mirabegron: package leaflet

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 and reduces neurogenic detrusor overactivity.

Betmiga is used to:
- treat the symptoms of a condition called overactive bladder in adults.
These symptoms include: 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).
- treat a condition called neurogenic detrusor overactivity in children aged 3 to less than 18 years.
Neurogenic detrusor overactivity is a condition in which involuntary bladder contractions occur due to a condition that you are born with or injury to the nerves, which control the bladder. If left untreated, neurogenic detrusor overactivity may lead to damage to your bladder and/or kidneys. Betmiga is used to increase the amount of urine your bladder can hold and reduce urine leakage.

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 or neurogenic detrusor overactivity 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;
o antipsychotic medicines (medicines for mental illness) such as thioridazine, mesoridazine, haloperidol, and chlorpromazine;
o anti-infectives such as pentamidine, moxifloxacin, erythromycin, and clarithromycin.

Betmiga 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 this medicine.
Children and adolescents
Do not give this medicine to children and adolescents under 18 years of age for the treatment of overactive bladder because the safety and efficacy of Betmiga in this population has not been established.

Betmiga is not to be used in children under 3 years of age for the treatment of neurogenic detrusor overactivity.
Other medicines and Betmiga
Tell your doctor or pharmacist if you are taking, have recently taken or might take 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 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 must 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 breast-feed. 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.

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Use in adults with overactive bladder
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 must 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.

Use in children and adolescents (age 3 to less than 18 years) with neurogenic detrusor overactivity Take this medicine by mouth once daily. You must take this medicine with liquids and swallow the tablet whole. Do not crush or chew the tablet. Betmiga must be taken with food. Your doctor will tell you which dose you/your child should take. Your doctor will calculate the correct dose for a patient depending on his or her body weight. You should carefully follow their instructions.
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.
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 12 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 or neurogenic detrusor overactivity.

Do not stop taking Betmiga without talking to your doctor first, as your symptoms of overactive bladder or neurogenic detrusor overactivity may come back.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

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 (may affect up to 1 in 10 people)
- Infection of the structures that carry urine (urinary tract infections)
- Headache
- Dizziness
- Increased heart rate (tachycardia)
- Feeling sick (nausea)
- Constipation
- Diarrhoea

Uncommon (may affect up to 1 in 100 people)
- Vaginal infection
- Bladder infection (cystitis)
- Feeling your heartbeat (palpitations)
- Heart rhythm problems (atrial fibrillation)
- Indigestion (dyspepsia)
- Infection of the stomach (gastritis)
- Itching, rash or hives (urticaria, rash, rash macular, rash papular, pruritus)
- Swelling of the joints
- Itching of the vulva or vagina (vulvovaginal pruritus)
- Increased blood pressure
- Increase in liver enzymes (GGT, AST and ALT)

Rare (may affect up to 1 in 1 000 people)
- Swelling of the eyelid (eyelid oedema)
- Swelling of the lip (lip oedema)
- Inflammation of small blood vessels mainly affecting the skin (leukocytoclastic vasculitis)
- Small purple spots on the skin (purpura)
- 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)
- Inability to completely empty the bladder (urinary retention)

Very rare (may affect up to 1 in 10 000 people)
- Severely high blood pressure (hypertensive crisis)

Not known (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.

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 or blister after EXP. The expiry date refers to the last day of that month.

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.

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).
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.

Not all pack sizes may be available in your country.
Marketing Authorisation Holder
Astellas Pharma Europe B.V.
Sylviusweg 62
2333 BE Leiden
The Netherlands
Manufacturer
Delpharm Meppel B.V.
Hogemaat 2
7942 JG Meppel
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
Astellas Pharma d.o.o.
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
Astellas Pharma d.o.o.
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
France
Astellas Pharma S.A.S.
Tél: + 33 (0)1 55917500

Portugal
Astellas Farma, Lda.
Tel: + 351 21 4401300
Hrvatska
Astellas d.o.o.
Tel: + 385 1670 0102

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

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

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

Ísland
Vistor
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
Astellas Pharma d.o.o.
Tel: + 371 67 619365

This leaflet was last revised in .
Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu.

• Let it stand until foam on the surface of the suspension is gone (approximately 1 to 2 minutes).

• Insert the oral syringe tip into central opening of the bottle adaptor until it is firmly in place.
• Do not withdraw the plunger of the syringe.

upside down.

withdraw the amount prescribed by your doctor from the upside-down bottle. The medicine must be taken within 1 hour of being transferred into the syringe.
• If your doctor prescribed more than 5 ml, the syringe will need to be used twice.

For example, if the dose is 8 ml, withdraw 5 ml first and administer the medicine, then withdraw 3 ml and administer the medicine again.

upright, making sure the plunger of the syringe does not move.
• Gently remove the syringe from the adaptor.
• After completion of dosing, close the bottle with the cap.

been accidently withdrawn.

7.
• Confirm the correct amount has been measured.
8.
• Place the syringe in the mouth and gently push the plunger down to administer the medicine.
9.
• Disassemble the syringe and rinse with warm water.
• Allow time to dry for reuse.

This medicine must not be mixed with other medicines.
If you take more Betmiga than you should
If you have taken too much Betmiga, or if someone else has accidentally taken Betmiga, 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.
If you forget to take Betmiga
If you forget to take your medicine, take the missed dose unless more than 12 hours have passed since the missed dose. If more than 12 hours have passed, 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 if you do not see an immediate effect. Your bladder might need some time to adapt. You should continue taking your medicine. Do not stop taking the medicine when your bladder condition improves. Stopping treatment may result in recurrence of neurogenic detrusor overactivity.

Do not stop taking Betmiga without talking to your doctor first, as your neurogenic detrusor overactivity 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 (may affect up to 1 in 10 people)
- Infection of the structures that carry urine (urinary tract infection)
- Headache
- Dizziness
- Increased heart rate (tachycardia)
- Feeling sick (nausea)
- Constipation
- Diarrhoea

Uncommon (may affect up to 1 in 100 people)
- Vaginal infection
- Bladder infection (cystitis)
- Feeling your heartbeat (palpitations)
- Heart rhythm problems (atrial fibrillation)
- Indigestion (dyspepsia)
- Infection of the stomach (gastritis)
- Itching, rash or hives (urticaria, rash, rash macular, rash papular, pruritus)
- Swelling of the joints
- Itching of the vulva or vagina (vulvovaginal pruritus)
- Increased blood pressure
- Increase in liver enzymes (GGT, AST and ALT)

Rare (may affect up to 1 in 1 000 people)
- Swelling of the eyelid (eyelid oedema)
- Swelling of the lip (lip oedema)
- Inflammation of small blood vessels mainly affecting the skin (leukocytoclastic vasculitis)
- Small purple spots on the skin (purpura)
- 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)
- Inability to completely empty the bladder (urinary retention)

Very rare (may affect up to 1 in 10 000 people)
- Severely high blood pressure (hypertensive crisis)

Not known (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, pouch, or bottle after EXP.
The expiry date refers to the last day of that month.

This medicine does not require any special temperature storage conditions. Store the bottle in the unopened pouch in order to protect from moisture until the time of reconstitution.

Store the oral syringe under clean and dry conditions and protect from sunlight and heat.

Store reconstituted suspension below 25 °C for up to 28 days after the date the suspension is prepared.
Do not refrigerate or freeze. Throw away any remaining medicine 28 days after reconstitution.

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. One bottle of granules for prolonged-release oral suspension contains 830 mg of mirabegron. After reconstitution, one bottle contains 105 ml of oral suspension. Each ml of oral suspension contains 8 mg of mirabegron.
- The other ingredients are methyl parahydroxybenzoate (E218); ethyl parahydroxybenzoate (E214); sodium polystyrene sulfonate; hydrochloric acid, dilute; xanthan gum; hypromellose;
mannitol (E421); magnesium stearate; acesulfame potassium; simethicone; silica, colloidal hydrated. See section 2 “Betmiga contains ethyl parahydroxybenzoate (E214), methyl parahydroxybenzoate (E218), and sodium”.

What Betmiga looks like and contents of the pack
Betmiga granules for prolonged-release oral suspension are yellowish white granules. After reconstitution, the oral suspension is pale brownish yellow suspension.

There are two presentations of Betmiga granules for prolonged-release oral suspension, and both are supplied as several components for reconstitution. One presentation contains:
- In the carton: pouch, 5 ml oral syringe, adaptor, and package leaflet
- In the pouch: measuring cup, amber polyethylene terephthalate (PET) bottle (118 ml) with polypropylene (PP) screw-cap, and desiccant

The other presentation contains:
- In the carton: pouch, 5 ml oral syringe, adaptor, and package leaflet
- In the pouch: amber polyethylene terephthalate (PET) bottle (118 ml) with polypropylene (PP) screw-cap, and desiccant

Not all pack sizes may be marketed.
Marketing Authorisation Holder
Astellas Pharma Europe B.V.
Sylviusweg 62
2333 BE Leiden
The Netherlands
Manufacturer
Delpharm Meppel B.V.
Hogemaat 2
7942 JG Meppel
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
Astellas Pharma d.o.o.
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
Astellas Pharma d.o.o.
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
France
Astellas Pharma S.A.S.
Tél: + 33 (0)1 55917500

Portugal
Astellas Farma, Lda.
Tel: + 351 21 4401300

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

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

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

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

Ísland
Vistor
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
Astellas Pharma d.o.o.
Tel: + 371 67 619365

This leaflet was last revised in .

Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu.