Prospect: Information for the user

SILOSTAR PLUS 5 mg/ 25 mg film-coated tablets

Nebivolol/ Hydrochlorothiazide

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

Silostar Plus contains nebivolol and hydrochlorothiazide as active ingredients.

• Nebivolol is 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 heart's pumping force. It also acts by widening blood vessels, which helps to lower blood pressure.
• Hydrochlorothiazide is a diuretic that acts by increasing urine production.

Silostar Plus is a combination of nebivolol and hydrochlorothiazide in a tablet and is used for the treatment of high blood pressure (hypertension). It is used in patients who are already taking the two products separately.

Do not take Silostar Plus

• If you are allergic to nebivolol, or to hydrochlorothiazide, or to any of the other components of this medication (listed in section 6).
• If you are allergic (hypersensitive) to other sulfonamide-derived substances (such as hydrochlorothiazide, which is a sulfonamide-derived medication).

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

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

-Other severe heart rhythm disorders (for example, heart block, atrioventricular block of 2or3degree).

-You have recently had an episode of heart failure or a worsening of the same, or you are receiving intravenous treatment to help the heart work, after suffering a circulatory collapse due to acute heart failure.

-Low blood pressure.

-Severe circulation problems in arms or legs.

-Phaeochromocytoma, a tumor located in the upper part of the kidneys (adrenal glands), that is not being treated.

-Severe kidney problems, complete absence of urine (anuria).

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

-Asthma or breathing difficulties (currently or in the past).

-Liver function disorders.

-Persistent and resistant high levels of calcium in the blood and low levels of potassium and sodium in the blood.

-High levels of uric acid with gout symptoms.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Silostar Plus.

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

• Angina of Prinzmetal, a type of chest pain due to spontaneous spasm of the coronary arteries.
• First-degree heart block (mild alteration of cardiac conduction that affects heart rate).
• Abnormally slow heart rate.
• Untreated chronic heart failure.
• Lupus erythematosus (a disorder of the immune system, which is the body's defense system).
• Psoriasis (a skin disease characterized by scaly, pink patches), or if you have ever had psoriasis.
• Hyperthyroidism: this medication may mask signs due to this condition, such as abnormally high heart rate.
• Circulation problems in arms or legs, such as Raynaud’s disease or syndrome, or walking pain similar to a cramp.
• Allergies: this medication may intensify your reaction to pollen or other substances to which you are allergic.
• Chronic respiratory problems.
• Diabetes: this medication may mask warning signs produced by a drop in blood sugar levels (e.g. palpitations, rapid heart rate); your doctor will advise you to control blood sugar levels more frequently while taking Silostar Plus, as you may need to adjust the dose of antidiabetic medications you are taking.
• Kidney problems: your doctor will check your kidney function to ensure it does not worsen. If you have severe kidney problems, do not take Silostar Plus (see section “Do not take Silostar Plus”).
• If you are prone to low potassium levels in the blood, and especially if you have the long QT syndrome (a type of abnormality in the ECG) or you are taking digitalis (to help the heart beat); you are more likely to have low potassium levels if you have liver cirrhosis, or if you have had excessive water loss due to strong diuretic treatment, or if your potassium intake with food and drink is inadequate.
• If you are to undergo surgery, inform your anesthetist that you are taking Silostar Plus before being anesthetized.
• If you have had skin cancer or if a skin lesion appears unexpectedly during treatment. The treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). Protect your skin from exposure to the sun and UV rays while taking Silostar Plus.
• If you experience a decrease in vision or eye pain, they may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure, which can occur within a few hours to several weeks after taking Silostar Plus. This can lead to permanent vision loss if not treated. If you have previously had an allergy to penicillins or sulfonamides, you may be at higher risk of developing it.
• If you have had respiratory or pulmonary problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience severe shortness of breath or difficulty breathing after taking Silostar Plus, seek medical attention immediately.

• Silostar Plus may increase levels of fats in the blood and uric acid. It may affect levels of certain substances in the blood, called electrolytes: your doctor will check them from time to time through blood tests.
• The hydrochlorothiazide in Silostar Plus may cause photosensitivity in your skin to sunlight or artificial UV light. If during treatment you develop a rash, itching, or sensitive skin, stop taking Silostar Plus and inform your doctor (see also Section 4).
• Antidoping tests: Silostar Plus may produce a positive analytical result in antidoping tests.

Children and adolescents

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

Use of Silostar Plus with other medications

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

Always inform your doctor if, in addition to Silostar Plus, you are using or receiving any of the following medications:

• Medications that, like Silostar Plus, may affect blood pressure and/or heart function:

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

-Sedatives and medications for psychosis (a mental disorder), for example amisulpiride, barbiturates (also used for epilepsy), chlorpromazine, ciamemazine, droperidol, haloperidol, levomepromazine, phenothiazine (also used for vomiting and nausea), pimozide, sulpiride, sultopride, thioridazine, tiapride, trifluoperazine.

-Medications for depression, for example amitriptyline, paroxetine, fluoxetine.

-Medications used for anesthesia during surgery.

-Medications for asthma, for nasal congestion, and to treat certain eye disorders such as glaucoma (increased eye pressure) or pupil dilation.

-Baclofen (an antispasmodic medication).

-Amifostine (a protective medication used during cancer treatment).

• Medications whose effect or toxicity may be increased by Silostar Plus:
• Lithium (used as a mood stabilizer).
• Cisapride (used for digestive problems).
• Bepridil (used for angina pectoris).
• Difemanil (used to treat excessive sweating).
• Medications for infections: erythromycin administered by infusion or injection, pentamidine, and ciprofloxacin, amphotericin, and penicillin G sodium, halofantrine (used for malaria).
• Vincamine (used for cerebral circulation problems).
• Mizolastine and terfenadine (used for allergies).
• Diuretics and laxatives.
• Medications to treat acute inflammation: steroids (e.g. cortisone and prednisone), ACTH (adrenocorticotropic hormone), and medications derived from salicylic acid (e.g. aspirin and other salicylates).
• Carbenoxolone (used for heartburn and stomach ulcers).
• Calcium salts (used as a supplement for bone health).
• Medications used to relax muscles (e.g. tubocurarine).
• Diaxozide (used to treat low blood sugar levels and high blood pressure).
• Amantadine, an antiviral medication.
• Ciclosporin, used to suppress the body's immune response.
• Iodinated contrast media, used to contrast in X-ray scans.
• Cancer chemotherapy medications (e.g. cyclophosphamide, fluorouracil, methotrexate).
• Medications whose effect may be decreased by Silostar Plus:
• Medications that lower blood sugar levels (insulin and oral antidiabetic medications, metformin).
• Medications for gout (e.g. allopurinol, probenecid, and sulfinpyrazone).
• Medications such as norepinephrine, used to treat low blood pressure and slow heart rate.
• Medications for pain and inflammation (non-steroidal anti-inflammatory medications), which may lower blood pressure by reducing the effect of Silostar Plus.
• Medications to treat excessive stomach acid or ulcers (antacids): take Silostar Plus with meals, and antacids between meals.

Taking Silostar Plus with alcohol

Be careful when taking alcohol while taking Silostar Plus, as you may feel dizzy or lightheaded. If this happens, do not drink any alcohol, including wine, beer, or drinks that contain alcohol.

Pregnancy and breastfeeding

Inform your doctor if you are pregnant or think you may be pregnant. Your doctor will advise you to take another medication instead of Silostar Plus, as this medication is not recommended during pregnancy. This is because the active ingredient hydrochlorothiazide crosses the placenta and its use after the third month of pregnancy may cause potentially harmful fetal and neonatal effects.

Inform your doctor if you are breastfeeding or plan to start. Silostar Plus is not recommended for mothers who are breastfeeding.

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

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

Silostar Plus contains lactose and sodium

This medication containslactose. If your doctor has told you that you have a certain sugar intolerance,consultyour doctor 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 medication administration instructions indicated by your doctor. In case of doubt, consult your doctor again.

Take one tablet a day with a little water, preferably at the same time of day.

Silostar Plus can be taken before, during, or after meals, but it can also be taken independently of them.

Use in children and adolescents

Do not administer Silostar Plus to children or adolescents.

If you take more Silostar Plus than you should

If you have accidentally taken an overdose of this medication, consultimmediatelyyour doctor, pharmacist, or call the Toxicological 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 overdose are very slow heart rate (bradycardia), low blood pressure with a possibility of fainting, difficulty breathing like in asthma, acute heart failure, excessive urine elimination with subsequent dehydration, nausea, and drowsiness, muscle spasms, and alterations in heart rhythm (especially if you are taking digitalis or medications to treat heart rhythm problems).

If you forgot to take Silostar Plus

If you forgot to take a dose of Silostar Plus, but remember a little later than when you should have taken it, take the daily dose as you normally do. However, if a lot of time has passed (several hours), so that you are near the next dose, skip the missed dose and take the next scheduled dose, 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 interrupt treatment with Silostar Plus

Always consult your doctor before interrupting treatment with Silostar Plus.

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

Like all medicines, this medicine can have side effects, although not everyone will experience them.

• The following side effects have been reported with the use of nebivolol:

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

• Headache.
• Dizziness.
• Fatigue.
• Uncommon sensation of burning, itching, or tingling in the skin.
• Diarrhea.
• Constipation.
• Nausea.
• Difficulty breathing, feeling of lack of air.
• Sweating of hands and feet.

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

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

• Generalized skin rash (hypersensitivity reactions);
• Sudden swelling, especially around the lips, eyes, or tongue with possible acute respiratory difficulty (angioedema).
• Characterized by pink, raised patches, with itching, of allergic or non-allergic cause (urticaria).

• The following side effects have been reported with the use of hydrochlorothiazide:

Unknown frequency: Skin and lip cancer (non-melanoma skin cancer)

Allergic reactions

• Systemic allergic reaction (anaphylactic reaction).

Heart and circulation

• Cardiac arrhythmias, palpitations.
• Changes in the electrocardiogram.
• Sudden fainting when standing up, formation of blood clots in the veins (thrombosis) and embolism, circulatory collapse (shock).

Blood

• Changes in the number of blood cells, such as: decrease in white blood cells, decrease in platelets, decrease in red blood cells; alteration of the production of new blood cells in the bone marrow.
• Alteration of the levels of body fluids (dehydration) and of the levels of chemical substances in the blood, particularly decrease in potassium, sodium, magnesium, chloride, and increase in calcium levels.
• Increased levels of uric acid, gout, increased blood glucose, diabetes, metabolic alkalosis (a metabolic disorder), increased cholesterol and/or triglycerides in the blood.

Stomach and intestines

• Loss of appetite, dry mouth, nausea, vomiting, stomach discomfort, abdominal pain, diarrhea, decrease in intestinal movements (constipation), absence of intestinal movements (paralytic ileus), flatulence.
• Inflammation of the salivary glands, inflammation of the pancreas, increase in amylase levels in the blood (a pancreatic enzyme).
• Yellow discoloration of the skin (jaundice), inflammation of the gallbladder.

Chest cavity

• Respiratory failure, inflammation of the lungs (pneumonitis), formation of fibrous tissue in the lungs (interstitial lung disease), accumulation of fluid in the lungs (pulmonary edema).
• Very rare: Acute respiratory difficulty (the signs include severe respiratory difficulty, fever, weakness, and confusion).

Nervous system

• Dizziness (sensation of spinning head)
• Convulsions, low level of consciousness, coma, headache, dizziness.
• Apathy, confused state, depression, nervousness, agitation, sleep disturbances.
• Uncommon sensation of burning, itching, or tingling in the skin.
• Muscle weakness (paresis).

Skin and hair

• Itching, purple patches on the skin (purpura), urticaria, increased skin sensitivity to light, rash, facial rash and/or red areas that may leave scars (cutaneous lupus erythematosus), inflammation of blood vessels with subsequent tissue death (necrotizing vasculitis), peeling, redness, detachment, and blistering of the skin (toxic epidermal necrolysis).

Eyes and ears

• Yellow vision, blurred vision, worsening of myopia, decrease in tear production.
• Decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal hemorrhage) or acute angle-closure glaucoma).

Joints and muscles

• Muscle spasms, muscle pain.

Urinary system

• Renal dysfunction, acute renal insufficiency (decrease in urine production and accumulation of fluids and waste in the body), inflammation of the renal connective tissue (interstitial nephritis), presence of sugar in the urine.

Sexual

• Alterations of erection.

General/ Others

• General weakness, fatigue, fever, thirst.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly throughthe Spanish System for the 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.

Keep this medication out of the sight and reach of children.

This medication does not require special storage conditions.

Do not use this medication after the expiration date that appears on the packaging and on the blister after ‘CAD.:’.The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at your pharmacy.If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Silostar Plus

The active ingredients are nebivolol and hydrochlorothiazide. Each tablet contains 5 mg of nebivolol ((as nebivolol hydrochloride) 2.5 mg of d-nebivolol and 2.5 mg of l-nebivolol) and 25 mg of hydrochlorothiazide.

The other components are:

• Core: lactose monohydrate, polisorbate 80 (E-433), hypromellose (E-464), cornstarch, croscarmellose sodium (E-468), microcrystalline cellulose (E-460(i)), anhydrous colloidal silica (E-551), magnesium stearate (E-470b).
• Coating: type I macrogol 40 estearate (E-431), titanium dioxide (E-171), carmines (aluminum lake carmine, E-120), hypromellose (E-464), microcrystalline cellulose (E-460(i)).

Appearance of the product and contents of the package

Silostar Plus is presented in the form of coated tablets, violet in color, round, slightly biconvex, with the inscription “5/25” in relief on one face and in packages of 7, 14, 28, 30, 56, and 90 coated tablets.

The tablets are packaged in blisters of (PP/COC/PP/Aluminum)

Not all package sizes may be marketed.

Marketing Authorization Holder

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

A. Menarini Manufacturing Logistics and Services S.r.l.

Via Sette Santi 3, 50131Florence,Italy

This medicine is authorized in the member states of the European Economic Area with the following names:

Austria: Nomexor plus HCT

Belgium: Hyporetic

Spain: Silostar Plus

France: CONEBILOX

Greece: Hypoloc-plus

Ireland: Nebilet Plus

Italy: Lobidiur

Luxembourg: Hyporetic

Netherlands: Hyporetic

Portugal: Hypoloc Plus

United Kingdom: Nebizide

Last review date of this leaflet: December 2021

For detailed and updated information on this medicine, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/