Nebivolol and hydrochlorothiazide Mylan

Patient Information Leaflet: Information for the patient

Nebivolol and Hydrochlorothiazide Mylan 5 mg/12.5 mg film-coated tablets, mg/25 mg film-coated tablets

Nebivolol / Hydrochlorothiazide
Generic Medicine
Please read this entire leaflet carefully before taking this medicine, as 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. Do not give it to others, 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, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Nebivolol and Hydrochlorothiazide Mylan is and what it is used for

Nebivolol and Hydrochlorothiazide Mylan 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 dilates blood vessels, helping to lower blood pressure.
• Hydrochlorothiazide is a diuretic that works by increasing the amount of urine produced.

Nebivolol and Hydrochlorothiazide Mylan combines nebivolol and hydrochlorothiazide in a single tablet. It is used to treat high blood pressure (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 Nebivolol and Hydrochlorothiazide Mylan

Do not take Nebivolol and Hydrochlorothiazide Mylan

• 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 to other sulfonamide-derived substances (such as hydrochlorothiazide, which is a sulfonamide-derived drug);
• if you suffer from one or more of the following conditions:
• very slow heart rate (less than 60 beats per minute);
• certain other serious heart rhythm disorders (e.g. sick sinus syndrome, sinoatrial block, second- or third-degree atrioventricular block);
• recently developed heart failure or recent worsening of heart failure, or if you are being treated for circulatory shock due to acute heart failure with intravenous therapy to support heart function;
• low blood pressure;
• severe circulatory problems in arms or legs;
• untreated pheochromocytoma, a tumour located above the kidneys (in the adrenal gland);
• severe kidney problems, complete absence of urine (anuria);
• a metabolic disorder (metabolic acidosis), such as diabetic ketoacidosis;
• asthma or breathing difficulties (currently or in the past);
• liver problems;
• persistently high levels of calcium in the blood, or persistently low levels of potassium and sodium in the blood that are resistant to treatment;
• high levels of uric acid with symptoms of gout.

Warnings and precautions
Talk to your doctor or pharmacist before taking Nebivolol and Hydrochlorothiazide Mylan.
Inform your doctor if you have or have had any of the following conditions:

• 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 Nebivolol and Hydrochlorothiazide Mylan;
• a specific type of chest pain due to spontaneous cardiac spasms known as Prinzmetal's angina;
• first-degree heart block (a mild cardiac conduction disorder affecting heart rhythm);
• abnormally slow heartbeat;
• untreated chronic heart failure;
• systemic lupus erythematosus (an autoimmune disorder, i.e. a disorder of the body's immune defence system);
• psoriasis (a skin disease characterized by scaly pink patches) or if you have previously suffered from psoriasis;
• overactive thyroid gland: this medicine may mask signs of abnormally rapid heartbeat caused by this condition;
• poor circulation in arms and legs, e.g. Raynaud’s disease or syndrome, cramp-like pain while walking;
• allergies: this medicine may intensify your reaction to pollen or other substances you are allergic to;
• prolonged breathing difficulties;
• 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 levels more frequently when taking Nebivolol and Hydrochlorothiazide Mylan, as your antidiabetic medication dose may need adjustment;
• kidney problems: your doctor will monitor your kidney function to ensure it does not worsen. Do not take Nebivolol and Hydrochlorothiazide Mylan if you have severe kidney problems (see section “Do not take Nebivolol and Hydrochlorothiazide Mylan”);
• 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); 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 have inadequate potassium intake through food and drinks;
• if you are scheduled for surgery, always inform the anaesthetist that you are taking Nebivolol and Hydrochlorothiazide Mylan before receiving anaesthesia.

During treatment

• Nebivolol and Hydrochlorothiazide Mylan may increase blood lipid levels and uric acid levels.

• Nebivolol and Hydrochlorothiazide Mylan may affect levels of certain electrolytes in the blood (such as magnesium, potassium, sodium, and chloride): your doctor may periodically check electrolyte levels with a blood test. This may cause symptoms such as dry mouth, thirst, weakness, fatigue, muscle weakness, muscle pain or cramps, rapid heartbeat, dizziness, low blood pressure, restlessness, feeling unwell, and reduced urination. Inform your doctor if any of these symptoms occur.

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

• Inform your doctor if you experience any changes in vision or eye pain during treatment with Nebivolol and Hydrochlorothiazide Mylan. This could indicate the development of glaucoma. Discontinue treatment with Nebivolol and Hydrochlorothiazide Mylan and consult your doctor.

Laboratory tests

• Anti-doping tests: Nebivolol and Hydrochlorothiazide Mylan may cause a positive anti-doping test result.
• Nebivolol and Hydrochlorothiazide Mylan may alter the results of parathyroid function tests. Inform your doctor or hospital staff that you are taking Nebivolol and Hydrochlorothiazide Mylan before undergoing these tests.

Children and adolescents
Due to lack of data on use in children and adolescents, the use of Nebivolol and Hydrochlorothiazide Mylan is not recommended for these age groups.

Other medicines and Nebivolol and Hydrochlorothiazide Mylan
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 receiving any of the following medicines concurrently with Nebivolol and Hydrochlorothiazide Mylan:

• Medicines that, like Nebivolol and Hydrochlorothiazide Mylan, 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, carbamazepine, 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 anaesthesia during surgery;

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

• baclofen (a muscle relaxant);

• amifostine (a protective agent used during anti-tumour therapy);

• cholestyramine or colestipol (medicines used to lower cholesterol levels);

• Medicines whose effect or toxicity may be increased by Nebivolol and Hydrochlorothiazide Mylan:

• 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 heartburn and gastric ulcers);

• calcium salts, used as bone health supplements;

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

• diazoxide, used to treat hypoglycaemia 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;

• certain anticancer drugs (e.g. cyclophosphamide, fluorouracil, methotrexate);

• Medicines whose effect may be reduced by Nebivolol and Hydrochlorothiazide Mylan:

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

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

• medicines such as noradrenaline, used to treat low blood pressure or slow heart rate;

• Pain and anti-inflammatory medicines (non-steroidal anti-inflammatory drugs), as these may reduce the blood pressure-lowering effect of Nebivolol and Hydrochlorothiazide Mylan.

• Medicines for treating gastric hyperacidity or ulcers (antacids), e.g. cimetidine, omeprazole: The use of these medicines together with Nebivolol and Hydrochlorothiazide Mylan is not recommended due to possible undesirable interactions.

Nebivolol and Hydrochlorothiazide Mylan and alcohol
Be cautious when consuming alcohol during treatment with Nebivolol and Hydrochlorothiazide Mylan, as fainting or dizziness may occur. If this happens, do not consume any more alcohol, including wine, beer, or carbonated alcoholic beverages.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
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 Nebivolol and Hydrochlorothiazide Mylan, as it is not recommended during pregnancy. This is because the active substance hydrochlorothiazide crosses the placenta. The use of Nebivolol and Hydrochlorothiazide Mylan during pregnancy may cause potentially harmful effects on the foetus and newborn.

Inform your doctor if you are breastfeeding or intend to breastfeed. Nebivolol and Hydrochlorothiazide Mylan is not recommended for women who are breastfeeding.

Driving and using machines
This medicine may cause dizziness or fatigue. Do not drive or operate machinery if you are affected by these symptoms.

Nebivolol and Hydrochlorothiazide Mylan contains lactose
This medicine contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take Nebivolol and Hydrochlorothiazide Mylan

Take this medicine exactly as instructed by your doctor. If you have any doubts, contact your doctor.
The recommended dose is 1 tablet daily with a little water, preferably always at the same time each day.
Nebivolol and Hydrochlorothiazide Mylan must be taken at least 30 minutes before meals on an empty stomach.

For Nebivolol and Hydrochlorothiazide Mylan 5 mg/12.5 mg film-coated tablets only:
The break line is intended solely to help divide the tablet if you have difficulty swallowing it whole.

Use in children and adolescents
Do not administer Nebivolol and Hydrochlorothiazide Mylan to children or adolescents.

If you take more Nebivolol and Hydrochlorothiazide Mylan than you should
If you accidentally take too much of this medicine, contact 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 cramps, and irregular heartbeat (especially if you are also taking digitalis or medicines for heart rhythm problems).

If you forget to take Nebivolol and Hydrochlorothiazide Mylan
If you forget to take a dose of Nebivolol and Hydrochlorothiazide Mylan but remember shortly afterwards, you may take the missed dose as usual. However, if you only remember after a longer period (e.g. several hours), such that it is already time for your next scheduled dose, skip the missed dose and take your next dose as planned. Do not take a double dose to make up for the forgotten dose. However, avoid missing too many doses.

If you stop taking Nebivolol and Hydrochlorothiazide Mylan
You must always consult your doctor before stopping treatment with Nebivolol and Hydrochlorothiazide Mylan.
If you have any doubts about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking Nebivolol and Hydrochlorothiazide Mylan and contact a doctor immediately if you experience any of the following reactions:

• severe allergic reactions affecting the whole body, including widespread skin rash (hypersensitivity reactions); sudden swelling, especially around the lips, eyes or tongue, possibly with sudden breathing difficulties (angioedema) Frequency not known (frequency cannot be estimated from the available data)

The following side effects have been reported with nebivolol:
Common (may affect up to 1 in 10 people):

• headache
• dizziness
• fatigue
• unusual sensations of burning, tingling, tickling or prickling (paraesthesia)
• diarrhoea
• constipation
• nausea
• shortness of breath
• swollen hands or feet

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

• slow heartbeat or other heart problems
• low blood pressure
• cramping pain in the legs when walking
• abnormal vision
• impotence
• feeling depressed
• digestive problems, bloating, vomiting
• skin rash, itching
• breathlessness, such as in asthma due to sudden cramping of the muscles around the airways (bronchospasm)
• nightmares

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

• fainting
• worsening of psoriasis (a skin condition characterised by scaly pink patches)

Not known (frequency cannot be estimated from the available data): The following side effects have been reported in isolated cases:

• a type of skin rash characterised by raised, itchy, pale red wheals of allergic or non-allergic origin (urticaria);
• seeing or hearing things that are not real (hallucinations);
• loss of contact with reality (psychosis);
• circulation problems in the fingers and toes, arms and legs, which may lead to paleness, bluish discolouration or tingling in the fingers and toes (Raynaud's syndrome);
• dry eyes, scarring or thickening of the eyelids or the white of the eye.

The following side effects have been reported with hydrochlorothiazide:

Allergic reactions

• severe allergic reactions affecting the whole body (anaphylactic reaction)

Heart and circulation

• heart rhythm disorders, 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: reduced white blood cells, reduced platelets, reduced red blood cells; reduced production of new blood cells by the bone marrow
• disturbances in body fluids (dehydration) and blood electrolytes, particularly reduced 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/or 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 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

• breathing difficulties, lung inflammation (pneumonitis), fibrous tissue formation in the lungs (interstitial lung disease), fluid accumulation in the lungs (pulmonary oedema)

Nervous system

• dizziness (sensation of spinning)
• seizures, reduced level of consciousness, coma, headache, dizziness
• apathy, confusion, depression, nervousness, restlessness, sleep disturbances
• unusual sensations of burning, tingling, tickling or prickling
• 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 (including erythema multiforme), facial rash and/or blotchy redness that may lead to scarring (cutaneous lupus erythematosus), inflammation of blood vessels leading to tissue death (necrotising vasculitis), peeling, redness, looseness and blistering of the skin (toxic epidermal necrolysis)
• skin and lip cancer (non-melanoma skin cancer) [Frequency not known (cannot be estimated from the available data)]

Eyes and ears

• yellow vision, blurred vision, worsening of myopia, reduced tear production, reduced vision and eye pain (possibly indicative of acute myopia or acute angle-closure glaucoma)

Joints and muscles

• muscle cramps, muscle pain

Urinary system

• kidney dysfunction, acute kidney failure (reduced urine production and accumulation of fluids and waste in the body), inflammation of the connective tissue within the kidneys (interstitial nephritis), sugar in the 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, pharmacist or nurse. You can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Nebivolol and Hydrochlorothiazide Mylan

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 packaging and blister after the word 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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Nebivolol and Hydrochlorothiazide Mylan contains
Nebivolol and Hydrochlorothiazide Mylan 5 mg / 12.5 mg film-coated tablets

• The active substances are nebivolol and hydrochlorothiazide. Each tablet contains 5 mg of nebivolol (as nebivolol hydrochloride) and 12.5 mg of hydrochlorothiazide.

Nebivolol and Hydrochlorothiazide Mylan 5 mg / 25 mg film-coated tablets

• The active substances are nebivolol and hydrochlorothiazide. Each tablet contains 5 mg of nebivolol (as nebivolol hydrochloride) and 25 mg of hydrochlorothiazide.
• The other components are:
• Tablet core: monohydrate lactose, polysorbate 80, hypromellose (13.6 mPas), maize starch, microcrystalline cellulose, monohydrate citric acid, anhydrous colloidal silica, magnesium stearate. Coating: Opadry White 03A 580004 [only 5/12.5 mg], Opadry Yellow 03A520012 [only 5/25 mg], hypromellose (6 mPas), titanium dioxide (E171), polyoxyl (Macrogol) stearate, microcrystalline cellulose, yellow iron oxide (E172) [only 5/25 mg].

Description of the appearance of Nebivolol and Hydrochlorothiazide Mylan and package contents
Nebivolol and Hydrochlorothiazide Mylan 5 mg/12.5 mg film-coated tablets are available as film-coated tablets, 9.2 mm in size, white to off-white in colour, round, biconvex, with "515" imprinted on one side and a break line on the other side.

Nebivolol and Hydrochlorothiazide Mylan 5 mg/25 mg film-coated tablets are available in the form of
film-coated tablets, 9.2 mm in size, light yellow, round, biconvex, with "525" engraved on one side.
Pack sizes:
28, 30 and 90 film-coated tablets
The tablets are supplied in blisters.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Mylan S.p.A., Via Vittor Pisani 20, 20124 Milan, Italy
Manufacturers
Balkanpharma – Dupnitsa AD, 3 Samokovsko Shosse Str., Dupnitza 2600, Bulgaria
Fine Foods & Pharmaceuticals N.T.M. S.p.A., Via Grignano 43, 24041 Brembate (BG), Italy
This medicinal product is authorized in the Member States of the European Economic Area under the
following names: