Nobizide

Italy
Brand name Nobizide
Form tablets, film-coated
Active substance / Dosage
NEBIVOLOL HYDROCHLORIDE
HYDROCHLOROTHIAZIDE
Prescription type Prescription only
ATC code
C07BB12
Registration number 039182
Manufacturer MENARINI INTERNATIONAL OPERATIONS LUXEMBOURG S.A.

Table of Contents

NOBIZIDE 5 mg/12.5 mg film-coated tablets

Package leaflet: Information for the user

NOBIZIDE 5 mg/12.5 mg film-coated tablets

Nebivolol / hydrochlorothiazide
Please read this leaflet carefully before using this medicine because it contains important
information for you. Keep this leaflet. You may need to read it again.
If you have any doubts, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms
are the same as yours, as it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor,
pharmacist, or nurse. See section 4.
Contents of this leaflet:

  1. What NOBIZIDE is and what it is used for
  2. What you need to know before taking NOBIZIDE
  3. How to take NOBIZIDE
  4. Possible side effects
  5. How to store NOBIZIDE
  6. Contents of the pack and other information

1. WHAT NOBIZIDE IS AND WHAT IT IS USED FOR

NOBIZIDE contains nebivolol and hydrochlorothiazide as active substances.
Nebivolol is a cardiovascular medicine belonging to the group of selective beta-blocking agents
(i.e. with selective action on the cardiovascular system). It prevents the increase in heart rate and controls the force of the heart's pumping action. In addition, it exerts a dilating effect on blood vessels, helping to lower blood pressure.
Hydrochlorothiazide is a diuretic that works by increasing the amount of urine produced by the patient.
NOBIZIDE combines nebivolol and hydrochlorothiazide in a single tablet. It is used to treat high blood pressure (arterial hypertension). It is used instead of the two separate medicines in patients who are already taking them simultaneously.

2. WHAT YOU SHOULD KNOW BEFORE TAKING NOBIZIDE

Do not take NOBIZIDE:

  • if you are allergic to nebivolol or 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 drug);
  • if you have one or more of the following conditions:

Page 1 of 20
NOBIZIDE 5 mg/12.5 mg film-coated tablets
o very slow heart rate (less than 60 beats per minute);
o other serious heart rhythm disorders (for example, sinoatrial node syndrome, sinoatrial block, second- or third-degree atrioventricular block);
o recently developed or recently worsened heart failure, or if you are being treated for circulatory shock due to acute heart failure with intravenous therapy to support heart function;
o low blood pressure;
o severe circulatory problems in the arms or legs;
o untreated pheochromocytoma, a tumor located above the kidneys (in the adrenal glands);
o severe kidney problems, complete absence of urine (anuria);
o a metabolic disorder (metabolic acidosis), for example diabetic ketoacidosis;
o asthma or breathing difficulties (currently or in the past);
o impaired liver function;
o high levels of calcium in the blood, low levels of potassium and sodium in the blood (persistent and resistant to treatment);
o high levels of uric acid with symptoms of gout.

Warnings and precautions
Talk to your doctor or pharmacist before taking NOBIZIDE.

  • Inform your doctor if you notice or develop any of the following conditions:
    o a type of chest pain caused by spontaneous spasm of blood vessels supplying the heart, called Prinzmetal's angina;
    o first-degree heart block (a mild cardiac conduction disorder affecting heart rhythm);
    o abnormally slow heartbeat;
    o untreated chronic heart failure;
    o lupus erythematosus (an immune system disorder, i.e. the body's defense system);
    o psoriasis (a skin disease causing scaly pink patches), or if you have previously suffered from psoriasis;
    o overactive thyroid gland: this medicine may mask signs of abnormally rapid heart rate caused by this condition;
    o poor circulation in the arms or legs, for example Raynaud's disease or syndrome, cramps when walking;
    o allergies: this medicine may intensify your reactions to pollen or other substances you are allergic to;
    o prolonged breathing difficulties;
    o diabetes: this medicine may mask warning signs of low blood glucose (e.g. palpitations, rapid heartbeat); your doctor will also advise you to monitor your blood glucose more frequently when taking NOBIZIDE, as it may be necessary to adjust the dose of your antidiabetic medications;
    o kidney problems: your doctor will monitor your kidney function to ensure it does not worsen. If you have severe kidney problems, do not take NOBIZIDE (see section "Do not take NOBIZIDE");

Page 2 of 20
NOBIZIDE 5 mg/12.5 mg film-coated tablets
o if you tend to have low potassium levels in the blood, especially if you have long QT syndrome (a type of electrocardiographic abnormality) or are taking digitalis (to support heart pumping function); you are more likely to have low blood potassium levels if you have liver cirrhosis, have experienced rapid fluid loss after intensive diuretic therapy, or if your dietary or fluid intake of potassium is inadequate;
o if you are scheduled for surgery, always inform the anesthesiologist that you are being treated with NOBIZIDE before undergoing anesthesia;
o if you have previously 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 cancer and lip cancer. Protect your skin from exposure to sunlight and UV radiation while taking NOBIZIDE.

  • NOBIZIDE may increase blood lipid levels and uric acid. It may affect levels of certain chemicals in the blood called electrolytes: your doctor will periodically check these with a blood test.
  • The hydrochlorothiazide contained in NOBIZIDE may make your skin hypersensitive to sunlight or artificial UV light. Stop taking NOBIZIDE and consult your doctor if you develop a skin rash, itchy spots, or skin sensitivity during treatment (see also section 4).
  • Anti-doping tests: NOBIZIDE may cause a positive result in anti-doping tests.

Children and adolescents
Due to lack of data on the use of this product in children and adolescents, the use of NOBIZIDE is not recommended in these age groups.

Other medicines and NOBIZIDE
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Always inform your doctor if you are using or have recently been given any of the following medicines in addition to NOBIZIDE.

  • Medicines that, like NOBIZIDE, may affect blood pressure and/or heart function:
  • medicines for controlling blood pressure or heart conditions (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 treatments for psychosis (a mental illness), e.g. amisulpride, barbiturates (also used for epilepsy), chlorpromazine, cyamemazine, droperidol, haloperidol, levomepromazine, narcotics, phenothiazines (also used for nausea and vomiting), pimozide, sulpiride, sultopride, thioridazine, tiapride, trifluoperazine;

Page 3 of 20
NOBIZIDE 5 mg/12.5 mg film-coated tablets

  • antidepressants, e.g. amitriptyline, fluoxetine, paroxetine;

  • medicines used for anesthesia during surgery;

  • medicines for asthma, nasal congestion, or certain eye disorders such as glaucoma (increased eye pressure) or pupil dilation (enlargement);

  • Baclofen (an antispastic drug);

  • Amifostine (a protective agent used during anticancer treatment).

  • Medicines whose effect or toxicity may be increased by NOBIZIDE:

  • lithium (used as a mood stabilizer);

  • cisapride (used for digestive problems);

  • bepridil (used for angina);

  • difemanyl (used for excessive sweating);

  • medicines used 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 used to treat 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 stomach burning and gastric ulcers);

  • calcium salts (used as bone health supplements);

  • medicines used to relax muscles (e.g. tubocurarine);

  • diazoxide, used to treat hypoglycemia and hypertension;

  • amantadine, an antiviral drug;

  • cyclosporine, used to suppress the body's immune response;

  • iodinated contrast media, used as contrast agents in X-rays;

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

  • Medicines whose effect may be reduced by NOBIZIDE:

  • medicines that lower blood glucose levels (insulin and oral antidiabetics, metformin);

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

  • medicines such as noradrenaline, used to treat low blood pressure or slow heart rate (bradycardia).

  • Non-steroidal anti-inflammatory drugs (NSAIDs) for pain and inflammation, as these may reduce the blood pressure-lowering effect of NOBIZIDE.

  • Medicines for excess stomach acid or ulcers (antacids): you should take NOBIZIDE during a meal and antacids between meals.

NOBIZIDE and alcohol
When taking NOBIZIDE, be careful not to drink alcohol, as you may feel confused or dizzy. If this occurs, do not drink alcohol, including wine, beer, or low-alcohol beverages.

Page 4 of 20
NOBIZIDE 5 mg/12.5 mg film-coated tablets

Pregnancy and breastfeeding
You must inform your doctor if you are or think you may be pregnant. Your doctor will usually advise you to take another medicine instead of NOBIZIDE, as NOBIZIDE is not recommended during pregnancy. This is because the active ingredient hydrochlorothiazide crosses the placenta. The use of NOBIZIDE during pregnancy may cause potentially harmful effects on the fetus and newborn.

Inform your doctor if you are breastfeeding or planning to breastfeed. NOBIZIDE is not recommended for women who are breastfeeding.

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Driving and using machines
This medicine may cause dizziness or fatigue. If these symptoms occur, do not drive and do not operate machinery.

NOBIZIDE contains lactose and sodium
This product contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, please contact him/her before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet, i.e., essentially "sodium-free".

3. HOW TO TAKE NOBIZIDE

Always take this medicine exactly as instructed by your doctor. If you have any doubts,
you must consult your doctor.
Take one tablet daily with a glass of water, preferably at the same time each day.
NOBIZIDE may be taken before, during, or after meals, or alternatively, independently of meals.
Use in children and adolescents
Do not administer NOBIZIDE to children or adolescents.
The break line is intended solely to facilitate tablet splitting if you have difficulty swallowing it whole.
If you take more NOBIZIDE than you should
If you accidentally take an excessive dose of this medicine, inform your doctor or pharmacist immediately.
The most common symptoms and signs of overdose include very slow heartbeat (bradycardia), low blood pressure with possible fainting, shortness of breath as in asthma, acute heart failure, excessive urination leading to dehydration, nausea and drowsiness, muscle spasms, and disturbances in heart rhythm (especially if you are also taking digitalis or medicines for heart rhythm disorders).
Page 5 of 20
NOBIZIDE 5 mg/12.5 mg film-coated tablets
If you forget to take NOBIZIDE
If you forget to take a dose of NOBIZIDE but remember shortly afterwards, you may take the missed dose as usual. However, if a long time has passed (e.g., several hours), such that it is nearly time for your next scheduled dose, skip the missed dose and take your next dose at the regular time. Do not take a double dose. However, avoid repeatedly skipping doses.
If you stop taking NOBIZIDE
Always consult your doctor before stopping treatment with NOBIZIDE.
If you have any doubts about how to use this product, consult your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The following side effects have been reported with nebivolol:
Common side effects (may affect up to 1 in 10 people):

  • headache
  • dizziness
  • fatigue
  • unusual sensations of burning, tingling, tickling, or prickling
  • diarrhoea
  • constipation
  • nausea
  • shortness of breath
  • swelling of the hands and feet.

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

  • slowed heart rate or other heart disturbances
  • low blood pressure
  • cramp-like leg pain while walking
  • abnormal vision
  • impotence
  • feeling of depression
  • digestive difficulties, stomach or intestinal gas, vomiting
  • skin rashes, itching
  • shortness of breath as in asthma, due to sudden cramping of the airway muscles (bronchospasm)
  • nightmares.

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

  • fainting
  • worsening of psoriasis (a skin disease causing scaly pink patches).

Page 6 of 20
NOBIZIDE 5 mg/12.5 mg film-coated tablets
The following side effects have been reported only in isolated cases:

  • widespread allergic reactions, including generalized skin rashes (hypersensitivity reactions);
  • rapidly developing swelling, especially around the lips, eyes, or tongue, possibly with sudden breathing difficulties (angioedema);
  • a type of skin rash characterized by itchy, raised, light-red wheals, either allergic or non-allergic in nature (urticaria).

The following undesirable effects have been reported with hydrochlorothiazide:
Frequency “not known”: skin and lip cancer (non-melanoma skin cancer)
Allergic reactions

  • generalized allergic reaction (anaphylactic reaction)

Heart and circulation

  • disturbances in heart rhythm, palpitations
  • changes in the 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; reduced production of new blood cells by the bone marrow
  • altered levels of body fluids (dehydration) and blood electrolytes, particularly decreased potassium, sodium, magnesium, chloride, and increased calcium
  • increased levels of uric acid, gout, increased blood glucose, diabetes, metabolic alkalosis (a metabolic disorder), increased cholesterol and triglycerides.

Stomach and intestines

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

Chest

  • Breathing difficulties, lung inflammation (pneumonia), development of fibrous tissue in the lungs (interstitial pneumonitis), fluid accumulation in the lungs (pulmonary edema)

Nervous system

  • Dizziness (sensation of spinning)
  • seizures, reduced level of consciousness, coma, headache, dizziness
  • apathy, confusion, depression, nervousness, restlessness, sleep disturbances

Page 7 of 20
NOBIZIDE 5 mg/12.5 mg film-coated tablets

  • unusual burning, tingling, tickling, or prickling sensations of the skin
  • muscle weakness (paresis)

Skin and hair

  • Itching, purple spots or patches on the skin (purpura), urticaria, increased sensitivity of the skin to sunlight, skin rashes, facial rash and/or blotchy redness that may lead to scarring (cutaneous lupus erythematosus), inflammation of blood vessels leading to tissue death (necrotizing vasculitis), skin peeling, redness, looseness, and blistering of the skin (toxic epidermal necrolysis)

Eyes and ears

  • Yellow vision, blurred vision, worsening of myopia, reduced tear production.

Muscles and joints

  • Muscle cramp, muscle pain

Urinary system

  • Kidney dysfunction, acute kidney failure (reduced urine production and accumulation of fluids and waste in the body), inflammation of connective tissue within the kidneys (interstitial nephritis), glucose in urine.

Sexual organs

  • Erectile dysfunction

General/Other

  • General weakness, fatigue, fever, thirst.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. HOW TO STORE NOBIZIDE

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use NOBIZIDE after the expiry date which is stated on the carton and blister after 'EXP.'. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste.
Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.
Page 8 of 20
NOBIZIDE 5 mg/12.5 mg film-coated tablets

6. PACK CONTENTS AND OTHER INFORMATION

What NOBIZIDE contains
The active substances are nebivolol and hydrochlorothiazide. Each tablet contains 5 mg of nebivolol
(as nebivolol hydrochloride) consisting of 2.5 mg of d-nebivolol and 2.5 mg of l-nebivolol, and 12.5 mg of
hydrochlorothiazide.
The excipients are:

  • tablet core: monohydrate lactose, polysorbate 80 (E433), hypromellose (E464), maize starch, sodium croscarmellose (E468), microcrystalline cellulose (E460), colloidal anhydrous silica (E551), magnesium stearate (E572)
  • tablet coating: macrogol 40 stearate type I, titanium dioxide (E171), carmine (carminic acid on aluminium lake, E120), hypromellose (E464), microcrystalline cellulose (E460)

Description of the appearance of NOBIZIDE and pack contents
NOBIZIDE is available as round, slightly biconvex, pink film-coated tablets, marked with "5/12.5" on one side and a dividing line on the other side, in packs of 7, 14, 28, 30, 56, and 90 film-coated tablets.
The tablets are supplied in blisters (PP/COC/PP/aluminium).
(It is possible that not all pack sizes are marketed)

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Menarini International Operations Luxembourg S.A.
1, Avenue de la Gare L-1611 Luxembourg
Marketing Authorization Holder for sale: GlaxoSmithKline S.p.A. - Via A. Fleming, 2 - Verona
Manufacturer
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, 50131 Florence, Italy
Page 9 of 20
NOBIZIDE 5 mg/12.5 mg film-coated tablets
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Italy: Nobizide
Netherlands: Lobiretic
This patient information leaflet was last updated on
Page 10 of 20
NOBIZIDE 5 mg/25 mg film-coated tablets

Package leaflet: information for the user

NOBIZIDE 5 mg/25 mg film-coated tablets

Nebivolol / hydrochlorothiazide
Please read this leaflet carefully before using this medicine because it contains important information for you.
Keep this leaflet. You may need to read it again.
If you have any doubts, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist or nurse. See section 4.
Contents of this leaflet:

  1. What NOBIZIDE is and what it is used for
  2. What you need to know before taking NOBIZIDE
  3. How to take NOBIZIDE
  4. Possible side effects
  5. How to store NOBIZIDE
  6. Contents of the pack and other information

1. WHAT NOBIZIDE IS AND WHAT IT IS USED FOR

NOBIZIDE contains nebivolol and hydrochlorothiazide as active substances.
Nebivolol is a cardiovascular medicine belonging to the group of selective beta-blocking agents (i.e. with selective action on the cardiovascular system). It prevents the increase in heart rate and controls the force of the cardiac pump. In addition, it exerts a dilating effect on blood vessels, thus helping to lower blood pressure.
Hydrochlorothiazide is a diuretic that works by increasing the amount of urine produced by the patient.
NOBIZIDE combines nebivolol and hydrochlorothiazide in a single tablet. It is used to treat high blood pressure (arterial hypertension). It is used instead of the two separate products in patients who are already taking them together.

2. WHAT YOU SHOULD KNOW BEFORE TAKING NOBIZIDE

Do not take NOBIZIDE:

  • 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 drug);
  • if you have one or more of the following conditions:
    o very slow heart rate (less than 60 beats per minute);
    o other serious heart rhythm disorders (e.g., sinoatrial syndrome, sinoatrial block, second- or third-degree atrioventricular block);
    o recently developed or recently worsened heart failure, or if you are being treated for circulatory shock due to acute heart failure with intravenous therapy to support heart function;
    o low blood pressure;
    o severe circulation problems in arms or legs;
    o untreated pheochromocytoma, a tumor located above the kidneys (in the adrenal glands);
    o severe kidney problems, complete absence of urine (anuria);
    o a metabolic disorder (metabolic acidosis), for example diabetic ketoacidosis;
    o asthma or breathing difficulties (current or past);
    o impaired liver function;
    o high levels of calcium in the blood, low levels of potassium and sodium in the blood (persistent and resistant to treatment);
    o high levels of uric acid with symptoms of gout.

Warnings and precautions

Talk to your doctor or pharmacist before taking NOBIZIDE

  • Inform your doctor if you notice or develop any of the following conditions:
    o a type of chest pain caused by spontaneous spasm of blood vessels supplying the heart, known as Prinzmetal's angina;
    o first-degree heart block (a mild heart conduction disorder affecting heart rhythm);
    o abnormally slow heartbeat;
    o untreated chronic heart failure;
    o lupus erythematosus (an immune system disorder, i.e., the body's defense system);
    o psoriasis (a skin disease causing scaly pink patches), or if you have previously suffered from psoriasis;
    o overactive thyroid gland: this medicine may mask signs of abnormally rapid heartbeat caused by this condition;
    o poor circulation in arms or legs, for example Raynaud’s disease or syndrome, cramps when walking;
    o allergy: this medicine may intensify your reactions to pollen or other substances you are allergic to;
    o prolonged breathing difficulties;
    o diabetes: this medicine may mask warning signs of low blood sugar (e.g., palpitations, rapid heartbeat); your doctor will also advise you to monitor your blood glucose levels more frequently while taking NOBIZIDE, as it may be necessary to adjust the dose of your antidiabetic medications;
    o kidney problems: your doctor will check your kidney function to ensure it does not worsen. If you have severe kidney problems, do not take NOBIZIDE (see section "Do not take NOBIZIDE");
    o if you tend to have low potassium levels in the blood, especially if you have long QT syndrome (a type of electrocardiographic abnormality), or if you are taking digitalis (to help your heart pump); you are more likely to have low potassium levels if you have liver cirrhosis, rapid fluid loss after intensive diuretic therapy, or inadequate potassium intake through food and drinks;
    o if you are scheduled for surgery, always inform the anesthetist that you are being treated with NOBIZIDE before undergoing anesthesia;
    o if you have previously had skin cancer or develop unexpected skin lesions during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. Protect your skin from exposure to sunlight and UV radiation during treatment with NOBIZIDE.

  • NOBIZIDE may increase levels of fats in the blood and uric acid. It may affect levels of certain chemicals in the blood called electrolytes: your doctor will periodically check these with a blood test.

  • The hydrochlorothiazide contained in NOBIZIDE may make your skin hypersensitive to sunlight or artificial UV light. Stop taking NOBIZIDE and consult your doctor if you develop a skin rash, itchy spots, or skin sensitivity during treatment (see also section 4).

  • Anti-doping tests: NOBIZIDE may cause a positive result in anti-doping tests.

Children and adolescents
Due to lack of data on the use of this product in children and adolescents, the use of NOBIZIDE is not recommended in these age groups.

Other medicines and NOBIZIDE
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Always inform your doctor if you are using or have recently been given any of the following medicines in addition to NOBIZIDE.

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

    • medicines for controlling blood pressure or 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 treatments for psychosis (a mental illness), e.g., amisulpride, barbiturates (also used for epilepsy), chlorpromazine, cyamemazine, droperidol, haloperidol, levomepromazine, narcotics, phenothiazines (also used for nausea and vomiting), pimozide, sulpiride, sultopride, thioridazine, tiapride, trifluoperazine;
    • medicines for depression, e.g., amitriptyline, fluoxetine, paroxetine;
    • medicines used for anesthesia during surgery;
    • medicines for asthma, nasal congestion, or certain eye disorders such as glaucoma (increased eye pressure) or pupil dilation (enlargement);
    • baclofen (a muscle relaxant drug);
    • amifostine (a protective agent used during anti-tumor therapy).

  • Medicines whose effect or toxicity may be increased by NOBIZIDE:

    • lithium (used as a mood stabilizer);
    • cisapride (used for digestive problems);
    • bepridil (used for angina);
    • difemanil (used for excessive sweating);
    • medicines used for infections: intravenous or injected erythromycin, pentamidine, sparfloxacin, amphotericin, sodium penicillin G, halofantrine (used for malaria);
    • vincamine (used for cerebral circulation disorders);
    • mizolastine and terfenadine (used for allergies);
    • diuretics and laxatives;
    • medicines used to treat 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 stomach burning and gastric ulcers);
    • calcium salts (used as bone health supplements);
    • medicines used to relax muscles (e.g., tubocurarine);
    • diazoxide, used to treat hypoglycemia and hypertension;
    • amantadine, an antiviral drug;
    • cyclosporine, used to suppress the body's immune response;
    • iodinated contrast media, used as contrast agents in X-rays;
    • anticancer medicines (e.g., cyclophosphamide, fluorouracil, methotrexate).

  • Medicines whose effect may be reduced by NOBIZIDE:

    • Medicines that lower blood glucose levels (insulin and oral antidiabetics, metformin);
    • Medicines for gout (e.g., allopurinol, probenecid, sulfinpyrazone);
    • Medicines such as noradrenaline, used to treat low blood pressure or slow heart rate (bradycardia).
    • Non-steroidal anti-inflammatory drugs (NSAIDs) for pain and inflammation, as these may reduce the blood pressure-lowering effect of NOBIZIDE.
    • Medicines for excess stomach acid or ulcers (antacids): you should take NOBIZIDE with a meal and antacids between meals.

NOBIZIDE and alcohol
When taking NOBIZIDE, be careful not to drink alcohol, as you may feel confused or dizzy. If this occurs, avoid alcohol, including wine, beer, or low-alcohol beverages.

Pregnancy and breastfeeding
You must inform your doctor if you are or think you may be pregnant. Your doctor will usually advise you to take another medicine instead of NOBIZIDE, as NOBIZIDE is not recommended during pregnancy. This is because the active ingredient hydrochlorothiazide crosses the placenta. Use of NOBIZIDE during pregnancy may cause potentially harmful effects on the fetus and newborn.
Inform your doctor if you are breastfeeding or planning to breastfeed. NOBIZIDE is not recommended for women who are breastfeeding.
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Driving and using machines
This medicine may cause dizziness or fatigue. If these symptoms occur, do not drive and do not operate machinery.

NOBIZIDE contains lactose and sodium
This product contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet, i.e., essentially "sodium-free".

3. HOW TO TAKE NOBIZIDE

Always take this medicine exactly as instructed by your doctor. If you have any doubts,
you must consult your doctor.
Take one tablet daily with a little water, preferably at the same time each day.
NOBIZIDE may be taken before, during or after meals, or alternatively, independently of meals.
Use in children and adolescents
Do not administer NOBIZIDE to children or adolescents.
If you take more NOBIZIDE than you should
If you accidentally take an excessive dose of this medicine, inform your doctor or
pharmacist immediately. The most common symptoms and signs of overdose are
very slow heartbeat (bradycardia), low blood pressure with possible fainting,
shortness of breath as in asthma, acute heart failure, excessive urination leading to
dehydration, nausea and drowsiness, muscle cramps, disturbances in heart rhythm
(especially if you are also taking digitalis or medicines for heart rhythm problems).
If you forget to take NOBIZIDE
If you forget to take a dose of NOBIZIDE but remember shortly afterwards, you may
take that dose as usual. However, if a long time has passed (for example, several hours),
so that it is nearly time for the next dose, skip the missed dose and
Page 15 of 20
NOBIZIDE 5 mg/25 mg film-coated tablets
take the next regular dose at the usual time. Do not take a double dose. However, avoid
repeatedly skipping doses.
If you stop taking NOBIZIDE
You must always consult your doctor before stopping treatment with NOBIZIDE.
If you have any questions about the use of this product, consult your doctor or pharmacist.
4 POSSIBLE ADVERSE REACTIONS
Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
The following side effects have been reported with nebivolol:
Common adverse reactions (may affect up to 1 in 10 people):

  • headache
  • dizziness
  • fatigue
  • unusual sensation of burning, tingling, tickling or prickling
  • diarrhoea
  • constipation
  • nausea
  • shortness of breath
  • swelling of the hands and feet.

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

  • slowed heart rate or other heart problems
  • low blood pressure
  • cramp-like pain in the legs while walking
  • abnormal vision
  • impotence
  • feeling of depression
  • difficulty in digestion, gas in the stomach or intestines, vomiting
  • skin rashes, itching
  • shortness of breath as in asthma, due to sudden cramps in the muscles of the airways (bronchospasm)
  • nightmares.

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

  • fainting
  • worsening of psoriasis (a skin disease causing scaly pink patches).

The following adverse reactions have been reported only in isolated cases:

  • widespread allergic reactions, including generalized skin rashes (hypersensitivity reactions); Page 16 of 20

NOBIZIDE 5 mg/25 mg film-coated tablets

  • rapidly developing swelling, especially around the lips, eyes or tongue, possibly with sudden breathing difficulties (angioedema);
  • a type of skin rash characterized by itchy, raised, light red welts, either allergic or non-allergic in nature (urticaria).

The following adverse reactions have been reported with hydrochlorothiazide:
Frequency “not known”: skin and lip cancer (non-melanoma skin cancer)
Allergic reactions

  • generalized allergic reaction (anaphylactic reaction)

Heart and circulation

  • disturbances in heart rhythm, palpitations
  • changes in the electrocardiogram
  • sudden fainting upon standing, formation of blood clots in veins (thrombosis) and embolism, circulatory collapse (shock)

Blood

  • changes in the number of blood cells, such as: reduction in white blood cells, reduction in platelets, reduction in red blood cells; reduced production of new blood cells by the bone marrow
  • altered levels of body fluids (dehydration) and blood electrolytes, particularly decreased potassium, sodium, magnesium, chloride, and increased calcium
  • increased levels of uric acid, gout, increased blood glucose, diabetes, metabolic alkalosis (a metabolic disorder), increased cholesterol and triglycerides.

Stomach and intestine

  • Loss of appetite, dry mouth, nausea, vomiting, stomach discomfort, abdominal pain, diarrhoea, reduced bowel movements (constipation), absence of bowel movements (paralytic ileus), flatulence
  • inflammation of the glands producing saliva, inflammation of the pancreas, increased levels of amylase in the blood (a pancreatic enzyme)
  • yellowing of the skin (jaundice), inflammation of the gallbladder

Chest

  • Breathing difficulties, inflammation of the lungs (pneumonia), formation of fibrous tissue in the lungs (interstitial lung disease), accumulation of fluid in the lungs (pulmonary edema)

Nervous system

  • Dizziness (sensation of spinning)
  • seizures, reduced level of consciousness, coma, headache, dizziness
  • apathy, confusion, depression, nervousness, restlessness, sleep disturbances
  • burning, tingling, tickling or unusual prickling sensations of the skin
  • muscle weakness (paresis)

Skin and hair
Page 17 of 20
NOBIZIDE 5 mg/25 mg film-coated tablets

  • Itching, purple spots or patches on the skin (purpura), urticaria, increased sensitivity of the skin to sunlight, skin rashes, facial rash and/or blotchy redness that may cause scarring (cutaneous lupus erythematosus), inflammation of blood vessels leading to tissue death (necrotizing vasculitis), exfoliation, redness, looseness and blistering of the skin (toxic epidermal necrolysis)

Eyes and ears

  • Yellow vision, blurred vision, worsening of myopia, reduced tear production.

Muscles and joints

  • Muscle spasm, muscle pain

Urinary system

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

Sexual organs

  • Erectile dysfunction

General/Other

  • General weakness, fatigue, fever, thirst.

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, consult your
doctor or pharmacist. You may also report adverse reactions directly via the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting adverse reactions, you can help provide more information on the
safety of this medicine.

5. HOW TO STORE NOBIZIDE

Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use NOBIZIDE after the expiry date stated on the carton and blister after 'EXP.'. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste.
Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. PACK CONTENT AND OTHER INFORMATION

What NOBIZIDE contains
Page 18 of 20
NOBIZIDE 5 mg/25 mg film-coated tablets
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 25 mg of
hydrochlorothiazide.
The excipients are:

  • tablet core: monohydrate lactose, polysorbate 80 (E433), hypromellose (E464), maize starch, sodium croscarmellose (E468), microcrystalline cellulose (E460), colloidal anhydrous silica (E551), magnesium stearate (E572)
  • tablet coating: macrogol 40 stearate type I, titanium dioxide (E171), carmine (carminic acid on aluminium lake, E120), hypromellose (E464), microcrystalline cellulose (E460)

Description of the appearance of NOBIZIDE and pack contents
NOBIZIDE is available as slightly biconvex, round, film-coated tablets, violet in colour, with "5/25" engraved on one side, in packs of 7, 14, 28, 30, 56, and 90 film-coated tablets.
The tablets are supplied in blisters (PP/COC/PP/aluminium).
(It is possible that not all pack sizes are marketed)

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Menarini International Operations Luxembourg S.A.
1, Avenue de la Gare L-1611 Luxembourg
Selling Agent: GlaxoSmithKline S.p.A. - Via A. Fleming, 2 - Verona

Manufacturer
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, 50131 Florence, Italy

This medicinal product is authorised in the European Economic Area member states under the following names:
Italy: Nobizide
Page 19 of 20
NOBIZIDE 5 mg/25 mg film-coated tablets
Netherlands: Lobiretic

This leaflet has been last revised:
Page 20 of 20