 
(Child-Pugh Class A), mean mirabegron Cmax and AUC were increased by 9% and 19% relative to 
volunteers with normal hepatic function. In volunteers with moderate hepatic impairment (Child-Pugh 
Class B), mean Cmax and AUC values were 175% and 65% higher. Mirabegron has not been studied in 
patients with severe hepatic impairment (Child-Pugh Class C). 
 
5.3 Preclinical safety data 
 
Pre-clinical studies have identified target organs of toxicity that are consistent with clinical 
observations. Transient increases in liver enzymes and hepatocyte changes (necrosis and decrease in 
glycogen particles) were seen in rats. An increase in heart rate was observed in rats, rabbits, dogs and 
monkeys. Genotoxicity and carcinogenicity studies have shown no genotoxic or carcinogenic potential 
in vivo. 
 
No effects on fertility were seen at sub-lethal doses (human equivalent dose was 19-fold higher than 
the maximum human recommended dose (MHRD)). The main findings in rabbit embryofetal 
development studies included malformations of the heart (dilated aorta, cardiomegaly) at systemic 
exposures 36-fold higher than observed at the MHRD. In addition, malformations of the lung (absent 



17 

accessory lobe of the lung) and increased post-implantation loss were observed in the rabbit at 
systemic exposures 14-fold higher than observed at the MHRD, while in the rat reversible effects on 
ossification were noted (wavy ribs, delayed ossification, decreased number of ossified sternebrae, 
metacarpi or metatarsi) at systemic exposures 22-fold higher than observed at the MHRD. The 
observed embryofetal toxicity occurred at doses associated with maternal toxicity. The cardiovascular 
malformations observed in the rabbit were shown to be mediated via activation of the 
beta 1-adrenoceptor. 
 
Pharmacokinetic studies performed with radio-labelled mirabegron have shown that the parent 
compound and/or its metabolites are excreted in the milk of rats at levels that were approximately 
1.7-fold higher than plasma levels at 4 hours post administration (see section 4.6). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Core tablet 
Macrogol 8,000 and 2,000,000 
Hydroxypropylcellulose 
Butylhydroxytoluene 
Magnesium stearate 
 
Film coating 
Betmiga 25 mg prolonged-release tablets 

Hypromellose 2910, 6 mPa.s 
Macrogol 8,000 
Iron oxide yellow (E172) 
Iron oxide red (E172) 
 
Betmiga 50 mg prolonged-release tablets 

Hypromellose 2910, 6 mPa.s 
Macrogol 8,000 
Iron oxide yellow (E172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
Shelf life after first opening of the bottle: 6 months 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
Alu-Alu blisters in cartons containing 10, 20, 30, 50, 60, 90, 100 or 200 tablets. 
HDPE bottles with child-resistant closure of polypropylene (PP) and a silica gel desiccant containing 
90 tablets. Each carton contains one bottle. 
 
Not all pack sizes may be marketed. 
 



18 

6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/809/001 - 018 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 December 2012 
Date of latest renewal: 18 September 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{DD/MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



20 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are 
set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of 
Directive 2001/83/EC and any subsequent updates published on the European medicines web-
portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



23 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Betmiga 25 mg prolonged-release tablets 
mirabegron 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 25 mg of mirabegron 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 prolonged-release tablets 
20 prolonged-release tablets 
30 prolonged-release tablets 
50 prolonged-release tablets 
60 prolonged-release tablets 
90 prolonged-release tablets 
100 prolonged-release tablets 
200 prolonged-release tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Swallow the tablet whole. Do not crush. 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



24 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/809/001 10 prolonged-release tablets 
EU/1/12/809/002 20 prolonged-release tablets 
EU/1/12/809/003 30 prolonged-release tablets 
EU/1/12/809/004 60 prolonged-release tablets 
EU/1/12/809/005 90 prolonged-release tablets 
EU/1/12/809/006 200 prolonged-release tablets 
EU/1/12/809/015 50 prolonged-release tablets 
EU/1/12/809/016 100 prolonged-release tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
betmiga 25 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: 



25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Betmiga 50 mg prolonged-release tablets 
mirabegron 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 50 mg of mirabegron 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
10 prolonged-release tablets 
20 prolonged-release tablets 
30 prolonged-release tablets 
50 prolonged-release tablets 
60 prolonged-release tablets 
90 prolonged-release tablets 
100 prolonged-release tablets 
200 prolonged-release tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Swallow the tablet whole. Do not crush. 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



26 

9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/809/008 10 prolonged-release tablets 
EU/1/12/809/009 20 prolonged-release tablets 
EU/1/12/809/010 30 prolonged-release tablets 
EU/1/12/809/011 60 prolonged-release tablets 
EU/1/12/809/012 90 prolonged-release tablets 
EU/1/12/809/013 200 prolonged-release tablets 
EU/1/12/809/017 50 prolonged-release tablets 
EU/1/12/809/018 100 prolonged-release tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
betmiga 50 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



27 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: 



28 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Betmiga 25 mg prolonged-release tablets 
mirabegron 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



29 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Betmiga 50 mg prolonged-release tablets 
mirabegron 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



30 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BOTTLES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Betmiga 25 mg prolonged-release tablets 
mirabegron 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 25 mg of mirabegron 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 prolonged-release tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Swallow the tablet whole. Do not crush. 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
Use within 6 months after opening of the bottle 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



31 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/809/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
betmiga 25 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: 



32 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BOTTLES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Betmiga 50 mg prolonged-release tablets 
mirabegron 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 50 mg of mirabegron 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 prolonged-release tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Swallow the tablet whole. Do not crush. 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
Use within 6 months after opening of the bottle 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



33 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/809/014 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
betmiga 50 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: 



34 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Betmiga 25 mg prolonged-release tablets 
mirabegron 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 25 mg of mirabegron 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 prolonged-release tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Swallow the tablet whole. Do not crush. 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
Use within 6 months after opening of the bottle 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 



35 

 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/809/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 



36 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Betmiga 50 mg prolonged-release tablets 
mirabegron 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 50 mg of mirabegron 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 prolonged-release tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Swallow the tablet whole. Do not crush. 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
Use within 6 months after opening of the bottle 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



37 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/12/809/014 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
 



38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



39 

Package leaflet: Information for the patient 
 

Betmiga 25 mg prolonged-release tablets 
Betmiga 50 mg prolonged-release tablets 

mirabegron 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
1. What Betmiga is and what it is used for 
2. What you need to know before you take Betmiga 
3. How to take Betmiga 
4. Possible side effects 
5. How to store Betmiga 
6. Contents of the pack and other information 
 
 
1. What Betmiga is and what it is used for 
 
Betmiga contains the active substance mirabegron. It is a bladder muscle relaxant (a so called 
beta 3-adrenoceptor agonist), which reduces the activity of an overactive bladder and treats the related 
symptoms. 
 
Betmiga is used to treat the symptoms of an overactive bladder in adults such as: 
- suddenly needing to empty your bladder (called urgency) 
- having to empty your bladder more than usual (called increased urinary frequency) 
- not being able to control when to empty your bladder (called urgency incontinence) 
 
 
2. What you need to know before you take Betmiga 
 
Do not take Betmiga: 
- if you are allergic to mirabegron or any of the other ingredients of this medicine (listed in 

section 6) 
- if you have very high uncontrolled blood pressure. 
 
Warnings and precautions 
Talk to your doctor or pharmacist before taking Betmiga: 
- if you have trouble emptying your bladder or you have a weak urine stream or if you take other 

medicines for the treatment of overactive bladder such as anticholinergic medicines. 
- if you have kidney or liver problems. Your doctor may need to reduce your dose or may tell you 

not to take Betmiga, especially if you are taking other medicines such as itraconazole, 
ketoconazole (fungal infections), ritonavir (HIV/AIDS) or clarithromycin (bacterial infections). 
Tell your doctor about the medicines that you take. 

- if you have an ECG (heart tracing) abnormality known as QT prolongation or you are taking 
any medicine known to cause this such as 

o medicines used for abnormal heart rhythm such as quinidine, sotalol, procainamide, 
ibutilide, flecainide, dofetilide, and amiodarone; 

o medicines used for allergic rhinitis; 



40 

o antipsychotic medicines (medicines for mental illness) such as thioridazine, 
mesoridazine, haloperidol, and chlorpromazine; 

o anti-infectives such as pentamidine, moxifloxacin, erythromycin, and clarithromycin. 
 
Mirabegron may cause your blood pressure to increase or make your blood pressure worse if you have 
a history of high blood pressure. It is recommended that your doctor check your blood pressure while 
you are taking Mirabegron 
 
Children and adolescents 
Do not give this medicine to children and adolescents under the age of 18 years because the safety and 
efficacy of Betmiga in this age group has not been established. 
 
Other medicines and Betmiga 
Tell your doctor or pharmacist if you are taking, have recently used or might use any other medicines. 
 
Betmiga may affect the way other medicines work, and other medicines may affect how this medicine 
works. 
- Tell your doctor if you use thioridazine (a medicine for mental illness), propafenone or 

flecainide (medicines for abnormal heart rhythm), imipramine or desipramine (medicines used 
for depression). These specific medicines may require dose adjustment by your doctor. 

- Tell your doctor if you use digoxin (a medicine for heart failure or abnormal heart rhythm). 
Blood levels of this medicine are measured by your doctor. If the blood level is out of range, 
your doctor may adjust the dose of digoxin. 

- Tell your doctor if you use dabigatran etexilate (a medicine which is used to reduce the risk of 
brain or body vessel obstruction by blood clot formation in adult patients with an abnormal 
heart beat (atrial fibrillation) and additional risk factors). This medicine may require dose 
adjustment by your doctor. 

 
Pregnancy and breast-feeding 
If you are pregnant, think you may be pregnant or are planning to have a baby you should not take 
Betmiga. 
 
If you are breast feeding, ask your doctor or pharmacist for advice before taking this medicine. It is 
likely that this medicine passes into your breast milk. You and your doctor should decide if you should 
take Betmiga or breastfeed. You should not do both. 
 
Driving and using machines 
There is no information to suggest that this medicine affects your ability to drive or use machines. 
 
 
3. How to take Betmiga 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
The recommended dose is one 50 mg tablet by mouth once daily. If you have kidney or liver 
problems, your doctor may need to reduce your dose to one 25 mg tablet by mouth once daily. You 
should take this medicine with liquids and swallow the tablet whole. Do not crush or chew the tablet. 
Betmiga can be taken with or without food. 
 
If you take more Betmiga than you should 
If you have taken more tablets than you have been told to take, or if someone else accidentally takes 
your tablets, contact your doctor, pharmacist or hospital for advice immediately. 
 
Symptoms of overdose may include a forceful beating of the heart, an increased pulse rate or an 
increased blood pressure. 



41 

 
If you forget to take Betmiga 
If you forget to take your medicine, take the missed dose as soon as you remember. If it is less than 
6 hours before your next scheduled dose, skip the dose and continue to take your medicine at the usual 
time. 
 
Do not take a double dose to make up for a forgotten dose. If you miss several doses, tell your doctor 
and follow the advice given to you. 
 
If you stop taking Betmiga 
Do not stop treatment with Betmiga early if you do not see an immediate effect. Your bladder might 
need some time to adapt. You should continue taking your tablets. Do not stop taking them when your 
bladder condition improves. Stopping treatment may result in recurrence of symptoms of overactive 
bladder. 
 
Do not stop taking Betmiga without talking to your doctor first, as your overactive bladder symptoms 
may come back. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most serious side effects may include irregular heart beat (atrial fibrillation). This is an 
uncommon side effect (may affect up to 1 in 100 people), but if this side effect occurs, immediately 
stop taking the medicine and seek urgent medical advice. 
 
If you get headaches, especially sudden, migraine-like (throbbing) headaches, tell your doctor. These 
may be signs of severely elevated blood pressure. 
 
Other side effects include: 
 
Common side effects (may affect up to 1 in 10 people) 
- Increased heart rate (tachycardia) 
- Infection of the structures that carry urine (urinary tract infections) 
- Nausea 
- Constipation 
- Headache 
- Diarrhoea 
- Dizziness 
 
Uncommon side effects (may affect up to 1 in 100 people) 
- Bladder infection (cystitis) 
- Feeling your heartbeat (palpitations) 
- Vaginal infection 
- Indigestion (dyspepsia) 
- Infection of the stomach (gastritis) 
- Swelling of the joints 
- Itching of the vulva or vagina (vulvovaginal pruritus) 
- Increased blood pressure 
- Increase in liver enzymes (GGT, AST and ALT) 
- Itching, rash or hives (urticaria, rash, rash macular, rash papular, pruritus) 
 



42 

Rare side effects (may affect up to 1 in 1,000 people) 
- Swelling of the eyelid (eyelid oedema) 
- Swelling of the lip (lip oedema) 
- Swelling of the deeper layers of the skin caused by a build-up of fluid, which can affect any part 

of the body including the face, tongue or throat and may cause difficulty in breathing 
(angioedema) 

- Small purple spots on the skin (purpura) 
- Inflammation of small blood vessels mainly affecting the skin (leukocytoclastic vasculitis) 
- Inability to completely empty the bladder (urinary retention) 
 
Very rare side effects (may affect up to 1 in 10,000 people) 
- Hypertensive crisis 
 
Not known side effects (frequency cannot be estimated from the available data) 
- Insomnia 
- Confusion 
 
Betmiga may increase your chances of not being able to empty your bladder if you have bladder outlet 
obstruction or if you are taking other medicines to treat overactive bladder. Tell your doctor right away 
if you are unable to empty your bladder. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Betmiga 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton, blister or bottle after EXP. 
The expiry date refers to the last day of that month. 
 
After first opening of the bottle, the tablets can be stored for 6 months. 
 
This medicine does not require any special storage conditions. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Betmiga contains 
- The active substance is mirabegron. 

Betmiga 25 mg prolonged-release tablets 
Each tablet contains 25 mg of mirabegron. 
Betmiga 50 mg prolonged-release tablets 
Each tablet contains 50 mg of mirabegron. 

- The other ingredients are: 
Tablet core: Macrogols, hydroxypropylcellulose, butylhydroxytoluene, magnesium stearate 
Film-coating: Hypromellose, macrogol, iron oxide yellow (E172), iron oxide red (E172) (25 mg 
tablet only). 



43 

 
What Betmiga looks like and contents of the pack 
Betmiga 25 mg prolonged release film-coated tablets are oval, brown film-coated tablets, debossed 
with the company logo and “325” on the same side. 
Betmiga 50 mg prolonged release film-coated tablets are oval, yellow film-coated tablets, debossed 
with the company logo and “355” on the same side. 
 
Betmiga is available in aluminium-aluminium blister in packs containing 10, 20, 30, 50, 60, 90, 100 or 
200 tablets and in high density polyethylene (HDPE) bottles with silica gel desiccant and 
child-resistant closures containing 90 tablets. 
 
Not all pack sizes may be available in your country. The bottle may not be available in your country. 
 
Marketing Authorisation Holder and Manufacturer 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Astellas Pharma B.V. Branch 
Tél/Tel: +32 (0)2 5580710 
 

Lietuva 
Biocodex UAB 
Tel.: +370 37 408 681 
 

България 
Астелас Фарма ЕООД 
Teл.: +359 2 862 53 72 
 

Luxembourg/Luxemburg 
Astellas Pharma B.V. Branch 
Belgique/Belgien 
Tél/Tel: +32 (0)2 5580710 
 

Česká republika 
Astellas Pharma s.r.o. 
Tel: +420 221 401 500 
 

Magyarország 
Astellas Pharma Kft. 
Tel.: +36 1 577 8200 
 

Danmark 
Astellas Pharma a/s 
Tlf: +45 43 430355 
 

Malta 
Astellas Pharmaceuticals AEBE 
Tel: +30 210 8189900 

Deutschland 
Astellas Pharma GmbH 
Tel.: +49 (0)89 454401 
 

Nederland 
Astellas Pharma B.V. 
Tel: +31 (0)71 5455745 
 

Eesti 
Biocodex OÜ 
Tel: +372 6 056 014 
 

Norge 
Astellas Pharma 
Tlf: +47 66 76 46 00 
 

Ελλάδα 
Astellas Pharmaceuticals AEBE 
Τηλ: +30 210 8189900 
 

Österreich 
Astellas Pharma Ges.m.b.H. 
Tel.: +43 (0)1 8772668 
 

España 
Astellas Pharma S.A. 
Tel: +34 91 4952700 
 

Polska 
Astellas Pharma Sp.z.o.o. 
Tel.: +48 225451 111 



44 

France 
Astellas Pharma S.A.S. 
Tél: +33 (0)1 55917500 
 

Portugal 
Astellas Farma, Lda. 
Tel: +351 21 4401320 

Hrvatska 
Astellas d.o.o 
Tel: +385 1670 0102 
 

România 
S.C.Astellas Pharma SRL 
Tel: +40 (0)21 361 04 95/96/92 
 

Ireland 
Astellas Pharma Co. Ltd. 
Tel: +353 (0)1 4671555 
 

Slovenija 
Astellas Pharma d.o.o 
Tel: +386 14011400 
 

Ísland 
Vistor hf 
Sími: +354 535 7000 
 

Slovenská republika 
Astellas Pharma s.r.o. 
Tel: +421 2 4444 2157 
 

Italia 
Astellas Pharma S.p.A. 
Tel: +39 (0)2 921381 
 

Suomi/Finland 
Astellas Pharma 
Puh/Tel: +358 (0)9 85606000 

Κύπρος 
Ελλάδα 
Astellas Pharmaceuticals AEBE 
Τηλ: +30 210 8189900 
 

Sverige 
Astellas Pharma AB 
Tel: +46 (0)40-650 15 00 
 

Latvija 
Biocodex SIA 
Tel: +371 67 619365 

United Kingdom 
Astellas Pharma Ltd. 
Tel: +44 (0) 203 379 8700 
 

  
 
This leaflet was last revised in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET