SILOSTAR PLUS 5mg/12.5mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

SILOSTAR PLUS 5 mg/ 12.5 mg film-coated tablets

Nebivolol/ Hydrochlorothiazide

Read all of this leaflet carefully before you start taking 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, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Silostar Plus and what is it used for
2. What you need to know before you take Silostar Plus
3. How to take Silostar Plus
4. Possible side effects
5. Storage of Silostar Plus

Contents of the pack and further information

1. What is Silostar Plus and what is it used for

Silostar Plus contains nebivolol and hydrochlorothiazide as active substances.

• Nebivolol is a medicine with cardiovascular action, 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 the heart's pumping. It also acts by widening blood vessels, which helps to decrease blood pressure.
• Hydrochlorothiazide is a diuretic that acts by increasing urine production.

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

2. What you need to know before you take Silostar Plus

Do not take Silostar Plus

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

• 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 (such as sinoatrial disease, second- and third-degree atrioventricular block).
• You have recently suffered a heart failure episode or worsening of it, or 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.
• Pheochromocytoma, 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 difficult breathing (currently or in the past).
• Liver function disorders.
• High levels of calcium in the blood and low levels of potassium and sodium in the blood that are persistent and resistant to treatment.
• High levels of uric acid with symptoms of gout.

Warnings and precautions

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

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

• A type of chest pain due to a spontaneous spasm of the heart's arteries, called Prinzmetal's angina.
• First-degree heart block (mild alteration of cardiac conduction that affects heart rhythm).
• Abnormally slow heart rate.
• Chronic heart failure that is not being treated.
• 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.
• Overactivity of the thyroid gland: this medicine may mask the signs due to this condition, such as abnormally high heart rate.
• Poor circulation in arms or legs, such as Raynaud's disease or syndrome, pain when walking similar to a cramp.
• Allergies: this medicine may intensify your reaction to pollen or other substances you are allergic to.
• Chronic respiratory problems.
• Diabetes: this medicine may mask the warning signs produced by low blood sugar levels (e.g., palpitations, rapid heart rate) and may increase the risk of severe hypoglycemia when used with certain types of antidiabetic medicines called sulfonylureas (e.g., gliquidone, gliclazide, glibenclamide, glipizide, glimepiride, or tolbutamide); your doctor will advise you to check your blood sugar more often while taking Silostar Plus, as it may be necessary to adjust the dose of the antidiabetic medicines 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 tend to have low potassium levels in your blood, and especially if you suffer from 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 in your blood if you have liver cirrhosis, or have suffered excessive water loss due to strong diuretic treatment, or if your potassium intake with food and drink is inadequate.
• If you need to undergo surgery, always inform your anesthesiologist that you are taking Silostar Plus before being anesthetized.
• If you have had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, in particular its long-term use at high doses, may increase the risk of certain types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from sun and UV ray exposure while taking Silostar Plus.
• If you experience a decrease in vision or eye pain, they could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase in eye pressure and can occur within a few hours to weeks after taking Silostar Plus. This can lead to permanent vision loss if left untreated. 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 blood fat levels and uric acid. It may affect the levels of certain chemicals in the blood, called electrolytes: your doctor will check them from time to time with a blood test.
• Hydrochlorothiazide in Silostar Plus may cause hypersensitivity of your skin to sunlight or artificial UV light. If a rash, itching, or sensitive skin appears during treatment, stop taking Silostar Plus and inform your doctor (see also Section 4).
• Doping tests: Silostar Plus may produce a positive analytical result in doping tests.

Children and adolescents

Do notrecommend the use of Silostar Plus in children and adolescents due to the absence of data on the use of this medicine in these patients.

Using Silostar Plus with other medicines

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

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

• Medicines that, like Silostar Plus, may have an effect on blood pressure and/or heart function:

• Medicines to control blood pressure or medicines 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 medicines for psychosis (a mental illness), such as amisulpride, barbiturates (also used for epilepsy), chlorpromazine, ciamemazine, droperidol, haloperidol, levomepromazine, narcotic derivatives, phenothiazine (also used for vomiting and nausea), pimozide, sulpiride, sultopride, thioridazine, tiaprida, trifluoperazine.
• Medicines for depression, such as amitriptyline, paroxetine, fluoxetine.
• Medicines used for anesthesia during an operation.
• Medicines for asthma, nasal congestion, and certain eye disorders such as glaucoma (increased eye pressure) or dilation (enlargement) of the pupil.
• Medicines for diabetes, such as insulin or oral antidiabetics.
• Baclofen (an antispastic medicine).
• Amifostine (a protective medicine used during cancer treatment).

• Medicines 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).
• Medicines for infections: erythromycin administered by infusion or injection, pentamidine, and sparfloxacin, amphotericin, and sodium penicillin G, halofantrine (used for malaria).
• Vincamine (used for cerebral circulation problems).
• Mizolastine and terfenadine (used for allergies).
• Diuretics and laxatives.
• Medicines to treat acute inflammation: steroids (such as cortisone and prednisone), ACTH (adrenocorticotropic hormone), and salicylic acid-derived medicines (such as acetylsalicylic acid/aspirin and other salicylates).
• Carbenoxolone (used for heartburn and stomach ulcers).
• Calcium salts (used as a supplement for bone health).
• Medicines used to relax muscles (such as tubocurarine).
• Diaxozide (used to treat low blood sugar and high blood pressure).
• Amantadine, an antiviral medicine.
• Cyclosporine, used to suppress the body's immune response.
• Iodinated contrast media, used to contrast in X-ray scans.
• Anticancer medicines (such as cyclophosphamide, fluorouracil, methotrexate).

• Medicines whose effect may be decreased by Silostar Plus:

• Medicines that lower blood sugar (insulin and oral antidiabetics, metformin).
• Medicines for gout (such as allopurinol, probenecid, and sulfinpyrazone).
• Medicines like noradrenaline, used to treat low blood pressure and slow heart rate.

• Pain and inflammation medicines (non-steroidal anti-inflammatory medicines), as they may lower blood pressure, reducing the effect of Silostar Plus.

• Medicines to treat excess stomach acid or ulcers (antacids): you should take Silostar Plus during meals, and the antacid between meals.

Taking Silostar Plus with alcohol

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

Pregnancy and breastfeeding

You must inform your doctor if you are pregnant or think you may be pregnant. Your doctor will advise you to take another medicine instead of Silostar Plus, as it 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.

Tell your doctor if you are breastfeeding or about to start breastfeeding. Silostar Plus is not recommended in breastfeeding mothers.

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

This medicine may cause dizziness or fatigue. If this is the case, avoiddriving and using machinery.

Silostar Plus contains lactose and sodium

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consultthem before taking this medicine .

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

3. How to take Silostar Plus

Follow exactly the administration instructions of the medicine 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 give Silostar Plus to children or adolescents.

The score line is only for breaking the tablet if you find it difficult to swallow it whole.

If you take more Silostar Plus than you should

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

It is recommended to take the package and the leaflet of the medicine to the healthcare professional.

The most frequent symptoms and signs of overdose are very slow heart rate (bradycardia), low blood pressure with possible fainting, difficulty breathing as in asthma, acute heart failure, excessive urine elimination with consequent dehydration, nausea, and drowsiness, muscle spasms, heart rhythm disorders (especially if you are taking digitalis or medicines for heart rhythm problems).

If you forget to take Silostar Plus

If you forgot to take a dose of Silostar Plus, but you remember shortly after when you should have taken it, take the daily dose as you usually do. However, if a lot of time has passed (several hours), so that it is close to the next dose, skip the missed dose and take the next scheduled dose at the usual time. Do not take a double dose. However, you should try to avoid repeatedly forgetting to take the medication.

If you stop taking Silostar Plus

Always consult your doctor before stopping treatment with Silostar Plus.

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

4. Possible Adverse Effects

Like all medicines, this medicine can have adverse effects, although not all people suffer from them.

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

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

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

Uncommon adverse effects (may affect up to 1 in 100 people):

• Slow heartbeat or other cardiac disorders.
• Low blood pressure.
• Pain in the legs similar to a cramp when walking.
• Abnormal vision.
• Sexual impotence.
• Feeling of depression.
• Difficulty digesting, gas in the stomach or intestine, vomiting.
• Skin rash, itching.
• Difficulty breathing like in asthma, due to sudden contraction of the muscles around the airways (bronchospasm).
• Nightmares.

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

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

The following adverse effects have been reported in only a few isolated cases:

• Allergic reactions throughout the body, with generalized skin rash (hypersensitivity reactions);
• Sudden swelling, especially around the lips, eyes, or tongue with possible acute difficulty breathing (angioedema).
• Skin rash characterized by pink, raised hives that cause itching, of allergic or non-allergic origin (urticaria).

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

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

Allergic reactions.

• Anaphylactic reaction throughout the body.

Heart and circulation.

• Cardiac rhythm disorders, 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 and chemical substances in the blood, in particular decrease in potassium, sodium, magnesium, chloride levels 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 intestine.

• Lack of appetite, dry mouth, nausea, vomiting, stomach discomfort, abdominal pain, diarrhea, decreased intestinal movements (constipation), absence of intestinal movements (paralytic ileus), flatulence.
• Inflammation of the salivary glands, pancreatitis, increased levels of amylase in the blood (a pancreatic enzyme).
• Yellowing of the skin (jaundice), inflammation of the gallbladder.

Chest cavity.

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

Nervous system.

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

Skin and hair.

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

Eyes and ears.

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

Joints and muscles.

• Muscle spasms, muscle pain.

Urinary system.

• Kidney dysfunction, acute kidney failure (decreased urine production and accumulation of fluids and waste in the body), inflammation of the kidney connective tissue (interstitial nephritis), presence of sugar in the urine.

Sexual.

• Erectile dysfunction.

General/Other.

• General weakness, fatigue, fever, thirst.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Medicines Monitoring System: www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Silostar Plus

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

This medicine does not require special storage conditions.

Do not use this medicine after the expiration date that appears on the carton and on the blister after 'EXP.'. The expiration date is the last day of the month indicated.

Medicines should not be thrown away through the sewers or in the trash. Deposit the containers and medicines you no longer need in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Silostar Plus Composition

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 12.5 mg of hydrochlorothiazide.

The other components are:

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

Product Appearance and Package Contents

Silostar Plus is presented in the form of film-coated tablets, pink, round, slightly biconvex, with the inscription "5/12.5" in relief on one side and with a score line on the other side, and in packages of 7, 14, 28, 30, 56, and 90 film-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.

Manufacturer

Berlin-Chemie AG.

Glienicker Weg 125 - 12489 Berlin, Germany.

or.

Menarini - Von Heyden GMBH.

Leipziger Strasse 7-13, 01097 – Dresden, Germany.

or.

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

Via Sette Santi 3, 50131 Florence, Italy.

This medicine is authorized in the Member States of the European Economic Area under the following names:

Austria: Nomexor plus HCT.

Spain: Silostar Plus.

France: CONEBILOX.

Greece: Hypoloc-plus.

Ireland: Nebilet Plus.

Italy: Lobidiur.

Netherlands: Hyporetic.

Date of the Last Revision of this Prospectus:April 2025.

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