LOBIVON PLUS 5 mg/12.5 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

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

Contents of the pack and further information

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

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

Lobivon Plus is a combination of nebivolol and hydrochlorothiazide in one tablet and is used to treat high blood pressure (hypertension). It is used in patients who are already taking both products separately.

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

Do not take Lobivon Plus

• If you are allergic to nebivolol or hydrochlorothiazide or 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 sick sinus syndrome, sinoatrial block, 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 calcium levels in the blood and low potassium and sodium levels in the blood that are persistent and resistant to treatment.
• High uric acid levels with symptoms of gout.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Lobivon 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 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 increase 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 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 Lobivon 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 make sure it does not worsen. If you have severe kidney problems, do not take Lobivon Plus (see section "Do not take Lobivon Plus").
• If you tend to have low potassium levels in your blood, and especially if you suffer from QT prolongation 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 suffer from 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 Lobivon 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 exposure while taking Lobivon 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 Lobivon 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 shortness of breath or severe difficulty breathing after taking Lobivon Plus, go to the doctor immediately.

• Lobivon 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 Lobivon 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 Lobivon Plus and inform your doctor (see also Section 4).
• Doping test: Lobivon Plus may produce a positive analytical result in doping tests.

Children and adolescents

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

Use of Lobivon 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 Lobivon Plus, you are using or receiving any of the following medicines:

• Medicines that, like Lobivon 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 Lobivon 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 salicylate-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 Lobivon Plus:

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

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

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

Taking Lobivon Plus with alcohol

Be careful when drinking alcohol while taking Lobivon Plus, as you may feel faint or dizzy. If this happens, do not drink any alcohol, including wine, beer, or soft 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 Lobivon Plus, as it is not recommended during pregnancy. This is because the active substance 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 about to start breastfeeding. Lobivon 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 so, avoiddriving and using machinery.

Lobivon Plus contains lactose and sodium

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them 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 Lobivon 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.

Lobivon 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 Lobivon 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 Lobivon 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 Lobivon Plus

If you forget to take a dose of Lobivon 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 forgotten dose and take the next scheduled dose at the usual time. Do not take a double dose. However, you should try to avoid repeated forgetfulness of taking the medication.

If you stop taking Lobivon Plus

Always consult your doctor before stopping treatment with Lobivon Plus.

If you have any other 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 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 with digestion, 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 patches 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 allergic reaction.

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 cells, decrease in platelets, decrease in red cells; alteration of the production of new blood cells in the bone marrow.
• Alteration of the levels of body fluids (dehydration) and the levels of chemicals in the blood, in particular decrease in the levels of potassium, sodium, magnesium, chloride and increase in the levels of calcium.
• Increased levels of uric acid, gout, increased glucose in the blood, 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, inflammation of the pancreas, increased levels of amylase in the blood (a pancreatic enzyme).
• Yellowing 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 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 the blood vessels with consequent 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, 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 Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Lobivon 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 'CAD.:'. 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 the 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

Composition of Lobivon 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 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)), colloidal anhydrous 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)).

Appearance of the Product and Package Contents

Lobivon Plus is presented in the form of film-coated tablets, pink in color, round, slightly biconvex, with the inscription "5/12.5" in relief on one face and with a score line on the other face, 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:

Laboratorios Menarini, S.A.

Alfons XII, 587 - 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:

Belgium: Nobiretic

Bulgaria: Nebilet Plus

Cyprus: Lobivon plus

Denmark: Hypoloc Comp

Slovakia: Nebilet HCTZ

Slovenia: Co-Nebilet

Spain: Lobivon Plus

Estonia: Nebilet Plus

Finland: Hypoloc Comp

France: Temeritduo

Greece: Lobivon-plus

Hungary: Nebilet Plus

Ireland: Hypoloc Plus

Italy: Aloneb

Latvia: Nebilet Plus

Lithuania: Nebilet Plus

Luxembourg: Nobiretic

Malta: Nebilet Plus

Poland: Nebilet HCT

Netherlands: Nebiretic

Portugal: Nebilet Plus

Czech Republic: Nebilet Plus H 5 mg/ 12,5 mg film-coated tablets

Romania: Co-Nebilet 5 mg/ 12.5 mg

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/