Package Insert: Information for the User

SILOSTAR 5 mg Tablets

(Nebivolol)

Read this package insert carefully before you start taking this medicine, because it contains important information for you.

Silostar contains nebivolol, a cardiovascular medication, belonging to the group of selective beta-blockers (with selective activity in the cardiovascular system). It prevents an increase in heart rate, and controls the force of heart pumping. It also exerts a vasodilatory action on blood vessels, which in turn contributes to reducing blood pressure.

It is used for the treatment of high blood pressure (hypertension). Silostar is also used for the treatment of mild to moderate chronic heart failure in patients aged 70 or older, administered in combination with other medications.

Do not take Silostar

• If you are allergic to nebivolol or any of its components (listed in section 6).

• If you have one or more of the following conditions:

-Low blood pressure.

-Severe circulation problems in arms or legs.

-Very slow heart rate (less than 60 beats per minute).

-Other severe heart rhythm disorders, such as second- and third-degree atrioventricular block or other conduction disorders.

-Recently experienced a heart failure episode or worsening of the same, or is receiving intravenous treatment to help the heart work, after experiencing circulatory collapse due to acute heart failure.

-Asthma or breathing difficulties (current or past).

-Phaeochromocytoma, a tumor located at the top of the kidneys (adrenal glands), that is not being treated.

-Liver function disorders.

-Metabolic disorders characterized by metabolic acidosis (e.g. diabetic ketoacidosis).

Warnings and precautions

Consult your doctor before starting to take Silostar

Inform your doctor if you have any of the following problems:

• Abnormally slow heart rate.
• A type of chest pain, due to spontaneous spasm of the coronary arteries, called Prinzmetal's angina.
• Untreated chronic heart failure.
• First-degree heart block (mild conduction disorder affecting heart rhythm).
• Poor circulation in arms or legs, such as Raynaud’s disease or pain while walking similar to a cramp.
• Chronic respiratory problems.
• Diabetes: this medication has no effect on blood sugar levels, but may mask warning signs of hypoglycemia (palpitations, rapid heart rate).
• Hyperthyroidism: this medication may mask signs of this disorder, such as abnormally high heart rate.
• Allergies: this medication may intensify your reaction to pollen or other substances to which you are allergic.
• If you have or have had psoriasis, a skin disease characterized by scaly pink patches.
• If you are undergoing surgery, inform your anesthesiologist that you are taking this medication.

If you have severe kidney problems, consult your doctor before taking Silostar to treat heart failure.

You should be regularly monitored by a doctor at the beginning of treatment for chronic heart failure (see section 3).

This treatment should not be stopped abruptly, unless clearly indicated and evaluated by your doctor (see section 3).

Children and adolescents

Do notrecommend the use of Silostar in children and adolescents due to the absence of data on the use of this medication in this type of patients.

Use of Silostar with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

It is essential to inform your doctor or pharmacist if, in addition to Silostar, you are using any of the following medications:

-Some heart medications or blood pressure control medications (such as amiodarone, amlodipine, cibenzoline, clonidine, digoxin, diltiazem, disopyramide, felodipine, flecainide, guanfacine, hydroquinidine, lacidipine, lidocaine, methyldopa, mexiletine, moxonidine, nicardipine, nifedipine, nimodipine, nitrendipine, propafenone, quinidine, rilmenidine, verapamil).

-Sedatives and psychotics (mental illness) medications, such as barbiturates (also used for epilepsy), phenothiazine (also used for vomiting and nausea), and thioridazine.

-Depression medications, such as amitriptyline, paroxetine, and fluoxetine.

-Anesthesia medications used during surgery.

-Asthma medications, decongestants, and some medications for eye disorders such as glaucoma (increased eye pressure) or pupil dilation.

-Baclofen (an antispasmodic medication); Amifostine (a protective medication used during cancer treatment)

All these medications, like Silostar, may affect blood pressure and heart function.

• Medications for treating excessive stomach acid or ulcers (antacids): take Silostar with meals, and the antacid between meals.

Taking Silostar with food and drinks

See section 3.

Pregnancy and breastfeeding

Silostar should not be administered during pregnancy unless your doctor considers it necessary.

It is not recommended to use this medication during breastfeeding.

If you are pregnant or breastfeeding, believe you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

This medication may cause dizziness or fatigue. If so,do notdrive and do not operate machinery.

Silostar contains lactose

This medication containslactose. If your doctor has indicated that you have an intolerance to certain sugars, consult them before taking this medication.

This medication contains less than 1 mmol of sodium (23 mg) per coated tablet; it is essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist.

Silostar can be taken before, during, or after meals, but it can also be taken independently of them. It is preferable to take the tablet with a little water.

Treatment of high blood pressure (hypertension):

• The usual dose is 1 tablet per day. It is preferable to take the dose at the same time every day.
• In elderly patients and/or those with renal impairment, it is recommended to start treatment with 1/2 tablet per day.

The therapeutic effect on blood pressure is achieved after 1-2 weeks of treatment. Occasionally, the optimal effect is not achieved until 4 weeks.

Treatment of chronic heart failure:

• Your treatment should always be initiated under medical supervision.
• Your doctor will start your treatment with 1/4 (quarter) of a tablet per day. The dose will be increased after 1-2 weeks to 1/2 (half) of a tablet per day, then to 1 tablet per day, and finally to 2 tablets per day until the optimal dose for you is achieved. Your doctor will prescribe the correct dose for you at each time and you should follow their instructions exactly.
• The maximum recommended dose is 2 tablets (10 mg) per day.
• The initiation of treatment and each dose increase will be performed under the supervision of an experienced doctor for a period of 2 hours.
• Your doctor will reduce your dose if necessary.
• Do not stop treatment abruptly, as this could worsen your heart failure.
• Patients with severe kidney problems should not take this medication.
• Take the medication once a day, preferably at the same time every day.

If your doctor has instructed you to take 1/4 (quarter) or 1/2 (half) of a tablet per day, follow the instructions below to split the 5 mg nebivolol tablets, scored in a cross shape.

• Place the tablets on a flat, hard surface (e.g. table or countertop), with the scored surface facing up.
• Break the tablet by pressing it with your index fingers from both hands placed on either side of one of the scores (figures 1 and 2).
• Proceed in the same way to split the half-tablet into a quarter (figures 3 and 4).

Figures 1 and 2: Easy breaking of the 5 mg nebivolol tablet scored in a cross shape into a half.

Figures 3 and 4:Easy breaking of the half-tablet of 5 mg nebivolol scored in a cross shape into a quarter.

• Your doctor will decide whether to combine Silostar with other medications to treat your condition.
• Do not administer to children or adolescents.

If you take more Silostar than you should

If you have accidentally taken an overdose of this medication, consult your doctor, pharmacist, or call the Toxicology Information Service, phone 91 562 04 20 indicating the medication and the amount taken.

It is recommended to bring the packaging and the medication leaflet to the healthcare professional.

The most frequent symptoms and signs of a Silostar overdose are a very slow heart rate (bradycardia), low blood pressure with a risk of fainting (hypotension), breathing difficulties like asthma (bronchospasm), and acute heart failure.

If you forget to take Silostar

If you forget to take a dose of Silostar, but remember shortly after the time when you should have taken it, take the daily dose as usual. If a lot of time has passed (several hours), so that you are close to the next dose, skip the missed dose and take the nextdose as scheduled, at the usual time. Do not take a double dose. However, it is essential to try to avoid repeated missed doses of the medication.

If you stop treatment with Silostar

Always consult your doctor before stopping treatment with Silostar, whether you are taking it for high blood pressure or chronic heart failure.

Do not stop treatment abruptly, as this could temporarily worsen your heart failure. If it is necessary to stop treatment for chronic heart failure, the daily dose should be gradually reduced, starting by halving the dose, at intervals of one week.

If you have any other questions about the use of this product, ask your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

WhenusingSilostarfor the treatment of high blood pressure, the possible side effects are:

Frequent side effects (may affect up to 1 in 10 people):

• Headache.
• Dizziness.
• Fatigue.
• Unusual itching or tingling sensation.
• Diarrhea.
• Constipation.
• Nausea.
• Difficulty breathing / feeling of lack of air.
• Sweating of hands and feet.

Rare side effects (may affect up to 1 in 100 people):

• Slow heart rate or other cardiac abnormalities.
• Low blood pressure.
• Painful walking similar to a cramp.
• Abnormal vision.
• Impotence
• Feeling of depression.
• Difficulty digesting (dyspepsia), gas in the stomach or intestines, vomiting.
• Skin rash, itching.
• Difficulty breathing like asthma, due to sudden contraction of the muscles around the airways (bronchial spasm).
• Nightmares.

Very rare side effects (may affect up to 1 in 10,000 people):

• Fainting.
• Worsening of psoriasis, a skin disease characterized by scaly pink patches.

The following side effects have been reported in isolated cases during treatment with Silostar:

• Allergic reactions, such as generalized skin rash (hypersensitivity reactions).
• Sudden swelling of the lips, eyelids, and/or tongue, which may be accompanied by acute difficulty breathing (angioedema).
• Red rash on the skin characterized by pink, raised patches that cause itching, of allergic or non-allergic cause (urticaria).

In a clinical study forchronic heart failure,the following side effects were seen:

Frequent side effects (may affect more than 1 in 10 people):

• Slow heart rate
• Dizziness

Frequent side effects (may affect up to 1 in 10 people):

• Worsening of heart failure.
• Low blood pressure (as feeling of fainting when standing up quickly).
• Intolerance to this medication.
• Mild alteration of cardiac conduction affecting heart rhythm (first-degree atrioventricular block).
• Swelling of the lower extremities (increased volume of ankles).

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of sightand out of reachof children.

Nospecial storage conditions are required.

Do not usethis medicationafter the expiration date that appears on the packaging and in the blisterafter ‘CAD’..The expiration date is the last day of the month indicated.

Do not dispose of medications through drains or regular trash. Dispose of packaging and unused medications at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Silostar

• The active ingredient is nebivolol. Each tablet contains 5 mg of nebivolol (as nebivolol hydrochloride): 2.5 mg of d-nebivolol and 2.5 mg of l-nebivolol.
• The other components are: lactose monohydrate, polisorbate 80 (E-433), hypromellose (E-464), cornstarch, croscarmellose sodium (E-468), microcrystalline cellulose (E-460), anhydrous colloidal silica (E-551), magnesium stearate (E-572).

Appearance of the product and contents of the packaging

Silostar is presented in the form of white, round, cross-scored tablets and in packaging of 7, 14, 28, 30, 50, 56, 90, 100, and 500 tablets.

The tablets are packaged in PVC/aluminum blisters.

Not all packaging sizes may be marketed.

Holder of the marketing authorization

Menarini International Operations Luxembourg S.A.,

1, Avenue de la Gare L-1611, Luxembourg

Local representative:

Guidotti Farma, S.L.

C/Alfons XII, 587

08918 Badalona

(Barcelona) Spain

Responsible for manufacturing

Berlin-Chemie AG

Glienicker Weg 125 - 12489 Berlin, Germany

or

Menarini-Von Heyden GmbH

Leipziger Strasse 7-13, 01097 – Dresden, Germany

or

Qualiphar N.V.

Rijsweg 9, 2880 Bornem, Belgium

This medicine is authorized in the member states of the European Economic Areaand in the United Kingdom (Northern Ireland)with the following names:

Austria: Nomexor

Belgium: Hypoloc

Spain: Silostar

Greece: Hypoloc

Ireland: Nebilet

Italy: Lobivon

Netherlands: Hypoloc

United Kingdom (Northern Ireland): Nebilet

Last review date of this leaflet:August 2018

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/