Silostar Plus 5 mg/12.5 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

SILOSTAR PLUS 5 mg/12.5 mg film-coated tablets

Nebivolol/Hydrochlorothiazide

Read the entire 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents:

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

Contents of the pack and other information

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

Silostar Plus contains nebivolol and hydrochlorothiazide as active substances.

• Nebivolol is a cardiovascular medicine belonging to the group of selective beta-blockers (with selective activity on the cardiovascular system). It prevents the increase in heart rate and controls the heart's pumping force. It also works by widening blood vessels, which helps lower blood pressure.
• Hydrochlorothiazide is a diuretic that works by increasing urine production.

Silostar Plus is a fixed-dose combination of nebivolol and hydrochlorothiazide in one tablet and is used for the treatment of high blood pressure (hypertension). It is used in patients who are already being treated with both components separately.

2. What you need to know before taking Silostar Plus

Do not take Silostar Plus

• If you are allergic to nebivolol, or to hydrochlorothiazide, or to any of the other components 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 serious heart rhythm disorders (e.g., sinoatrial block, second- or third-degree atrioventricular block).

• Recently experienced an episode of heart failure or worsening of heart failure, or are receiving intravenous treatment to support heart function following 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), which is not being treated.

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

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

• Asthma or difficulty breathing (currently or in the past).

• Liver function disorders.

• Persistently high calcium levels and persistently low potassium and sodium levels in blood that are resistant to treatment.

• High uric acid levels with symptoms of gout.

Warnings and precautions

Talk to your doctor or pharmacist before starting Silostar Plus.

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

• A type of chest pain caused by spontaneous spasm of the heart arteries, called Prinzmetal's angina.

• First-degree heart block (a mild conduction disorder affecting heart rhythm).

• Abnormally slow heart rate.

• Chronic heart failure that is not being treated.

• Lupus erythematosus (an immune system disorder, which is your body’s defense system).

• Psoriasis (a skin disease characterized by scaly pink patches), or if you have ever had psoriasis.

• Overactive thyroid gland: this medicine may mask signs of this condition, such as abnormally high heart rate.

• Poor circulation in arms or legs, such as Raynaud’s disease or syndrome, or leg pain similar to cramps when walking.

• Allergies: this medicine may intensify your reaction to pollen or other substances you are allergic to.

• Chronic respiratory problems.

• Diabetes: this medicine may mask warning signs of low blood sugar (e.g., palpitations, rapid heartbeat) 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 may advise you to monitor your blood sugar more frequently while taking Silostar Plus, as your antidiabetic medicine dose may need adjustment.

• Kidney problems: your doctor will check your kidney function to ensure it does not worsen. Do not take Silostar Plus if you have severe kidney problems (see section “Do not take Silostar Plus”).

• If you tend to have low potassium levels in blood, especially if you have long QT syndrome (a type of ECG abnormality) or are taking digitalis (to help the heart beat); low blood potassium is more likely if you have liver cirrhosis, have experienced excessive fluid loss due to strong diuretic treatment, or have inadequate potassium intake through food and drink.

• If you are scheduled for surgery, always inform your anesthetist that you are taking Silostar Plus before anesthesia.

• If you have had skin cancer or develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin and lip cancer. Protect your skin from sun exposure and UV rays while taking Silostar Plus.

• If you experience vision loss or eye pain, which could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure, occurring within hours to weeks after taking Silostar Plus. This may lead to permanent vision loss if untreated. If you have previously had an allergy to penicillins or sulfonamides, you may be at higher risk.

• If you have had respiratory or lung problems (such as lung inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you develop shortness of breath or severe breathing difficulty after taking Silostar Plus, contact your doctor immediately.

• Silostar Plus may increase blood lipid and uric acid levels. It may affect levels of certain blood chemicals called electrolytes: your doctor will monitor these periodically with blood tests.

• The hydrochlorothiazide in Silostar Plus may cause skin hypersensitivity to sunlight or artificial UV light. If you develop a rash, itching, or skin sensitivity during treatment, stop taking Silostar Plus and inform your doctor (see also section 4).

• Anti-doping tests: Silostar Plus may produce a positive result in anti-doping tests.

Children and adolescents

Not recommended for use in children and adolescents due to lack of data on the use of this medicine in this patient group.

Taking Silostar Plus with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

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

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

• Medicines to control blood pressure or treat heart problems (e.g., 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), e.g., amisulpride, barbiturates (also used for epilepsy), chlorpromazine, cyamemazine, droperidol, haloperidol, levomepromazine, narcotic derivatives, phenothiazines (also used for nausea and vomiting), pimozide, sulpiride, sultopride, thioridazine, tiapride, trifluoperazine.

• Medicines for depression, e.g., amitriptyline, paroxetine, fluoxetine.

• Medicines used for anesthesia during surgery.

• Medicines for asthma, nasal congestion, and certain eye conditions such as glaucoma (increased eye pressure) or pupil dilation.

• Medicines for diabetes, such as insulin or oral antidiabetics.

• Baclofen (a muscle relaxant).

• Amifostine (a protective agent 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 given by infusion or injection, pentamidine, sparfloxacin, amphotericin, sodium penicillin G, halofantrine (used for malaria).

• Vincamine (used for cerebral circulation problems).

• Mizolastine and terfenadine (used for allergies).

• Diuretics and laxatives.

• Medicines for acute inflammation: steroids (e.g., cortisone and prednisone), ACTH (adrenocorticotropic hormone), and salicylic acid derivatives (e.g., acetylsalicylic acid/aspirin and other salicylates).

• Carbenoxolone (used for heartburn and stomach ulcers).

• Calcium salts (used as bone health supplements).

• Medicines used to relax muscles (e.g., tubocurarine).

• Diazoxide (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 in X-ray imaging.

• Anticancer medicines (e.g., cyclophosphamide, fluorouracil, methotrexate).

• Medicines whose effect may be reduced by Silostar Plus:

• Medicines that lower blood sugar (insulin and oral antidiabetic medicines, metformin).

• Medicines for gout (e.g., allopurinol, probenecid, sulfinpyrazone).

• Medicines such as noradrenaline, used to treat low blood pressure and slow heart rate.

• Non-steroidal anti-inflammatory drugs (NSAIDs) for pain and inflammation, as they may reduce blood pressure-lowering effects of Silostar Plus.

• Medicines for stomach acidity or ulcers (antacids): take Silostar Plus with food, and antacids between meals.

Taking Silostar Plus with alcohol

Be cautious when consuming alcohol while taking Silostar Plus, as you may feel faint or dizzy. If this occurs, avoid alcohol, including wine, beer, or alcoholic beverages.

Pregnancy and breastfeeding

Inform your doctor if you are pregnant or think you might be pregnant. Your doctor will likely advise you to take an alternative 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.

Inform your doctor if you are breastfeeding or planning to breastfeed. Silostar Plus is not recommended for breastfeeding mothers.

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

This medicine may cause dizziness or fatigue. If so, do not drive or operate machinery.

Silostar Plus contains lactose and sodium

This medicine contains lactose. If your doctor has informed you of an intolerance to certain sugars, consult them before taking this medicine.

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

3. How to take Silostar Plus

Follow exactly the dosage instructions given by your doctor. If in doubt, consult your doctor again.

Take one tablet daily with some water, preferably at the same time each day.

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

Use in children and adolescents

Do not administer Silostar Plus to children or adolescents.

The tablet scoring is intended solely for splitting the tablet if you find it difficult to swallow 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 immediately at 91 562 04 20, indicating the medicine and the amount taken.

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

The most frequent symptoms and signs of overdose include very slow heartbeat (bradycardia), low blood pressure with possible fainting, breathing difficulties resembling asthma, acute heart failure, excessive urination leading to consequent dehydration, nausea and drowsiness, muscle spasms, and disturbances in heart rhythm (especially if you are taking digitalis or medications for heart rhythm disorders).

If you forget to take Silostar Plus

If you forget to take a dose of Silostar Plus but remember shortly after the time you were supposed to take it, take the daily dose as usual. However, if a long time has passed (several hours), so that it is close to the time of your next scheduled dose, skip the missed dose and take the next dose at the usual time. Do not take a double dose. Nevertheless, you should try to avoid repeatedly forgetting to take your medication.

If you discontinue treatment with Silostar Plus

Always consult your doctor before stopping treatment with Silostar Plus.

If you have any further questions about 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 everyone experiences 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.
• Unusual sensation of burning, tingling, or prickling on the skin.
• Diarrhea.
• Constipation.
• Nausea.
• Difficulty breathing, shortness of breath.
• Sweating of hands and feet.

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

• Slow heartbeat or other heart disturbances.
• Low blood pressure.
• Leg pain resembling cramps when walking.
• Abnormal vision.
• Sexual impotence.
• Difficulty digesting, stomach or intestinal gas, vomiting.
• Skin rash, itching.
• Difficulty breathing as 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:

• Generalized allergic reactions with widespread skin rash (hypersensitivity reactions);

• Sudden swelling, especially around the lips, eyes, or tongue, possibly with acute breathing difficulty (angioedema).

• Skin rash characterized by raised, itchy, pink welts, due to either allergic or non-allergic causes (urticaria).

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

Frequency not known: Skin and lip cancer (non-melanoma skin cancer)

Allergic reactions

• Generalized allergic reaction (anaphylactic reaction).

Heart and circulation

• Heart rhythm disturbances, palpitations.
• Changes in electrocardiogram.
• Sudden fainting upon standing, formation of blood clots in veins (thrombosis) and embolism, circulatory collapse (shock).

Blood

• Changes in blood cell counts, such as: decreased white blood cells, decreased platelets, decreased red blood cells; altered production of new blood cells in the bone marrow.
• Disturbances in body fluid levels (dehydration) and in levels of chemicals in the blood, particularly decreased levels of potassium, sodium, magnesium, chloride, and increased levels of calcium.
• 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

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

Chest

• 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 frequency: Acute breathing difficulty (symptoms include severe shortness of breath, fever, weakness, and confusion).

Nervous system

• Dizziness (sensation of spinning).
• Seizures, decreased level of consciousness, coma, headache, dizziness.
• Apathy, confusion, depression, nervousness, agitation, sleep disturbances.
• Unusual sensation of burning, tingling, or prickling on 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 red patches that may leave scars (cutaneous lupus erythematosus), inflammation of blood vessels leading to tissue death (necrotizing vasculitis), skin peeling, redness, shedding, and blister formation (toxic epidermal necrolysis).

Eyes and ears

• Yellow vision, blurred vision, worsening of myopia, decreased tear production.
• Decreased vision or eye pain due to elevated 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 connective tissue of the kidneys (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 adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide 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 any special storage conditions.

Do not use this medicine after the expiry date stated on the carton and blister after 'EXP.:'. The expiry date refers to the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Silostar Plus

The active substances 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: monohydrate lactose, 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 (carmine lake of aluminic acid, E-120), hypromellose (E-464), microcrystalline cellulose (E-460(i)).

Appearance of the product and contents of the pack

Silostar Plus is presented as film-coated tablets, pink in colour, round, slightly biconvex, with the engraved mark “5/12.5” on one side and a score line on the other side. The tablets are available in packs containing 7, 14, 28, 30, 56 and 90 film-coated tablets.

The tablets are packaged in blisters made of (PP/COC/PP/Aluminium).

Not all pack 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 responsible

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 medicinal product 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 most recent revision of this leaflet: April 2025

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/